MPP+-Lesioned Mice: an Experimental Model of Motor, Emotional, Memory/Learning, and Striatal Neurochemical Dysfunctions.

PubMed

Cunha, Mauricio P; Pazini, Francis L; Lieberknecht, Vicente; Budni, Josiane; Oliveira, Ágatha; Rosa, Júlia M; Mancini, Gianni; Mazzardo, Leidiane; Colla, André R; Leite, Marina C; Santos, Adair R S; Martins, Daniel F; de Bem, Andreza F; Gonçalves, Carlos Alberto S; Farina, Marcelo; Rodrigues, Ana Lúcia S

2017-10-01

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces motor and nonmotor dysfunctions resembling Parkinson's disease (PD); however, studies investigating the effects of 1-methyl-4-phenylpyridinium (MPP + ), an active oxidative product of MPTP, are scarce. This study investigated the behavioral and striatal neurochemical changes (related to oxidative damage, glial markers, and neurotrophic factors) 24 h after intracerebroventricular administration of MPP + (1.8-18 μg/mouse) in C57BL6 mice. MPP + administration at high dose (18 μg/mouse) altered motor parameters, since it increased the latency to leave the first quadrant and reduced crossing, rearing, and grooming responses in the open-field test and decreased rotarod latency time. MPP + administration at low dose (1.8 μg/mouse) caused specific nonmotor dysfunctions as it produced a depressive-like effect in the forced swim test and tail suspension test, loss of motivational and self-care behavior in the splash test, anxiety-like effect in the elevated plus maze test, and short-term memory deficit in the step-down inhibitory avoidance task, without altering ambulation. MPP + at doses of 1.8-18 μg/mouse increased tyrosine hydroxylase (TH) immunocontent and at 18 μg/mouse increased α-synuclein and decreased parkin immunocontent. The astrocytic calcium-binding protein S100B and glial fibrillary acidic protein (GFAP)/S100B ratio was decreased following MPP + administration (18 μg/mouse). At this highest dose, MPP + increased the ionized calcium-binding adapter molecule 1 (Iba-1) immunocontent, suggesting microglial activation. Also, MPP + at a dose of 18 μg/mouse increased thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels and increased glutathione peroxidase (GPx) and hemeoxygenase-1 (HO-1) immunocontent, suggesting a significant role for oxidative stress in the MPP + -induced striatal damage. MPP + (18 μg/mouse) also increased striatal fibroblast growth factor 2 (FGF-2) and brain-derived neurotrophic factor (BDNF) levels. Moreover, MPP + decreased tropomyosin receptor kinase B (TrkB) immunocontent. Finally, MPP + (1.8-18 μg/mouse) increased serum corticosterone levels and did not alter acetylcholinesterase (AChE) activity in the striatum but increased it in cerebral cortex and hippocampus. Collectively, these results indicate that MPP + administration at low doses may be used as a model of emotional and memory/learning behavioral deficit related to PD and that MPP + administration at high dose could be useful for analysis of striatal dysfunctions associated with motor deficits in PD.

Algorithms and programming tools for image processing on the MPP:3

NASA Technical Reports Server (NTRS)

Reeves, Anthony P.

1987-01-01

This is the third and final report on the work done for NASA Grant 5-403 on Algorithms and Programming Tools for Image Processing on the MPP:3. All the work done for this grant is summarized in the introduction. Work done since August 1986 is reported in detail. Research for this grant falls under the following headings: (1) fundamental algorithms for the MPP; (2) programming utilities for the MPP; (3) the Parallel Pascal Development System; and (4) performance analysis. In this report, the results of two efforts are reported: region growing, and performance analysis of important characteristic algorithms. In each case, timing results from MPP implementations are included. A paper is included in which parallel algorithms for region growing on the MPP is discussed. These algorithms permit different sized regions to be merged in parallel. Details on the implementation and peformance of several important MPP algorithms are given. These include a number of standard permutations, the FFT, convolution, arbitrary data mappings, image warping, and pyramid operations, all of which have been implemented on the MPP. The permutation and image warping functions have been included in the standard development system library.

Increased Serum Interleukin-10 but not Interleukin-4 Level in Children with Mycoplasma pneumoniae Pneumonia.

PubMed

Medjo, Biljana; Atanaskovic-Markovic, Marina; Nikolic, Dimitrije; Radic, Snezana; Lazarevic, Ivana; Cirkovic, Ivana; Djukic, Slobodanka

2017-08-01

Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia in children, and it has been associated with wheezing. The aim of this study was to examine the serum level of interleukin (IL)-4 and IL-10 in children with Mycoplasma pneumoniae pneumonia (MPP) and to analyse them in relation to the presence of wheezing. The study included 166 children with radiologically confirmed pneumonia. MP infection was confirmed by enzyme-linked immunosorbent assay (ELISA) serum MP-IgM and MP-IgG test and throat swab MP DNA with real-time polymerase chain reaction. Serum levels of IL-4 and IL-10 were measured using ELISA. There was no significant difference in serum level of IL-4 between children with MPP and those with non-MPP. Among children with MPP, we found similar level of IL-4 regardless of the personal and family history of allergy and asthma or the presence of wheezing. A significantly higher level of IL-10 was found in children with MPP than in children with non-MPP (32.92±18.582 vs. 27.01±14.100 pg/ml, p =0.022). Furthermore, wheezing children with MPP had a significantly higher level of IL-10 than children with MPP without wheezing (43.75±26.644 vs. 27.50±10.211 pg/ml, p=0.027). Our results show significantly increased serum level of IL-10 in children with MPP, which was significantly higher in children with wheezing. These findings may suggest a role of IL-10 in the pathogenesis of MPP and in the occurrence of wheezing during acute MP infection. © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Striatal MPP+ levels do not necessarily correlate with striatal dopamine levels after MPTP treatment in mice.

PubMed

Vaglini, F; Fascetti, F; Tedeschi, D; Cavalletti, M; Fornai, F; Corsini, G U

1996-06-01

The present study offers confirmation of the fact that an MAO-B inhibitor, (-) deprenyl and a DA uptake blocker, GBR-12909, prevent MPTP-induced striatal DA decrease. This protective effect is accompanied by an almost complete prevention of MPP+ production induced by (-) deprenyl and an accelerated MPP+ clearance induced by GBR-12909 within the striatum. Similarly, the MPTP toxicity enhancers, DDC and acetaldehyde, both increase striatal MPP+ levels, as previously reported. On the contrary, the treatment with MK 801, although uneffective in preventing the long-term MPTP-induced striatal DA decrease, causes an increase in the striatal amount of MPP+. In a similar way, the administration of nicotine in combination with MPTP produces a significant increase in the levels of striatal MPP+, which does not elicit any effect on striatal DA. The effect of clonidine is consistent with these results and in sharp contrast with the current belief that a direct relationship exists between striatal MPP+ concentrations and the degree of MPTP-induced depletion of striatal DA. In this study, using different treatments, we failed to confirm the correlation between MPP+ striatal levels and dopaminergic lesions after MPTP administration in mice. We suggest that this correlation is not a rule and exceptions may depend on a different compartimentalization of the toxic metabolite.

Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine.

PubMed

Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew; Xu, Alex; Duhart, Helen; Ali, Syed F

2004-10-01

The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity.

Report from the MPP Working Group to the NASA Associate Administrator for Space Science and Applications

NASA Technical Reports Server (NTRS)

Fischer, James R.; Grosch, Chester; Mcanulty, Michael; Odonnell, John; Storey, Owen

1987-01-01

NASA's Office of Space Science and Applications (OSSA) gave a select group of scientists the opportunity to test and implement their computational algorithms on the Massively Parallel Processor (MPP) located at Goddard Space Flight Center, beginning in late 1985. One year later, the Working Group presented its report, which addressed the following: algorithms, programming languages, architecture, programming environments, the way theory relates, and performance measured. The findings point to a number of demonstrated computational techniques for which the MPP architecture is ideally suited. For example, besides executing much faster on the MPP than on conventional computers, systolic VLSI simulation (where distances are short), lattice simulation, neural network simulation, and image problems were found to be easier to program on the MPP's architecture than on a CYBER 205 or even a VAX. The report also makes technical recommendations covering all aspects of MPP use, and recommendations concerning the future of the MPP and machines based on similar architectures, expansion of the Working Group, and study of the role of future parallel processors for space station, EOS, and the Great Observatories era.

Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome

PubMed Central

Kharde, Satyavati; Ahmed, Yasar Luqman; Stier, Gunter; Kunze, Ruth; Sinning, Irmgard

2017-01-01

In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA. Here we report the crystal structure of a complex between Imp4 and a short helical element of Mpp10 to a resolution of 1.88 Å. Furthermore, we extend the interaction network of Mpp10 and characterize two novel interactions. Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome. PMID:28813493

Guidance document publications list - Office of Environmental Policy and Assistance RCRA/CERCLA Division (EH-413)

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

NONE

1995-08-01

This document provides a listing of Guidance Documents from the RCRA/CERCLA Division for August 1995. Documents are listed under the following categories: RCRA Guidance Manuals; RCRA Information Briefs; CERCLA Guidance Manuals; CERCLA Regulatory Bulletins; RCRA/CERCLA Guidance Manuals; TSCA Guidance Manuals; TSCA Information Briefs; and, Cross Cut Manuals.

[Muenster Parental Programme--Feedback from Parents: How do parents evaluate an early intervention programme for improving the communication with their baby or toddler with hearing impairment?].

PubMed

Glanemann, R; Reichmuth, K; am Zehnhoff-Dinnesen, A

2016-02-01

With the implementation of the UNHS, early educational services' existing concepts of early intervention have to be adapted to the situation and needs of families with a preverbal child who is deaf or hard of hearing. The Muenster Parental Programme (MPP), a module in early family-centered intervention, fulfils this requirement. We report feedback from participating parents regarding processes and outcomes of the MPP. The self-developed questionnaire was checked for its suitability as feedback instrument for measuring parental satisfaction with the MPP. 29 parents who participated in the MPP assessed the programme by using the standardised FBB and the self-developed questionnaire FB-MEP, which is specific to the MPP. Using the FBB, 96% of parents judged the MPP to be good or very good. With the FB-MEP, parents rated setting, contents and didactics as highly as they did using the FBB (r = 0.7, p < 0.01). In particular, parents judged both the contact and exchange with other affected parents, and the specific individual support for communicating with their child (including video feedback) as especially helpful. The results reflect parents' high level of satisfaction with the setting, content, didactics and individual benefit gained by their child and themselves from the MPP. The parents are aware of the efficacy of the MPP, which was shown in the controlled intervention study. The self-developed questionnaire FB-MEP was shown to be a suitable instrument for quality assurance measurements of the MPP.

Effects of Agmatine on Depressive-Like Behavior Induced by Intracerebroventricular Administration of 1-Methyl-4-phenylpyridinium (MPP(+)).

PubMed

Moretti, Morgana; Neis, Vivian Binder; Matheus, Filipe Carvalho; Cunha, Mauricio Peña; Rosa, Priscila Batista; Ribeiro, Camille Mertins; Rodrigues, Ana Lúcia S; Prediger, Rui Daniel

2015-10-01

Considering that depression is a common non-motor comorbidity of Parkinson's disease and that agmatine is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system disorders, this study investigated the antidepressant-like effect of agmatine in mice intracerebroventricularly (i.c.v.) injected with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Male C57BL6 mice were treated with agmatine (0.0001, 0.1 or 1 mg/kg) and 60 min later the animals received an i.c.v. injection of MPP(+) (1.8 µg/site). Twenty-four hours after MPP(+) administration, immobility time, anhedonic behavior, and locomotor activity were evaluated in the tail suspension test (TST), splash test, and open field test, respectively. Using Western blot analysis, we investigated the putative modulation of MPP(+) and agmatine on striatal and frontal cortex levels of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF). MPP(+) increased the immobility time of mice in the TST, as well as induced an anhedonic-like behavior in the splash test, effects which were prevented by pre-treatment with agmatine at the three tested doses. Neither drug, alone or in combination, altered the locomotor activity of mice. I.c.v. administration of MPP(+) increased the striatal immunocontent of TH, an effect prevented by the three tested doses of agmatine. MPP(+) and agmatine did not alter the immunocontent of BDNF in striatum and frontal cortex. These results demonstrate for the first time the antidepressant-like effects of agmatine in an animal model of depressive-like behavior induced by the dopaminergic neurotoxin MPP(+).

Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition.

PubMed

Park, Jong-Chan; Han, Sun-Ho; Cho, Hyun Jin; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Kang, Seokjo; Jung, Eun Sun; Won, Su Jin; Kim, Eun Hye; Kim, Yu Kyeong; Lee, Dong Young; Mook-Jung, Inhee

2017-03-22

Plasma β-amyloid (Aβ) is a potential candidate for an Alzheimer's disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis. We predicted the brain amyloid deposit by measuring the plasma Aβ levels. This cross-sectional study included 353 participants (215 cognitively normal, 79 with mild cognitive impairment, and 59 with AD dementia) who underwent Pittsburgh-compound B positron emission tomography (PiB-PET) scans. We treated a mixture of protease inhibitors and phosphatase inhibitors (MPP) and detected plasma Aβ42 and Aβ40 (MPP-Aβ42 and MPP-Aβ40) in a stable manner using xMAP technology. MPP-Aβ40 and MPP-Aβ42/40 (MPP-Aβs) were significantly different between subjects with positive amyloid deposition (PiB+) and those with negative amyloid deposition (PiB-) (P < 0.0001). Furthermore, MPP-Aβ40 (P < 0.0001, r = 0.23) and MPP-Aβ42/40 ratio (P < 0.0001, r = -0.23) showed significant correlation with global PiB deposition (standardized uptake value ratio). In addition, our integrated multivariable (MPP-Aβ42/40, gender, age, and apolipoprotein E genotypes) logistic regression model proposes a new standard for the prediction of cerebral amyloid deposition. MPP-Aβ might be one of the potential blood biomarkers for the prediction of PiB-PET positivity in the brain.

Evidence for hydroxyl radical scavenging action of nitric oxide donors in the protection against 1-methyl-4-phenylpyridinium-induced neurotoxicity in rats.

PubMed

Banerjee, Rebecca; Saravanan, Karuppagounder S; Thomas, Bobby; Sindhu, Kizhake M; Mohanakumar, Kochupurackal P

2008-06-01

In the present study we provide evidence for hydroxyl radical (*OH) scavenging action of nitric oxide (NO*), and subsequent dopaminergic neuroprotection in a hemiparkinsonian rat model. Reactive oxygen species are strongly implicated in the nigrostriatal dopaminergic neurotoxicity caused by the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Since the role of this free radical as a neurotoxicant or neuroprotectant is debatable, we investigated the effects of some of the NO* donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) on in vitro *OH generation in a Fenton-like reaction involving ferrous citrate, as well as in MPP+-induced *OH production in the mitochondria. We also tested whether co-administration of NO* donor and MPP+ could protect against MPP+-induced dopaminergic neurotoxicity in rats. While NG, SNAP and SIN-1 attenuated MPP+-induced *OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up to 18-fold increase in *OH production in the latter reaction. Striatal dopaminergic depletion following intranigral infusion of MPP+ in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO*, when administered similarly failed to attenuate MPP+-induced neurotoxicity in vivo. Conversely, long-time air-exposed SNP solution when administered in rats intranigrally, caused a dose-dependent depletion of the striatal dopamine. These results confirm the involvement of *OH in the nigrostriatal degeneration caused by MPP+, indicate the *OH scavenging ability of NO*, and demonstrate protection by NO* donors against MPP+-induced dopaminergic neurotoxicity in rats.

Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation

PubMed Central

Schneider, Craig S.; Xu, Qingguo; Boylan, Nicholas J.; Chisholm, Jane; Tang, Benjamin C.; Schuster, Benjamin S.; Henning, Andreas; Ensign, Laura M.; Lee, Ethan; Adstamongkonkul, Pichet; Simons, Brian W.; Wang, Sho-Yu S.; Gong, Xiaoqun; Yu, Tao; Boyle, Michael P.; Suk, Jung Soo; Hanes, Justin

2017-01-01

Mucoadhesive particles (MAP) have been widely explored for pulmonary drug delivery because of their perceived benefits in improving particle residence in the lungs. However, retention of particles adhesively trapped in airway mucus may be limited by physiologic mucus clearance mechanisms. In contrast, particles that avoid mucoadhesion and have diameters smaller than mucus mesh spacings rapidly penetrate mucus layers [mucus-penetrating particles (MPP)], which we hypothesized would provide prolonged lung retention compared to MAP. We compared in vivo behaviors of variously sized, polystyrene-based MAP and MPP in the lungs following inhalation. MAP, regardless of particle size, were aggregated and poorly distributed throughout the airways, leading to rapid clearance from the lungs. Conversely, MPP as large as 300 nm exhibited uniform distribution and markedly enhanced retention compared to size-matched MAP. On the basis of these findings, we formulated biodegradable MPP (b-MPP) with an average diameter of <300 nm and examined their behavior following inhalation relative to similarly sized biodegradable MAP (b-MAP). Although b-MPP diffused rapidly through human airway mucus ex vivo, b-MAP did not. Rapid b-MPP movements in mucus ex vivo correlated to a more uniform distribution within the airways and enhanced lung retention time as compared to b-MAP. Furthermore, inhalation of b-MPP loaded with dexamethasone sodium phosphate (DP) significantly reduced inflammation in a mouse model of acute lung inflammation compared to both carrier-free DP and DP-loaded MAP. These studies provide a careful head-to-head comparison of MAP versus MPP following inhalation and challenge a long-standing dogma that favored the use of MAP for pulmonary drug delivery. PMID:28435870

Development of a stereo analysis algorithm for generating topographic maps using interactive techniques of the MPP

NASA Technical Reports Server (NTRS)

Strong, James P.

1987-01-01

A local area matching algorithm was developed on the Massively Parallel Processor (MPP). It is an iterative technique that first matches coarse or low resolution areas and at each iteration performs matches of higher resolution. Results so far show that when good matches are possible in the two images, the MPP algorithm matches corresponding areas as well as a human observer. To aid in developing this algorithm, a control or shell program was developed for the MPP that allows interactive experimentation with various parameters and procedures to be used in the matching process. (This would not be possible without the high speed of the MPP). With the system, optimal techniques can be developed for different types of matching problems.

Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging.

PubMed

Young, Kira; Borikar, Sneha; Bell, Rebecca; Kuffler, Lauren; Philip, Vivek; Trowbridge, Jennifer J

2016-10-17

Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of changes with age in the heterogeneous multipotent progenitor (MPP) cell compartment, which is long lived and responsible for dynamically regulating output of mature hematopoietic cells. In this study, we observe an early and progressive loss of lymphoid-primed MPP cells (LMPP/MPP4) with aging, concomitant with expansion of HSCs. Transcriptome and in vitro functional analyses at the single-cell level reveal a concurrent increase in cycling of aging LMPP/MPP4 with loss of lymphoid priming and differentiation potential. Impaired lymphoid differentiation potential of aged LMPP/MPP4 is not rescued by transplantation into a young bone marrow microenvironment, demonstrating cell-autonomous changes in the MPP compartment with aging. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging. © 2016 Young et al.

MPP1 directly interacts with flotillins in erythrocyte membrane - Possible mechanism of raft domain formation.

PubMed

Biernatowska, Agnieszka; Augoff, Katarzyna; Podkalicka, Joanna; Tabaczar, Sabina; Gajdzik-Nowak, Weronika; Czogalla, Aleksander; Sikorski, Aleksander F

2017-11-01

Flotillins are prominent, oligomeric protein components of erythrocyte (RBC) membrane raft domains and are considered to play an important structural role in lateral organization of the plasma membrane. In our previous work on erythroid membranes and giant plasma membrane vesicles (GPMVs) derived from them we have shown that formation of functional domains (resting state rafts) depends on the presence of membrane palmitoylated protein 1 (MPP1/p55), pointing to its new physiological role. Exploration of the molecular mechanism of MPP1 function in organizing membrane domains described here, through searching for its molecular partners in RBC membrane by using different methods, led to the identification of the raft-marker proteins, flotillin 1 and flotillin 2, as hitherto unreported direct MPP1 binding-partners in the RBC membrane. These proteins are found in high molecular-weight complexes in native RBC membrane and, significantly, their presence was shown to be separate from the well-known protein 4.1-dependent interactions of MPP1 with membrane proteins. Furthermore, FLIM analysis revealed that loss of the endogenous MPP1-flotillins interactions resulted in significant changes in RBC membrane-fluidity, emphasizing the physiological importance of such interactions in vivo. Therefore, our data establish a new perspective on the role of MPP1 in erythroid cells and suggests that direct MPP1-flotillins interactions could be the major driving-force behind the formation of raft domains in RBC. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Effects of blue light on pigment biosynthesis of Monascus.

PubMed

Chen, Di; Xue, Chunmao; Chen, Mianhua; Wu, Shufen; Li, Zhenjing; Wang, Changlu

2016-04-01

The influence of different illumination levels of blue light on the growth and intracellular pigment yields of Monascus strain M9 was investigated. Compared with darkness, constant exposure to blue light of 100 lux reduced the yields of six pigments, namely, rubropunctatamine (RUM), monascorubramine (MOM), rubropunctatin (RUN), monascorubrin (MON), monascin (MS), and ankaflavin (AK). However, exposure to varying levels of blue light had different effects on pigment production. Exposure to 100 lux of blue light once for 30 min/day and to 100 lux of blue light once and twice for 15 min/day could enhance RUM, MOM, MS, and AK production and reduce RUN and MON compared with non-exposure. Exposure to 100 lux twice for 30 min/day and to 200 lux once for 45 min/day decreased the RUM, MOM, MS, and AK yields and increased the RUN and MON. Meanwhile, the expression levels of pigment biosynthetic genes were analyzed by real-time quantitative PCR. Results indicated that gene MpPKS5, mppR1, mppA, mppB, mmpC, mppD, MpFasA, MpFasB, and mppF were positively correlated with the yields of RUN and MON, whereas mppE and mppR2 were associated with RUM, MOM, MS, and AK production.

Projected savings through public health voluntary licences of HIV drugs negotiated by the Medicines Patent Pool (MPP).

PubMed

Juneja, Sandeep; Gupta, Aastha; Moon, Suerie; Resch, Stephen

2017-01-01

The Medicines Patent Pool (MPP) was established in 2010 to ensure timely access to low-cost generic versions of patented antiretroviral (ARV) medicines in low- and middle-income countries (LMICs) through the negotiation of voluntary licences with patent holders. While robust data on the savings generated by MPP and other major global public health initiatives is important, it is also difficult to quantify. In this study, we estimate the savings generated by licences negotiated by the MPP for ARV medicines to treat HIV/AIDS in LMICs for the period 2010-2028 and generate a cost-benefit ratio-based on people living with HIV (PLHIVs) in any new countries which gain access to an ARV due to MPP licences and the price differential between originator's tiered price and generics price, within the period where that ARV is patented. We found that the direct savings generated by the MPP are estimated to be USD 2.3 billion (net present value) by 2028, representing an estimated cost-benefit ratio of 1:43, which means for every USD 1 spent on MPP, the global public health community saves USD 43. The saving of USD 2.3 billion is equivalent to more than 24 million PLHIV receiving first-line ART in LMICs for 1 year at average prices today.

Cyclophilin B protects SH-SY5Y human neuroblastoma cells against MPP(+)-induced neurotoxicity via JNK pathway.

PubMed

Oh, Yoojung; Jeong, Kwon; Kim, Kiyoon; Lee, Young-Seok; Jeong, Suyun; Kim, Sung Soo; Yoon, Kyung-Sik; Ha, Joohun; Kang, Insug; Choe, Wonchae

2016-09-23

Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. PD involves a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyidine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) inhibit the complex I of the mitochondrial electron transport chain, and have been widely used to construct PD models. Cyclophilin B (CypB) is an endoplasmic reticulum protein that binds to cyclosporine A as a cyclophilin family member. CypB has peptidyl-prolyl cis-trans isomerase (PPIase) activity. We investigated the protective effects of overexpressed CypB on MPP+-induced neurocytotoxicity in SH-SY5Y human neuroblastoma cells. Overexpressed CypB decreased MPP(+)-induced oxidative stress through the modulation of antioxidant enzymes including manganese superoxide dismutase and catalase, and prevented neurocytotoxicity via mitogen-activated protein kinase, especially the c-Jun N-terminal kinase pathway. In addition, CypB inhibited the activation of MPP(+)-induced the pro-apoptotic molecules poly (ADP-ribose) polymerase, Bax, and Bcl-2, and attenuated MPP(+)-induced mitochondrial dysfunction. The data suggest that overexpressed CypB protects neuronal cells from MPP+-induced dopaminergic neuronal cell death. Copyright © 2016 Elsevier Inc. All rights reserved.

Conversion-Integration of MSFC Nonlinear Signal Diagnostic Analysis Algorithms for Realtime Execution of MSFC's MPP Prototype System

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1996-01-01

NASA's advanced propulsion system Small Scale Magnetic Disturbances/Advanced Technology Development (SSME/ATD) has been undergoing extensive flight certification and developmental testing, which involves large numbers of health monitoring measurements. To enhance engine safety and reliability, detailed analysis and evaluation of the measurement signals are mandatory to assess its dynamic characteristics and operational condition. Efficient and reliable signal detection techniques will reduce the risk of catastrophic system failures and expedite the evaluation of both flight and ground test data, and thereby reduce launch turn-around time. During the development of SSME, ASRI participated in the research and development of several advanced non- linear signal diagnostic methods for health monitoring and failure prediction in turbomachinery components. However, due to the intensive computational requirement associated with such advanced analysis tasks, current SSME dynamic data analysis and diagnostic evaluation is performed off-line following flight or ground test with a typical diagnostic turnaround time of one to two days. The objective of MSFC's MPP Prototype System is to eliminate such 'diagnostic lag time' by achieving signal processing and analysis in real-time. Such an on-line diagnostic system can provide sufficient lead time to initiate corrective action and also to enable efficient scheduling of inspection, maintenance and repair activities. The major objective of this project was to convert and implement a number of advanced nonlinear diagnostic DSP algorithms in a format consistent with that required for integration into the Vanderbilt Multigraph Architecture (MGA) Model Based Programming environment. This effort will allow the real-time execution of these algorithms using the MSFC MPP Prototype System. ASRI has completed the software conversion and integration of a sequence of nonlinear signal analysis techniques specified in the SOW for real-time execution on MSFC's MPP Prototype. This report documents and summarizes the results of the contract tasks; provides the complete computer source code; including all FORTRAN/C Utilities; and all other utilities/supporting software libraries that are required for operation.

Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration.

PubMed

Duan, Yuwei; Zhang, Baomei; Chu, Lianjun; Tong, Henry Hy; Liu, Weidong; Zhai, Guangxi

2016-05-01

The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin. Copyright © 2016 Elsevier B.V. All rights reserved.

Bragg peak prediction from quantitative proton computed tomography using different path estimates

PubMed Central

Wang, Dongxu; Mackie, T Rockwell

2015-01-01

This paper characterizes the performance of the straight-line path (SLP) and cubic spline path (CSP) as path estimates used in reconstruction of proton computed tomography (pCT). The GEANT4 Monte Carlo simulation toolkit is employed to simulate the imaging phantom and proton projections. SLP, CSP and the most-probable path (MPP) are constructed based on the entrance and exit information of each proton. The physical deviations of SLP, CSP and MPP from the real path are calculated. Using a conditional proton path probability map, the relative probability of SLP, CSP and MPP are calculated and compared. The depth dose and Bragg peak are predicted on the pCT images reconstructed using SLP, CSP, and MPP and compared with the simulation result. The root-mean-square physical deviations and the cumulative distribution of the physical deviations show that the performance of CSP is comparable to MPP while SLP is slightly inferior. About 90% of the SLP pixels and 99% of the CSP pixels lie in the 99% relative probability envelope of the MPP. Even at an imaging dose of ~0.1 mGy the proton Bragg peak for a given incoming energy can be predicted on the pCT image reconstructed using SLP, CSP, or MPP with 1 mm accuracy. This study shows that SLP and CSP, like MPP, are adequate path estimates for pCT reconstruction, and therefore can be chosen as the path estimation method for pCT reconstruction, which can aid the treatment planning and range prediction of proton radiation therapy. PMID:21212472

76 FR 72736 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

... the migration to the MPP.\\15\\ In connection with these communications, FINRA noted that, although subject to Commission approval of the proposed rule change, FINRA anticipates that the MPP migration would... requested that the MPP migration and the proposed rule changes be implemented not earlier than the end of...

The language parallel Pascal and other aspects of the massively parallel processor

NASA Technical Reports Server (NTRS)

Reeves, A. P.; Bruner, J. D.

1982-01-01

A high level language for the Massively Parallel Processor (MPP) was designed. This language, called Parallel Pascal, is described in detail. A description of the language design, a description of the intermediate language, Parallel P-Code, and details for the MPP implementation are included. Formal descriptions of Parallel Pascal and Parallel P-Code are given. A compiler was developed which converts programs in Parallel Pascal into the intermediate Parallel P-Code language. The code generator to complete the compiler for the MPP is being developed independently. A Parallel Pascal to Pascal translator was also developed. The architecture design for a VLSI version of the MPP was completed with a description of fault tolerant interconnection networks. The memory arrangement aspects of the MPP are discussed and a survey of other high level languages is given.

