The stringent response regulates adaptation to darkness in the cyanobacterium Synechococcus elongatus

PubMed Central

Hood, Rachel D.; Higgins, Sean A.; Flamholz, Avi; Nichols, Robert J.

2016-01-01

The cyanobacterium Synechococcus elongatus relies upon photosynthesis to drive metabolism and growth. During darkness, Synechococcus stops growing, derives energy from its glycogen stores, and greatly decreases rates of macromolecular synthesis via unknown mechanisms. Here, we show that the stringent response, a stress response pathway whose genes are conserved across bacteria and plant plastids, contributes to this dark adaptation. Levels of the stringent response alarmone guanosine 3′-diphosphate 5′-diphosphate (ppGpp) rise after a shift from light to dark, indicating that darkness triggers the same response in cyanobacteria as starvation in heterotrophic bacteria. High levels of ppGpp are sufficient to stop growth and dramatically alter many aspects of cellular physiology, including levels of photosynthetic pigments and polyphosphate, DNA content, and the rate of translation. Cells unable to synthesize ppGpp display pronounced growth defects after exposure to darkness. The stringent response regulates expression of a number of genes in Synechococcus, including ribosomal hibernation promoting factor (hpf), which causes ribosomes to dimerize in the dark and may contribute to decreased translation. Although the metabolism of Synechococcus differentiates it from other model bacterial systems, the logic of the stringent response remains remarkably conserved, while at the same time having adapted to the unique stresses of the photosynthetic lifestyle. PMID:27486247

Stringent and reproducible tetracycline-regulated transgene expression by site-specific insertion at chromosomal loci with pre-characterised induction characteristics

PubMed Central

Brough, Rachel; Papanastasiou, Antigoni M; Porter, Andrew CG

2007-01-01

Background The ability to regulate transgene expression has many applications, mostly concerning the analysis of gene function. Desirable induction characteristics, such as low un-induced expression, high induced expression and limited cellular heterogeneity, can be seriously impaired by chromosomal position effects at the site of transgene integration. Many clones may therefore need to be screened before one with optimal induction characteristics is identified. Furthermore, such screens must be repeated for each new transgene investigated, and comparisons between clones with different transgenes is complicated by their different integration sites. Results To circumvent these problems we have developed a "screen and insert" strategy in which clones carrying a transgene for a fluorescent reporter are first screened for those with optimal induction characteristics. Site-specific recombination (SSR) is then be used repeatedly to insert any new transgene at the reporter transgene locus of such clones so that optimal induction characteristics are conferred upon it. Here we have tested in a human fibrosarcoma cell line (HT1080) two of many possible implementations of this approach. Clones (e.g. Rht14-10) in which a GFP reporter gene is very stringently regulated by the tetracycline (tet) transactivator (tTA) protein were first identified flow-cytometrically. Transgenes encoding luciferase, I-SceI endonuclease or Rad52 were then inserted by SSR at a LoxP site adjacent to the GFP gene resulting stringent tet-regulated transgene expression. In clone Rht14-10, increases in expression from essentially background levels (+tet) to more than 104-fold above background (-tet) were reproducibly detected after Cre-mediated insertion of either the luciferase or the I-SceI transgenes. Conclusion Although previous methods have made use of SSR to integrate transgenes at defined sites, none has effectively combined this with a pre-selection step to identify integration sites that support optimal regulatory characteristics. Rht14-10 and similar HT1080-derived clones can now be used in conjunction with a convenient delivery vector (pIN2-neoMCS), in a simple 3-step protocol leading to stringent and reproducible transgene regulation. This approach will be particularly useful for transgenes whose products are very active at low concentrations and/or for comparisons of multiple related transgenes. PMID:17493262

49 CFR 350.333 - What are the guidelines for the compatibility review?

Code of Federal Regulations, 2010 CFR

2010-10-01

... to interstate or intrastate commerce Less stringent or more stringent Action authorized (1) Yes Compatible—Interstate and intrastate commerce enforcement authorized. (2) No Intrastate Refer to § 350.341 (3... authorized if the State can demonstrate the law or regulation has a safety benefit or does not create an...

Circuitry linking the Csr and stringent response global regulatory systems.

PubMed

Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

2011-06-01

CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

UV disinfection for reuse applications in North America.

PubMed

Sakamoto, G; Schwartzel, D; Tomowich, D

2001-01-01

In an effort to conserve and protect limited water resources, the States of Florida and California have actively promoted wastewater reclamation and have implemented comprehensive regulations covering a range of reuse applications. Florida has a semi-tropical climate with heavy summer rains that are lost due to run off and evaporation. Much of California is arid and suffers periodic droughts, low annual rainfall and depleted ground water supplies. The high population density combined with heavy irrigation demands has depleted ground water supplies resulting in salt-water intrusion. During the past decade, Florida reuse sites have increased dramatically from 118 to 444 plants representing a total flow capacity of 826 MGD. California presently has over 250 plants producing 1 BGD with a projected increase of 160 sites over the next 20 years. To prevent the transmission of waterborne diseases, disinfection of reclaimed water is controlled by stringent regulations. Many states regulate wastewater treatment processes, nutrient removal, final effluent quality and disinfection criteria based upon the specific reuse application. As a rule, the resulting effluents have low turbidity and suspended solids. For such effluents, UV technology can economically achieve the most stringent disinfection targets that are required by the States of California and Florida for restricted and unrestricted reuse. This paper compares UV disinfection for wastewater reuse sites in California and Florida and discusses the effect of effluent quality on UV disinfection.

Occurrence of the regulatory nucleotides ppGpp and pppGpp following induction of the stringent response in staphylococci.

PubMed Central

Cassels, R; Oliva, B; Knowles, D

1995-01-01

The stringent response in Escherichia coli and many other organisms is regulated by the nucleotides ppGpp and pppGpp. We show here for the first time that at least six staphylococcal species also synthesize ppGpp and pppGpp upon induction of the stringent response by mupirocin. Spots corresponding to ppGpp and pppGpp on thin-layer chromatograms suggest that pppGpp is the principal regulatory nucleotide synthesized by staphylococci in response to mupirocin, rather than ppGpp as in E. coli. PMID:7665499

Mercury emission trend influenced by stringent air pollutants regulation for coal-fired power plants in Korea

NASA Astrophysics Data System (ADS)

Pudasainee, Deepak; Kim, Jeong-Hun; Seo, Yong-Chil

2009-12-01

Regulatory control of mercury emission from anthropogenic sources has become a global concern in the recent past. Coal-fired power plants are one of the largest sources of anthropogenic mercury emission into the atmosphere. This paper summarizes the current reducing trend of mercury emission as co-beneficial effect by more stringent regulation changes to control primary air pollutants with introducing test results from the commercial coal-fired facilities and suggesting a guideline for future regulatory development in Korea. On average, mercury emission concentrations ranged 16.3-2.7 μg Sm -3, 2.4-1.1 μg Sm -3, 3.1-0.7 μg Sm -3 from anthracite coal-fired power plants equipped with electrostatic precipitator (ESP), bituminous coal-fired power plants with ESP + flue gas desulphurization (FGD) and bituminous coal-fired power plants with selective catalytic reactor (SCR) + cold side (CS) - ESP + wet FGD, respectively. Among the existing air pollution control devices, the best configuration for mercury removal in coal-fired power plants was SCR + CS - ESP + wet FGD, which were installed due to the stringent regulation changes to control primary air pollutants emission such as SO 2, NOx and dust. It was estimated that uncontrolled and controlled mercury emission from coal-fired power plants as 10.3 ton yr -1 and 3.2 ton yr -1 respectively. After the installation of ESP, FGD and SCR system, following the enforcement of the stringent regulation, 7.1 ton yr -1 of mercury emission has been reduced (nearly 69%) from coal-fired power plants as a co-benefit control. Based on the overall study, a sample guideline including emission limits were suggested which will be applied to develop a countermeasure for controlling mercury emission from coal-fired power plants.

Review of electrotechnologies used in the disinfection of water and wastewater. Final report

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

VandeVenter, L.W.

This report provides an overview of the disinfection practices used in water and wastewater treatment. Chlorine historically has been the disinfectant of choice for both water and wastewater, but with increased research and more stringent regulations, other disinfectants, namely ozone and ultraviolet irradiation, are being considered. The report summarizes the present and future applications of these technologies and defines possible opportunities for Demand- Side Management (DSM).

Review of electrotechnologies used in the disinfection of water and wastewater

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

VandeVenter, L.W.

This report provides an overview of the disinfection practices used in water and wastewater treatment. Chlorine historically has been the disinfectant of choice for both water and wastewater, but with increased research and more stringent regulations, other disinfectants, namely ozone and ultraviolet irradiation, are being considered. The report summarizes the present and future applications of these technologies and defines possible opportunities for Demand- Side Management (DSM).

20 CFR 658.701 - Statements of policy.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ensure that State agencies comply with all requirements established by JS regulations. (b) It is the... continual violations of JS regulations if less stringent remedial actions taken in accordance with this... alleged violations by State agencies of the JS regulations received from any person or organization. ...

76 FR 75913 - Notice of Lodging of Modification of Consent Decree Under the Clean Water Act

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-05

... (``Regulated Bacteria'') and to comply with interim effluent limitations for those pollutants. The proposed Modification provides new, more stringent interim effluent limitations for Regulated Bacteria and requires... effluent limitations for Regulated Bacteria set forth in the Facility's National Pollutant Discharge...

49 CFR 218.4 - Preemptive effect.

Code of Federal Regulations, 2010 CFR

2010-10-01

... negligence standards apply where there is no Federal action covering the subject matter. Under 49 U.S.C. 20106 (section 20106), issuance of the regulations in this part preempts any State law, regulation, or order covering the same subject matter, except an additional or more stringent law, regulation, or order...