Climate Change, Population Immunity, and Hyperendemicity in the Transmission Threshold of Dengue

PubMed Central

Oki, Mika; Yamamoto, Taro

2012-01-01

Background It has been suggested that the probability of dengue epidemics could increase because of climate change. The probability of epidemics is most commonly evaluated by the basic reproductive number (R0), and in mosquito-borne diseases, mosquito density (the number of female mosquitoes per person [MPP]) is the critical determinant of the R0 value. In dengue-endemic areas, 4 different serotypes of dengue virus coexist–a state known as hyperendemicity–and a certain proportion of the population is immune to one or more of these serotypes. Nevertheless, these factors are not included in the calculation of R0. We aimed to investigate the effects of temperature change, population immunity, and hyperendemicity on the threshold MPP that triggers an epidemic. Methods and Findings We designed a mathematical model of dengue transmission dynamics. An epidemic was defined as a 10% increase in seroprevalence in a year, and the MPP that triggered an epidemic was defined as the threshold MPP. Simulations were conducted in Singapore based on the recorded temperatures from 1980 to 2009 The threshold MPP was estimated with the effect of (1) temperature only; (2) temperature and fluctuation of population immunity; and (3) temperature, fluctuation of immunity, and hyperendemicity. When only the effect of temperature was considered, the threshold MPP was estimated to be 0.53 in the 1980s and 0.46 in the 2000s, a decrease of 13.2%. When the fluctuation of population immunity and hyperendemicity were considered in the model, the threshold MPP decreased by 38.7%, from 0.93 to 0.57, from the 1980s to the 2000s. Conclusions The threshold MPP was underestimated if population immunity was not considered and overestimated if hyperendemicity was not included in the simulations. In addition to temperature, these factors are particularly important when quantifying the threshold MPP for the purpose of setting goals for vector control in dengue-endemic areas. PMID:23144746

Climate change, population immunity, and hyperendemicity in the transmission threshold of dengue.

PubMed

Oki, Mika; Yamamoto, Taro

2012-01-01

It has been suggested that the probability of dengue epidemics could increase because of climate change. The probability of epidemics is most commonly evaluated by the basic reproductive number (R(0)), and in mosquito-borne diseases, mosquito density (the number of female mosquitoes per person [MPP]) is the critical determinant of the R(0) value. In dengue-endemic areas, 4 different serotypes of dengue virus coexist-a state known as hyperendemicity-and a certain proportion of the population is immune to one or more of these serotypes. Nevertheless, these factors are not included in the calculation of R(0). We aimed to investigate the effects of temperature change, population immunity, and hyperendemicity on the threshold MPP that triggers an epidemic. We designed a mathematical model of dengue transmission dynamics. An epidemic was defined as a 10% increase in seroprevalence in a year, and the MPP that triggered an epidemic was defined as the threshold MPP. Simulations were conducted in Singapore based on the recorded temperatures from 1980 to 2009 The threshold MPP was estimated with the effect of (1) temperature only; (2) temperature and fluctuation of population immunity; and (3) temperature, fluctuation of immunity, and hyperendemicity. When only the effect of temperature was considered, the threshold MPP was estimated to be 0.53 in the 1980s and 0.46 in the 2000s, a decrease of 13.2%. When the fluctuation of population immunity and hyperendemicity were considered in the model, the threshold MPP decreased by 38.7%, from 0.93 to 0.57, from the 1980s to the 2000s. The threshold MPP was underestimated if population immunity was not considered and overestimated if hyperendemicity was not included in the simulations. In addition to temperature, these factors are particularly important when quantifying the threshold MPP for the purpose of setting goals for vector control in dengue-endemic areas.

IGF-1 protects SH-SY5Y cells against MPP+-induced apoptosis via PI3K/PDK-1/Akt pathway.

PubMed

Kim, Chanyang; Park, Seungjoon

2018-03-01

Insulin-like growth factor (IGF)-1 is a well-known anti-apoptotic pro-survival factor and phosphatidylinositol-3-kinase (PI3K)/Akt pathway is linked to cell survival induced by IGF-1. It is also reported that Akt signaling is modulated by 3-phosphoinositide-dependent kinase-1 (PDK1). In the current study, we investigated whether the anti-apoptotic effect of IGF-1 in SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP + ) is associated with the activity of PI3K/PDK1/Akt pathway. Treatment of cells with IGF-1 inhibited MPP + -induced apoptotic cell death. IGF-1-induced activation of Akt and the protective effect of IGF-1 on MPP + -induced apoptosis were abolished by chemical inhibition of PDK1 (GSK2334470) or PI3K (LY294002). The phosphorylated levels of Akt and PDK1 were significantly suppressed after MPP + exposure, while IGF-1 treatment completely restored MPP+-induced reductions in phosphorylation. IGF-1 protected cells from MPP + insult by suppressing intracellular reactive oxygen species (ROS) production and malondialdehyde levels and increasing superoxide dismutase activity. Mitochondrial ROS levels were also increased during MPP + exposure, which were attenuated by IGF-1 treatment. In addition, IGF-1-treated cells showed increased activities of succinate dehydrogenase and citrate synthase, stabilization of mitochondrial transmembrane potential, increased ratio of Bcl-2 to Bax, prevention of cytochrome c release and inhibition of caspase-3 activation with PARP cleavage. Furthermore, the protective effects of IGF-1 on oxidative stress and mitochondrial dysfunction were attenuated when cells were preincubated with GSK2334470 or LY294002. Our data suggest that IGF-1 protects SH-SY5Y cells against MPP + -associated oxidative stress by preserving mitochondrial integrity and inhibiting mitochondrial apoptotic cascades via the activation of PI3K/PDK1/Akt pathway. © 2018 The authors.

IGF-1 protects SH-SY5Y cells against MPP+-induced apoptosis via PI3K/PDK-1/Akt pathway

PubMed Central

Kim, Chanyang; Park, Seungjoon

2018-01-01

Insulin-like growth factor (IGF)-1 is a well-known anti-apoptotic pro-survival factor and phosphatidylinositol-3-kinase (PI3K)/Akt pathway is linked to cell survival induced by IGF-1. It is also reported that Akt signaling is modulated by 3-phosphoinositide-dependent kinase-1 (PDK1). In the current study, we investigated whether the anti-apoptotic effect of IGF-1 in SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+) is associated with the activity of PI3K/PDK1/Akt pathway. Treatment of cells with IGF-1 inhibited MPP+-induced apoptotic cell death. IGF-1-induced activation of Akt and the protective effect of IGF-1 on MPP+-induced apoptosis were abolished by chemical inhibition of PDK1 (GSK2334470) or PI3K (LY294002). The phosphorylated levels of Akt and PDK1 were significantly suppressed after MPP+ exposure, while IGF-1 treatment completely restored MPP+-induced reductions in phosphorylation. IGF-1 protected cells from MPP+ insult by suppressing intracellular reactive oxygen species (ROS) production and malondialdehyde levels and increasing superoxide dismutase activity. Mitochondrial ROS levels were also increased during MPP+ exposure, which were attenuated by IGF-1 treatment. In addition, IGF-1-treated cells showed increased activities of succinate dehydrogenase and citrate synthase, stabilization of mitochondrial transmembrane potential, increased ratio of Bcl-2 to Bax, prevention of cytochrome c release and inhibition of caspase-3 activation with PARP cleavage. Furthermore, the protective effects of IGF-1 on oxidative stress and mitochondrial dysfunction were attenuated when cells were preincubated with GSK2334470 or LY294002. Our data suggest that IGF-1 protects SH-SY5Y cells against MPP+-associated oxidative stress by preserving mitochondrial integrity and inhibiting mitochondrial apoptotic cascades via the activation of PI3K/PDK1/Akt pathway. PMID:29459421

A maximum power point tracking algorithm for photovoltaic applications

NASA Astrophysics Data System (ADS)

Nelatury, Sudarshan R.; Gray, Robert

2013-05-01

The voltage and current characteristic of a photovoltaic (PV) cell is highly nonlinear and operating a PV cell for maximum power transfer has been a challenge for a long time. Several techniques have been proposed to estimate and track the maximum power point (MPP) in order to improve the overall efficiency of a PV panel. A strategic use of the mean value theorem permits obtaining an analytical expression for a point that lies in a close neighborhood of the true MPP. But hitherto, an exact solution in closed form for the MPP is not published. This problem can be formulated analytically as a constrained optimization, which can be solved using the Lagrange method. This method results in a system of simultaneous nonlinear equations. Solving them directly is quite difficult. However, we can employ a recursive algorithm to yield a reasonably good solution. In graphical terms, suppose the voltage current characteristic and the constant power contours are plotted on the same voltage current plane, the point of tangency between the device characteristic and the constant power contours is the sought for MPP. It is subject to change with the incident irradiation and temperature and hence the algorithm that attempts to maintain the MPP should be adaptive in nature and is supposed to have fast convergence and the least misadjustment. There are two parts in its implementation. First, one needs to estimate the MPP. The second task is to have a DC-DC converter to match the given load to the MPP thus obtained. Availability of power electronics circuits made it possible to design efficient converters. In this paper although we do not show the results from a real circuit, we use MATLAB to obtain the MPP and a buck-boost converter to match the load. Under varying conditions of load resistance and irradiance we demonstrate MPP tracking in case of a commercially available solar panel MSX-60. The power electronics circuit is simulated by PSIM software.

77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

...; Class II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the... Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the...

Peripheral Administration of Tetanus Toxin Hc Fragment Prevents MPP+ Toxicity In Vivo.

PubMed

Moreno-Galarza, Natalia; Mendieta, Liliana; Palafox-Sánchez, Victoria; Herrando-Grabulosa, Mireia; Gil, Carles; Limón, Daniel I; Aguilera, José

2018-02-19

Several studies have shown that intrastriatal application of 1-methyl-4-phenylpyridinium (MPP + ) produces similar biochemical changes in rat to those seen in Parkinson's disease (PD), such as dopaminergic terminal degeneration and consequent appearance of motor deficits, making the MPP + lesion a widely used model of parkinsonism in rodents. Previous results from our group have shown a neuroprotective effect of the carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) under different types of stress. In the present study, pretreatment with the intraperitoneal injection of Hc-TeTx in rats prevents the decrease of tyrosine hydroxylase immunoreactivity in the striatum due to injury with MPP + , when applied stereotaxically in the striatum. Similarly, striatal catecholamine contents are restored, as well as the levels of two other dopaminergic markers, the dopamine transporter (DAT) and the vesicular monoamine transporter-2 (VMAT-2). Additionally, uptake studies of [ 3 H]-dopamine and [ 3 H]-MPP + reveal that DAT action is not affected by Hc-TeTx, discarding a protective effect due to a reduced entry of MPP + into nerve terminals. Behavioral assessments show that Hc-TeTx pretreatment improves the motor skills (amphetamine-induced rotation, forelimb use, and adjusting steps) of MPP + -treated rats. Our results lead us to consider Hc-TeTx as a potential therapeutic tool in pathologies caused by impairment of dopaminergic innervation in the striatum, as is the case of PD.

Projected savings through public health voluntary licences of HIV drugs negotiated by the Medicines Patent Pool (MPP)

PubMed Central

Juneja, Sandeep; Gupta, Aastha; Moon, Suerie; Resch, Stephen

2017-01-01

The Medicines Patent Pool (MPP) was established in 2010 to ensure timely access to low-cost generic versions of patented antiretroviral (ARV) medicines in low- and middle-income countries (LMICs) through the negotiation of voluntary licences with patent holders. While robust data on the savings generated by MPP and other major global public health initiatives is important, it is also difficult to quantify. In this study, we estimate the savings generated by licences negotiated by the MPP for ARV medicines to treat HIV/AIDS in LMICs for the period 2010–2028 and generate a cost-benefit ratio–based on people living with HIV (PLHIVs) in any new countries which gain access to an ARV due to MPP licences and the price differential between originator’s tiered price and generics price, within the period where that ARV is patented. We found that the direct savings generated by the MPP are estimated to be USD 2.3 billion (net present value) by 2028, representing an estimated cost-benefit ratio of 1:43, which means for every USD 1 spent on MPP, the global public health community saves USD 43. The saving of USD 2.3 billion is equivalent to more than 24 million PLHIV receiving first-line ART in LMICs for 1 year at average prices today. PMID:28542239

75 FR 48179 - Comprehensive List of Guidance Documents at the Food and Drug Administration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-09

...The Food and Drug Administration (FDA) is publishing a comprehensive list of all guidance documents currently in use at the agency. This list is being published under FDA's Good Guidance Practices (GGPs). It is intended to inform the public of the existence and availability of all of our current guidance documents. It also provides information on guidance documents that have been added or withdrawn in the past 5 years.

76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... Concerning Electronic Signatures and Documents AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of regulatory guidance. SUMMARY: FMCSA issues regulatory guidance concerning the... regulatory guidance concerning the use of electronic signatures and documents to comply with FMCSA...

Neural nets on the MPP

NASA Technical Reports Server (NTRS)

Hastings, Harold M.; Waner, Stefan

1987-01-01

The Massively Parallel Processor (MPP) is an ideal machine for computer experiments with simulated neural nets as well as more general cellular automata. Experiments using the MPP with a formal model neural network are described. The results on problem mapping and computational efficiency apply equally well to the neural nets of Hopfield, Hinton et al., and Geman and Geman.

MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells.

PubMed

Ito, Keisuke; Eguchi, Yutaka; Imagawa, Yusuke; Akai, Shuji; Mochizuki, Hideki; Tsujimoto, Yoshihide

2017-01-01

Regulation of cell death is potentially a powerful treatment modality for intractable diseases such as neurodegenerative diseases. Although there have been many reports about the possible involvement of various types of cell death in neurodegenerative diseases, it is still unclear exactly how neurons die in patients with these diseases, thus treatment strategies based on cell death regulation have not been established yet. To obtain some insight into the mechanisms of cell death involved in neurodegenerative diseases, we studied the effect of 1-methyl-4-phenylpyridinium (MPP+) on the human neuroblastoma cell line SH-SY5Y (a widely used model of Parkinson's disease). We found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3'-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson's disease.

MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells

PubMed Central

Ito, Keisuke; Eguchi, Yutaka; Imagawa, Yusuke; Akai, Shuji; Mochizuki, Hideki; Tsujimoto, Yoshihide

2017-01-01

Regulation of cell death is potentially a powerful treatment modality for intractable diseases such as neurodegenerative diseases. Although there have been many reports about the possible involvement of various types of cell death in neurodegenerative diseases, it is still unclear exactly how neurons die in patients with these diseases, thus treatment strategies based on cell death regulation have not been established yet. To obtain some insight into the mechanisms of cell death involved in neurodegenerative diseases, we studied the effect of 1-methyl-4-phenylpyridinium (MPP+) on the human neuroblastoma cell line SH-SY5Y (a widely used model of Parkinson’s disease). We found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3′-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson’s disease. PMID:28250973

Substance P prevents 1-methyl-4-phenylpyridinium-induced cytotoxicity through inhibition of apoptosis via neurokinin-1 receptors in MES23.5 cells.

PubMed

Wang, Shuang-Yan; Chen, Lei; Xue, Yan; Xia, Yu-Jun

2015-12-01

[Sar9, Met(O2)11] termed Substance P (SP), is an effective and selective agonist for the neurokinin‑1 (NK‑1) receptors, which are synthetic peptides, similar in structure to SP. SP is an important neurotransmitter or neuromodulator mediated by neurokinin receptors, namely the SP receptor in the central nervous system. The excitatory effects induced by SP may be selectively inhibited by a neurokinin‑1 receptor antagonist, such as SR140333B. It has been proposed that Parkinson's disease (PD) is primarily caused by the loss of trophic peptidergic neurotransmitter, possibly SP, which may lead to the degeneration of neurons. In previous studies, 1‑methyl‑4‑phenylpyridinium (MPP+) has been frequently utilized to establish animal or cell models of PD. In the present study, to further investigate the effects of SP in PD, MPP+ was employed to investigate the promising anti‑apoptotic effects of SP, and examine the underlying mechanisms of the pathology in the MES23.5 dopaminergic cell line. The results indicated that MPP+‑triggered apoptosis was prevented by treatment with SP. SP treatment also decreased the MPP+‑triggered Ca2+ influx, caspase‑3 re‑activity, reactive oxygen species production and mitochondrial membrane potential decrease. Treatment with MPP+ also induced phosphorylation of c‑Jun N‑terminal kinase and p38 mitogen‑activated protein kinase. In addition, treatment with SP inhibited the MPP+‑triggered neurotoxicity in MES23.5 cells. However, no changes were observed in SR140333B+SP+MPP+‑treated MES23.5 cell lines. In conclusion, SP could protect the cells from MPP+‑induced cytotoxicity by inhibiting the apoptosis via NK-1 receptors.

Edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating heme oxygenase-1 expression.

PubMed

Cheng, Baohua; Guo, Yunliang; Li, Chuangang; Ji, Bingyuan; Pan, Yanyou; Chen, Jing; Bai, Bo

2014-08-15

Oxidative stress is involved in the pathogenesis of Parkinson's disease (PD). Edaravone has been shown to have a neuroprotective effect. In the present work, we investigated the effect of edaravone on 1-methyl-4-phenylpyridinium (MPP(+))-treated PC12 cells. Edaravone inhibited the decrease of cell viability and apoptosis induced by MPP(+) in PC12 cells. In addition, edaravone alleviated intracellular reactive oxygen species (ROS) production. MPP(+) induced heme oxygenase-1 (HO-1) expression, which was further enhanced by edaravone. The inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of edaravone. So edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating HO-1 expression. The data showed that edaravone was neuroprotective and could be potentially therapeutics for PD in future. Copyright © 2014 Elsevier B.V. All rights reserved.

Sound absorption of a finite micro-perforated panel backed by a shunted loudspeaker.

PubMed

Tao, Jiancheng; Jing, Ruixiang; Qiu, Xiaojun

2014-01-01

Deep back cavities are usually required for micro-perforated panel (MPP) constructions to achieve good low frequency absorption. To overcome the problem, a close-box loudspeaker with a shunted circuit is proposed to substitute the back wall of the cavity of the MPP constructions to constitute a composite absorber. Based on the equivalent circuit model, the acoustic impedance of the shunted loudspeaker is formulated first, then a prediction model of the sound absorption of the MPP backed by shunted loudspeaker is developed by employing the mode solution of a finite size MPP coupled by an air cavity with an impendence back wall. The MPP absorbs mid to high frequency sound, and with properly adjusted electrical parameters of its shunted circuit, the shunted loudspeaker absorbs low frequency sound, so the composite absorber provides a compact solution to broadband sound control. Numerical simulations and experiments are carried out to validate the model.

Simultaneous recovery of phosphorus and potassium as magnesium potassium phosphate from synthetic sewage sludge effluent.

PubMed

Nakao, Satoshi; Nishio, Takayuki; Kanjo, Yoshinori

2017-10-01

Bench-scale experiments were performed to investigate simultaneous recovery of phosphorus and potassium from synthetic sewage sludge effluent as crystals of magnesium potassium phosphate (MPP or struvite-(K), MgKPO 4 ·6H 2 O). The optimal pH of MPP formation was 11.5. A phosphorus level of at least 3 mM and K:P molar ratio over 3 were necessary to form MPP, which showed higher content rate of phosphorus and potassium in precipitate. MPP crystallization was confirmed by analysing the precipitates using a scanning electron microscope-energy dispersive X-ray spectroscopy (SEM-EDX) apparatus and an X-ray Diffractometer (XRD). Inhibition of MPP crystallization by iron and aluminium was confirmed by precipitation experiments and SEM-EDX analysis. Potassium ratio against magnesium in precipitate decreased for iron concentrations greater than over 0.2 mM and aluminium concentrations over 0.05 mM.

Design of a plasmonic micromotor for enhanced photo-remediation of polluted anaerobic stagnant waters.

PubMed

Zhang, Zhijun; Zhao, Andong; Wang, Faming; Ren, Jinsong; Qu, Xiaogang

2016-04-25

A motor plasmonic photocatalyst (MPP) is developed to promote photocatalysis in an anaerobic stagnant environment. The MPP is fabricated through the newly developed nano/micromotor fabrication method: template-assisted aqueous phase synthesis. With the help of H2O2 (fuel), the solar photocatalytic efficiency of the MPP can be enhanced more than 110 times.

Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway.

PubMed

Zhong, Jianbin; Li, Xie; Wan, Limei; Chen, Zhibang; Zhong, Simin; Xiao, Songhua; Yan, Zhengwen

2016-02-01

NogoA is a myelin‑associated protein, which is important in the inhibition of axonal fiber growth and in regeneration following injury of the mammalian central nervous system. A previous study suggested that NogoA may be key in the process of Parkinson's disease (PD), which is the second most common chronic neurodegenerative disorder worldwide. The regulatory mechanism underlying the effect of NogoA on the process of PD remains to be fully elucidated. The present study aimed to investigate the effect and underlying mechanism of NogoA on cellular viability, apoptosis and autophagy induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells, a commonly used in vitro PD model. PC12 cells were treated with 1 mM MPP+ for 24 h and the cells were harvested for western blotting. The results demonstrated that the protien expression levels of NogoA were increased in the PC12 cells treated with MPP+. Subsequently, NogoA small interfering RNA was synthesized and transfected into PC12 cells to silence the expression of NogoA. NogoA knockdown significantly reduced the MPP+‑induced decrease in cell viability and apoptosis, detected using a cell counting kit‑8 and flow cytometric analysis, respectively. Interference in the expression of NogoA increased the MPP+‑induced decrease in mitochondrial membrane potential, determined quantitatively by flow cytometry using JC-1 dye, and the protein levels of Beclin‑1. In addition, MPP+ treatment activated the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Knockdown of NogoA significantly inhibited the expression levels of mTOR and STAT3. Furthermore, overexpression of NogoA had similar neurotoxic effects on the PC12 cells as MPP+ treatment. Treatment with rapamycin, an inhibitor of the mTOR/STAT3 signaling pathway had a similar effect to that of NogoA knockdown in the MPP+‑treated PC12 cells. Taken together, the results from the present study demonstrated that NogoA may regulate MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway and provided an explanation regarding the regulatory mechanism of NogoA on the process of PD.

The American Geological Institute Minority Participation Program

NASA Astrophysics Data System (ADS)

Smith, M. J.; Byerly, G. R.; Callahan, C. N.

2001-12-01

Since 1971, the American Geological Institute (AGI) Minority Participation Program (MPP) has supported scholarships for underrepresented minorities in the geosciences at the undergraduate and graduate levels. Some of our MPP scholars have gone on to hugely successful careers in the geosciences. MPP scholars include corporate leaders, university professors, a NASA scientist-astronaut and a National Science Foundation (NSF) CAREER awardee. Yet as ethnic minorities continue to be underrepresented in the geosciences, AGI plans to expand its efforts beyond its traditional undergraduate and graduate scholarships to include diversity programs for secondary school geoscience teacher internships, undergraduate research travel support, and doctoral research fellowships. Funding for the MPP has come from multiple sources, including industry, scientific societies, individuals, and during the last 10 years, the NSF. College-level students apply for the MPP awards or award renewals, and the MPP Advisory Committee selects scholarship recipients based upon student academic performance, financial need, and potential for success as a geoscience professional. Mentoring is a long-standing hallmark of the AGI MPP. Every AGI MPP scholar is assigned a professional geoscientist as a mentor. The mentor is responsible for regular personal contacts with MPP scholars. The MPP Advisory Committee aims to match the profession of the mentor with the scholar's academic interest. Throughout the year, mentors and scholars communicate about possible opportunities in the geosciences such as internships, participation in symposia, professional society meetings, and job openings. Mentors have also been active in helping younger students cope with the major changes involved in relocating to a new region of the country or a new college culture. We believe that AGI is well-positioned to advance diversity in the geosciences through its unique standing as the major professional organization in the geosciences. AGI maintains strong links to its 37 professional Member Societies, state and federal agencies, and funding programs, many with distinctive programs in the geoscience education. AGI Corporate Associates have consistently pledged to support diversity issues in geoscience education. Current plans include seeking funding for 48 undergraduate awards at 2500 each and 24,000 to support undergraduate travel to professional meetings. We also expect to increase the size of our graduate scholarship program to 30 students and raise an additional $30,000 to support graduate travel to professional meetings.

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

NASA Astrophysics Data System (ADS)

Ensign-Hodges, Laura

A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPP improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week.

Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake

PubMed Central

Ensign, Laura M.; Hoen, Timothy; Maisel, Katharina; Cone, Richard; Hanes, Justin

2013-01-01

Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and muco-inert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated “free” drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders. PMID:23769419

76 FR 1173 - Draft Guidance for Industry on Electronic Source Documentation in Clinical Investigations...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...] Draft Guidance for Industry on Electronic Source Documentation in Clinical Investigations; Availability... Documentation in Clinical Investigations.'' This document provides guidance to sponsors, contract research organizations (CROs), data management centers, and clinical investigators on capturing, using, and archiving...

Transition to Postsecondary: New Documentation Guidance for Access to Accommodations

ERIC Educational Resources Information Center

Klotz, Mary Beth

2012-01-01

The Association on Higher Education and Disability (AHEAD) recently developed a conceptual framework that substantially revises its guidance for disability documentation for accommodations in higher education settings. This new document, "Supporting Accommodation Requests: Guidance on Documentation Practices," was written in response to the…

Cardiac resynchronization therapy by multipoint pacing improves response of left ventricular mechanics and fluid dynamics: a three-dimensional and particle image velocimetry echo study.

PubMed

Siciliano, Mariachiara; Migliore, Federico; Badano, Luigi; Bertaglia, Emanuele; Pedrizzetti, Gianni; Cavedon, Stefano; Zorzi, Alessandro; Corrado, Domenico; Iliceto, Sabino; Muraru, Denisa

2017-11-01

To characterize the effect of multipoint pacing (MPP) compared to biventricular pacing (BiV) on left ventricle (LV) mechanics and intraventricular fluid dynamics by three-dimensional echocardiography (3DE) and echocardiographic particle imaging velocimetry (Echo-PIV). In 11 consecutive patients [8 men; median age 65 years (57-75)] receiving cardiac resynchronization therapy (CRT) with a quadripolar LV lead (Quartet,St.Jude Medical,Inc.), 3DE and Echo-PIV data were collected for each pacing configuration (CRT-OFF, BiV, and MPP) at follow-up after 6 months. 3DE data included LV volumes, LV ejection fraction (LVEF), strain, and systolic dyssynchrony index (SDI). Echo-PIV was used to evaluate the directional distribution of global blood flow momentum, ranging from zero, when flow force is predominantly along the base-apex direction, up to 90° when it becomes transversal. MPP resulted in significant reduction in end-diastolic and end-systolic volumes compared with both CRT-OFF (P = 0.02; P = 0.008, respectively) and BiV (P = 0.04; P = 0.03, respectively). LVEF and cardiac output were significant superior in MPP compared with CRT-OFF, but similar between MPP and BiV. Statistical significant differences when comparing global longitudinal and circumferential strain and SDI with MPP vs. CRT-OFF were observed (P = 0.008; P = 0.008; P = 0.01, respectively). There was also a trend towards improvement in strain between BiV and MPP that did not reach statistical significance. MPP reflected into a significant reduction of the deviation of global blood flow momentum compared with both CRT-OFF and BiV (P = 0.002) indicating a systematic increase of longitudinal alignment from the base-apex orientation of the haemodynamic forces. These preliminary results suggest that MPP resulted in significant improvement of LV mechanics and fluid dynamics compared with BiV. However, larger studies are needed to confirm this hypothesis. © Crown copyright 2016.

76 FR 28688 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-18

... Controls Guidance Document: In Vitro Diagnostic Devices for Bacillus Species Detection AGENCY: Food and... Guidance Document: In Vitro Diagnostic Devices for Bacillus spp. Detection.'' This draft guidance document describes means by which in vitro diagnostic devices for Bacillus species (spp.) detection may comply with...

Reducing retrogradation and lipid oxidation of normal and glutinous rice flours by adding mango peel powder.

PubMed

Siriamornpun, Sirithon; Tangkhawanit, Ekkarat; Kaewseejan, Niwat

2016-06-15

Green and ripe mango peel powders (MPP) were added to normal rice flour (NRF) and glutinous rice flour (GRF) at three levels (400, 800 and 1200 ppm) and their effects on physicochemical properties and lipid oxidation inhibition were investigated. Overall, MPP increased the breakdown viscosity and reduced the final viscosity in rice flours when compared to the control. Decreasing in retrogradation was observed in both NRF and GRF with MPP added of all levels. MPP addition also significantly inhibited the lipid oxidation of all flours during storage (30 days). Retrogradation values were strongly negatively correlated with total phenolic and flavonoid contents, but not with fiber content. The hydrogen bonds and hydrophilic interactions between phenolic compounds with amylopectin molecule may be involved the decrease of starch retrogradation, especially GRF. We suggest that the addition of MPP not only reduced the retrogradation but also inhibited the lipid oxidation of rice flour. Copyright © 2016 Elsevier Ltd. All rights reserved.

Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP+ injection in rats.

PubMed

Geed, Milind; Garabadu, Debapriya; Ahmad, Ausaf; Krishnamurthy, Sairam

2014-02-01

Silymarin commonly known for its hepatoprotective effect is reported to show protection against 6-hydroxydopamine-induced neurotoxicity. Silibinin forms the major active constituent of silymarin. Therefore, the neuroprotective effect of silibinin (50, 100 and 200 mg/kg) was evaluated in the unilaterally injected 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neurotoxicity in male rats. A battery of tests such as elevated plus maze (EPM), narrow beam walk, open field, bar catalepsy, grip strength, and foot print analysis was performed to evaluate the behavioral symptoms of striatal dopaminergic toxicity. Furthermore, the mechanism of action of silibinin was investigated by evaluating the mitochondrial complex enzyme activities, mitochondrial integrity and oxidative status. Striatal caspase-3 and NFκB were expressed to evaluate the effect of silibinin on apoptosis and inflammation respectively. Silibinin (100 and 200 mg/kg) protected against MPP(+)-induced dopamine depletion in striatum. Silibinin reversed MPP(+)-induced decrease in transfer latency indicating memory consolidation in the EPM test. Silibinin (100 and 200 mg/kg) attenuated MPP(+)-induced motor deficits, such as fine motor movements and gait. MPP(+)-induced mitochondrial dysfunction, loss of integrity and oxidative stress were attenuated by silibinin. Silibinin decreased striatal caspase-3 and NFκB expression indicating potential anti-apoptotic and anti-inflammatory effects respectively. Hence, silibinin exhibited neuroprotective effect in the MPP(+) induced striatal toxicity augmenting dopamine levels. The mechanism of action may be linked to maintenance of mitochondrial bioenergetics and integrity apart from anti-apoptotic and anti-inflammatory activities. Copyright © 2013 Elsevier Inc. All rights reserved.

Inhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells.

PubMed

Lee, Chung Soo; Park, Se Young; Ko, Hyun Hee; Song, Jin Ho; Shin, Yong Kyoo; Han, Eun Sook

2005-01-01

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of trifluoperazine and W-7 on the MPP+-induced mitochondrial damage and cell death in undifferentiated PC12 cells. Calmodulin antagonists (trifluoperazine, W-7 and calmidazolium) at 0.5-1 microM significantly reduced the loss of cell viability in PC12 cells treated with 500 microM MPP+. Trifluoperazine and W-7 (0.5-1 microM) inhibited the nuclear damage, the loss of the mitochondrial transmembrane potential followed by cytochrome c release, and the elevation of intracellular Ca2+ levels due to MPP+ in PC12 cells and attenuated the formation of reactive oxygen species and the depletion of GSH. Calmodulin antagonists at 5-10 microM exhibited a cytotoxic effect on PC12 cells, and compounds at 10 microM did not attenuate cytotoxicity of MPP+. Calmodulin antagonists (0.5-1 microM) significantly reduced rotenone-induced mitochondrial damage and cell death, whereas they did not attenuate cell death and elevation of intracellular Ca2+ levels due to H2O2 or ionomycin. The results show that trifluoperazine and W-7 exhibit a differential inhibitory effect against cytotoxicity of MPP+ depending on concentration. Both compounds at the concentrations less than 5 microM may attenuate the MPP+-induced viability loss in PC12 cells by suppressing change in the mitochondrial membrane permeability and by lowering the intracellular Ca2+ levels.

A review of the FDA draft guidance document for software validation: guidance for industry.

PubMed

Keatley, K L

1999-01-01

A Draft Guidance Document (Version 1.1) was issued by the United States Food and Drug Administration (FDA) to address the software validation requirement of the Quality System Regulation, 21 CFR Part 820, effective June 1, 1997. The guidance document outlines validation considerations that the FDA regards as applicable to both medical device software and software used to "design, develop or manufacture" medical devices. The Draft Guidance is available at the FDA web site http:@www.fda.gov/cdrh/comps/swareval++ +.html. Presented here is a review of the main features of the FDA document for Quality System Regulation (QSR), and some guidance for its implementation in industry.

Free-electron laser simulations on the MPP

NASA Technical Reports Server (NTRS)

Vonlaven, Scott A.; Liebrock, Lorie M.

1987-01-01

Free electron lasers (FELs) are of interest because they provide high power, high efficiency, and broad tunability. FEL simulations can make efficient use of computers of the Massively Parallel Processor (MPP) class because most of the processing consists of applying a simple equation to a set of identical particles. A test version of the KMS Fusion FEL simulation, which resides mainly in the MPPs host computer and only partially in the MPP, has run successfully.

On the simultaneous inversion of micro-perforated panels' parameters: Application to single and double air-cavity backed systems.

PubMed

Tayong, Rostand B; Manyo Manyo, Jacques A; Siryabe, Emmanuel; Ntamack, Guy E

2018-04-01

This study deals with the deduction of parameters of Micro-Perforated Panel (MPP) systems from impedance tube data. It is shown that there is an ambiguity problem that exists between the MPP thickness and its open area ratio. This problem makes it difficult to invert the reflection coefficient data fitting and therefore to deduct the MPP parameters. A technique is proposed to reduce this ambiguity by using an equation that links the hole diameter to the open area ratio. Reflection coefficient data obtained for two specimens with different characteristics is employed for searching the MPP parameters using a simulated annealing algorithm. The results obtained demonstrate the effectiveness of this technique.

Comment on "Effect of coal-fired power generation on visibility in a nearby National Park (Terhorst and Berkman, 2010)"

NASA Astrophysics Data System (ADS)

White, W. H.; Farber, R. J.; Malm, W. C.; Nuttall, M.; Pitchford, M. L.; Schichtel, B. A.

2012-08-01

Few electricity generating stations received more environmental scrutiny during the last quarter of the twentieth century than did the Mohave Power Project (MPP), a coal-fired facility near Grand Canyon National Park. Terhorst and Berkman (2010) examine regional aerosol monitoring data collected before and after the plant's 2006 retirement for retrospective evidence of MPP's impact on visibility in the Park. The authors' technical analysis is thoughtfully conceived and executed, but is misleadingly presented as discrediting previous studies and their interpretation by regulators. In reality the Terhorst-Berkman analysis validates a consensus on MPP's visibility impact that was established years before its closure, in a collaborative assessment undertaken jointly by Federal regulators and MPP's owners.

TECHNICAL GUIDANCE DOCUMENT: QUALITY ASSURANCE AND QUALITY CONTROL FOR WASTE CONTAINMENT FACILITIES

EPA Science Inventory

This Technical Guidance Document provides comprehensive guidance on procedures for quality assurance and quality control for waste containment facilities. he document includes a discussion of principles and concepts, compacted soil liners, soil drainage systems, geosynthetic drai...

TECHNICAL GUIDANCE DOCUMENT: QUALITY ASSURANCE AND QUALITY CONTROL FOR WASTE CONTAINMENT FACILITIES

EPA Science Inventory

This Technical Guidance Document provides comprehensive guidance on procedures for quality assurance and quality control for waste containment facilities. The document includes a discussion of principles and concepts, compacted soil liners, soil drainage systems, geosynthetic dr...

Assay Characterization Guidance Documents | Office of Cancer Clinical Proteomics Research

Cancer.gov

CPTAC characterized assays are defined as those that meet the criteria described in the Assay Characterization Guidance Document. This guidance document aligns with recommendations by the research community as “fit-for-purpose” validation requirements of targeted proteomics assays.

The American Geological Institute Minority Participation Program (MPP): Thirty Years of Improving Access to Opportunities in the Geosciences Through Undergraduate and Graduate Scholarships for Underrepresented Minorities

NASA Astrophysics Data System (ADS)

Callahan, C. N.; Byerly, G. R.; Smith, M. J.

2001-05-01

Since 1971, the American Geological Institute (AGI) Minority Participation Program (MPP) has supported scholarships for underrepresented minorities in the geosciences at the undergraduate and graduate levels. Some of our MPP scholars have gone on to hugely successful careers in the geosciences. MPP scholars include corporate leaders, university professors, a NASA scientist-astronaut and a National Science Foundation (NSF) CAREER awardee. Yet as ethnic minorities continue to be underrepresented in the geosciences, AGI plans to expand its efforts beyond its traditional undergraduate and graduate scholarships to include diversity programs for secondary school geoscience teacher internships, undergraduate research travel support, and doctoral research fellowships. AGI promotes its MPP efforts primarily through its web pages, which are very successful in attracting visitors; through its publications, especially Geotimes; and through its Corporate Associates and Member Societies. Funding for the MPP has come from multiple sources over the past 30 years. Industry, non-profit organizations, and individuals have been the primary source of funding for graduate scholarships. The NSF has regularly funded the undergraduate scholarships. AGI Corporate Associates have contributed to both scholarship programs. The MPP Advisory Committee selects scholarship recipients based upon student academic performance, financial need, and potential for success as a geoscience professional. AGI currently has 29 MPP scholars, including 11 undergraduate and 18 graduate students. Undergraduate scholarships range from \\1000 to \\5000, with an average award of approximately \\2500. Graduate scholarships range from \\500 to \\4000, with an average award of approximately \\1300. In addition to financial assistance, every MPP scholar is assigned a professional geoscientist as a mentor. The mentor is responsible for regular personal contacts with MPP scholars, and with writing evaluation reports that are used to gauge the needs of the scholar, and to access the success of the overall program. The MPP Advisory Committee aims to match the profession of the mentor with the scholar's academic interest. Throughout the year, mentors and scholars communicate about possible opportunities in the geosciences such as internships, participation in symposia, professional society meetings, and job openings. Mentors have also been active in helping younger students cope with the major changes involved in relocating to a new region of the country or a new college culture. We believe that AGI is well positioned to advance diversity in the geosciences through its unique standing as the major professional organization in the geosciences. AGI maintains strong links to its professional Member Societies, state and federal agencies and funding programs, many with distinctive programs in the geoscience education. AGI Corporate Associates have consistently pledged to support diversity issues in geoscience education. Current plans include seeking funding for 48 undergraduate awards at \\2500 each and \\24,000 to support undergraduate travel to professional meetings. We also expect to increase the size of our graduate scholarship program to 30 students and raise an additional \\$30,000 to support graduate travel to professional meetings.

76 FR 43332 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

...: Focused Ultrasound Stimulator System for Aesthetic Use; Availability AGENCY: Food and Drug Administration... the guidance entitled, ``Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use.'' This guidance document describes a means by which focused ultrasound...

Impairment of Atg5-Dependent Autophagic Flux Promotes Paraquat- and MPP+-Induced Apoptosis But Not Rotenone or 6-Hydroxydopamine Toxicity

PubMed Central

Franco, Rodrigo

2013-01-01

Controversial reports on the role of autophagy as a survival or cell death mechanism in dopaminergic cell death induced by parkinsonian toxins exist. We investigated the alterations in autophagic flux and the role of autophagy protein 5 (Atg5)-dependent autophagy in dopaminergic cell death induced by parkinsonian toxins. Dopaminergic cell death induced by the mitochondrial complex I inhibitors 1-methyl-4-phenylpyridinium (MPP+) and rotenone, the pesticide paraquat, and the dopamine analog 6-hydroxydopamine (6-OHDA) was paralleled by increased autophagosome accumulation. However, when compared with basal autophagy levels using chloroquine, autophagosome accumulation was a result of impaired autophagic flux. Only 6-OHDA induced an increase in autophagosome formation. Overexpression of a dominant negative form of Atg5 increased paraquat- and MPP+-induced cell death. Stimulation of mammalian target of rapamycin (mTOR)-dependent signaling protected against cell death induced by paraquat, whereas MPP+-induced toxicity was enhanced by wortmannin, a phosphoinositide 3-kinase class III inhibitor, rapamycin, and trehalose, an mTOR-independent autophagy activator. Modulation of autophagy by either pharmacological or genetic approaches had no effect on rotenone or 6-OHDA toxicity. Cell death induced by parkinsonian neurotoxins was inhibited by the pan caspase inhibitor (Z-VAD), but only caspase-3 inhibition was able to decrease MPP+-induced cell death. Finally, inhibition of the lysosomal hydrolases, cathepsins, increased the toxicity by paraquat and MPP+, supporting a protective role of Atg5-dependent autophagy and lysosomes degradation pathways on dopaminegic cell death. These results demonstrate that in dopaminergic cells, Atg5-dependent autophagy acts as a protective mechanism during apoptotic cell death induced by paraquat and MPP+ but not during rotenone or 6-OHDA toxicity. PMID:23997112

Synthesis and Neuroprotective Action of Xyloketal Derivatives in Parkinson’s Disease Models

PubMed Central

Li, Shichang; Shen, Cunzhou; Guo, Wenyuan; Zhang, Xuefei; Liu, Shixin; Liang, Fengyin; Xu, Zhongliang; Pei, Zhong; Song, Huacan; Qiu, Liqin; Lin, Yongcheng; Pang, Jiyan

2013-01-01

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting people over age 55. Oxidative stress actively participates in the dopaminergic (DA) neuron degeneration of PD. Xyloketals are a series of natural compounds from marine mangrove fungus strain No. 2508 that have been reported to protect against neurotoxicity through their antioxidant properties. However, their protection versus 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity is only modest, and appropriate structural modifications are necessary to discover better candidates for treating PD. In this work, we designed and synthesized 39 novel xyloketal derivatives (1–39) in addition to the previously reported compound, xyloketal B. The neuroprotective activities of all 40 compounds were evaluated in vivo via respiratory burst assays and longevity-extending assays. During the zebrafish respiratory burst assay, compounds 1, 9, 23, 24, 36 and 39 strongly attenuated reactive oxygen species (ROS) generation at 50 μM. In the Caenorhabditis elegans longevity-extending assay, compounds 1, 8, 15, 16 and 36 significantly extended the survival rates (p < 0.005 vs. dimethyl sulfoxide (DMSO)). A total of 15 compounds were tested for the treatment of Parkinson’s disease using the MPP+-induced C. elegans model, and compounds 1 and 8 exhibited the highest activities (p < 0.005 vs. MPP+). In the MPP+-induced C57BL/6 mouse PD model, 40 mg/kg of 1 and 8 protected against MPP+-induced dopaminergic neurodegeneration and increased the number of DA neurons from 53% for the MPP+ group to 78% and 74%, respectively (p < 0.001 vs. MPP+ group). Thus, these derivatives are novel candidates for the treatment of PD. PMID:24351912

Sophora flavescens Aiton Decreases MPP+-Induced Mitochondrial Dysfunction in SH-SY5Y Cells

PubMed Central

Kim, Hee-Young; Jeon, Hyongjun; Kim, Hyungwoo; Koo, Sungtae; Kim, Seungtae

2018-01-01

Sophora flavescens Aiton (SF) has been used to treat various diseases including fever and inflammation in China, South Korea and Japan. Several recent reports have shown that SF has anti-inflammatory and anti-apoptotic effects, indicating that it is a promising candidate for treatment of Parkinson’s disease (PD). We evaluated the protective effect of SF against neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+)-induced mitochondrial dysfunction in SH-SY5Y human neuroblastoma cells, an in vitro PD model. SH-SY5Y cells were incubated with SF for 24 h, after which they were treated with MPP+. MPP+-induced cytotoxicity and apoptosis were confirmed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay. MitoSOX red mitochondrial superoxide indicator, tetramethylrhodamine methyl ester perchlorate and Parkin, PTEN-induced putative kinase 1 (PINK1), and DJ-1 immunofluorescent staining were conducted to confirm the mitochondrial function. In addition, western blot was performed to evaluate apoptosis factors (Bcl-2, Bax, caspase-3 and cytochrome c) and mitochondrial function-related factors (Parkin, PINK1 and DJ-1). SF suppressed MPP+-induced cytotoxicity, apoptosis and collapse of mitochondrial membrane potential by inhibiting the increase of reactive oxidative species (ROS) and DNA fragmentation, and controlling Bcl-2, Bax, caspase-3 and cytochrome c expression. Moreover, it attenuated Parkin, PINK1 and DJ-1 expression from MPP+-induced decrease. SF effectively suppressed MPP+-induced cytotoxicity, apoptosis and mitochondrial dysfunction by regulating generation of ROS, disruption of mitochondrial membrane potential, mitochondria-dependent apoptosis and loss or mutation of mitochondria-related PD markers including Parkin, PINK1 and DJ-1. PMID:29740311

Sophora flavescens Aiton Decreases MPP+-Induced Mitochondrial Dysfunction in SH-SY5Y Cells.

PubMed

Kim, Hee-Young; Jeon, Hyongjun; Kim, Hyungwoo; Koo, Sungtae; Kim, Seungtae

2018-01-01

Sophora flavescens Aiton (SF) has been used to treat various diseases including fever and inflammation in China, South Korea and Japan. Several recent reports have shown that SF has anti-inflammatory and anti-apoptotic effects, indicating that it is a promising candidate for treatment of Parkinson's disease (PD). We evaluated the protective effect of SF against neurotoxin 1-methyl-4-phenylpyridinium ion (MPP + )-induced mitochondrial dysfunction in SH-SY5Y human neuroblastoma cells, an in vitro PD model. SH-SY5Y cells were incubated with SF for 24 h, after which they were treated with MPP + . MPP + -induced cytotoxicity and apoptosis were confirmed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay. MitoSOX red mitochondrial superoxide indicator, tetramethylrhodamine methyl ester perchlorate and Parkin, PTEN-induced putative kinase 1 (PINK1), and DJ-1 immunofluorescent staining were conducted to confirm the mitochondrial function. In addition, western blot was performed to evaluate apoptosis factors (Bcl-2, Bax, caspase-3 and cytochrome c) and mitochondrial function-related factors (Parkin, PINK1 and DJ-1). SF suppressed MPP + -induced cytotoxicity, apoptosis and collapse of mitochondrial membrane potential by inhibiting the increase of reactive oxidative species (ROS) and DNA fragmentation, and controlling Bcl-2, Bax, caspase-3 and cytochrome c expression. Moreover, it attenuated Parkin, PINK1 and DJ-1 expression from MPP + -induced decrease. SF effectively suppressed MPP + -induced cytotoxicity, apoptosis and mitochondrial dysfunction by regulating generation of ROS, disruption of mitochondrial membrane potential, mitochondria-dependent apoptosis and loss or mutation of mitochondria-related PD markers including Parkin, PINK1 and DJ-1.

Essential Function of Protein 4.1G in Targeting of Membrane Protein Palmitoylated 6 into Schmidt-Lanterman Incisures in Myelinated Nerves

PubMed Central

Saitoh, Yurika; Ohno, Nobuhiko; Komada, Masayuki; Saitoh, Sei; Peles, Elior; Ohno, Shinichi

2012-01-01

Protein 4.1G is a membrane skeletal protein found in specific subcellular structures in myelinated Schwann cells and seminiferous tubules. Here, we show that in the mouse sciatic nerve, protein 4.1G colocalized at Schmidt-Lanterman incisures (SLI) and the paranodes with a member of the membrane-associated guanylate kinase (MAGUK) family, membrane protein palmitoylated 6 (MPP6). Coimmunoprecipitation experiments revealed that MPP6 was interacting with protein 4.1G. In contrast to wild-type nerves, in 4.1G knockout mice, MPP6 was found largely in the cytoplasm near Schwann cell nuclei, indicating an abnormal protein transport. Although the SLI remained in the 4.1G knockout sciatic nerves, as confirmed by E-cadherin immunostaining, their shape was altered in aged 4.1G knockout nerves compared to their shape in wild-type nerves. In the seminiferous tubules, MPP6 was localized similarly to protein 4.1G along cell membranes of the spermatogonium and early spermatocytes. However, in contrast to myelinated peripheral nerves, the specific localization of MPP6 in the seminiferous tubules was unaltered in the absence of protein 4.1G. These results indicate that 4.1G has a specific role in the targeting of MPP6 to the SLI and the assembly of these subcellular structures. PMID:22025680

Chrysotoxine, a novel bibenzyl compound selectively antagonizes MPP⁺, but not rotenone, neurotoxicity in dopaminergic SH-SY5Y cells.

PubMed

Song, Ju-Xian; Shaw, Pang-Chui; Wong, Ngok-Shun; Sze, Cho-Wing; Yao, Xin-Sheng; Tang, Chi-Wai; Tong, Yao; Zhang, Yan-Bo

2012-07-11

Chrysotoxine is a naturally occurring bibenzyl compound found in medicinal Dendrobium species. We previously reported that chrysotoxine structure-specifically suppressed 6-hydroxydopamine (6-OHDA)-induced dopaminergic cell death. Whether chrysotoxine and other structurally similar bibenzyl compounds could also inhibit the neurotoxicity of 1-methyl-4-phenyl pyridinium (MPP(+)) and rotenone has not been investigated. We showed herein that chrysotoxine inhibited MPP(+), but not rotenone, induced dopaminergic cell death in SH-SY5Y cells. The overproduction of reactive oxygen species (ROS), mitochondrial dysfunction as indexed by the decrease in membrane potential, increase in calcium concentration and NF-κB activation triggered by MPP(+) were blocked by chrysotoxine pretreatment. The imbalance between the pro-apoptotic signals (Bax, caspase-3, ERK and p38 MAPK) and the pro-survival signals (Akt/PI3K/GSK-3β) induced by MPP(+) was partially or totally rectified by chrysotoxine. The results indicated that ROS inhibition, mitochondria protection, NF-κB modulation and regulation of multiple signals determining cell survival and cell death were involved in the protective effects of chrysotoxine against MPP(+) toxicity in SH-SY5Y cells. Given the different toxic profiles of 6-OHDA and MPP(+) as compared to rotenone, our results also indicated that DAT inhibition may partially account for the neuroprotective effects of chrysotoxine. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

Sound transmission through a microperforated-panel structure with subdivided air cavities.

PubMed

Toyoda, Masahiro; Takahashi, Daiji

2008-12-01

The absorption characteristics of a microperforated-panel (MPP) absorber have been widely investigated, and MPPs are recognized as a next-generation absorbing material due to their fiber-free nature and attractive appearance. Herein, further possibilities of MPPs are investigated theoretically from a sound transmission viewpoint. Employing an analytical model composed of a typical MPP and a back wall with an infinite extent, transmission loss through the structure is obtained. Although MPP structures generally have great potential for sound absorption, an improvement in the transmission loss at midfrequencies, which is important for architectural sound insulation, is not sufficient when using a backing cavity alone. Hence, to improve transmission loss at midfrequencies, an air-cavity-subdivision technique is applied to MPP structures. By subdividing the air cavity with partitions, each cell can create a local one-dimensional sound field as well as lead to a normal incidence into the apertures, which is the most effective condition for Helmholtz-type resonance absorption. Moreover, by providing the same motion as the back wall to the MPP, the sound-insulation performance can be further improved at midfrequencies.

Cold Shock Induced Protein RBM3 but Not Mild Hypothermia Protects Human SH-SY5Y Neuroblastoma Cells From MPP+-Induced Neurotoxicity.

PubMed

Yang, Hai-Jie; Shi, Xiang; Ju, Fei; Hao, Bei-Ning; Ma, Shuang-Ping; Wang, Lei; Cheng, Bin-Feng; Wang, Mian

2018-01-01

The cold shock protein RBM3 can mediate mild hypothermia-related protection in neurodegeneration such as Alzheimer's disease. However, it remains unclear whether RBM3 and mild hypothermia provide same protection in model of Parkinson's disease (PD), the second most common neurodegenerative disorder. In this study, human SH-SY5Y neuroblastoma cells subjected to insult by 1-methyl-4-phenylpyridinium (MPP + ) served as an in-vitro model of PD. Mild hypothermia (32°C) aggravated MPP + -induced apoptosis, which was boosted when RBM3 was silenced by siRNA. In contrast, overexpression of RBM3 significantly reduced this apoptosis. MPP + treatment downregulated the expression of RBM3 both endogenously and exogenously and suppressed its induction by mild hypothermia (32°C). In conclusion, our data suggest that cold shock protein RBM3 provides neuroprotection in a cell model of PD, suggesting that RBM3 induction may be a suitable strategy for PD therapy. However, mild hypothermia exacerbates MPP + -induced apoptosis even that RBM3 could be synthesized during mild hypothermia.

Knockdown of cytosolic NADP(+) -dependent isocitrate dehydrogenase enhances MPP(+) -induced oxidative injury in PC12 cells.

PubMed

Yang, Eun Sun; Park, Jeen-Woo

2011-05-01

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridium ion (MPP(+)) have been shown to induce Parkinson's disease-like symptoms as well as neurotoxicity in humans and animal species. Recently, we reported that maintenance of redox balance and cellular defense against oxidative damage are primary functions of the novel antioxidant enzyme cytosolic NADP(+) -dependent isocitrate dehydrogenase (IDPc). In this study, we examined the role of IDPc in cellular defense against MPP(+) -induced oxidative injury using PC12 cells transfected with IDPc small interfering RNA (siRNA). Our results demonstrate that MPP(+) -mediated disruption of cellular redox status, oxidative damage to cells, and apoptotic cell death were significantly enhanced by knockdown of IDPc.

Phase space simulation of collisionless stellar systems on the massively parallel processor

NASA Technical Reports Server (NTRS)

White, Richard L.

1987-01-01

A numerical technique for solving the collisionless Boltzmann equation describing the time evolution of a self gravitating fluid in phase space was implemented on the Massively Parallel Processor (MPP). The code performs calculations for a two dimensional phase space grid (with one space and one velocity dimension). Some results from calculations are presented. The execution speed of the code is comparable to the speed of a single processor of a Cray-XMP. Advantages and disadvantages of the MPP architecture for this type of problem are discussed. The nearest neighbor connectivity of the MPP array does not pose a significant obstacle. Future MPP-like machines should have much more local memory and easier access to staging memory and disks in order to be effective for this type of problem.

76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

...: Low Level Laser System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS... guidance entitled ``Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use.'' This guidance document describes a means by which low level laser systems for aesthetic use may comply...

75 FR 24718 - Guidance for Industry on Documenting Statistical Analysis Programs and Data Files; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

...] Guidance for Industry on Documenting Statistical Analysis Programs and Data Files; Availability AGENCY... Programs and Data Files.'' This guidance is provided to inform study statisticians of recommendations for documenting statistical analyses and data files submitted to the Center for Veterinary Medicine (CVM) for the...

SNJ-1945, a calpain inhibitor, protects SH-SY5Y cells against MPP(+) and rotenone.

PubMed

Knaryan, Varduhi H; Samantaray, Supriti; Park, Sookyoung; Azuma, Mitsuyoshi; Inoue, Jun; Banik, Naren L

2014-07-01

Complex pathophysiology of Parkinson's disease involves multiple CNS cell types. Degeneration in spinal cord neurons alongside brain has been shown to be involved in Parkinson's disease and evidenced in experimental parkinsonism. However, the mechanisms of these degenerative pathways are not well understood. To unravel these mechanisms SH-SY5Y neuroblastoma cells were differentiated into dopaminergic and cholinergic phenotypes, respectively, and used as cell culture model following exposure to two parkinsonian neurotoxicants MPP(+) and rotenone. SNJ-1945, a cell-permeable calpain inhibitor was tested for its neuroprotective efficacy. MPP(+) and rotenone dose-dependently elevated the levels of intracellular free Ca(2+) and induced a concomitant rise in the levels of active calpain. SNJ-1945 pre-treatment significantly protected cell viability and preserved cellular morphology following MPP(+) and rotenone exposure. The neurotoxicants elevated the levels of reactive oxygen species more profoundly in SH-SY5Y cells differentiated into dopaminergic phenotype, and this effect could be attenuated with SNJ-1945 pre-treatment. In contrast, significant levels of inflammatory mediators cyclooxygenase-2 (Cox-2 and cleaved p10 fragment of caspase-1) were up-regulated in the cholinergic phenotype, which could be dose-dependently attenuated by the calpain inhibitor. Overall, SNJ-1945 was efficacious against MPP(+) or rotenone-induced reactive oxygen species generation, inflammatory mediators, and proteolysis. A post-treatment regimen of SNJ-1945 was also examined in cells and partial protection was attained with calpain inhibitor administration 1-3 h after exposure to MPP(+) or rotenone. Taken together, these results indicate that calpain inhibition is a valid target for protection against parkinsonian neurotoxicants, and SNJ-1945 is an efficacious calpain inhibitor in this context. SH-SY5Y cells, differentiated as dopaminergic (TH positive) and cholinergic (ChAT positive), were used as in vitro models for Parkinson's disease. MPP+ and rotenone induced up-regulation of calpain, expression, and activity as a common mechanism of neurodegeneration. SNJ-1945, a novel calpain inhibitor, protected both the cell phenotypes against MPP+ and rotenone. © 2013 International Society for Neurochemistry.

Dynamic Neuromuscular Control of the Lower Limbs in Response to Unexpected Single-Planar versus Multi-Planar Support Perturbations in Young, Active Adults.

PubMed

Malfait, Bart; Staes, Filip; de Vries, Aijse; Smeets, Annemie; Hawken, Malcolm; Robinson, Mark A; Vanrenterghem, Jos; Verschueren, Sabine

2015-01-01

An anterior cruciate ligament (ACL) injury involves a multi-planar injury mechanism. Nevertheless, unexpected multi-planar perturbations have not been used to screen athletes in the context of ACL injury prevention yet could reveal those more at risk. The objective of this study was to compare neuromuscular responses to multi-planar (MPP) and single-planar perturbations (SPP) during a stepping-down task. These results might serve as a basis for future implementation of external perturbations in ACL injury screening programs. Thirteen young adults performed a single leg stepping-down task in eight conditions (four MPP and four SPP with a specified amplitude and velocity). The amplitudes of vastus lateralis (VL), vastus medialis (VM), hamstrings lateralis (HL), hamstrings medialis (HM) EMG activity, medio-lateral and anterior-posterior centre of mass (COM) displacements, the peak knee flexion and abduction angles were compared between conditions using an one-way ANOVA. Number of stepping responses were monitored during all conditions. Significantly greater muscle activity levels were found in response to the more challenging MPP and SPP compared to the less challenging conditions (p < 0.05). No differences in neuromuscular activity were found between the MPP conditions and their equivalents in the SPP. Eighteen stepping responses were monitored in the SPP versus nine in the MPP indicating that the overall neuromuscular control was even more challenged during the SPP which was supported by greater COM displacements in the SPP. The more intense MPP and SPP evoked different neuromuscular responses resulting in greater muscle activity levels compared to small perturbations. Based on the results of COM displacements and based on the amount of stepping responses, dynamic neuromuscular control of the knee joint appeared less challenged during the MPP. Therefore, future work should investigate extensively if other neuromuscular differences (i.e. co-activation patterns and kinetics) exist between MPP and SPP. In addition, future work should examine the influence on the neuromuscular control of the magnitude of the perturbations and the magnitude of stepping height and stepping distance.

Supercomputing on massively parallel bit-serial architectures

NASA Technical Reports Server (NTRS)

Iobst, Ken

1985-01-01

Research on the Goodyear Massively Parallel Processor (MPP) suggests that high-level parallel languages are practical and can be designed with powerful new semantics that allow algorithms to be efficiently mapped to the real machines. For the MPP these semantics include parallel/associative array selection for both dense and sparse matrices, variable precision arithmetic to trade accuracy for speed, micro-pipelined train broadcast, and conditional branching at the processing element (PE) control unit level. The preliminary design of a FORTRAN-like parallel language for the MPP has been completed and is being used to write programs to perform sparse matrix array selection, min/max search, matrix multiplication, Gaussian elimination on single bit arrays and other generic algorithms. A description is given of the MPP design. Features of the system and its operation are illustrated in the form of charts and diagrams.

Draft Updates to the Planning for Natural Disaster Debris Guidance and to Related Documents

EPA Pesticide Factsheets

EPA is requesting comment on the draft update of the Planning for Natural Disaster Debris Guidance, along with two other documents. This Guidance is an update of the Planning for Natural Disaster Debris guidance that EPA published in March 2008.

75 FR 35510 - License Renewal Interim Staff Guidance Process, Revision 2 Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-22

... Related Regulatory Functions.'' An electronic copy of the revised LR-ISG process is available in the NRC's Agencywide Documents Access and Management System (ADAMS) under Accession No. ML100920158. The revised LR-ISG... interim changes to certain NRC license renewal guidance documents. These guidance documents facilitate the...

Guidance on Annual Compliance Certifications

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PSD and Title V Permitting Guidance for GHGs

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Annual Compliance Certification Guidance

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title IV-Title V Interface Guidance for States

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

76 FR 44594 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0465] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... guidance document will serve as the special control for rTMS systems. Section 513(f)(2) of the Federal Food...

Genetic correlational analysis reveals no association between MPP+ and the severity of striatal dopaminergic damage following MPTP treatment in BXD mouse strains.

PubMed

Jones, Byron C; O'Callaghan, James P; Lu, Lu; Williams, Robert W; Alam, Gelareh; Miller, Diane B

2014-01-01

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a pro-neurotoxicant that must be metabolized to 1-methyl-4-phenylpyridinium (MPP(+)) and taken up into striatal dopaminergic neurons to produce neurodegeneration. Recently, we showed wide genetic variability in MPTP-associated neuronal damage in a panel of recombinant inbred mouse strains. Here we examined the amount of MPP(+) produced in the striatum in the same strains of inbred BXD mice. This allowed us to determine if the differences in the dopaminergic neurotoxicity and associated astrogliosis among the BXD mouse strains were due to differential metabolism of MPTP to MPP(+). Using the same BXD mouse strains examined previously (Jones et al., 2013) we found that the extent of the striatal damage produced following MPTP treatment is not correlated quantitatively with the production of MPP(+) in the striatum. Our findings also extend those of others regarding strain differences in MPTP-induced dopaminergic neurotoxicity. Importantly, our finding suggests that additional factors influence the neurodegenerative response other than the presence and amount of the toxicant at the target site. Published by Elsevier Inc.

GPR30 Activation Contributes to the Puerarin-Mediated Neuroprotection in MPP+-Induced SH-SY5Y Cell Death.

PubMed

Cheng, Yue-Fa; Zhu, Guoqi; Wu, Qing-Wen; Xie, Yue-Sheng; Jiang, Yan; Guo, Lan; Guan, Ya-Li; Liu, Ying-Shuo; Zhang, Jun

2017-02-01

The neuroprotective action of puerarin in Parkinson's disease (PD) models has been well investigated. However, the mechanisms involved in protection have not been completely understood. G protein-coupled receptor 30 (GPR30) is a G protein-coupled estrogen receptor and considered a potential target in the neuroprotection against PD. In this study, we investigated whether puerarin prevented against 1-methyl-4-phenylpyridinium (MPP + )-induced cell death via GPR30. Our results showed that the GPR30 agonist, G1, exhibited puerarin-mediated neuroprotection against MPP + -induced cell death of SH-SY5Y cells. This protective action was reversed by the GPR30 antagonist. Moreover, a time- and concentration-dependent effect of puerarin on GPR30 expression was verified at the protein level but not at the mRNA level. Further, we showed that an mTor-dependent new GPR30 synthesis contributed to the protection conferred by puerarin. Finally, glial cell line-derived neurotrophic factor (GDNF) levels were enhanced by puerarin and G1 in both control and MPP + -lesioned cells via GPR30. Taken together, our data strongly suggest that puerarin prevents MPP + -induced cell death via facilitating GPR30 expression and GDNF release.

Feasibility of using the Massively Parallel Processor for large eddy simulations and other Computational Fluid Dynamics applications

NASA Technical Reports Server (NTRS)

Bruno, John

1984-01-01

The results of an investigation into the feasibility of using the MPP for direct and large eddy simulations of the Navier-Stokes equations is presented. A major part of this study was devoted to the implementation of two of the standard numerical algorithms for CFD. These implementations were not run on the Massively Parallel Processor (MPP) since the machine delivered to NASA Goddard does not have sufficient capacity. Instead, a detailed implementation plan was designed and from these were derived estimates of the time and space requirements of the algorithms on a suitably configured MPP. In addition, other issues related to the practical implementation of these algorithms on an MPP-like architecture were considered; namely, adaptive grid generation, zonal boundary conditions, the table lookup problem, and the software interface. Performance estimates show that the architectural components of the MPP, the Staging Memory and the Array Unit, appear to be well suited to the numerical algorithms of CFD. This combined with the prospect of building a faster and larger MMP-like machine holds the promise of achieving sustained gigaflop rates that are required for the numerical simulations in CFD.

Public Comment Period Open for the Draft Update to the Planning for Natural Disaster Debris Guidance and to Related Documents

EPA Pesticide Factsheets

EPA is requesting comment on the draft Planning for Natural Disaster Debris Guidance, and two other documents. The Guidance is an update of the Planning for Natural Disaster Debris guidance that EPA published in March 2008.

76 FR 22906 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

...: Topical Oxygen Chamber for Extremities; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled, ``Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities.'' This guidance document was developed as a special control to support the reclassification of the topical oxygen...

76 FR 9028 - Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-16

...] Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products; Availability AGENCY: Food and... the availability of a document entitled ``Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products'' dated January 2011. The guidance document provides manufacturers of cellular and gene...

Identification of Licopyranocoumarin and Glycyrurol from Herbal Medicines as Neuroprotective Compounds for Parkinson's Disease

PubMed Central

Fujimaki, Takahiro; Saiki, Shinji; Tashiro, Etsu; Yamada, Daisuke; Kitagawa, Mitsuhiro; Hattori, Nobutaka; Imoto, Masaya

2014-01-01

In the course of screening for the anti-Parkinsonian drugs from a library of traditional herbal medicines, we found that the extracts of choi-joki-to and daio-kanzo-to protected cells from MPP+-induced cell death. Because choi-joki-to and daio-kanzo-to commonly contain the genus Glycyrrhiza, we isolated licopyranocoumarin (LPC) and glycyrurol (GCR) as potent neuroprotective principals from Glycyrrhiza. LPC and GCR markedly blocked MPP+-induced neuronal PC12D cell death and disappearance of mitochondrial membrane potential, which were mediated by JNK. LPC and GCR inhibited MPP+-induced JNK activation through the suppression of reactive oxygen species (ROS) generation, thereby inhibiting MPP+-induced neuronal PC12D cell death. These results indicated that LPC and GCR derived from choi-joki-to and daio-kanzo-to would be promising drug leads for PD treatment in the future. PMID:24960051

Kinship-based politics and the optimal size of kin groups

PubMed Central

Hammel, E. A.

2005-01-01

Kin form important political groups, which change in size and relative inequality with demographic shifts. Increases in the rate of population growth increase the size of kin groups but decrease their inequality and vice versa. The optimal size of kin groups may be evaluated from the marginal political product (MPP) of their members. Culture and institutions affect levels and shapes of MPP. Different optimal group sizes, from different perspectives, can be suggested for any MPP schedule. The relative dominance of competing groups is determined by their MPP schedules. Groups driven to extremes of sustainability may react in Malthusian fashion, including fission and fusion, or in Boserupian fashion, altering social technology to accommodate changes in size. The spectrum of alternatives for actors and groups, shaped by existing institutions and natural and cultural selection, is very broad. Nevertheless, selection may result in survival of particular kinds of political structures. PMID:16091466

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

Haba, Naoyuki; Ishida, Hiroyuki; Okada, Nobuchika

Here, we suggest a scalar singlet extension of the standard model, in which the multiple-point principle (MPP) condition of a vanishing Higgs potential at the Planck scale is realized. Although there have been lots of attempts to realize the MPP at the Planck scale, the realization with keeping naturalness is quite difficult. This model can easily achieve the MPP at the Planck scale without large Higgs mass corrections. It is worth noting that the electroweak symmetry can be radiatively broken in our model. In the naturalness point of view, the singlet scalar mass should be of O(1 TeV) or less.more » Also, we consider right-handed neutrino extension of the model for neutrino mass generation. The model does not affect the MPP scenario, and might keep the naturalness with the new particle mass scale beyond TeV, thanks to accidental cancellation of Higgs mass corrections.« less

Multiple-point principle with a scalar singlet extension of the standard model

DOE PAGES

Haba, Naoyuki; Ishida, Hiroyuki; Okada, Nobuchika; ...

2017-01-21

Here, we suggest a scalar singlet extension of the standard model, in which the multiple-point principle (MPP) condition of a vanishing Higgs potential at the Planck scale is realized. Although there have been lots of attempts to realize the MPP at the Planck scale, the realization with keeping naturalness is quite difficult. This model can easily achieve the MPP at the Planck scale without large Higgs mass corrections. It is worth noting that the electroweak symmetry can be radiatively broken in our model. In the naturalness point of view, the singlet scalar mass should be of O(1 TeV) or less.more » Also, we consider right-handed neutrino extension of the model for neutrino mass generation. The model does not affect the MPP scenario, and might keep the naturalness with the new particle mass scale beyond TeV, thanks to accidental cancellation of Higgs mass corrections.« less

Kinship-based politics and the optimal size of kin groups.

PubMed

Hammel, E A

2005-08-16

Kin form important political groups, which change in size and relative inequality with demographic shifts. Increases in the rate of population growth increase the size of kin groups but decrease their inequality and vice versa. The optimal size of kin groups may be evaluated from the marginal political product (MPP) of their members. Culture and institutions affect levels and shapes of MPP. Different optimal group sizes, from different perspectives, can be suggested for any MPP schedule. The relative dominance of competing groups is determined by their MPP schedules. Groups driven to extremes of sustainability may react in Malthusian fashion, including fission and fusion, or in Boserupian fashion, altering social technology to accommodate changes in size. The spectrum of alternatives for actors and groups, shaped by existing institutions and natural and cultural selection, is very broad. Nevertheless, selection may result in survival of particular kinds of political structures.

Guidance and Control Software Project Data - Volume 4: Configuration Management and Quality Assurance Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes configuration management and quality assurance documents from the GCS project. Volume 4 contains six appendices: A. Software Accomplishment Summary for the Guidance and Control Software Project; B. Software Configuration Index for the Guidance and Control Software Project; C. Configuration Management Records for the Guidance and Control Software Project; D. Software Quality Assurance Records for the Guidance and Control Software Project; E. Problem Report for the Pluto Implementation of the Guidance and Control Software Project; and F. Support Documentation Change Reports for the Guidance and Control Software Project.

76 FR 69040 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

...: In Vitro Diagnostic Devices for Yersinia Species Detection; Availability AGENCY: Food and Drug... availability of a draft guidance entitled ``Class II Special Controls Guidance Document: In Vitro Diagnostic Devices for Yersinia Species Detection.'' This draft guidance document describes a means by which in vitro...

76 FR 6622 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

...: Contact Cooling System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled ``Class II Special Controls Guidance Document: Contact Cooling System for Aesthetic Use.'' This guidance document describes a means by which contact cooling systems for aesthetic use may comply with the...

Calculating Potential to Emit (PTE) and Other Guidance for Grain Handling Facilities

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Region 9 Guidance on EPA's 45-Day Review Period forTitle V Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Permit Guidance and Template for the Cross-State Air Pollution Rule

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Coordination Title IV/Title V Permitting Schedules

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Potential to Emit (PTE) Guidance for Specific Source Categories

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to Request for Guidance in Defining Adjacent with Respect to Source Aggregation

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Additional Guidance on Funding for State and Local Air Programs

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Technical Guidance for Title V Permitting of Printing Facilities

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Limiting Potential to Emit in New Source Permitting

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Acid Rain Guidance On Phase II Permitting NOx And Opt-ins

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Fee Demonstration And Additional Fee Demonstation Guidance

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Acid Rain-Title V Guidance on Fees and Incorporation by Reference

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification of Guidance for Calculating Actual or Potential Emissions

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on the Major Source Determination for Certain Hazardous Air Pollutants

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Periodic Monitoring Guidance for Title V Operating Permits Programs

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Topical Ocular Drug Delivery to the Back of the Eye by Mucus-Penetrating Particles

PubMed Central

Schopf, Lisa R.; Popov, Alexey M.; Enlow, Elizabeth M.; Bourassa, James L.; Ong, Winston Z.; Nowak, Pawel; Chen, Hongming

2015-01-01

Purpose: Enhanced drug exposure to the ocular surface typically relies on inclusion of viscosity-enabling agents, whereas delivery to the back of the eye generally focuses on invasive means, such as intraocular injections. Using our novel mucus-penetrating particle (MPP) technology, which rapidly and uniformly coats and penetrates mucosal barriers, we evaluated if such drug formulations could increase ocular drug exposure and improve topical drug delivery. Methods: Pharmacokinetic (PK) profiling of topically administered loterprednol etabonate formulated as MPP (LE-MPP) was performed in rabbits and a larger species, the mini-pig. Pharmacodynamic evaluation was done in a rabbit model of VEGF-induced retinal vascular leakage. Cellular potency and PK profile were determined for a second compound, KAL821, a novel receptor tyrosine kinase inhibitor (RTKi). Results: We demonstrated in animals that administration of LE-MPP increased exposure at the ocular surface and posterior compartments. Furthermore using a rabbit vascular leakage model, we demonstrated that biologically effective drug concentrations of LE were delivered to the back of the eye using the MPP technology. We also demonstrated that a novel RTKi formulated as MPPs provided drug levels to the back of the eye above its cellular inhibitory concentration. Conclusions: Topical dosing of MPPs of LE or KAL821 enhanced drug exposure at the front of the eye, and delivered therapeutically relevant drug concentrations to the back of the eye, in animals. Translational Relevance: These preclinical data support using MPP technology to engineer topical formulations to deliver therapeutic drug levels to the back of the eye and could provide major advancements in managing sight-threatening diseases. PMID:26101724

Polynomial algorithms for the Maximal Pairing Problem: efficient phylogenetic targeting on arbitrary trees

PubMed Central

2010-01-01

Background The Maximal Pairing Problem (MPP) is the prototype of a class of combinatorial optimization problems that are of considerable interest in bioinformatics: Given an arbitrary phylogenetic tree T and weights ωxy for the paths between any two pairs of leaves (x, y), what is the collection of edge-disjoint paths between pairs of leaves that maximizes the total weight? Special cases of the MPP for binary trees and equal weights have been described previously; algorithms to solve the general MPP are still missing, however. Results We describe a relatively simple dynamic programming algorithm for the special case of binary trees. We then show that the general case of multifurcating trees can be treated by interleaving solutions to certain auxiliary Maximum Weighted Matching problems with an extension of this dynamic programming approach, resulting in an overall polynomial-time solution of complexity (n4 log n) w.r.t. the number n of leaves. The source code of a C implementation can be obtained under the GNU Public License from http://www.bioinf.uni-leipzig.de/Software/Targeting. For binary trees, we furthermore discuss several constrained variants of the MPP as well as a partition function approach to the probabilistic version of the MPP. Conclusions The algorithms introduced here make it possible to solve the MPP also for large trees with high-degree vertices. This has practical relevance in the field of comparative phylogenetics and, for example, in the context of phylogenetic targeting, i.e., data collection with resource limitations. PMID:20525185

Unified powered flight guidance

NASA Technical Reports Server (NTRS)

Brand, T. J.; Brown, D. W.; Higgins, J. P.

1973-01-01

A complete revision of the orbiter powered flight guidance scheme is presented. A unified approach to powered flight guidance was taken to accommodate all phases of exo-atmospheric orbiter powered flight, from ascent through deorbit. The guidance scheme was changed from the previous modified version of the Lambert Aim Point Maneuver Mode used in Apollo to one that employs linear tangent guidance concepts. This document replaces the previous ascent phase equation document.

A Most Probable Point-Based Method for Reliability Analysis, Sensitivity Analysis and Design Optimization

NASA Technical Reports Server (NTRS)

Hou, Gene J.-W; Newman, Perry A. (Technical Monitor)

2004-01-01

A major step in a most probable point (MPP)-based method for reliability analysis is to determine the MPP. This is usually accomplished by using an optimization search algorithm. The minimum distance associated with the MPP provides a measurement of safety probability, which can be obtained by approximate probability integration methods such as FORM or SORM. The reliability sensitivity equations are derived first in this paper, based on the derivatives of the optimal solution. Examples are provided later to demonstrate the use of these derivatives for better reliability analysis and reliability-based design optimization (RBDO).

Effect of a Traditional Chinese Herbal Medicine Formulation on Cell Survival and Apoptosis of MPP+-Treated MES 23.5 Dopaminergic Cells

PubMed Central

Koon, Ho Kee; Fan, Wen; Wei, Wei; Xu, Chuanshan

2017-01-01

Progressive degeneration of dopaminergic neurons in the substantia nigra (SN) is implicated in Parkinson's disease (PD). The efficacy of these currently used drugs is limited while traditional Chinese medicine (TCM) has been used in the management of neurodegenerative diseases for many years. This study was designed to evaluate the effect of a modified traditional Chinese herbal medicine decoction, Cong Rong Jing (CRJ), on cell survival and apoptosis of 1-methyl-4-phenylpyridinium- (MPP+-) treated MES23.5 dopaminergic cells. CRJ was prepared as a decoction from three Chinese herbs, namely, Herba Cistanches, Herba Epimedii, and Rhizoma Polygonati. We reported here that CRJ significantly enhanced the cell survival of MES23.5 cells after the exposure of MPP+ and inhibited the production of intracellular reactive oxygen species (ROS) induced by MPP+. CRJ also prevented the MPP+-treated MES23.5 cells from apoptosis by reducing the externalization of phosphatidylserine and enhancing the Bcl-2/Bax protein expression ratio. Signaling proteins such as JAK2, STAT3, and ERK1/2 were also involved in the action of CRJ. Taken together, these results provide a preliminary mechanism to support clinical application of the TCM formulation in PD and possibly other neurodegenerative diseases associated with ROS injury and apoptosis. PMID:28607800

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

PubMed

Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie

2017-03-01

Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

New hydroxypyridinone iron-chelators as potential anti-neurodegenerative drugs.

PubMed

Arduino, Daniela; Silva, Daniel; Cardoso, Sandra M; Chaves, Silvia; Oliveira, Catarina R; Santos, M Amelia

2008-05-01

The neuroprotective action of a set of new hydroxypyridinone-based (3,4-HP) compounds (A, B and C), which are iron chelators extra-functionalized with a propargylamino group for potential MAO-B inhibition, was evaluated after cell treatment with MPP+ (an in vivo inducer of parkinsonism) and Abeta(1-40) and/or Abeta(1-42) peptides. Our results show that all these compounds improved cell viability in cells treated with MPP+ and Abeta(1-40) peptide or Abeta(1-42) peptide. In order to evaluate the cellular mechanisms underlying the activity of these compounds, we studied their protective role in caspase activation. All compounds tested were able to prevent MPP+ and Brefeldin A induced caspase-2 activation. They also showed quite effective in the inhibition of caspase-4 and caspase-3 activity, an effector caspase in the apoptotic process. Finally, detection of apoptotic-like cell death after cell exposure to MPP+ was also performed by TUNEL assay. Our results demonstrated that all tested compounds prevented DNA fragmentation by decreasing TUNEL positive cells. A, B and C were more effective than DFP (a 3,4-HP iron-chelating agent in clinical use) in MPP+ induced cell death. Therefore, these results evidenced a neuroprotective and antiapoptotic role for the compounds studied.

The neuroprotective effect of lovastatin on MPP(+)-induced neurotoxicity is not mediated by PON2.

PubMed

Aguirre-Vidal, Yoshajandith; Montes, Sergio; Tristan-López, Luis; Anaya-Ramos, Laura; Teiber, John; Ríos, Camilo; Baron-Flores, Verónica; Monroy-Noyola, Antonio

2015-05-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of the pigmented dopaminergic neurons in the substantia nigra pars compacta with subsequent striatal dopamine (DA) deficiency and increased lipid peroxidation. The etiology of the disease is still unclear and it is thought that PD may be caused by a combination of genetic and environmental factors. In the search of new pharmacological options, statins have been recognized for their potential application to treat PD, due to their antioxidant effect. The aim of this work is to contribute in the characterization of the neuroprotective effect of lovastatin in a model of PD induced by 1-methyl-4-phenylpyridinium (MPP(+)). Male Wistar rats (200-250 g) were randomly allocated into 4 groups and administered for 7 days with different pharmacological treatments. Lovastatin administration (5 mg/kg) diminished 40% of the apomorphine-induced circling behavior, prevented the striatal DA depletion and lipid peroxides formation by MPP(+) intrastriatal injection, as compared to the group of animals treated only with MPP(+). Lovastatin produced no change in paraoxonase-2 (PON2) activity. It is evident that lovastatin conferred neuroprotection against MPP(+)-induced protection but this effect was not associated with the induction of PON2 in the rat striatum. Copyright © 2015. Published by Elsevier B.V.

Draft federal GHG accounting and reporting : technical support document

DOT National Transportation Integrated Search

2010-07-01

This is a technical support document (TSD) that accompanies the Federal Greenhouse Gas Accounting and Reporting Guidance (or Guidance). This document provides detailed information on the inventory reporting process and accepted calculation methodolog...

78 FR 52776 - Documents to Support Submission of an Electronic Common Technical Document; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-26

... obtain the documents at either http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmission...BloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm . Dated: August 20, 2013...

78 FR 10181 - Documents To Support Submission of an Electronic Common Technical Document; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... obtain the documents at either http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmission...BloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm . Dated: February 8, 2013...

Implementation Guidance on Annual Compliance Certification Reporting and Statement of Basis Requirements for Title V Operating Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

National Guidance on Interpretation of the New Source Performance Standards - Subpart Y (Standards of Performance for Coal Preparation Plants)

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Major Modification Provisions of PSD Rules as Applied to Re-Permitting at Acme Steel Co.

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance for State Rules for Optional Federally-Enforceable Emissions Limits Based on Volatile Organic Compound (VOC) Use

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance To States On Authority Necessary To Implement The Operating Permits Program In Title V Of The Clean Air Act Amendments of 1990

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Enforceability Requirements for Limiting Potential to Emit Through SIP and Section 112 Rules and General Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Reissuance of Guidance on Agency Review of State Fee Schedules for Operating Permits Program Under Title V

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

EPA Determination Regarding the Consistency of the Elmendorf ENVVEST/XL Project Proposal and EPA's Guidance for Military Installations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

Consensus of recommendations guiding comparative effectiveness research methods.

PubMed

Morton, Jacob B; McConeghy, Robert; Heinrich, Kirstin; Gatto, Nicolle M; Caffrey, Aisling R

2016-12-01

Because of an increasing demand for quality comparative effectiveness research (CER), methods guidance documents have been published, such as those from the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI). Our objective was to identify CER methods guidance documents and compare them to produce a summary of important recommendations which could serve as a consensus of CER method recommendations. We conducted a systematic literature review to identify CER methods guidance documents published through 2014. Identified documents were analyzed for methods guidance recommendations. Individual recommendations were categorized to determine the degree of overlap. We identified nine methods guidance documents, which contained a total of 312 recommendations, 97% of which were present in two or more documents. All nine documents recommended transparency and adaptation for relevant stakeholders in the interpretation and dissemination of results. Other frequently shared CER methods recommendations included: study design and operational definitions should be developed a priori and allow for replication (n = 8 documents); focus on areas with gaps in current clinical knowledge that are relevant to decision-makers (n = 7); validity of measures, instruments, and data should be assessed and discussed (n = 7); outcomes, including benefits and harms, should be clinically meaningful, and objectively measured (n = 7). Assessment for and strategies to minimize bias (n = 6 documents), confounding (n = 6), and heterogeneity (n = 4) were also commonly shared recommendations between documents. We offer a field-consensus guide based on nine CER methods guidance documents that will aid researchers in designing CER studies and applying CER methods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

AAA (2010) CAPD clinical practice guidelines: need for an update.

PubMed

DeBonis, David A

2017-09-01

Review and critique of the clinical value of the AAA CAPD guidance document in light of criteria for credible and useful guidance documents, as discussed by Field and Lohr. A qualitative review of the of the AAA CAPD guidelines using a framework by Field and Lohr to assess their relative value in supporting the assessment and management of CAPD referrals. Relevant literature available through electronic search tools and published texts were used along with the AAA CAPD guidance document and the chapter by Field and Lohr. The AAA document does not meet many of the key requirements discussed by Field and Lohr. It does not reflect the current literature, fails to help clinicians understand for whom auditory processing testing and intervention would be most useful, includes contradictory suggestions which reduce clarity and appears to avoid conclusions that might cast the CAPD construct in a negative light. It also does not include input from diverse affected groups. All of these reduce the document's credibility. The AAA CAPD guidance document will need to be updated and re-conceptualised in order to provide meaningful guidance for clinicians.

78 FR 22554 - Document to Support Submission of an Electronic Common Technical Document-Specifications for File...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

... documents at either http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements...Vaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm . Dated: April 10, 2013. Leslie Kux...

Multipoint Pacing versus conventional ICD in Patients with a Narrow QRS complex (MPP Narrow QRS trial): study protocol for a pilot randomized controlled trial.

PubMed

Gasparini, Maurizio; Galimberti, Paola; Bragato, Renato; Ghio, Stefano; Raineri, Claudia; Landolina, Maurizio; Chieffo, Enrico; Lunati, Maurizio; Mulargia, Ederina; Proclemer, Alessandro; Facchin, Domenico; Rordorf, Roberto; Vicentini, Alessandro; Marcantoni, Lina; Zanon, Francesco; Klersy, Catherine

2016-12-03

Despite an intensive search for predictors of the response to cardiac resynchronization therapy (CRT), the QRS duration remains the simplest and most robust predictor of a positive response. QRS duration of ≥ 130 ms is considered to be a prerequisite for CRT; however, some studies have shown that CRT may also be effective in heart failure (HF) patients with a narrow QRS (<130 ms). Since CRT can now be performed by pacing the left ventricle from multiple vectors via a single quadripolar lead, it is possible that multipoint pacing (MPP) might be effective in HF patients with a narrow QRS. This article reports the design of the MPP Narrow QRS trial, a prospective, randomized, multicenter, controlled feasibility study to investigate the efficacy of MPP using two LV pacing vectors in patients with a narrow QRS complex (100-130 ms). Fifty patients with a standard ICD indication will be enrolled and randomized (1:1) to either an MPP group or a Standard ICD group. All patients will undergo a low-dose dobutamine stress echo test and only those with contractile reserve will be included in the study and randomized. The primary endpoint will be the percentage of patients in each group that have reverse remodeling at 12 months, defined as a reduction in left ventricular end-systolic volume (LVESV) of >15% from the baseline. This feasibility study will determine whether MPP improves reverse remodeling, as compared with standard ICD, in HF patients who have a narrow QRS complex (100-130 ms). ClinicalTrials.gov, NCT02402816 . Registered on 25 March 2015.

SNJ-1945, a calpain inhibitor, protects SH-SY5Y cells against MPP+ and rotenone

PubMed Central

Knaryan, Varduhi H.; Samantaray, Supriti; Sookyoung, Park; Azuma, Mitsuyoshi; Inoue, Jun; Banik, Naren L.

2014-01-01

Complex pathophysiology of Parkinson’s disease (PD) involves multiple CNS cell types. Degeneration in spinal cord neurons alongside brain has been shown to be involved in PD and evidenced in experimental parkinsonism. However, the mechanisms of these degenerative pathways are not well understood. In order to unravel these mechanisms SH-SY5Y neuroblastoma cells were differentiated into dopaminergic and cholinergic phenotypes respectively and used as cell culture model following exposure to two parkinsonian neurotoxicants MPP+ and rotenone. SNJ-1945, a cell-permeable calpain inhibitor was tested for its neuroprotective efficacy. MPP+ and rotenone dose-dependently elevated the levels of intracellular free Ca2+ and induced a concomitant rise in the levels of active calpain. SNJ-1945 pre-treatment significantly protected cell viability and preserved cellular morphology following MPP+ and rotenone exposure. The neurotoxicants elevated the levels of reactive oxygen species (ROS) more profoundly in SH-SY5Y cells differentiated into dopaminergic phenotype, and this effect could be attenuated with SNJ-1945 pre-treatment. In contrast, significant levels of inflammatory mediators (cyclooxygenase-2, Cox-2 and cleaved p10 fragment of caspase-1) were upregulated in the cholinergic phenotype, which could be dose-dependently attenuated by the calpain inhibitor. Overall, SNJ-1945 was efficacious against MPP+ or rotenone-induced ROS generation, inflammatory mediators, and proteolysis. A post-treatment regimen of SNJ-1945 was also examined in cells and partial protection was attained with calpain inhibitor administration 1–3 h after exposure to MPP+ or rotenone. Taken together these results indicate that calpain inhibition is a valid target for protection against parkinsonian neurotoxicants, and SNJ-1945 is an efficacious calpain inhibitor in this context. PMID:24341912

Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus.

PubMed

Davis, Angela M; Mao, Jiude; Naz, Bushra; Kohl, Jessica A; Rosenfeld, Cheryl S

2008-10-01

Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17beta-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer arrays to determine gene expression changes in uteri of ovariectomized mice treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI 182 780, raloxifene, and combinations of high dose of estradiol with one of the SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene + estradiol in the second group. Surprisingly, combining a high dose of estradiol with a SERM markedly increased (P<0.02) the number of regulated genes compared with each individual treatment. Analysis of expression for selected genes in uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally supported the microarray results. For some cancer-associated genes, including Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI 182 780 suppressed more genes governing DNA replication compared with MPP and raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and raloxifene to treat estrogen-induced endometrial cancer in women.

Policy & Guidance

EPA Pesticide Factsheets

Policy documents represent EPA's official interpretation or view of specific issues. Guidance documents are published to further clarify regulations and to assist in implementation of environmental regulations.

Cost consideration in the clinical guidance documents of physician specialty societies in the United States.

PubMed

Schwartz, Jennifer A T; Pearson, Steven D

2013-06-24

Despite increasing concerns regarding the cost of health care, the consideration of costs in the development of clinical guidance documents by physician specialty societies has received little analysis. To evaluate the approach to consideration of cost in publicly available clinical guidance documents and methodological statements produced between 2008 and 2012 by the 30 largest US physician specialty societies. Qualitative document review. Whether costs are considered in clinical guidance development, mechanism of cost consideration, and the way that cost issues were used in support of specific clinical practice recommendations. Methodological statements for clinical guidance documents indicated that 17 of 30 physician societies (57%) explicitly integrated costs, 4 (13%) implicitly considered costs, 3 (10%) intentionally excluded costs, and 6 (20%) made no mention. Of the 17 societies that explicitly integrated costs, 9 (53%) consistently used a formal system in which the strength of recommendation was influenced in part by costs, whereas 8 (47%) were inconsistent in their approach or failed to mention the exact mechanism for considering costs. Among the 138 specific recommendations in these guidance documents that included cost as part of the rationale, the most common form of recommendation (50 [36%]) encouraged the use of a specific medical service because of equal effectiveness and lower cost. Slightly more than half of the largest US physician societies explicitly consider costs in developing their clinical guidance documents; among these, approximately half use an explicit mechanism for integrating costs into the strength of recommendations. Many societies remain vague in their approach. Physician specialty societies should demonstrate greater transparency and rigor in their approach to cost consideration in documents meant to influence care decisions.

Parallel VLSI architecture emulation and the organization of APSA/MPP

NASA Technical Reports Server (NTRS)

Odonnell, John T.

1987-01-01

The Applicative Programming System Architecture (APSA) combines an applicative language interpreter with a novel parallel computer architecture that is well suited for Very Large Scale Integration (VLSI) implementation. The Massively Parallel Processor (MPP) can simulate VLSI circuits by allocating one processing element in its square array to an area on a square VLSI chip. As long as there are not too many long data paths, the MPP can simulate a VLSI clock cycle very rapidly. The APSA circuit contains a binary tree with a few long paths and many short ones. A skewed H-tree layout allows every processing element to simulate a leaf cell and up to four tree nodes, with no loss in parallelism. Emulation of a key APSA algorithm on the MPP resulted in performance 16,000 times faster than a Vax. This speed will make it possible for the APSA language interpreter to run fast enough to support research in parallel list processing algorithms.

Treg Cells Protect Dopaminergic Neurons against MPP+ Neurotoxicity via CD47-SIRPA Interaction.

PubMed

Huang, Yan; Liu, Zhan; Cao, Bei-Bei; Qiu, Yi-Hua; Peng, Yu-Ping

2017-01-01

Regulatory T (Treg) cells have been associated with neuroprotection by inhibiting microglial activation in animal models of Parkinson's disease (PD), a progressive neurodegenerative disease characterized by dopaminergic neuronal loss in the nigrostriatal system. Herein, we show that Treg cells directly protect dopaminergic neurons against 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity via an interaction between the two transmembrane proteins CD47 and signal regulatory protein α (SIRPA). Primary ventral mesencephalic (VM) cells or VM neurons were pretreated with Treg cells before MPP+ treatment. Transwell co-culture of Treg cells and VM neurons was used to assess the effects of the Treg cytokines transforming growth factor (TGF)-β1 and interleukin (IL)-10 on dopaminergic neurons. Live cell imaging system detected a dynamic contact of Treg cells with VM neurons that were stained with CD47 and SIRPA, respectively. Dopaminergic neuronal loss, which was assessed by the number of tyrosine hydroxylase (TH)-immunoreactive cells, was examined after silencing CD47 in Treg cells or silencing SIRPA in VM neurons. Treg cells prevented MPP+-induced dopaminergic neuronal loss and glial inflammatory responses. TGF-β1 and IL-10 secreted from Treg cells did not significantly prevent MPP+-induced dopaminergic neuronal loss in transwell co-culture of Treg cells and VM neurons. CD47 and SIRPA were expressed by Treg cells and VM neurons, respectively. CD47-labeled Treg cells dynamically contacted with SIRPA-labeled VM neurons. Silencing CD47 gene in Treg cells impaired the ability of Treg cells to protect dopaminergic neurons against MPP+ toxicity. Similarly, SIRPA knockdown in VM neurons reduced the ability of Treg cell neuroprotection. Rac1/Akt signaling pathway in VM neurons was activated by CD47-SIRPA interaction between Treg cells and the neurons. Inhibiting Rac1/Akt signaling in VM neurons compromised Treg cell neuroprotection. Treg cells protect dopaminergic neurons against MPP+ neurotoxicity by a cell-to-cell contact mechanism underlying CD47-SIRPA interaction and Rac1/Akt activation. © 2017 The Author(s)Published by S. Karger AG, Basel.

40 CFR 132.1 - Scope, purpose, and availability of documents.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS WATER QUALITY GUIDANCE FOR THE GREAT LAKES SYSTEM § 132.1 Scope, purpose, and availability of documents. (a) This part constitutes the Water Quality Guidance for the Great Lakes System (Guidance... identifies minimum water quality standards, antidegradation policies, and implementation procedures for the...

40 CFR 132.1 - Scope, purpose, and availability of documents.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS WATER QUALITY GUIDANCE FOR THE GREAT LAKES SYSTEM § 132.1 Scope, purpose, and availability of documents. (a) This part constitutes the Water Quality Guidance for the Great Lakes System (Guidance... identifies minimum water quality standards, antidegradation policies, and implementation procedures for the...

40 CFR 132.1 - Scope, purpose, and availability of documents.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS WATER QUALITY GUIDANCE FOR THE GREAT LAKES SYSTEM § 132.1 Scope, purpose, and availability of documents. (a) This part constitutes the Water Quality Guidance for the Great Lakes System (Guidance... identifies minimum water quality standards, antidegradation policies, and implementation procedures for the...

40 CFR 132.1 - Scope, purpose, and availability of documents.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS WATER QUALITY GUIDANCE FOR THE GREAT LAKES SYSTEM § 132.1 Scope, purpose, and availability of documents. (a) This part constitutes the Water Quality Guidance for the Great Lakes System (Guidance... identifies minimum water quality standards, antidegradation policies, and implementation procedures for the...

76 FR 29251 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

...: Topical Oxygen Chamber for Extremities; Availability; Correction AGENCY: Food and Drug Administration, HHS... Special Controls Guidance Documents: Topical Oxygen Chamber for Extremities.'' The document published... Oxygen Chamber for Extremities'' to the Division of Small Manufacturers, International, and Consumer...

Applicability of the May 16, 1995 Memorandum Potential to Emit for MACT Standards - Guidance on Timing Issues for Subpart T Sources Who Become Non-major after the Compliance Date of the Standard

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Protection of MES23.5 dopaminergic cells by obestatin is mediated by proliferative rather than anti-apoptotic action.

PubMed

Shen, Xiao-Li; Jia, Feng-Ju; Song, Ning; Xie, Jun-Xia; Jiang, Hong

2014-02-01

Obestatin is an endogenous peptide sharing a precursor with ghrelin. This study aims to investigate whether and how obestatin protects MES23.5 dopaminergic cells against 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity. MES23.5 cells were pretreated with obestatin (10(-13)-10(-6) mol/L) for 20 min prior to incubation with 200 μmol/L MPP(+) for 12 or 24 h, or treated with obestatin alone (10(-13) to 10(-6) mol/L) for 0, 6, 12, and 24 h. The methyl thiazolyl tetrazolium (MTT) assay was used to measure cell viability. Flow cytometry was used to measure the caspase-3 activity and the mitochondrial transmembrane potential. Proliferating cell nuclear antigen (PCNA) protein levels were determined by Western blotting. Obestatin (10(-13) to 10(-7) mol/L) pretreatment blocked or even reversed the MPP(+)-induced reduction of viability in MES23.5 cells, but had no effect on MPP(+)-induced mitochondrial transmembrane potential collapse and caspase-3 activation. When applied alone, obestatin increased viability. Elevated PCNA levels occurred with 10(-7), 10(-9), 10(-11) and 10(-13) mol/L obestatin treatment for 12 h. The results suggest that the protective effects of obestatin against MPP(+) in MES23.5 cells are due to its proliferation-promoting rather than anti-apoptotic effects.

Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI).

PubMed

Yu, Tao; Chan, Kannie W Y; Anonuevo, Abraham; Song, Xiaolei; Schuster, Benjamin S; Chattopadhyay, Sumon; Xu, Qingguo; Oskolkov, Nikita; Patel, Himatkumar; Ensign, Laura M; van Zjil, Peter C M; McMahon, Michael T; Hanes, Justin

2015-02-01

Mucus barriers lining mucosal epithelia reduce the effectiveness of nanocarrier-based mucosal drug delivery and imaging ("theranostics"). Here, we describe liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, e.g., the diaCEST MRI contrast agent barbituric acid (BA). We observed that polyethylene glycol (PEG)-coated liposomes containing ≥7 mol% PEG diffused only ~10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol%-PEG liposomes contained sufficient BA loading for diaCEST contrast, and provided improved vaginal distribution compared to 0 and 3mol%-PEG liposomes. However, increasing PEG content to ~12 mol% compromised BA loading and vaginal distribution, suggesting that PEG content must be optimized to maintain drug loading and stability. Non-invasive diaCEST MRI illustrated uniform vaginal coverage and longer retention of BA-loaded 7 mol%-PEG liposomes compared to unencapsulated BA. Liposomal MPP with optimized PEG content hold promise for drug delivery and imaging at mucosal surfaces. This team of authors characterized liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, such as barbituric acid (a diaCEST MRI contrast agent) and concluded that liposomal MPP with optimized PEG coating enables drug delivery and imaging at mucosal surfaces. Copyright © 2015 Elsevier Inc. All rights reserved.

Cleavage of precursors by the mitochondrial processing peptidase requires a compatible mature protein or an intermediate octapeptide

PubMed Central

1991-01-01

Many precursors of mitochondrial proteins are processed in two successive steps by independent matrix peptidases (MPP and MIP), whereas others are cleaved in a single step by MPP alone. To explain this dichotomy, we have constructed deletions of all or part of the octapeptide characteristic of a twice cleaved precursor (human ornithine transcarbamylase [pOTC]), have exchanged leader peptide sequences between once-cleaved (human methylmalonyl-CoA mutase [pMUT]; yeast F1ATPase beta-subunit [pF1 beta]) and twice-cleaved (pOTC; rat malate dehydrogenase (pMDH); Neurospora ubiquinol-cytochrome c reductase iron-sulfur subunit [pFe/S]) precursors, and have incubated these proteins with purified MPP and MIP. When the octapeptide of pOTC was deleted, or when the entire leader peptide of a once-cleaved precursor (pMUT or pF1 beta) was joined to the mature amino terminus of a twice-cleaved precursor (pOTC or pFe/S), no cleavage was produced by either protease. Cleavage of these constructs by MPP was restored by re- inserting as few as two amino-terminal residues of the octapeptide or of the mature amino terminus of a once-cleaved precursor. We conclude that the mature amino terminus of a twice-cleaved precursor is structurally incompatible with cleavage by MPP; such proteins have evolved octapeptides cleaved by MIP to overcome this incompatibility. PMID:1672532

CDC Guidance for State and Local Public Health Officials and School Administrators for School (K-12) Responses to Influenza during the 2009-2010 School Year

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2009

2009-01-01

This document provides guidance to help decrease the spread of flu among students and school staff during the 2009-2010 school year. This document expands upon earlier school guidance documents by providing a menu of tools that school and health officials can choose from based on conditions in their area. It recommends actions to take this school…

Stressor Identification Guidance Document

EPA Science Inventory

EPA has made availabile the Stressor Identification Guidance Document (EPA 822-B-00-025) published under the authority of Section 304(a)(2) of the Clean Water Act (CWA). This technical guidance doc...

75 FR 44267 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-28

... Physical Medicine Device Guidance Document; Reopening of Comment Period AGENCY: Food and Drug... for 11 neurological and physical medicine devices. FDA is reopening the comment period to allow... announcing the availability of draft special controls guidance documents for 11 neurological and physical...

76 FR 64228 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-17

...: External Pacemaker Pulse Generator; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... entitled ``Class II Special Controls Guidance Document: External Pacemaker Pulse Generator.'' This draft guidance document describes a means by which external pacemaker pulse generators may comply with the...

Scientific and Regulatory Policy Committee Review: Review of the Organisation for Economic Co-operation and Development (OECD) Guidance on the GLP Requirements for Peer Review of Histopathology.

PubMed

Fikes, James D; Patrick, Daniel J; Francke, Sabine; Frazier, Kendall S; Reindel, James F; Romeike, Annette; Spaet, Robert H; Tomlinson, Lindsay; Schafer, Kenneth A

2015-10-01

In 2014, the Organisation for Economic Co-operation and Development (OECD) issued guidance no. 16, Guidance on the GLP Requirements for Peer Review of Histopathology. The stated purpose of the guidance document is "to provide guidance to pathologists, test facility management, study directors and quality assurance personnel on how the peer review of histopathology should be planned, managed, documented, and reported in order to meet Good Laboratory Practice (GLP) expectations and requirements." On behalf of and in collaboration with the global societies of toxicologic pathology, the Society of Toxicologic Pathology initiated a review of OECD guidance no. 16. The objectives of this review are to provide a unified interpretation of the guidance, to recommend compliant processes for organizations to implement, and to avoid inconsistent process adaptations across the industry. This review of the guidance document is the product of a global collaboration with other societies of toxicologic pathology and provides a section-by-section international consensus view and interpretation of the OECD guidance on peer review. © 2015 by The Author(s).

Online Education in Public Affairs

ERIC Educational Resources Information Center

Ginn, Martha H.; Hammond, Augustine

2012-01-01

This exploratory study provides an overview of the current landscape of online education in the fields of Master of Public Administration and Master of Public Policy (MPA/MPP) utilizing a dataset compiled from content analysis of MPA/MPP programs' websites and survey of 96 National Association of Schools of Public Affairs and Administration…

TECHNICAL GUIDANCE DOCUMENT: CONSTRUCTION QUALITY MANAGEMENT FOR REMEDIAL ACTION AND REMEDIAL DESIGN WASTE CONTAINMENT SYSTEMS

EPA Science Inventory

This Technical Guidance Document is intended to augment the numerous construction quality control and construction quality assurance (CQC and CQA) documents that are available far materials associated with waste containment systems developed for Superfund site remediation. In ge...

78 FR 56752 - Interim Staff Guidance Specific Environmental Guidance for Integral Pressurized Water Reactors...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... (iPWR). This guidance applies to environmental reviews associated with iPWR applications for limited... received on or before this date. ADDRESSES: You may submit comments by any of the following methods (unless... this document. You may access publicly-available information related to this document by any of the...

Guidance Document on Anaerobic Digester Foaming Prevention and Control Methods (WERF Report INFR1SG10a)

EPA Science Inventory

The development of this anaerobic digester (AD) foaming guidance document is based on the need for a specific detailed methodology that water resource recovery facilities (WRRF) personnel can follow and implement to manage or mitigate AD foam incidents. This guidance manual is th...

75 FR 17143 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

... Physical Medicine Device Guidance Documents; Availability AGENCY: Food and Drug Administration, HHS. ACTION... controls guidance documents for 11 neurological and physical medicine devices. FDA has developed a draft... stimulator device achieves ``aesthetic effects through physical change to the structure of the body'' as well...

76 FR 36542 - Draft Guidance for Industry and Food and Drug Administration Staff: The Content of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

...The Food and Drug Administration (FDA) is announcing the availability of the draft guidance document entitled ``Draft Guidance for Industry and Food and Drug Administration Staff: The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Low Glucose Suspend (LGS) Device Systems.'' This draft guidance document provides industry and Agency staff with recommendations that are intended to improve the safety and effectiveness of LGS Device Systems. This draft guidance is not final nor is it in effect at this time.

Restoration Planning: Guidance Document for Natural Resource Damage Assessment Under the Oil Pollution Act of 1990

DOT National Transportation Integrated Search

1996-08-01

The purpose of this document is to provide trustees with general guidance to develop restoration plans under OPA that comply with NEPA's procedural requirements. The focus of this document is to more fully describe the processes and products required...

Guidance Documents for Inert Ingredients

EPA Pesticide Factsheets

These guidance documents provide information on various inert ingredient issues, including the general process for submitting petitions or requests, adding trade names to our database, and doing searches related to inert ingredients.

PSD Guidance Document

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Association of the ACE, GSTM1, IL-6, NOS3, and CYP1A1 polymorphisms with susceptibility of mycoplasma pneumoniae pneumonia in Chinese children

PubMed Central

Zhao, Jie; Zhang, Wen; Shen, Li; Yang, Xiaomeng; Liu, Yi; Gai, Zhongtao

2017-01-01

Abstract Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) and the clinical presentation of mycoplasma pneumoniae pneumonia (MPP) varies widely. Genetic variability affecting the host response may also influence the susceptibility to MPP. Several studies have investigated the association between single nucleotide polymorphism (SNP) of some genes and the risks of CAP; however, the results were inconsistent. Here, we investigated the association of 5 functional genes and the risks of MPP, including ACE (rs4340), GSTM1 (Ins/del), IL-6 (rs1800795), NOS3 (rs1799983), and CYP1A1 (rs2606345) in a total of 715 subjects (415 cases, 300 controls) by using tetra-primer allele-specific polymerase chain reaction (PCR) and Sanger sequencing. The gene–gene interactions were analyzed using the Multifactor Dimensionality Reduction and cumulative genetic risk score approaches. Our results showed that 3 SNPs of ACE rs4340, IL-6 rs1800795, and NOS3 rs1799983 were significantly associated with the risks of MPP, while no differences were observed in genotype frequencies of GSTM1 (Ins/del) and CYP1A1 rs2606345 between both groups. The combinations of ACE rs4340D/NOS3 rs1799983T/CYP1A1 rs2606345G and ACE rs4340D/NOS3 rs1799983T contribute to the genetic susceptibility of MPP in Chinese children. PMID:28403117

TiO2 dye sensitized solar cell (DSSC): linear relationship of maximum power point and anthocyanin concentration

NASA Astrophysics Data System (ADS)

Ahmadian, Radin

2010-09-01

This study investigated the relationship of anthocyanin concentration from different organic fruit species and output voltage and current in a TiO2 dye-sensitized solar cell (DSSC) and hypothesized that fruits with greater anthocyanin concentration produce higher maximum power point (MPP) which would lead to higher current and voltage. Anthocyanin dye solution was made with crushing of a group of fresh fruits with different anthocyanin content in 2 mL of de-ionized water and filtration. Using these test fruit dyes, multiple DSSCs were assembled such that light enters through the TiO2 side of the cell. The full current-voltage (I-V) co-variations were measured using a 500 Ω potentiometer as a variable load. Point-by point current and voltage data pairs were measured at various incremental resistance values. The maximum power point (MPP) generated by the solar cell was defined as a dependent variable and the anthocyanin concentration in the fruit used in the DSSC as the independent variable. A regression model was used to investigate the linear relationship between study variables. Regression analysis showed a significant linear relationship between MPP and anthocyanin concentration with a p-value of 0.007. Fruits like blueberry and black raspberry with the highest anthocyanin content generated higher MPP. In a DSSC, a linear model may predict MPP based on the anthocyanin concentration. This model is the first step to find organic anthocyanin sources in the nature with the highest dye concentration to generate energy.

Ameliorative effects of Qingfei Tongluo formula on experimental mycoplasmal pneumonia in mice.

PubMed

Jiang, Yong-hong; Yu, Jian-er; Guo, Ai-hua; Li, Xiao; Lin, Yan; Jiang, Zhi-yan; Xiao, Zhen

2016-04-01

Mycoplasma pneumoniae pneumonia (MPP) is a common disease in children. Qingfei Tongluo formula (QTF) has been used for the treatment of MPP clinically, but the chemical constituents and mechanism involved remain unclear. This study aimed to analyze the main chemical constituents and to explore the possible mechanism of action associated with QTF treatment of MPP. Liquid chromatography-mass spectrometry was employed to identify the compounds contained in the QTF extract. A BALB/c mouse model of MP infection was established. After treatment with QTF (0.85 and 1.70 g/kg) for 3 days, hematoxylin and eosin staining was performed in lung tissues for histological examination. Inflammatory cytokines were detected by ELISA. Western blot analysis was used for detecting phosphorylated proteins involved in MAPK and nuclear factor (NF)-κB signaling pathways. In the mouse model, a large amount of pulmonary interstitial infiltration of lymphocytes and plasmacytes were seen as well as bronchus and vasodilation congestion. Following QTF treatment, inflammation was alleviated significantly compared with the model group. Inflammatory cytokines [interleukin (IL)-6, transforming growth factor-β1, IL-8, IL-1β and tumor necrosis factor-α] in bronchoalveolar lavage fluid were decreased dramatically. In addition, we found that QTF inhibited activation of phosphorylation of JNK, ERK and NF-κB. In conclusion, QTF alleviates MPP inflammation possibly via inhibitory activation of MAPK/NF-κB pathways, which can act as a new agent for MPP treatment.

N-methyltetrahydropyridines and pyridinium cations as toxins and comparison with naturally-occurring alkaloids.

PubMed

Herraiz, Tomás

2016-11-01

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium cation (MPP + ) are selective dopaminergic neurotoxins producing Parkinsonism. MPTP is activated by monoamine oxidase-B (MAO-B) to MPP + that inhibits mitochondrial function. Molecules resembling MPTP which afford pyridinium cations are also neurotoxins. The herbicide paraquat (a bipyridinium dication) and the naturally-occurring β-carboline and isoquinoline alkaloids are structural analogues of MPTP/MPP + . Paraquat generates reactive oxygen species (ROS) producing neurotoxicity by a mechanism that differs from MPTP/MPP + . Human exposure to PQ is increasingly associated with neurodegeneration. Tetrahydro-β-carbolines (THβCs), β-carbolines (βCs) and tetrahydroisoquinolines (TIQ s ) are bioactive compounds occurring in foods and the human body. They are not MPTP-like toxins and do not appear to induce neurotoxicity at normal levels of exposure. Among TIQs, endogenous dopamine-derived TIQs (i.e. salsolinol) and 1-benzyl-TIQ are toxic through ROS generation. In contrast, β-carbolinium (βC + s) and isoquinolinium cations (IQ + s) are neurotoxicants resembling MPP + although they are less potent and selective. βC + s and IQ + s have been detected in the human brain but their toxicological significance remains unknown. THβCs/βCs and TIQs are activated to toxic cations by N-methyltransferases (NMT) and/or heme peroxidases and are metabolized by cytochrome P450 enzymes. Remarkably, recent findings suggest, instead, that βCs and TIQs are neuroprotectants and neurorestorative, raising the interest of these molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroglobin overexpression plays a pivotal role in neuroprotection through mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells.

PubMed

Garofalo, Tina; Ferri, Alberto; Sorice, Maurizio; Azmoon, Pardis; Grasso, Maria; Mattei, Vincenzo; Capozzi, Antonella; Manganelli, Valeria; Misasi, Roberta

2018-04-01

Since stressing conditions induce a relocalization of endogenous human neuroglobin (NGB) to mitochondria, this research is aimed to evaluate the protective role of NGB overexpression against neurotoxic stimuli, through mitochondrial lipid raft-associated complexes. To this purpose, we built a neuronal model of oxidative stress by the use of human dopaminergic neuroblastoma cells, SK-N-BE2, stably overexpressing NGB by transfection and treated with 1-methyl-4-phenylpyridinium ion (MPP+). We preliminary observed the redistribution of NGB to mitochondria following MPP+ treatment. The analysis of mitochondrial raft-like microdomains revealed that, following MPP+ treatment, NGB translocated to raft fractions (Triton X-100-insoluble), where it interacts with ganglioside GD3. Interestingly, the administration of agents capable of perturbating microdomain before MPP+ treatment, significantly affected viability in SK-N-BE2-NGB cells. The overexpression of NGB was able to abrogate the mitochondrial injuries on complex IV activity or mitochondrial morphology induced by MPP+ administration. The protective action of NGB on mitochondria only takes place if the mitochondrial lipid(s) rafts-like microdomains are intact, indeed NGB fails to protect complex IV activity when purified mitochondria were treated with the lipid rafts disruptor methyl-β-cyclodextrin. Thus, our unique in vitro model of stably transfected cells overexpressing endogenous NGB allowed us to suggest that the role in neuroprotection played by NGB is reliable only through interaction with mitochondrial lipid raft-associated complexes. Copyright © 2018 Elsevier Inc. All rights reserved.

The epigenetic regulation of HIF-1α by SIRT1 in MPP{sup +} treated SH-SY5Y cells

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

Dong, Su-Yan; Guo, Yan-Jie; Feng, Ya

Both silent information regulator 1 (SIRT1) and hypoxia inducible factor 1 (HIF-1) have been found to play important roles in the pathophysiology of Parkinson's disease (PD). However, their mechanisms and their relationship still require further study. In the present study, we focused on the change and relationship of SIRT1 and HIF-1α in PD. PD cell models were established by using methyl-4-phenylpyridinium (MPP{sup +}), which induced inhibition of cell proliferation, cell cycle arrest and apoptosis. We found that the expression of HIF-1α and its target genes VEGFA and LDHA increased and that SIRT1 expression was inhibited in MPP{sup +} treated cells.more » With further analysis, we found that the acetylation of H3K14 combined with the HIF-1α promoter was dramatically increased in cells treated with MPP{sup +}, which resulted in the transcriptional activation of HIF-1α. Moreover, the acetylation of H3K14 and the expression of HIF-1α increased when SIRT1 was knocked down, suggesting that SIRT1 was involved in the epigenetic regulation of HIF-1α. At last, phenformin, another mitochondrial complex1 inhibitor, was used to testify that the increased HIF-1a was not due to off target effects of MPP{sup +}. Therefore, our results support a link between PD and SIRT1/HIF-1α signaling, which may serve as a clue for understanding PD.« less

75 FR 45678 - Notice of Availability of Interim Staff Guidance Document for Fuel Cycle Facilities

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... Document for Fuel Cycle Facilities AGENCY: Nuclear Regulatory Commission. ACTION: Notice of availability..., Division of Fuel Cycle Safety and Safeguards, Office of Nuclear Material Safety and Safeguards, U.S... Commission (NRC) prepares and issues Interim Staff Guidance (ISG) documents for fuel cycle facilities. These...

Inhibition of Protein Ubiquitination by Paraquat and 1-Methyl-4-Phenylpyridinium Impairs Ubiquitin-Dependent Protein Degradation Pathways.

PubMed

Navarro-Yepes, Juliana; Anandhan, Annadurai; Bradley, Erin; Bohovych, Iryna; Yarabe, Bo; de Jong, Annemieke; Ovaa, Huib; Zhou, You; Khalimonchuk, Oleh; Quintanilla-Vega, Betzabet; Franco, Rodrigo

2016-10-01

Intracytoplasmic inclusions of protein aggregates in dopaminergic cells (Lewy bodies) are the pathological hallmark of Parkinson's disease (PD). Ubiquitin (Ub), alpha (α)-synuclein, p62/sequestosome 1, and oxidized proteins are the major components of Lewy bodies. However, the mechanisms involved in the impairment of misfolded/oxidized protein degradation pathways in PD are still unclear. PD is linked to mitochondrial dysfunction and environmental pesticide exposure. In this work, we evaluated the effects of the pesticide paraquat (PQ) and the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP(+)) on Ub-dependent protein degradation pathways. No increase in the accumulation of Ub-bound proteins or aggregates was observed in dopaminergic cells (SK-N-SH) treated with PQ or MPP(+), or in mice chronically exposed to PQ. PQ decreased Ub protein content, but not its mRNA transcription. Protein synthesis inhibition with cycloheximide depleted Ub levels and potentiated PQ-induced cell death. The inhibition of proteasomal activity by PQ was found to be a late event in cell death progression and had neither effect on the toxicity of either MPP(+) or PQ, nor on the accumulation of oxidized sulfenylated, sulfonylated (DJ-1/PARK7 and peroxiredoxins), and carbonylated proteins induced by PQ. PQ- and MPP(+)-induced Ub protein depletion prompted the dimerization/inactivation of the Ub-binding protein p62 that regulates the clearance of ubiquitinated proteins by autophagy. We confirmed that PQ and MPP(+) impaired autophagy flux and that the blockage of autophagy by the overexpression of a dominant-negative form of the autophagy protein 5 (dnAtg5) stimulated their toxicity, but there was no additional effect upon inhibition of the proteasome. PQ induced an increase in the accumulation of α-synuclein in dopaminergic cells and membrane-associated foci in yeast cells. Our results demonstrate that the inhibition of protein ubiquitination by PQ and MPP(+) is involved in the dysfunction of Ub-dependent protein degradation pathways.

Functional characterization of the organic cation transporters (OCTs) in human airway pulmonary epithelial cells.

PubMed

Ingoglia, Filippo; Visigalli, Rossana; Rotoli, Bianca Maria; Barilli, Amelia; Riccardi, Benedetta; Puccini, Paola; Dall'Asta, Valeria

2015-07-01

Organic cation transporters (OCT1-3) mediate the transport of organic cations including inhaled drugs across the cell membrane, although their role in lung epithelium hasn't been well understood yet. We address here the expression and functional activity of OCT1-3 in human airway epithelial cells A549, Calu-3 and NCl-H441. Kinetic and inhibition analyses, employing [(3)H]1-methyl-4-phenylpyridinium (MPP+) as substrate, and the compounds quinidine, prostaglandine E2 (PGE2) and corticosterone as preferential inhibitors of OCT1, OCT2, and OCT3, respectively, have been performed. A549 cells present a robust MPP+ uptake mediated by one high-affinity component (Km~50μM) which is identifiable with OCT3. Corticosterone, indeed, completely inhibits MPP+ transport, while quinidine and PGE2 are inactive and SLC22A3/OCT3 silencing with siRNA markedly lowers MPP+ uptake. Conversely, Calu-3 exhibits both a high (Km<20μM) and a low affinity (Km>0.6mM) transport components, referable to OCT3 and OCT1, respectively, as demonstrated by the inhibition analysis performed at proper substrate concentrations and confirmed by the use of specific siRNA. These transporters are active also when cells are grown under air-liquid interface (ALI) conditions. Only a very modest saturable MPP+ uptake is measurable in NCl-H441 cells and the inhibitory effect of quinidine points to OCT1 as the subtype functionally involved in this model. Finally, the characterization of MPP+ transport in human bronchial BEAS-2B cells suggests that OCT1 and OCT3 are operative. These findings could help to identify in vitro models to be employed for studies concerning the specific involvement of each transporter in drug transportation. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of glycolysis and gluconeogenesis in the cytoprotection of neuroblastoma cells against 1-methyl 4-phenylpyridinium ion toxicity.

PubMed

Mazzio, Elizabeth; Soliman, Karam F A

2003-01-01

1-Methyl-4-phenylpyridinium (MPP+) is a mitochondrial Complex I inhibitor and is frequently used to investigate the pathological degeneration of neurons associated with Parkinson's disease (PD). In vitro, extracellular concentration of glucose is one of the most critical factors in establishing the vulnerability of neurons to MPP+ toxicity. While glucose is the primary energy fuel for the brain, central nervous system (CNS) neurons can also take up and utilize other metabolic intermediates for energy. In this study, we compared various monosaccharides, disaccharides, nutritive/non-nutritive sugar alcohols, glycolytic and gluconeogenic metabolic intermediates for their cytoprotection against MPP+ in murine brain neuroblastoma cells. Several monosaccharides were effective against MMP+ (500 microM) including glucose, fructose and mannose, which restored cell viability to 109 +/- 5%, 70 +/- 5%, 99 +/- 3% of live controls, respectively. Slight protective effects were observed in the presence of 3-phosphoglyceric acid and glucose-6-phosphate; however, no protective effects were exhibited by galactose, sucrose, sorbitol, mannitol, glycerol or various gluconeogenic and ketogenic amino acids. On the other hand, fructose 1,6 bisphosphate and gluconeogenic energy intermediates [pyruvic acid, malic acid and phospho(enol)pyruvate (PEP)] were neuroprotective against MPP+. The gluconeogenic intermediates elevated intracellular levels of ATP and reduced propidium iodide (PI) nucleic acid staining to live controls, but did not alter the MPP(+)-induced loss of mitochondrial O2 consumption. These data indicate that malic acid, pyruvic acid and PEP contribute to anaerobic substrate level phosphorylation. The use of hydrazine sulfate to impede gluconeogenesis through PEP carboxykinase (PEPCK) inhibition heightened the protective effects of energy substrates possibly due to attenuated ATP demands from pyruvate carboxylase (PC) activity and pyruvate mitochondrial transport. It was concluded from these studies that several metabolic intermediates are effective in fueling anaerobic glycolysis during mitochondrial inhibition by MPP+.

Mitochondrial inhibitor models of Huntington's disease and Parkinson's disease induce zinc accumulation and are attenuated by inhibition of zinc neurotoxicity in vitro or in vivo.

PubMed

Sheline, Christian T; Zhu, Julia; Zhang, Wendy; Shi, Chunxiao; Cai, Ai-Li

2013-01-01

Inhibition of mitochondrial function occurs in many neurodegenerative diseases, and inhibitors of mitochondrial complexes I and II are used to model them. The complex II inhibitor, 3-nitroproprionic acid (3-NPA), kills the striatal neurons susceptible in Huntington's disease. The complex I inhibitor N-methyl-4-phenylpyridium (MPP(+)) and 6-hydroxydopamine (6-OHDA) are used to model Parkinson's disease. Zinc (Zn(2+)) accumulates after 3-NPA, 6-OHDA and MPP(+) in situ or in vivo. We will investigate the role of Zn(2+) neurotoxicity in 3-NPA, 6-OHDA and MPP(+). Murine striatal/midbrain tyrosine hydroxylase positive, or near-pure cortical neuronal cultures, or animals were exposed to 3-NPA or MPP(+) and 6-OHDA with or without neuroprotective compounds. Intracellular zinc ([Zn(2+)](i)), nicotinamide adenine dinucleotide (NAD(+)), NADH, glycolytic intermediates and neurotoxicity were measured. We showed that compounds or genetics which restore NAD(+) and attenuate Zn(2+) neurotoxicity (pyruvate, nicotinamide, NAD(+), increased NAD(+) synthesis, sirtuin inhibition or Zn(2+) chelation) attenuated the neuronal death induced by these toxins. The increase in [Zn(2+)](i) preceded a reduction in the NAD(+)/NADH ratio that caused a reversible glycolytic inhibition. Pyruvate, nicotinamide and NAD(+) reversed the reductions in the NAD(+)/NADH ratio, glycolysis and neuronal death after challenge with 3-NPA, 6-OHDA or MPP(+), as was previously shown for exogenous Zn(2+). To test efficacy in vivo, we injected 3-NPA into the striatum of rats and systemically into mice, with or without pyruvate. We observed early striatal Zn(2+) fluorescence, and pyruvate significantly attenuated the 3-NPA-induced lesion and restored behavioral scores. Together, these studies suggest that Zn(2+) accumulation caused by MPP(+) and 3-NPA is a novel preventable mechanism of the resultant neurotoxicity. Copyright © 2012 S. Karger AG, Basel.

Down-regulation of natural resistance-associated macrophage protein-1 (Nramp1) is associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP+ )-induced α-synuclein accumulation and neurotoxicity.

PubMed

Wu, K-C; Liou, H-H; Lee, C-Y; Lin, C-J

2018-04-21

The accumulation of α-synuclein is a hallmark in the pathogenesis of Parkinson's disease (PD). Natural resistance-associated macrophage protein-1 (Nramp1) was previously shown to contribute to the degradation of extracellular α-synuclein in microglia under conditions of iron overload. This study was aimed at investigating the role of Nramp1 in α-synuclein pathology in the neurone under 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP + ) treatment. The expression of Nramp1 and pathological features (including iron and α-synuclein accumulation) were examined in the dopaminergic neurones of humans (with and without PD) and of mice [with and without receiving chronic MPTP intoxication]. The effects of Nramp1 expression on low-dose MPP + -induced α-synuclein expression and neurotoxicity were determined in human dopaminergic neuroblastoma SH-SY5Y cells. Similar to the findings in the substantia nigra of human PD, lower expression of Nramp1 but higher levels of iron and α-synuclein were identified in the dopaminergic neurones of mice receiving chronic MPTP intoxication, compared to controls. In parallel to the loss of dopaminergic neurones, the numbers of glial fibrillary acidic protein- and ionized calcium-binding adapter molecule-1-positive cells were significantly increased in the substantia nigra of MPTP-treated mice. Likewise, in human neuroblastoma SH-SY5Y cells exposed to low-dose MPP + , Nramp1 expression and cathepsin D activity were decreased, along with an increase in α-synuclein protein expression and aggregation. Overexpression of functional Nramp1 restored cathepsin D activity and attenuated α-synuclein up-regulation and neuronal cell death caused by MPP + treatment. These data suggest that the neuronal expression of Nramp1 is important for protecting against the development of MPTP/MPP + -induced α-synuclein pathology and neurotoxicity. © 2018 British Neuropathological Society.

Medicinal herbs Oenanthe javanica (Blume) DC., Casuarina equisetifolia L. and Sorghum bicolor (L.) Moench protect human cells from MPP+ damage via inducing FBXO7 expression.

PubMed

Chen, Chiung-Mei; Chen, I-Cheng; Chen, Ying-Lin; Lin, Te-Hsien; Chen, Wan-Ling; Chao, Chih-Ying; Wu, Yih-Ru; Lu, Yeah-Ting; Lee, Cheng-Yu; Chien, Hong-Chi; Chen, Ting-Shou; Lee-Chen, Guey-Jen; Lee, Chi-Mei

2016-11-15

The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP + -treated cells. Promoter reporter assay in HEK-293 cells was used to examine the cis/trans elements controlling FBXO7 expression and to screen extracts of medicinal herbs enhancing FBXO7 expression. MTT assay was performed to assess cell viability of MPP + -treated HEK-293/SH-SY5Y cells. In addition, proteasome activity, mitochondrial membrane potential and FBXO7/TRAF2/GATA2 protein expression were evaluated. We demonstrated that -202--57 region of the FBXO7 promoter is likely to contain sequences that are bound by positive trans protein factors to activate FBXO7 expression and GATA2 is the main trans protein factor enhancing FBXO7 expression. Extracts of medicinal herbs Oenanthe javanica (Blume) DC. (Umbelliferae), Casuarina equisetifolia L. (Casuarinaceae), and Sorghum bicolor (L.) Moench (Gramineae) improved cell viability of both MPP + -treated HEK-293 and SH-SY5Y cells, rescued proteasome activity in MPP + -treated HEK-293 cells, and restored mitochondrial membrane potential in MPP + -treated SH-SY5Y cells. These protection effects of herbal extracts are acting through enhancing FBXO7 and decreasing TRAF2 expression, which is probably mediated by GATA2 induction. Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD. Copyright © 2016 Elsevier GmbH. All rights reserved.

Estimation of the effects of multipoint pacing on battery longevity in routine clinical practice.

PubMed

Akerström, Finn; Narváez, Irene; Puchol, Alberto; Pachón, Marta; Martín-Sierra, Cristina; Rodríguez-Mañero, Moisés; Rodríguez-Padial, Luis; Arias, Miguel A

2017-09-23

Multipoint pacing (MPP) permits simultaneous multisite pacing of the left ventricle (LV); initial studies suggest haemodynamic and clinical benefits over conventional (single LV site) cardiac resynchronization therapy (CRT). The aim of this study was to estimate the impact of MPP activation on battery longevity in routine clinical practice. Patient (n = 46) and device data were collected from two centres at least 3 months after MPP-CRT device implantation. Multipoint pacing programming was based on the maximal possible anatomical LV1/LV2 separation according to three predefined LV pacing capture threshold (PCT) cut-offs (≤1.5 V; ≤4.0 V; and ≤6.5 V). Estimated battery longevity was calculated using the programmed lower rate limit, lead impedances, outputs, and pacing percentages. Relative to the longevity for conventional CRT using the lowest PCT (8.9 ± 1.2 years), MPP activation significantly shortened battery longevity for all three PCT cut-offs (≤1.5 V, -5.6%; ≤4.0 V, -16.9%; ≤6.5 V, -21.3%; P's <0.001). When compared with conventional CRT based on longest right ventricle-LV delay (8.3 ± 1.3 years), battery longevity was significantly shortened for the MPP ≤ 4.0 V and ≤6.5 V cut-offs (-10.8 and -15.7%, respectively; P's <0.001). Maximal LV1/LV2 spacing was possible in 23.9% (≤1.5 V), 56.5% (≤4.0 V), and 69.6% (≤6.5 V) of patients. Multipoint pacing activation significantly reduces battery longevity compared with that for conventional CRT configuration. When reasonable MPP LV vector PCTs (≤4.0 V) are achieved, the decrease in battery longevity is relatively small which may prompt the clinician to activate MPP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Inhibition of protein ubiquitination by paraquat and 1-methyl-4-phenylpyridinium impairs ubiquitin-dependent protein degradation pathways

PubMed Central

Navarro-Yepes, Juliana; Anandhan, Annadurai; Bradley, Erin; Bohovych, Iryna; Yarabe, Bo; de Jong, Annemieke; Ovaa, Huib; Zhou, You; Khalimonchuk, Oleh; Quintanilla-Vega, Betzabet; Franco, Rodrigo

2016-01-01

Intracytoplasmic inclusions of protein aggregates in dopaminergic cells (Lewy bodies) are the pathological hallmark of Parkinson’s disease (PD). Ubiquitin (Ub), alpha [α]-synuclein, p62/sequestosome 1 and oxidized proteins are major components of Lewy bodies. However, the mechanisms involved in the impairment of misfolded/oxidized protein degradation pathways in PD are still unclear. PD is linked to mitochondrial dysfunction and environmental pesticide exposure. In this work, we evaluated the effect of the pesticide paraquat (PQ) and the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) on Ub-dependent protein degradation pathways. No increase in the accumulation of Ub-bound proteins or aggregates was observed in dopaminergic cells (SK-N-SH) treated with PQ or MPP+, or in mice chronically exposed to PQ. PQ decreased Ub protein content, but not its mRNA transcription. Protein synthesis inhibition with cycloheximide depleted Ub levels and potentiated PQ–induced cell death. Inhibition of proteasomal activity by PQ was found to be a late event in cell death progression, and had no effect on either the toxicity of MPP+ or PQ, or the accumulation of oxidized sulfenylated, sulfonylated (DJ-1/PARK7 and peroxiredoxins) and carbonylated proteins induced by PQ. PQ- and MPP+-induced Ub protein depletion prompted the dimerization/inactivation of the Ub-binding protein p62 that regulates the clearance of ubiquitinated proteins by autophagic. We confirmed that PQ and MPP+ impaired autophagy flux, and that the blockage of autophagy by the overexpression of a dominant-negative form of the autophagy protein 5 (dnAtg5) stimulated their toxicity, but there was no additional effect upon inhibition of the proteasome. PQ induced an increase in the accumulation of α-synuclein in dopaminergic cells and membrane associated foci in yeast cells. Our results demonstrate that inhibition of protein ubiquitination by PQ and MPP+ is involved in the dysfunction of Ub-dependent protein degradation pathways. PMID:26409479

Guidance and Control Software Project Data - Volume 1: Planning Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes the planning documents from the GCS project. Volume 1 contains five appendices: A. Plan for Software Aspects of Certification for the Guidance and Control Software Project; B. Software Development Standards for the Guidance and Control Software Project; C. Software Verification Plan for the Guidance and Control Software Project; D. Software Configuration Management Plan for the Guidance and Control Software Project; and E. Software Quality Assurance Activities.

Guidance and Control Software Project Data - Volume 3: Verification Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes the verification documents from the GCS project. Volume 3 contains four appendices: A. Software Verification Cases and Procedures for the Guidance and Control Software Project; B. Software Verification Results for the Pluto Implementation of the Guidance and Control Software; C. Review Records for the Pluto Implementation of the Guidance and Control Software; and D. Test Results Logs for the Pluto Implementation of the Guidance and Control Software.

Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.

PubMed

Moldzio, Rudolf; Pacher, Thomas; Krewenka, Christopher; Kranner, Barbara; Novak, Johannes; Duvigneau, Johanna Catharina; Rausch, Wolf-Dieter

2012-06-15

Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP(+) induced cell death. Copyright © 2012 Elsevier GmbH. All rights reserved.

21 CFR 316.50 - Guidance documents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... USE ORPHAN DRUGS Availability of Information § 316.50 Guidance documents. FDA's Office of Orphan... the regulations in this part. The list is maintained on the Internet and is published annually in the...

Energy Efficiency/Renewable Energy Programs in State Implementation Plans - Guidance Documents

EPA Pesticide Factsheets

final document that provides guidance to States and local areas on quantifying and including emission reductions from energy efficiency and renewable energy measures in State Implementation Plans (SIPS).

Bioassay-guided Isolation of Neuroprotective Fatty Acids from Nigella sativa against 1-methyl-4-phenylpyridinium-induced Neurotoxicity

PubMed Central

Hosseinzadeh, Leila; Monaghash, Hoda; Ahmadi, Farahnaz; Ghiasvand, Nastaran; Shokoohinia, Yalda

2017-01-01

Objective: Parkinson's disease, a slowly progressive neurological disease, is associated with degeneration of the basal ganglia of the brain and a deficiency of the neurotransmitter dopamine. The main aspects of researches are the protection of normal neurons against degeneration. Fatty acids (FAs), the key structural elements of dietary lipids, are carboxylic straight chains and notable parameters in nutritional and industrial usefulness of a plant. Materials and Methods: Black cumin, a popular anti-inflammatory and antioxidant food seasoning, contains nonpolar constituents such as FAs which were extracted using hexane. Different fractions and subfractions were apt to cytoprotection against apoptosis and inflammation induced by 1-methyl-4-phenylpyridinium (MPP+) in rat pheochromocytoma cell line (PC12) as a neural cell death model. The experiment consisted of examination of cell viability assessment, mitochondrial membrane potential (MMP), caspase-3 and -9 activity, and measurement of cyclooxygenase (COX) activity. Results: MPP+ induced neurotoxicity in PC12 cells. Pretreatment with subfractions containing FA mixtures attenuated MPP+-mediated apoptosis partially dependent on the inhibition of caspase-3 and -9 activity and increasing the MMP. A mixture of linoleic acid, oleic acid, and palmitic acid also decreased the COX activity induced by MPP+ in PC12 cells. Conclusion: Our observation indicated that subtoxic concentration of FA from Nigella sativa may exert cytoprotective effects through their anti-apoptotic and anti-inflammation actions and could be regarded as a dietary supplement. SUMMARY MPP+ induced neurotoxicity in PC12 cellsNigella sativa contains bioactive fatty acidsPretreatment with fatty acids attenuated MPP+ mediated apoptosis through inhibition of caspase 3 and 9 activityA mixture of linoleic acid, oleic acid, and palmitic acid decreased the COX activity induced by MPP+ in PC12 cellsDue to cytoprotective, anti apoptotic and anti inflammation actions of N. sativa, it could be regarded as a dietary supplement. Abbreviations used: ANOVA: Analysis of variance; Ca: Calcium; CDCl3: Chloroform; COX: Cyclooxygenase; DMSO: Dimethyl sulfoxide; EA: Elidic acid; EDTA: Ethylene diamine tetraacetic acid; ELISA: Enzyme Linked Immunosorbent Assay; ESI-MS: Electron spray mass spectroscopy; FAs: Fatty acids; FBS: Fetal bovine serum; GC: Gas chromatography; 1HNMR: Hydrogen nuclear magnetic resonance; LA: Linoleic acid; MPP+: 1-Methyl-4-phenylpyridinium; MPTP: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine; MTT: 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide; N. sativa: Nigella sativa; OA: Oleic acid; PA: Palmitic acid; PBS: Phosphate buffer saline; PC12: Rat pheochromocytoma cell line; PD: Parkinson's disease; PDA: Photo diode array detector; PGE2: Prostaglandin E2; TLC: Thin layer chromatography; TMPD: N,N,N’,N’-tetramethyl-p-phenylenediamine; USA: United states of America. PMID:29200724

Consideration of health inequalities in systematic reviews: a mapping review of guidance.

PubMed

Maden, Michelle

2016-11-28

Given that we know that interventions shown to be effective in improving the health of a population may actually widen the health inequalities gap while others reduce it, it is imperative that all systematic reviewers consider how the findings of their reviews may impact (reduce or increase) on the health inequality gap. This study reviewed existing guidance on incorporating considerations of health inequalities in systematic reviews in order to examine the extent to which they can help reviewers to incorporate such issues. A mapping review was undertaken to identify guidance documents that purported to inform reviewers on whether and how to incorporate considerations of health inequalities. Searches were undertaken in Medline, CINAHL and The Cochrane Library Methodology Register. Review guidance manuals prepared by international organisations engaged in undertaking systematic reviews, and their associated websites were scanned. Studies were included if they provided an overview or discussed the development and testing of guidance for dealing with the incorporation of considerations of health inequalities in evidence synthesis. Results are summarised in narrative and tabular forms. Twenty guidance documents published between 2009 and 2016 were included. Guidance has been produced to inform considerations of health inequalities at different stages of the systematic review process. The Campbell and Cochrane Equity Group have been instrumental in developing and promoting such guidance. Definitions of health inequalities and guidance differed across the included studies. All but one guidance document were transparent in their method of production. Formal methods of evaluation were reported for six guidance documents. Most of the guidance was operationalised in the form of examples taken from published systematic reviews. The number of guidance items to operationalise ranges from 3 up to 26 with a considerable overlap noted. Adhering to the guidance will require more work for the reviewers. It requires a deeper understanding of how reviewers can operationalise the guidance taking into consideration the barriers and facilitators involved. This has implications not only for understanding the usefulness and burden of the guidance but also for the uptake of guidance and its ultimate goal of improving health inequalities considerations in systematic reviews.

Guidance Documents for Marine Fuel

EPA Pesticide Factsheets

The following guidance documents apply to marine fuel used in ocean-going vessels. All vessels that operate in the North American Emission Control Area (ECA) must generally use fuel with 1,000 ppm sulfur or less.

Guidance Documents on Substantial Risk Notifications under TSCA

EPA Pesticide Factsheets

Guidance documents for TSCA Section 8(e) which states 'Any person who manufactures a chemical substance and obtains information that the chemical is harmful to health or the environment shall inform the EPA.'

Air pollution and public health: a guidance document for risk managers.

PubMed

Craig, Lorraine; Brook, Jeffrey R; Chiotti, Quentin; Croes, Bart; Gower, Stephanie; Hedley, Anthony; Krewski, Daniel; Krupnick, Alan; Krzyzanowski, Michal; Moran, Michael D; Pennell, William; Samet, Jonathan M; Schneider, Jurgen; Shortreed, John; Williams, Martin

2008-01-01

This guidance document is a reference for air quality policymakers and managers providing state-of-the-art, evidence-based information on key determinants of air quality management decisions. The document reflects the findings of five annual meetings of the NERAM (Network for Environmental Risk Assessment and Management) International Colloquium Series on Air Quality Management (2001-2006), as well as the results of supporting international research. The topics covered in the guidance document reflect critical science and policy aspects of air quality risk management including i) health effects, ii) air quality emissions, measurement and modeling, iii) air quality management interventions, and iv) clean air policy challenges and opportunities.

The Challenge of Creating a More Diverse Economics: Lessons from the UCR Minority Pipeline Project

ERIC Educational Resources Information Center

Dymski, Gary A.

2017-01-01

This paper reflects on the experience of the 1999-2002 minority pipeline program (MPP) at the University of California, Riverside. With support from the American Economic Association, the MPP identified students of color interested in economics, let them explore economic issues affecting minority communities, and encouraged them to consider…

Maximum power point tracking algorithm based on sliding mode and fuzzy logic for photovoltaic sources under variable environmental conditions

NASA Astrophysics Data System (ADS)

Atik, L.; Petit, P.; Sawicki, J. P.; Ternifi, Z. T.; Bachir, G.; Della, M.; Aillerie, M.

2017-02-01

Solar panels have a nonlinear voltage-current characteristic, with a distinct maximum power point (MPP), which depends on the environmental factors, such as temperature and irradiation. In order to continuously harvest maximum power from the solar panels, they have to operate at their MPP despite the inevitable changes in the environment. Various methods for maximum power point tracking (MPPT) were developed and finally implemented in solar power electronic controllers to increase the efficiency in the electricity production originate from renewables. In this paper we compare using Matlab tools Simulink, two different MPP tracking methods, which are, fuzzy logic control (FL) and sliding mode control (SMC), considering their efficiency in solar energy production.

Evaluation of all African clinical practice guidelines for hypertension: Quality and opportunities for improvement.

PubMed

Okwen, Patrick Mbah; Maweu, Irene; Grimmer, Karen; Margarita Dizon, Janine

2018-06-14

Good-quality clinical practice guidelines (CPGs) provide recommendations based on current best-evidence summaries. Hypertension is a prevalent noncommunicable disease in Africa, with disastrous sequelae (stroke, heart, and kidney disease). Its effective management relies on good quality, current, locally relevant evidence. This paper reports on an all African review of the guidance documents currently informing hypertension management. Attempts were made to contact 62 African countries for formal guidance documents used nationally to inform diagnosis and management of hypertension. Their quality was assessed by using Appraisal of Guidelines for Research & Evaluation (AGREE) II, scored by 2 independent reviewers. Differences in domain scores were compared between documents written prior to 2011 and 2011 onward. Findings were compared with earlier African CPG reviews. Guidelines and protocols were provided by 26 countries. Six used country-specific stand-alone hypertension guidelines, and 10 used protocols embedded in Standard Treatment Guidelines for multiple conditions. Six used guidelines developed by the World Health Organization, and 4 indicated ad hoc use of international guidance (US, Portugal, and Brazil). Only 1 guidance document met CPG construction criteria, and none scored well on all AGREE domain scores. The lowest-scoring domain was rigour of development. There was no significant quality difference between pre-2011 and post-2011 guidance documents, and there were variable AGREE II scores for the same CPGs when comparing the African reviews. The quality of hypertension guidance used by African nations could be improved. The need for so many guidance documents is questioned. Adopting a common evidence base from international good-quality CPGs and layering it with local contexts offer 1 way to efficiently improve African hypertension CPG quality and implementation. © 2018 John Wiley & Sons, Ltd.

76 FR 76166 - Draft Guidance for Industry and Food and Drug Administration Staff; the Content of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

...The Food and Drug Administration (FDA) is announcing the availability of the draft guidance document entitled ``Draft Guidance for Industry and FDA Staff: The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems.'' This draft guidance document provides industry and the Agency staff with guidelines for developing premarket submissions for artificial pancreas device systems, in particular, the Control-to-Range (CTR) and Control-to-Target (CTT) device systems. This draft guidance is not final nor is it in effect at this time.

BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

EPA Pesticide Factsheets

The purpose of this document is to provide guidance for the Agency on the application of the benchmark dose approach in determining the point of departure (POD) for health effects data, whether a linear or nonlinear low dose extrapolation is used. The guidance includes discussion on computation of benchmark doses and benchmark concentrations (BMDs and BMCs) and their lower confidence limits, data requirements, dose-response analysis, and reporting requirements. This guidance is based on today's knowledge and understanding, and on experience gained in using this approach.

77 FR 70449 - Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... of guidance documents that the Center for Devices and Radiological Health (CDRH) is intending to... notice announces the Web site location of the two lists of guidance documents which CDRH is intending to... list. FDA and CDRH priorities are subject to change at any time. Topics on this and past guidance...

76 FR 61367 - Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... the Agency will post a list of guidance documents the Center for Devices and Radiological Health (CDRH... guidance documents that CDRH is considering for development and providing stakeholders an opportunity to.... This notice announces the Web site location of the list of guidances on which CDRH is intending to work...

78 FR 42086 - Draft Guidance for Industry on Arsenic in Apple Juice: Action Level; Supporting Document for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... Level for Arsenic in Apple Juice; A Quantitative Assessment of Inorganic Arsenic in Apple Juice... Arsenic in Apple Juice'' (the draft supporting document) and ``A Quantitative Assessment of Inorganic... document entitled ``A Quantitative Assessment of Inorganic Arsenic in Apple Juice.'' The draft guidance...

Surface Water Treatment Rules State Implementation Guidance

EPA Pesticide Factsheets

These documents provide guidance to states, tribes and U.S. EPA Regions exercising primary enforcement responsibility under the Safe Drinking Water Act. The documents contain EPA’s recommendations for implementation of the Surface Water Treatment Rules.

Moisture Control Guidance for Commercial and Public ...

EPA Pesticide Factsheets

This document provides guidance to designers, construction mangers, and building operation/maintenance managers to improve IEQ and reduce risks of encountering IEQ problems due to insufficient moisture control. EPA will be producing a document entitled

TECHNICAL GUIDANCE DOCUMENT: THE FABRICATION OF POLYETHYLENE FML FIELD SEAMS

EPA Science Inventory

This technical guidance document is meant to augment the numerous construction quality control and construction assurance (CQC and CQA) guidelines that are presently available for high density polyethylene (HDPE) liner installation and inspection.

76 FR 66311 - Draft Documents To Support Submission of an Electronic Common Technical Document; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

.../DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm253101.htm , http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm , or http...

Announcement—guidance document for acquiring reliable data in ecological restoration projects

USGS Publications Warehouse

Stapanian, Martin A.; Rodriguez, Karen; Lewis, Timothy E.; Blume, Louis; Palmer, Craig J.; Walters, Lynn; Schofield, Judith; Amos, Molly M.; Bucher, Adam

2016-01-01

The Laurentian Great Lakes are undergoing intensive ecological restoration in Canada and the United States. In the United States, an interagency committee was formed to facilitate implementation of quality practices for federally funded restoration projects in the Great Lakes basin. The Committee's responsibilities include developing a guidance document that will provide a common approach to the application of quality assurance and quality control (QA/QC) practices for restoration projects. The document will serve as a “how-to” guide for ensuring data quality during each aspect of ecological restoration projects. In addition, the document will provide suggestions on linking QA/QC data with the routine project data and hints on creating detailed supporting documentation. Finally, the document will advocate integrating all components of the project, including QA/QC applications, into an overarching decision-support framework. The guidance document is expected to be released by the U.S. EPA Great Lakes National Program Office in 2017.

Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

PubMed Central

Calvert, Melanie; Kyte, Derek; Duffy, Helen; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; Ives, Jonathan; Draper, Heather; Brundage, Michael; Blazeby, Jane; King, Madeleine

2014-01-01

Background Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers. Methods and Findings We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency. Conclusions PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care. PMID:25333995

Guidance on including ITS elements in transportation projects

DOT National Transportation Integrated Search

2001-01-01

The purpose of this document is to provide guidance for including ITS equipment and technologies as part of traditional transportation construction or maintenance projects. This document is not intended to simplify the planning process, rather it is ...

Lead (Pb) National Ambient Air Quality Standards (NAAQS) Implementation Guidance Documents

EPA Pesticide Factsheets

This page contains implementation guidance documents for the 1978 and 2008 Lead (Pb) NAAQS. Some of the topics covered are: RACM/RACT, RFP, new source review, designations, emissions inventories, attainment dates, and transition policy

Clean Air Act Section 112(r) Inspection Guidance Distribution Memorandum

EPA Pesticide Factsheets

This memorandum issues and makes immediately effective the document, Guidance for Conducting Risk Management Program Inspections under Clean Air Act Section 112(r), which supersedes the 1999 document on auditing risk management plans/programs.

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

PubMed Central

Gori, Jennifer L.; Butler, Jason M.; Chan, Yan-Yi; Chandrasekaran, Devikha; Poulos, Michael G.; Ginsberg, Michael; Nolan, Daniel J.; Elemento, Olivier; Wood, Brent L.; Adair, Jennifer E.; Rafii, Shahin; Kiem, Hans-Peter

2015-01-01

Pluripotent stem cells (PSCs) represent an alternative hematopoietic stem cell (HSC) source for treating hematopoietic disease. The limited engraftment of human PSC–derived (hPSC-derived) multipotent progenitor cells (MPP) has hampered the clinical application of these cells and suggests that MPP require additional cues for definitive hematopoiesis. We hypothesized that the presence of a vascular niche that produces Notch ligands jagged-1 (JAG1) and delta-like ligand-4 (DLL4) drives definitive hematopoiesis. We differentiated hes2 human embryonic stem cells (hESC) and Macaca nemestrina–induced PSC (iPSC) line-7 with cytokines in the presence or absence of endothelial cells (ECs) that express JAG1 and DLL4. Cells cocultured with ECs generated substantially more CD34+CD45+ hematopoietic progenitors compared with cells cocultured without ECs or with ECs lacking JAG1 or DLL4. EC-induced cells exhibited Notch activation and expressed HSC-specific Notch targets RUNX1 and GATA2. EC-induced PSC-MPP engrafted at a markedly higher level in NOD/SCID/IL-2 receptor γ chain–null (NSG) mice compared with cytokine-induced cells, and low-dose chemotherapy-based selection further increased engraftment. Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction were similar to levels achieved for cord blood–derived MPP and up to 20-fold higher than those achieved with hPSC-derived MPP engraftment. Our findings indicate that endothelial Notch ligands promote PSC-definitive hematopoiesis and production of long-term engrafting CD34+ cells, suggesting these ligands are critical for HSC emergence. PMID:25664855

Binding preference of p62 towards LC3-ll during dopaminergic neurotoxin-induced impairment of autophagic flux.

PubMed

Lim, Junghyun; Kim, Hyun-Wook; Youdim, Moussa B H; Rhyu, Im Joo; Choe, Kwang-Min; Oh, Young J

2011-01-01

Accumulating evidence has revealed that autophagy may be beneficial for treatment of neurodegenerative diseases through removal of abnormal protein aggregates. However, the critical autophagic events during neurodegeneration remain to be elucidated. Here, we investigated whether prototypic autophagic events occur in the MN9D dopaminergic neuronal cell line upon exposure to N-methyl-4-phenylpyridinium (MPP (+) ), a well-known dopaminergic neurotoxin. MPP (+) treatment induced both morphological and biochemical characteristics of autophagy, such as accumulation of autophagic vacuoles and LC3-II form and decreased p62 levels. Further investigation revealed that these phenomena were largely the consequences of blocked autophagic flux. Following MPP (+) treatment, levels of LC3-II formed and p62 dramatically increased in the Triton X-100-insoluble fraction. Levels of ubiquitinated proteins also increased in this fraction. Further colocalization analyses revealed that the punctated spots positive for both p62 and LC3 were more intense following MPP (+) treatment, suggesting drug-induced enrichment of these two proteins in the insoluble fraction. Intriguingly, reciprocal immunoprecipitation analysis revealed that p62 mainly precipitated with LC3-II form following MPP (+) treatment. Transient transfection of the mutant form of Atg4B, Atg4B (C74A) , which inhibits LC3 processing, dramatically decreased binding between p62 and LC3-II form. Taken together, our results indicate that p62 can be efficiently localized to autophagic compartments via preferential binding with LC3-II form. This colocalization may assist in removal of detergent-insoluble forms of damaged cellular proteins during dopaminergic neurotoxin-induced impairment of autophagic flux.

Silibinin attenuates MPP⁺-induced neurotoxicity in the substantia nigra in vivo.

PubMed

Jung, Un Ju; Jeon, Min-Tae; Choi, Myung-Sook; Kim, Sang Ryong

2014-05-01

Parkinson's disease (PD) is characterized by degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of neuronal death in PD is largely unknown, but it is becoming clear that inflammation plays a significant role in the pathophysiology of PD. Silibinin is a major flavonoid in milk thistle which has an anti-inflammatory activity. We investigated whether silibinin could have neuroprotective effects on DA neurons in the 1-methyl-4-phenylpyridinium ion (MPP(+))-treated animal model of PD in vivo. To address this question, animals received intraperitoneal (i.p.) injections 10, 50, or 100 mg/kg of silibinin, starting 1 day before MPP(+) injection and continued daily until 6 days post-lesion for tyrosine hydroxylase (TH) staining, or until 1 hour prior to the MPP(+) injection to examine the expression levels of inflammatory proteins. Finally, their brains were harvested at the indicated time points for the analyses. Silibinin treatment with 10 mg/kg had no significantly neuroprotective effects in the substantia nigra (SN). However, 50 and 100 mg/kg of silibinin ameliorated the MPP(+)-induced neurotoxicity in the SN in a dose-dependent manner, and the increased levels of inflammatory molecules such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) by MPP(+) treatment were attenuated by treatment with 100 mg/kg of silibinin. These results indicate that silibinin could be a useful and beneficial natural product offering promise for the prevention of DA neuronal degeneration involved in PD.

[Changes of masseter muscle asymmetry due to unilateral mastication after intervention: a electromyographic analysis].

PubMed

Wang, Yun; Teng, Chen; Wang, Meng-Ya

2015-04-01

To explore the effect of intervention with unilateral mastication on masseter muscle asymmetry. Forty-three subjects (19 males and 24 females, mean age 20.0∓0.5 years) with unilateral chewing were divided into group A0 with motivation and without intervention, group A1 with motivation and intervention, group B0 without motivation or intervention, and group B1 without motivation but with intervention. In groups A0 and A1, the motivation was removed and groups A1 and group B1 received interventions. Surface electromyography was recorded using surface electromyography in all the subjects in mandible postural position (MPP), with maximum clenching in intercuspal position (ICP) and during chewing. The sEMG of the left and right masseter muscle were separately recorded to assess the asymmetry index of the masseter muscles (ASMM) and its changes after intervention. In groupA0, the ASMM at MPP, during maximum clenching and chewing had no obvious changes after removal of the motivation. In group A1, the ASMM at MPP, during maximum clenching and chewing were obviously decreased after intervention. In group B0, the ASMM at MPP and during maximum clenching showed no obvious changes but ASMM during chewing significantly increased after removal of the motivation. In group B1, the ASMM at MPP, during maximum clenching and chewing all decreased obviously after intervention. Interventions can significantly improve the bilateral symmetry of the masseter muscles in subjects with unilateral chewing, and the motivation for unilateral chewing should be removed before intervention.

Protection against MPP(+)-induced neurotoxicity in SH-SY5Y cells by tormentic acid via the activation of PI3-K/Akt/GSK3β pathway.

PubMed

Zhao, Qing; Ye, Junli; Wei, Na; Fong, Chichun; Dong, Xiaoli

2016-07-01

The cause of Parkinson's disease (PD) could be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of tormentic acid (TA), a naturally occurring triterpene extracted from medicinal plants such as Rosa rugosa and Potentilla chinensis, were evaluated in a widely used cellular PD model in which neurotoxicity was induced by MPP(+) in cultured SH-SY5Y cells. We found that TA at 1-30 μM substantially protected against MPP(+)-induced neurotoxicity, as evidenced by the increase in cell viability, decrease in lactate dehydrogenase release and the reduction in apoptotic nuclei. Moreover, TA effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as Bax/Bcl-2 ratio caused by MPP(+). Most importantly, TA markedly reversed the inhibition of protein expression of phosphorylated Akt (Ser 473) and phosphorylated GSK3β (Ser 9) caused by MPP(+). LY294002, the specific inhibitor of PI3-K, significantly abrogated the up-regulated phosphorylated Akt and phosphorylated GSK3β offered by TA, suggesting that the neuroprotection of TA was mainly dependent on the activation of PI3-K/Akt/GSK3β signaling pathway. The results taken together indicate that TA may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse.

PubMed

Maisel, Katharina; Ensign, Laura; Reddy, Mihika; Cone, Richard; Hanes, Justin

2015-01-10

It is believed that mucoadhesive surface properties on particles delivered to the gastrointestinal (GI) tract improve oral absorption or local targeting of various difficult-to-deliver drug classes. To test the effect of nanoparticle mucoadhesion on distribution of nanoparticles in the GI tract, we orally and rectally administered nano- and microparticles that we confirmed possessed surfaces that were either strongly mucoadhesive or non-mucoadhesive. We found that mucoadhesive particles (MAP) aggregated in mucus in the center of the GI lumen, far away from the absorptive epithelium, both in healthy mice and in a mouse model of ulcerative colitis (UC). In striking contrast, water absorption by the GI tract rapidly and uniformly transported non-mucoadhesive mucus-penetrating particles (MPP) to epithelial surfaces, including reaching the surfaces between villi in the small intestine. When using high gavage fluid volumes or injection into ligated intestinal loops, common methods for assessing oral drug and nanoparticle absorption, we found that both MAP and MPP became well-distributed throughout the intestine, indicating that the barrier properties of GI mucus were compromised. In the mouse colorectum, MPP penetrated into mucus in the deeply in-folded surfaces to evenly coat the entire epithelial surface. Moreover, in a mouse model of UC, MPP were transported preferentially into the disrupted, ulcerated tissue. Our results suggest that delivering drugs in non-mucoadhesive MPP is likely to provide enhanced particle distribution, and thus drug delivery, in the GI tract, including to ulcerated tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

Acetyl-L-carnitine prevents total body hydroxyl free radical and uric acid production induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the rat.

PubMed

Loots, Du Toit; Mienie, Lodewyk J; Bergh, Jacobus J; Van der Schyf, Cornelis J

2004-07-23

Acetyl-L-carnitine (ALCAR) is intimately involved in the transport of long chain fatty acids across the inner mitochondrial membrane during oxidative phosphorylation. ALCAR also has been reported to attenuate the occurrence of parkinsonian symptoms associated with 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo, and protects in vitro against the toxicity of the neurotoxic 1-methyl-4-phenylpyridinium (MPP+) metabolite of MPTP. The mechanism for these protective effects remains unclear. ALCAR may attenuate hydroxyl (HO*) free radical production in the MPTP/MPP+ neurotoxic pathway through several mechanisms. Most studies on MPTP/MPP+ toxicity and protection by ALCAR have focused on in vivo brain chemistry and in vitro neuronal culture studies. The present study investigates the attenuative effects of ALCAR on whole body oxidative stress markers in the urine of rats treated with MPTP. In a first study, ALCAR totally prevented the MPTP-induced formation of HO* measured by salicylate radical trapping. In a second study, the production of uric acid after MPTP administration-a measure of oxidative stress mediated through xanthine oxidase-was also prevented by ALCAR. Because ALCAR is unlikely to be a potent radical scavenger, these studies suggest that ALCAR protects against MPTP/MPP+-mediated oxidative stress through other mechanisms. We speculate that ALCAR may operate through interference with organic cation transporters such as OCTN2 and/or carnitine-acylcarnitine translocase (CACT), based partly on the above findings and on semi-empirical electronic similarity calculations on ALCAR, MPP+, and two other substrates for these transporters.

What does recovery mean in practice? A qualitative analysis of international recovery-oriented practice guidance.

PubMed

Le Boutillier, Clair; Leamy, Mary; Bird, Victoria J; Davidson, Larry; Williams, Julie; Slade, Mike

2011-12-01

Recovery is a multifaceted concept, and the need for operationalization in practice has been identified. Although guidance on recovery-oriented practice exists, it is from disparate sources and is difficult to apply. The aims of the study were to identify the key characteristics of recovery-oriented practice guidance on the basis of current international perspectives and to develop an overarching conceptual framework to aid the translation of recovery guidance into practice. A qualitative analysis of 30 international documents offering recovery-oriented practice guidance was conducted. Inductive, semantic-level, thematic analysis was used to identify dominant themes. Interpretive analysis was then undertaken to group the themes into practice domains. The guidance documents were diverse; from six countries-the United States, England, Scotland, Republic of Ireland, Denmark, and New Zealand-and varied in document type, categories of guidance, and level of service user involvement in guidance development. The emerging conceptual framework consists of 16 dominant themes, grouped into four practice domains: promoting citizenship, organizational commitment, supporting personally defined recovery, and working relationship. A key challenge for mental health services is the lack of clarity about what constitutes recovery-oriented practice. The conceptual framework contributes to this knowledge gap and provides a synthesis of recovery-oriented practice guidance.

Organize or Die: Farm School Pedagogy and the Political Ecology of the Agroecological Transition in Rural Haiti

ERIC Educational Resources Information Center

Moore, Sophie Sapp

2017-01-01

This article examines the political and pedagogical role of the farm school in Haiti's largest and oldest peasants' movement, the Peasants' Movement of Papaye (MPP). It draws upon ongoing ethnographic research with MPP as well as documentary and historical analyses of agrarian politics in Haiti to situate the movement's land-based decolonial…

Alterations in bioenergetic function induced by Parkinson's disease mimetic compounds: Lack of correlation with superoxide generation

PubMed Central

Dranka, Brian P.; Zielonka, Jacek; Kanthasamy, Anumantha G.; Kalyanaraman, Balaraman

2012-01-01

In vitro and in vivo models of Parkinson's disease (PD) suggest that increased oxidant production leads to mitochondrial dysfunction in dopaminergic neurons and subsequent cell death. However, it remains unclear if cell death in these models is caused by inhibition of mitochondrial function or oxidant production. The objective of the present study was to determine the relationship between mitochondrial dysfunction and oxidant production in response to multiple PD neurotoxicant mimetics. MPP+ caused a dose-dependent decrease in the basal oxygen consumption rate (OCR) in dopaminergic N27 cells, indicating a loss of mitochondrial function. In parallel, we found that MPP+ only modestly increased oxidation of hydroethidine as a diagnostic marker of superoxide production in these cells. Similar results were found using rotenone as a mitochondrial inhibitor, or 6-hydroxydopamine as a mechanistically distinct PD neurotoxicant, but not with exposure to paraquat. Additionally, the Extracellular Acidification Rate, used as a marker of glycolysis, was stimulated to compensate for OCR inhibition after exposure to MPP+, rotenone, or 6-hydroxydopamine, but not paraquat. Together these data indicate that MPP+, rotenone and 6-hydroxydopamine dramatically shift bioenergetic function away from the mitochondria and towards glycolysis in N27 cells. PMID:22708893

Anti-diabetic effect of dietary mango (Mangifera indica L.) peel in streptozotocin-induced diabetic rats.

PubMed

Gondi, Mahendranath; Basha, Shaik Akbar; Bhaskar, Jamuna J; Salimath, Paramahans V; Rao, Ummiti J S Prasada

2015-03-30

In the present study, the composition of mango peel powder (MPP) collected from the mango pulp industry was determined and the effect of MPP on ameliorating diabetes and its associated complications was studied. Mango peel was rich in polyphenols, carotenoids and dietary fibre. Peel extract contained various bioactive compounds and was found to be rich in soluble dietary fibre. Peel extract exhibited antioxidant properties and protected against DNA damage. Therefore, the effect of peel on ameliorating diabetes was investigated in a rat model of diabetes. A significant increase in urine sugar, urine volume, fasting blood glucose, total cholesterol, triglycerides and low density lipoprotein, and decrease in high density lipoprotein were observed in the rats; however, these parameters were ameliorated in diabetic rats fed with diet supplemented with mango peel at 5% and 10% levels in basal diet. Treatment of diabetic rats with MPP increased antioxidant enzyme activities and decreased lipid peroxidation in plasma, kidney and liver compared to untreated diabetic rats. Glomerular filtration rate and microalbuminuria levels were ameliorated in MPP treated diabetic group. Mango peel, a by-product, can be used as an ingredient in functional and therapeutic foods. © 2014 Society of Chemical Industry.

Sound absorption of microperforated panels inside compact acoustic enclosures

NASA Astrophysics Data System (ADS)

Yang, Cheng; Cheng, Li

2016-01-01

This paper investigates the sound absorption effect of microperforated panels (MPPs) in small-scale enclosures, an effort stemming from the recent interests in using MPPs for noise control in compact mechanical systems. Two typical MPP backing cavity configurations (an empty backing cavity and a honeycomb backing structure) are studied. Although both configurations provide basically the same sound absorption curves from standard impedance tube measurements, their in situ sound absorption properties, when placed inside a small enclosure, are drastically different. This phenomenon is explained using a simple system model based on modal analyses. It is shown that the accurate prediction of the in situ sound absorption of the MPPs inside compact acoustic enclosures requires meticulous consideration of the configuration of the backing cavity and its coupling with the enclosure in front. The MPP structure should be treated as part of the entire system, rather than an absorption boundary characterized by the surface impedance, calculated or measured in simple acoustic environment. Considering the spatial matching between the acoustic fields across the MPP, the possibility of attenuating particular enclosure resonances by partially covering the enclosure wall with a properly designed MPP structure is also demonstrated.

WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity.

PubMed

Antenor-Dorsey, Jo Ann V; O'Malley, Karen L

2012-02-08

The WldS mouse mutant ("Wallerian degeneration-slow") delays axonal degeneration in a variety of disorders including in vivo models of Parkinson's disease. The mechanisms underlying WldS -mediated axonal protection are unclear, although many studies have attributed WldS neuroprotection to the NAD+-synthesizing Nmnat1 portion of the fusion protein. Here, we used dissociated dopaminergic cultures to test the hypothesis that catalytically active Nmnat1 protects dopaminergic neurons from toxin-mediated axonal injury. Using mutant mice and lentiviral transduction of dopaminergic neurons, the present findings demonstrate that WldS but not Nmnat1, Nmnat3, or cytoplasmically-targeted Nmnat1 protects dopamine axons from the parkinsonian mimetic N-methyl-4-phenylpyridinium (MPP+). Moreover, NAD+ synthesis is not required since enzymatically-inactive WldS still protects. In addition, NAD+ by itself is axonally protective and together with WldS is additive in the MPP+ model. Our data suggest that NAD+ and WldS act through separate and possibly parallel mechanisms to protect dopamine axons. As MPP+ is thought to impair mitochondrial function, these results suggest that WldS might be involved in preserving mitochondrial health or maintaining cellular metabolism.

32 CFR 701.64 - Publication of adopted regulatory documents for the guidance of the public.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 false Publication of adopted regulatory documents for the guidance of the public. 701.64 Section 701.64 National Defense Department of Defense (Continued..., Department of the Navy and Department of Defense documents published in the Federal Register should be made...

32 CFR 701.64 - Publication of adopted regulatory documents for the guidance of the public.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false Publication of adopted regulatory documents for the guidance of the public. 701.64 Section 701.64 National Defense Department of Defense (Continued..., Department of the Navy and Department of Defense documents published in the Federal Register should be made...

32 CFR 701.64 - Publication of adopted regulatory documents for the guidance of the public.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 false Publication of adopted regulatory documents for the guidance of the public. 701.64 Section 701.64 National Defense Department of Defense (Continued..., Department of the Navy and Department of Defense documents published in the Federal Register should be made...

32 CFR 701.64 - Publication of adopted regulatory documents for the guidance of the public.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Publication of adopted regulatory documents for the guidance of the public. 701.64 Section 701.64 National Defense Department of Defense (Continued..., Department of the Navy and Department of Defense documents published in the Federal Register should be made...

Guidance and Control Software Project Data - Volume 2: Development Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes the development documents from the GCS project. Volume 2 contains three appendices: A. Guidance and Control Software Development Specification; B. Design Description for the Pluto Implementation of the Guidance and Control Software; and C. Source Code for the Pluto Implementation of the Guidance and Control Software

Guidance on Mobile Energy Services Company Burning Tire Derived Fuel

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on the Definition of Fuel Conversion Plants

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification of Guidance for Calculating Actual or Potential Emissions

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Additional Guidance on Prevention of Significant Deterioration (PSD) Regulations

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Supplemental Guidance on Implementing the North County PSD Remand

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Applicability of NSR Review Circumvention Guidance to 3M - Maplewood, Minnesota

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Operational Guidance on Control Technology for New and Modified MWC's

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

NSR Program Transitional Guidance

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Whether Replacing the Refractory Brick Constitutes a Major Modification

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Extension of Prevention of Significant Deterioration (PSD) Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Request for Guidance on PSD Applicability Determinations for Boiler Emissions

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Implementation of the Revised Modeling Guidance for PSD

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance On Enforcement of PSD Requirements Under the Clean Air Act

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Potential to Emit (PTE) Guidance for Specific Source Categories

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PSD Increment Consumption Guidance

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on PSD Applicability for Refuse-to-Energy Facilities

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PSD and Title V Permitting Guidance for GHGs

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance for Determining BACT Under PSD

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification of PSD Guidance For Modeling Class 1 Area Impacts

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Limiting Potential to Emit in New Source Permitting

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Implementing the Nitrogen Dioxide (NO2) PSD Increments

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

NSR and PSD Policy and Guidance Index

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance on Determining LAER

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance for Proposed Construction at Buckeye Cellulose Corporation

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance for PM2.5 Permit Modeling

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Permit Objection Communication Strategy

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification on Fugitive Emissions Policy

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

December 6, 2000, Kentucky Notice of Deficiency

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Temporary and Contracted Operations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Permitting Authority, Vol. 1, No. 2

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Extension of Interim Approvals of Operating Permits Programs

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Permitting Authority, Vol. 2, No. 1

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Georgetown Cogeneration Project as a Minor Source

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

January 21,1993 Letter To Wallace N. Davis

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for Washington's Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for Texas' Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Summit Petroleum Corporation Single Source Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Great Salt Lake Minerals Source Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Permit Shields and NSR

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Watts Bar Nuclear Plant Title V Applicability

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Letter to Bay Area on Periodic Monitoring

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

White Paper To William Becker

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Applicability for Fort Drum

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

GPC Single Source Letter

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Source Determinations for Oil and Gas Industries

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Tesoro (BP Amoco) Consent Decree

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

40 CFR Part 60, Supbart GG, Applicability Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification of Title I Modifications

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Ships Docked at Title V Permitted Facilities

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Interface Issues

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Determination Regarding Applicability of Federal Operating Permit Requirements

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Credible Evidence Boilerplate Language

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

August 6, 1996 Letter to Martin Bauer

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Re: Schering Corporation - MACT Applicability Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Renewable Operating Permit Program Air Emission Fees

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to Petition on Roosevelt Regional Landfill

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Operating Permit Program Approval Issues

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Operating Permits Program Review Process

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for Indiana's Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Consideration of Fugitive Emissions in Major Source Determinations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

State Experience Intergrating Pollution Prevention Into Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Representational Standing

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Interim Title V Program Approvals

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Consideration of Fugitive Emissions from Grain Elevators

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Region 3 James Madison University Single Source Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Single Source Determination for Coors/TriGen

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

ESCO Corp. Source Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

March 30, 1993 Letter to Dr. Lents

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

United Salt Northeast PSD Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Deferrals and Exemptions for Area Sources

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Policy on Title V Permit Program Data Elements

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Emissions from Landfills

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for Hawaii's Operating Permits Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Consideration of Fugitive Emissions at Oilseed Processing Plants

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Initial Operating Permit Application Compliance Certification Policy

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Section 112 (l) Delegations and Title V Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Implementating the Part 71 Program in Indian Country

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Model State Acid Rain Rule

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

June 3, 1996 Ohio Letter

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Approaches to Creating Federally-Enforceable Emissions Limits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Calculating Potential to Emit (PTE) for Emergency Generators

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Colorado's Proposed Short Term Limits Policy

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PowerSecure Common Control Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Consideration of Fugitives in Open-Air Cattle Operations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Request for PSD Applicability Determination, Golden Aluminum Company

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Single Source Determination for General Dynamics

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Air Curtain Incinerators and Title V Operating Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Statement of Basis Guidelines

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for Michigan's Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Model Implementation Agreement

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for Missouri's Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

NSPS Subpart DD Applicability Determination Request

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Common Control Question -- Dupont and Dupont Dow Elastomers

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Source Definition for Colonial Terminals, Inc.

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Model Attorney General's Opinion

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Region 7 Policy on Periodic Monitoring for Opacity

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Regulated Pollutant

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Georgia Power's Coal-Derived Synfuel Proposal

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Definition of Source

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PSD Definition of Source

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to Questions Regarding Volatile Organic Compounds

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

November 30, 1998, Oregon Notice of Deficiency

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidance Documents and Sample Forms for Central Data Exchange (CDX) Registration and e-PMN Software (Thin Client)

EPA Pesticide Factsheets

For users submitting electronic notices through CDX, this page contains guidance documents and sample forms to help you, submit Premanufacture Notices (PMN), Bona Fide and biotechnology notices, among others.

76 FR 60022 - Endocrine Disruptor Screening Program; Weight-of-Evidence Guidance Document; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

... evaluate results from the battery of Tier 1 screening assays along with other scientific and technical... guidance document that requested additional detail and clarification of the following: 1. Tier 1 battery of...

TECHNICAL RESOURCE DOCUMENT ON MONITORED NATURAL RECOVERY

EPA Science Inventory

In 2005, the United States Environmental Protection Agency (EPA) published a document entitled Contaminated Sediment Remediation Guidance for Hazardous Waste Sites (EPA, 2005), which provides technical and policy guidance for project managers and teams making risk manageme...

International perspectives on social media guidance for nurses: a content analysis.

PubMed

Ryan, Gemma

2016-12-01

Aim This article reports the results of an analysis of the content of national and international professional guidance on social media for the nursing profession. The aim was to consolidate good practice examples of social media guidelines, and inform the development of comprehensive guidance. Method A scoping search of professional nursing bodies' and organisations' social media guidance documents was undertaken using google search. Results 34 guidance documents were located, and a content analysis of these was conducted. Conclusion The results, combined with a review of competency hearings and literature, indicate that guidance should cover the context of social media, and support nurses to navigate and negotiate the differences between the real and online domains to help them translate awareness into actions.

Effects of a Pre-workout Supplement on Lean Mass, Muscular Performance, Subjective Workout Experience and Biomarkers of Safety

PubMed Central

Kedia, A. William; Hofheins, Jennifer E.; Habowski, Scott M.; Ferrando, Arny A.; Gothard, M. David; Lopez, Hector L.

2014-01-01

In this prospective, randomized, double-blind, trial conducted in two parts, we examined the effects of a multi-ingredient pre-exercise workout supplement blend of creatine, betaine and a dendrobium extract (MMP) on safety, performance, and body composition in healthy men and women undergoing a supervised program of resistance exercise. Part 1 was an acute hemodynamic safety study wherein forty young, healthy men and women (26.2 ± 5.3 years, 70.4 ± 3.3 inches, 83.7 ± 14.9 kg, 26.0 ± 3.2 kg●m-2) ingest one dose of either the MMP or comparator in a randomized, double-blind, comparator controlled, crossover fashion before having their resting heart rate, blood, ECG and comprehensive blood chemistry and blood counts completed. Systolic (SBP) and diastolic (DBP) blood pressures were generally raised (3.0-5.4 mm Hg, p<0.01) following supplementation with MPP whereas in the comparator group SBP was marginally reduced by 0.3 to 1.2 mm Hg, p>0.05 at all time points) and DBP was increased (3.0 - 3.9 mm Hg, p<0.05 at all time points). No changes in EKG-corrected QT interval were observed, and no serious adverse events were reported. Part 2 was a six-week training study wherein forty-three young, healthy men and women (24.3 ± 2.9 years, 70.5 ± 3.1 inches, 83.8 ± 9.6 kg, 26.1 ± 2.7 kg●m-2) supplemented with daily pre-workout doses of either the MPP or a comparator in a randomized, double-blind, comparator-controlled fashion while following a standardized resistance training program for six weeks. MPP and the comparator were isocaloric and delivered the same amount of caffeine. Significant improvements in visual analog scale (VAS) scores for energy (p<0.024) and concentration (p<0.041) were found along with consistently higher levels of focus accompanied by less fatigue when MPP was consumed in comparison to comparator during upper body muscular strength-endurance tests at weeks 3 and 6. MPP supplementation for 6 weeks did not improve dual-energy x-ray absorptiometry (DEXA) measures of body composition or objective assessments of exercise performance. Overall, MPP use and administration was well tolerated. Self-reported scores for energy and concentration were significantly greater. Over a six-week training and supplementation period, MPP use was not associated with improvements in performance or body composition. Future studies should confirm these effects over a more prolonged training period. PMID:24465156

Effects of a pre-workout supplement on lean mass, muscular performance, subjective workout experience and biomarkers of safety.

PubMed

Kedia, A William; Hofheins, Jennifer E; Habowski, Scott M; Ferrando, Arny A; Gothard, M David; Lopez, Hector L

2014-01-01

In this prospective, randomized, double-blind, trial conducted in two parts, we examined the effects of a multi-ingredient pre-exercise workout supplement blend of creatine, betaine and a dendrobium extract (MMP) on safety, performance, and body composition in healthy men and women undergoing a supervised program of resistance exercise. Part 1 was an acute hemodynamic safety study wherein forty young, healthy men and women (26.2 ± 5.3 years, 70.4 ± 3.3 inches, 83.7 ± 14.9 kg, 26.0 ± 3.2 kg●m(-2)) ingest one dose of either the MMP or comparator in a randomized, double-blind, comparator controlled, crossover fashion before having their resting heart rate, blood, ECG and comprehensive blood chemistry and blood counts completed. Systolic (SBP) and diastolic (DBP) blood pressures were generally raised (3.0-5.4 mm Hg, p<0.01) following supplementation with MPP whereas in the comparator group SBP was marginally reduced by 0.3 to 1.2 mm Hg, p>0.05 at all time points) and DBP was increased (3.0 - 3.9 mm Hg, p<0.05 at all time points). No changes in EKG-corrected QT interval were observed, and no serious adverse events were reported. Part 2 was a six-week training study wherein forty-three young, healthy men and women (24.3 ± 2.9 years, 70.5 ± 3.1 inches, 83.8 ± 9.6 kg, 26.1 ± 2.7 kg●m(-2)) supplemented with daily pre-workout doses of either the MPP or a comparator in a randomized, double-blind, comparator-controlled fashion while following a standardized resistance training program for six weeks. MPP and the comparator were isocaloric and delivered the same amount of caffeine. Significant improvements in visual analog scale (VAS) scores for energy (p<0.024) and concentration (p<0.041) were found along with consistently higher levels of focus accompanied by less fatigue when MPP was consumed in comparison to comparator during upper body muscular strength-endurance tests at weeks 3 and 6. MPP supplementation for 6 weeks did not improve dual-energy x-ray absorptiometry (DEXA) measures of body composition or objective assessments of exercise performance. Overall, MPP use and administration was well tolerated. Self-reported scores for energy and concentration were significantly greater. Over a six-week training and supplementation period, MPP use was not associated with improvements in performance or body composition. Future studies should confirm these effects over a more prolonged training period.

Overseas Environmental Baseline Guidance Document

DTIC Science & Technology

2007-05-01

The primary purpose of this Overseas Environmental Baseline Guidance Document (OEBGD) is to provide criteria and management practices to be used by ...establishes standards for environmental compliance at Department of Defense controlled or operated installations in countries for which no FGS have been established.

In Situ Soil Venting - Full Scale Test Hill AFB, Guidance Document, Literature Review. Volume 1

DTIC Science & Technology

1991-08-01

AD-A254 924 1’) VOL I IN SITU SOIL VENTING - FULL SCALE TEST HILL AFB, GUIDANCE DOCUMENT, LITERATURE REVIEW D. W. DEPAO, S. E. HERBES, J. H . WILSON...D. K. SOLOMON, AND H . L. JENNINGS MARTIN-MARIETTA ENERGY SYSTEMS OAK RIDGE NATIONAL LABORATORY P. O. BOX 2008 OAK RIDGE TN 37831 OTI AUGUST 1991 S...sificat,cn) (U) In Situ Soil Ver.ting - Full Scale Test Hill AFB, Guidance Document, Literature Review 2 PERSO’.AL AUTH-O’.S, a W ApP li- S_ T’.- erber:. H

Content of system design descriptions

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

NONE

A System Design Description (SDD) describes the requirements and features of a system. This standard provides guidance on the expected technical content of SDDs. The need for such a standard was recognized during efforts to develop SDDs for safety systems at DOE Hazard Category 2 nonreactor nuclear facilities. Existing guidance related to the corresponding documents in other industries is generally not suitable to meet the needs of DOE nuclear facilities. Across the DOE complex, different contractors have guidance documents, but they vary widely from site to site. While such guidance documents are valuable, no single guidance document has all themore » attributes that DOE considers important, including a reasonable degree of consistency or standardization. This standard is a consolidation of the best of the existing guidance. This standard has been developed with a technical content and level of detail intended to be most applicable to safety systems at DOE Hazard Category 2 nonreactor nuclear facilities. Notwithstanding that primary intent, this standard is recommended for other systems at such facilities, especially those that are important to achieving the programmatic mission of the facility. In addition, application of this standard should be considered for systems at other facilities, including non-nuclear facilities, on the basis that SDDs may be beneficial and cost-effective.« less

Neuroprotective Ganglioside Derivatives

DTIC Science & Technology

2006-09-01

SH - SY5Y human neuroblastoma cell line . Derivatives determined to have therapeutic potential are tested in vitro for their...to be cytoprotective in in vitro models using the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP+) and the SH - SY5Y cell line . Derivatives...action of these two compounds remains unknown. The ability of GM1 (no preincubation) to protect RA- differentiated SH - SY5Y cells from MPP+

Modelling of OGTT curve identifies 1 h plasma glucose level as a strong predictor of incident type 2 diabetes: results from two prospective cohorts.

PubMed

Alyass, Akram; Almgren, Peter; Akerlund, Mikael; Dushoff, Jonathan; Isomaa, Bo; Nilsson, Peter; Tuomi, Tiinamaija; Lyssenko, Valeriya; Groop, Leif; Meyre, David

2015-01-01

The relevance of the OGTT in predicting type 2 diabetes is unclear. We assessed the performance of 14 OGTT glucose traits in type 2 diabetes prediction. We studied 2,603 and 2,386 Europeans from the Botnia study and Malmö Prevention Project (MPP) cohorts with baseline OGTT data. Over a follow-up period of 4.94 years and 23.5 years, 155 (5.95%) and 467 (19.57%) participants, respectively, developed type 2 diabetes. The main outcome was incident type 2 diabetes. One-hour plasma glucose (1h-PG) was a fair/good predictor of incident type 2 diabetes in the Botnia study and MPP (AUC for receiver operating characteristic [AUCROC] 0.80 [0.77, 0.84] and 0.70 [0.68, 0.73]). 1h-PG alone outperformed the prediction model of multiple clinical risk factors (age, sex, BMI, family history of type 2 diabetes) in the Botnia study and MPP (AUCROC 0.75 [0.72, 0.79] and 0.67 [0.64, 0.70]). The same clinical risk factors added to 1h-PG modestly increased prediction for incident type 2 diabetes (Botnia, AUCROC 0.83 [0.80, 0.86]; MPP, AUCROC 0.74 [0.72, 0.77]). 1h-PG also outperformed HbA1c in predicting type 2 diabetes in the Botnia cohort. A 1h-PG value of 8.9 mmol/l and 8.4 mmol/l was the optimal cut-point for initial screening and selection of high-risk individuals in the Botnia study and MPP, respectively, and represented 30% and 37% of all participants in these cohorts. High-risk individuals had a substantially increased risk of incident type 2 diabetes (OR 8.0 [5.5, 11.6] and 3.8 [3.1, 4.7]) and captured 75% and 62% of all incident type 2 diabetes in the Botnia study and MPP. 1h-PG is a valuable prediction tool for identifying adults at risk for future type 2 diabetes.

Quality Assurance Guidance for the Collection of Meteorological Data Using Passive Radiometers

EPA Science Inventory

This document augments the February 2000 guidance entitled Meteorological Monitoring Guidance for Regulatory Modeling Applications and the March 2008 guidance entitled Quality Assurance Handbook for Air Pollution Measurement Systems Volume IV: Meteorological Measurements Version ...

Mass Casualty Decontamination Guidance and Psychosocial Aspects of CBRN Incident Management: A Review and Synthesis

PubMed Central

Carter, Holly; Amlôt, Richard

2016-01-01

Introduction: Mass casualty decontamination is an intervention employed by first responders at the scene of an incident involving noxious contaminants.  Many countries have sought to address the challenge of decontaminating large numbers of affected casualties through the provision of rapidly deployable temporary showering structures, with accompanying decontamination protocols.  In this paper we review decontamination guidance for emergency responders and associated research evidence, in order to establish to what extent psychosocial aspects of casualty management have been considered within these documents. The review focuses on five psychosocial aspects of incident management: likely public behaviour; responder management style; communication strategy; privacy/ modesty concerns; and vulnerable groups. Methods: Two structured literature reviews were carried out; one to identify decontamination guidance documents for first responders, and another to identify evidence which is relevant to the understanding of the psychosocial aspects of mass decontamination.  The guidance documents and relevant research were reviewed to identify whether the guidance documents contain information relating to psychosocial issues and where it exists, that the guidance is consistent with the existing evidence-base. Results: Psychosocial aspects of incident management receive limited attention in current decontamination guidance.  In addition, our review has identified a number of gaps and inconsistencies between guidance and research evidence.  For each of the five areas we identify: what is currently presented in guidance documents, to what extent this is consistent with the existing research evidence and where it diverges.  We present a series of evidence-based recommendations for updating decontamination guidance to address the psychosocial aspects of mass decontamination. Conclusions: Effective communication and respect for casualties’ needs are critical in ensuring decontamination is completed quickly and effectively.  We identify a number of areas requiring further research including: identifying effective methods for communicating in an emergency; better understanding of the needs of vulnerable groups during decontamination; effective training for emergency responders on psychosocial issues, and pre-incident public education for incidents involving emergency decontamination.  It is essential that the psychosocial aspects of mass decontamination are not neglected in the pursuit of solely technical solutions. PMID:27790383

78 FR 13069 - Draft Guidance for Industry: Recommendations for Screening, Testing, and, Management of Blood...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

... components, including Source Plasma. The guidance announced in this notice replaces the draft guidance... before it begins work on the final version of the guidance, submit either electronic or written comments... the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document. Submit...

75 FR 70254 - PSD and Title V Permitting Guidance for Greenhouse Gases

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2010-0841; FRL-9228-2] PSD and Title V Permitting..., ``PSD and Title V Permitting Guidance for Greenhouse Gases'' on its significant guidance Internet Web... guidance titled, ``PSD and Title V Permitting Guidance for Greenhouse Gases.'' This document has been...

75 FR 54146 - Science Advisory Board Staff Office; Notification of a Public Meeting of the Clean Air Scientific...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... guidance document, and pilot monitoring study can be directed to Mr. Nealson Watkins at 919-541-5522 or watkins[email protected] . Availability of Meeting Materials: The EPA draft guidance documents are posted...

Moisture Control Guidance for Commercial and Public Buildings (EPA 402-F-13053)

EPA Science Inventory

This document provides guidance to designers, construction mangers, and building operation/maintenance managers to improve IEQ and reduce risks of encountering IEQ problems due to insufficient moisture control. EPA will be producing a document entitled "Moisture Control Guida...

77 FR 20826 - Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

...] Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and Industry... Administration (FDA) is announcing the availability of the guidance entitled ``Guidance for Industry and Food and... written requests for single copies of the guidance document entitled ``Guidance for Industry and Food and...

Neuroprotective effects of three different sizes nanochelating based nano complexes in MPP(+) induced neurotoxicity.

PubMed

Maghsoudi, Amirhossein; Fakharzadeh, Saideh; Hafizi, Maryam; Abbasi, Maryam; Kohram, Fatemeh; Sardab, Shima; Tahzibi, Abbas; Kalanaky, Somayeh; Nazaran, Mohammad Hassan

2015-03-01

Parkinson's disease (PD) is the world's second most common dementia, which the drugs available for its treatment have not had effects beyond slowing the disease process. Recently nanotechnology has induced the chance for designing and manufacturing new medicines for neurodegenerative disease. It is demonstrated that by tuning the size of a nanoparticle, the physiological effect of the nanoparticle can be controlled. Using novel nanochelating technology, three nano complexes: Pas (150 nm), Paf (100 nm) and Pac (40 nm) were designed and in the present study their neuroprotective effects were evaluated in PC12 cells treated with 1-methyl-4-phenyl-pyridine ion (MPP (+)). PC12 cells were pre-treated with the Pas, Paf or Pac nano complexes, then they were subjected to 10 μM MPP (+). Subsequently, cell viability, intracellular free Calcium and reactive oxygen species (ROS) levels, mitochondrial membrane potential, catalase (CAT) and superoxide dismutase (SOD) activity, Glutathione (GSH) and malondialdehyde (MDA) levels and Caspase 3 expression were evaluated. All three nano complexes, especially Pac, were able to increase cell viability, SOD and CAT activity, decreased Caspase 3 expression and prevented the generation of ROS and the loss of mitochondrial membrane potential caused by MPP(+). Pre-treatment with Pac and Paf nano complexes lead to a decrease of intracellular free Calcium, but Pas nano complex could not decrease it. Only Pac nano complex decreased MDA levels and other nano complexes could not change this parameter compared to MPP(+) treated cells. Hence according to the results, all nanochelating based nano complexes induced neuroprotective effects in an experimental model of PD, but the smallest nano complex, Pac, showed the best results.

MicroRNA-7 Promotes Glycolysis to Protect against 1-Methyl-4-phenylpyridinium-induced Cell Death.

PubMed

Chaudhuri, Amrita Datta; Kabaria, Savan; Choi, Doo Chul; Mouradian, M Maral; Junn, Eunsung

2015-05-08

Parkinson disease is associated with decreased activity of the mitochondrial electron transport chain. This defect can be recapitulated in vitro by challenging dopaminergic cells with 1-methyl-4-phenylpyridinium (MPP(+)), a neurotoxin that inhibits complex I of electron transport chain. Consequently, oxidative phosphorylation is blocked, and cells become dependent on glycolysis for ATP production. Therefore, increasing the rate of glycolysis might help cells to produce more ATP to meet their energy demands. In the present study, we show that microRNA-7, a non-coding RNA that protects dopaminergic neuronal cells against MPP(+)-induced cell death, promotes glycolysis in dopaminergic SH-SY5Y and differentiated human neural progenitor ReNcell VM cells, as evidenced by increased ATP production, glucose consumption, and lactic acid production. Through a series of experiments, we demonstrate that targeted repression of RelA by microRNA-7, as well as subsequent increase in the neuronal glucose transporter 3 (Glut3), underlies this glycolysis-promoting effect. Consistently, silencing Glut3 expression diminishes the protective effect of microRNA-7 against MPP(+). Further, microRNA-7 fails to prevent MPP(+)-induced cell death when SH-SY5Y cells are cultured in a low glucose medium, as well as when differentiated ReNcell VM cells or primary mouse neurons are treated with the hexokinase inhibitor, 2-deoxy-d-glucose, indicating that a functional glycolytic pathway is required for this protective effect. In conclusion, microRNA-7, by down-regulating RelA, augments Glut3 expression, promotes glycolysis, and subsequently prevents MPP(+)-induced cell death. This protective effect of microRNA-7 could be exploited to correct the defects in oxidative phosphorylation in Parkinson disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The precipitation of magnesium potassium phosphate hexahydrate for P and K recovery from synthetic urine.

PubMed

Xu, Kangning; Li, Jiyun; Zheng, Min; Zhang, Chi; Xie, Tao; Wang, Chengwen

2015-09-01

Nutrients recovery from urine to close the nutrient loop is one of the most attractive benefits of source separation in wastewater management. The current study presents an investigation of the thermodynamic modeling of the recovery of P and K from synthetic urine via the precipitation of magnesium potassium phosphate hexahydrate (MPP). Experimental results show that maximum recovery efficiencies of P and K reached 99% and 33%, respectively, when the precipitation process was initiated only through adding dissolvable Mg compound source. pH level and molar ratio of Mg:P were key factors determining the nutrient recovery efficiencies. Precipitation equilibrium of MPP and magnesium sodium phosphate heptahydrate (MSP) was confirmed via precipitates analysis using a Scanning Electron Microscope/Energy Dispersive Spectrometer and an X-ray Diffractometer. Then, the standard solubility products of MPP and MSP in the synthetic urine were estimated to be 10(-12.2 ± 0.0.253) and 10(-11.6 ± 0.253), respectively. The thermodynamic model formulated on chemical software PHREEQC could well fit the experimental results via comparing the simulated and measured concentrations of K and P in equilibrium. Precipitation potentials of three struvite-type compounds were calculated through thermodynamic modeling. Magnesium ammonium phosphate hexahydrate (MAP) has a much higher tendency to precipitate than MPP and MSP in normal urine while MSP was the main inhibitor of MPP in ammonium-removed urine. To optimize the K recovery, ammonium should be removed prior as much as possible and an alternative alkaline compound should be explored for pH adjustment rather than NaOH. Copyright © 2015 Elsevier Ltd. All rights reserved.

July 15, 1997 Region V Letter on LTV Steel, Stein, Inc., and Allega, Inc.

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Fugitive Emissions From Coal Unloading At Coal Preparation Plant

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

BP American Production Company's Florida River Compression Facility Single Source Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Incorporation of Startup, Shutdown, and Malfunction Plans into Source's Title V Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Use Of Clean Air Act Title V Permit Fees As Match For Section 105 Grants

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Comments on Louisiana's Title V Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Valley Watch, Inc. Comments on Indiana's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Reissuance of Position on the Use of Emergency Backup Generators During Power Shortage

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Michigan Environmental Council Comments on Michigan's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Matrix of Title V-Related And Air Grant-Eligible Activities

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification - State Implementation Plans (SIPs): Policy Regarding Excess Emissions During Malfunctions, Startup, and Shutdown

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Letter to Charles W. Whitmore Dated June 14, 1993

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Citizen's Organized Watch, Inc. Comments on Indiana's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Applicability of NSPS for Coal Preparation to Coal Unloading Operations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Determination of Whether Emissions From Seagram and Sons Whiskey Storage Facility are Fugitive

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Comments on Maryland's Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

White Paper for Streamlined Development of Part 70 Permit Applications

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Area Source Deferrals and Exemptions from Title V Permitting

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Sierra Club Comments on District of Columbia's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Region 10 Question and Answers #2: Title V Permit Development

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Disapproval of Michigan's Renewable Operating Permit Program Fee Demonstration

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to Appeal Dated May 21, 1992 From Reserve Coal Properties Company

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for 34 Clean Air Act Operating Permits Programs in California

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

EPA Review of Proposed Title V Operating Permit for TriGen-Colorado Energy Corporation

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Policy Determination on Limiting Potential to Emit for Koch Refining Company's Clean Fuels Project

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Definition of Regulated Pollutant for Particulate Matter for Purposes of Title V

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Limitation of Potential to Emit with Respect to Title V Applicability Thresholds

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Comments on the Draft Permit for Conoco Coker and Sulfur Recovery

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Federal Enforceability of State's Existing Minor New Source Review (NSR) Programs

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

The Radionuclide NESHAP and the Title V Operating Permits Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Issuance of the Clean Air Act Stationary Source Compliance Monitoring Strategy

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Second Extension of January 25, 1995 Potential to Emit

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Letter Regarding Possible Deficiencies in Delaware's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title III/Title IV Authorities Necessary for Full and Interim Title V Program Approval

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Region 4 Formal Objection to the Century Aluminum of Kentucky Title V Permit

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Applicability of Title V Permitting Requirements to Gasoline Bulk Terminals Owned by Williams Energy Ventures, Inc.

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Region IV's 1997 Objection to Florida Power and Light Title V Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Periodic Monitoring in Title V Permits for Turbines Subject to NSPS Subpart GG

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Extension of January 25, 1995 Potential to Emit Transition Policy

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Comments on Alaska's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Responce to Letter from Congressman Goode Regarding Title V Permit Fees

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Applicability Issues Related to the Cincinnati/Northern Kentucky International Airport

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PSD Applicability Determination for Multiple Owner/Operator Point Sources Within a Single Facility

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

State Implementation Plans: Policy Regarding Excess Emissions During Malfunctions, Startup, and Shutdown

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Applicability of One-time Reporting Provisions for Nonmajor Sources

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Applicability of Policy on Limiting Potenial to Emit to GM Morrain Assembly Plant, Dayton, Ohio

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Program Responsibilities Concerning the Accidental Release Prevention Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Semiannual Title V Permit Data Report (TOPS) and Instructions

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

December 6, 2002 Request for Information to Review Wisconsin's Revised Part 70 Permit Program Submittal

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response toEarth Day Coalition's March 9, 2001 Comments on Ohio's Title V Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Update to Sanctions Policy for State Title V Operating Permits Programs

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

February 3, 1997 Region V Letter Regarding Title V Permitting Issues

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Supersession and Credible Evidence Language in Title V Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Effect of Audit Immunity/Privilege Laws on State's Ability to Enforce Title V Requirements

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Air Quality Operating Permits Programs Which Apply to Tribal Lands

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Pollution Control Projects and New Source Review (NSR) Applicability

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Identification of Provisions of EPA's Part 70 Operating Permits Regulation Applicable to Tribal Operating Permits Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 National Wildlife Federation Comments on Minnesota's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 National Wildlife Federation Comments on Michigan's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification of EPA's Position on the Use of Emergency Backup Generators During Power Shortage

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Procedures for EPA to Address Deficient New Source Permits Under the Clean Air Act

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 10, 2001 Comments on Texas' Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

April 18, 2002 Notice of Deficiency for Ohio's Title V Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Responce to Memo Reguarding Clean Air Act Title III

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Classification of Emissions from Landfills for NSR Applicability Purposes

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Grand Canyon Trust Comments on Arizona's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Common Control, September 18, 1995 Letter to Peter Hamlin

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Monroe Electric Generating Plant Petition No. 6-99-2

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

4/5/95 Letter on Definition of Major Source

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Release of Interim Policy on Federal Enforceability of Limitations on Potential to Emit

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

NSR and Title V Permitting Applicability for Dynamometer Chassis Testing of Transportation Vehicles

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Outstanding Issues at the Al Turi Landfill in Goshen, NY

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Common Control Determination for Ocean County Landfill and Manchester Renewable Power Corp./LES

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

EnerVest San Juan Operations, Title V Applicability Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Aerospace Ground Equipment, Hush Houses, and Jet Engine Test Cells

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Sierra Club Midwest Office Comments on Wisconsin's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 National Parks Conservation Association Comments on Tennessee's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Is a Solvent Reclamation Facility Considered a Chemical Process Plant

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Federal Enforceability of Terms and Conditions in Preconstruction Perimts

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 19, 2001 comments on Ohio's Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Agency Review of State Fee Schedules for Operating Permits Programs Under Title V

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Common Control for Maplewood Landfill and Industrial Power Generating Corporation

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Title V Program Approval Criteria for Section 112 Activities

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Policy on Excess Emissions During Startup, Shutdown, Maintenance and Malfunctions

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Policy on Excess Emissions During Startup, Shutdown, Maintenance, and Malfunctions

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Comments on Georgia's Title V Operating Permits Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Notice of Deficiency for District of Columbia's Operating Permit Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Municipal Solid Waste (MSW) Landfill NSPS/EG Rule and Related Title V Applicability Concerns

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Follow-up on Tesoro Title V Permit, Boiler #5 Repair and Our Children's Earth Petition

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Implementation of Part 71 Programs at the Expiration of Part 70 Interim Approvals

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Definition of Regulated Air Pollutant for Purposes of Title V

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Developing Approvable State Enabling Legislation Required to Implement Title V

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Potential to Emit Transition Policy for Part 71 Implementation in Indian Country

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Straight Delegation Issues Concerning Sections 111 and 112 Requirements and Title V

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Use of Long Term Rolling Averages to Limit Potential to Emit

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PSD Applicability Request, Valero Transmission Company Yoakum, DeWitt County, Texas

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Feb. 11, 1998 Letter to Terry Godar on MSW Landfills

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Withdrawal of Source Determinations for Oil and Gas Industries

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Third Extension of January 25, 1995 Potential to Emit Transition Policy

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Are Emissions From Rocket Launching Fugitive, Mobile Source Emissions, or Nonfugitive Stationary Source Emissions

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Comments on Washington State's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Citation Oil and Gas Corporation... Title V Applicability Determination

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Relationship Between the Part 70 Operating Permit Program and Section 112(r)

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Interpretation of the Definition of Fugitive Emissions in Parts 70 and 71

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to March 12, 2001 Nevada Environmental Coalition Comments on Clark County's Title V Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Questions and Answers on the Requirements of Operating Permits Program Regulations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Sanctions Policy for State Title V Operating Permits Programs

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Letter to Robert Shinn, Jr. Dated 2-10-98

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Region 10 Questions and Answers #1: Title V Permit Development

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Lincolnway Energy Cooperative and Co-location with Existing Grain Cooperative

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Guidelines for Implementation of Section 507 of the 1990 Clean Air Act Amendments

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

The Term Affected States as it Concerns Local Authorities in the Context of Part 71

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to your Request dated April 8, 2000 on Streamlining of Multiple Applicable Requirements

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Clarification of Methodology for Calculating Potential to Emit (PTE) for Batch Chemical Production Operations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Determinations for Four Different Situations Involving Contiguous and Adjacent Facilities

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Reduced Penalties for Disclosures of Certain Clean Air Act Violations

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Order Responding to Wyoming Outdoor Council's Request that the Administrator Object to Two PacificCorp Permits

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Should DuPont and DUSA International be Considered a Single Source for Title V and PSD

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

White Paper Number 2 for Improved Implementation of The Part 70 Operating Permits Program

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Rapid detection of IHNV by molecular padlock recognition and surface-associated isothermal amplification

NASA Astrophysics Data System (ADS)

McCarthy, Erik L.; Egeler, Teressa J.; Bickerstaff, Lee E.; Pereira da Cunha, Mauricio; Millard, Paul J.

2005-11-01

RNA sequences derived from infectious hematopoeitic necrosis virus (IHNV) could be detected using a combination of surface-associated molecular padlock DNA probes (MPP) and rolling circle amplification (RCA) in microcapillary tubes. DNA oligonucleotides with base sequences identical to RNA obtained from IHNV were recognized by MPP. Circularized MPP were then captured on the inner surface of glass microcapillary tubes by immobilized DNA oligonucleotide primers. Extension of the immobilized primers by isothermal RCA gave rise to DNA concatamers, which were in turn bound by the fluorescent reporter SYBR Green II nucleic acid stain, and measured by microfluorimetry. Surface-associated molecular padlock technology, combined with isothermal RCA, exhibited high selectivity and sensitivity without thermal cycling. This technology is applicable to direct RNA and DNA detection, permitting detection of a variety of viral or bacterial pathogens.

Animated computer graphics models of space and earth sciences data generated via the massively parallel processor

NASA Technical Reports Server (NTRS)

Treinish, Lloyd A.; Gough, Michael L.; Wildenhain, W. David

1987-01-01

The capability was developed of rapidly producing visual representations of large, complex, multi-dimensional space and earth sciences data sets via the implementation of computer graphics modeling techniques on the Massively Parallel Processor (MPP) by employing techniques recently developed for typically non-scientific applications. Such capabilities can provide a new and valuable tool for the understanding of complex scientific data, and a new application of parallel computing via the MPP. A prototype system with such capabilities was developed and integrated into the National Space Science Data Center's (NSSDC) Pilot Climate Data System (PCDS) data-independent environment for computer graphics data display to provide easy access to users. While developing these capabilities, several problems had to be solved independently of the actual use of the MPP, all of which are outlined.

The factorization of large composite numbers on the MPP

NASA Technical Reports Server (NTRS)

Mckurdy, Kathy J.; Wunderlich, Marvin C.

1987-01-01

The continued fraction method for factoring large integers (CFRAC) was an ideal algorithm to be implemented on a massively parallel computer such as the Massively Parallel Processor (MPP). After much effort, the first 60 digit number was factored on the MPP using about 6 1/2 hours of array time. Although this result added about 10 digits to the size number that could be factored using CFRAC on a serial machine, it was already badly beaten by the implementation of Davis and Holdridge on the CRAY-1 using the quadratic sieve, an algorithm which is clearly superior to CFRAC for large numbers. An algorithm is illustrated which is ideally suited to the single instruction multiple data (SIMD) massively parallel architecture and some of the modifications which were needed in order to make the parallel implementation effective and efficient are described.

Additional Clarification of Guidance for Implementation of the 1-hour NO2 NAAQS Under PSD

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Response to Request for Guidance Concerning Installation of Nitrogen Oxides Continuous Emissions Monitoring Systems

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.