49 CFR 217.2 - Preemptive effect.

Code of Federal Regulations, 2010 CFR

2010-10-01

... negligence standards apply where there is no Federal action covering the subject matter. Under 49 U.S.C. 20106 (section 20106), issuance of the regulations in this part preempts any State law, regulation, or order covering the same subject matter, except an additional or more stringent law, regulation, or order...

Regulation of Phospholipid Synthesis in Escherichia coli by Guanosine Tetraphosphate

PubMed Central

Merlie, John P.; Pizer, Lewis I.

1973-01-01

Phospholipid synthesis has been reported to be subject to stringent control in Escherichia coli. We present evidence that demonstrates a strict correlation between guanosine tetraphosphate accumulation and inhibition of phospholipid synthesis. In vivo experiments designed to examine the pattern of phospholipid labeling with 32P-inorganic phosphate and 32P-sn-glycerol-3-phosphate suggest that regulation must occur at the glycerol-3-phosphate acyltransferase step. Assay of phospholipid synthesis by cell-free extracts and semipurified preparations revealed that guanosine tetraphosphate inhibits at least two enzymes specific for the biosynthetic pathway, sn-glycerol-3-phosphate acyltransferase as well as sn-glycerol-3-phosphate phosphatidyl transferase. These findings provide a biochemical basis for the stringent control of lipid synthesis as well as regulation of steady-state levels of phospholipid in growing cells. Images PMID:4583220

The Streptococcus agalactiae Stringent Response Enhances Virulence and Persistence in Human Blood

PubMed Central

Hooven, Thomas A.; Catomeris, Andrew J.; Bonakdar, Maryam; Tallon, Luke J.; Santana-Cruz, Ivette; Ott, Sandra; Daugherty, Sean C.; Tettelin, Hervé

2017-01-01

ABSTRACT Streptococcus agalactiae (group B Streptococcus [GBS]) causes serious infections in neonates. We previously reported a transposon sequencing (Tn-seq) system for performing genomewide assessment of gene fitness in GBS. In order to identify molecular mechanisms required for GBS to transition from a mucosal commensal lifestyle to bloodstream invasion, we performed Tn-seq on GBS strain A909 with human whole blood. Our analysis identified 16 genes conditionally essential for GBS survival in blood, of which 75% were members of the capsular polysaccharide (cps) operon. Among the non-cps genes identified as conditionally essential was relA, which encodes an enzyme whose activity is central to the bacterial stringent response—a conserved adaptation to environmental stress. We used blood coincubation studies of targeted knockout strains to confirm the expected growth defects of GBS deficient in capsule or stringent response activation. Unexpectedly, we found that the relA knockout strains demonstrated decreased expression of β-hemolysin/cytolysin, an important cytotoxin implicated in facilitating GBS invasion. Furthermore, chemical activation of the stringent response with serine hydroxamate increased β-hemolysin/cytolysin expression. To establish a mechanism by which the stringent response leads to increased cytotoxicity, we performed transcriptome sequencing (RNA-seq) on two GBS strains grown under stringent response or control conditions. This revealed a conserved decrease in the expression of genes in the arginine deiminase pathway during stringent response activation. Through coincubation with supplemental arginine and the arginine antagonist canavanine, we show that arginine availability is a determinant of GBS cytotoxicity and that the pathway between stringent response activation and increased virulence is arginine dependent. PMID:29109175

Global Rsh-dependent transcription profile of Brucella suis during stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses

PubMed Central

2013-01-01

Background In the intracellular pathogen Brucella spp., the activation of the stringent response, a global regulatory network providing rapid adaptation to growth-affecting stress conditions such as nutrient deficiency, is essential for replication in the host. A single, bi-functional enzyme Rsh catalyzes synthesis and hydrolysis of the alarmone (p)ppGpp, responsible for differential gene expression under stringent conditions. Results cDNA microarray analysis allowed characterization of the transcriptional profiles of the B. suis 1330 wild-type and Δrsh mutant in a minimal medium, partially mimicking the nutrient-poor intramacrophagic environment. A total of 379 genes (11.6% of the genome) were differentially expressed in a rsh-dependent manner, of which 198 were up-, and 181 were down-regulated. The pleiotropic character of the response was confirmed, as the genes encoded an important number of transcriptional regulators, cell envelope proteins, stress factors, transport systems, and energy metabolism proteins. Virulence genes such as narG and sodC, respectively encoding respiratory nitrate reductase and superoxide dismutase, were under the positive control of (p)ppGpp, as well as expression of the cbb3-type cytochrome c oxidase, essential for chronic murine infection. Methionine was the only amino acid whose biosynthesis was absolutely dependent on stringent response in B. suis. Conclusions The study illustrated the complexity of the processes involved in adaptation to nutrient starvation, and contributed to a better understanding of the correlation between stringent response and Brucella virulence. Most interestingly, it clearly indicated (p)ppGpp-dependent cross-talk between at least three stress responses playing a central role in Brucella adaptation to the host: nutrient, oxidative, and low-oxygen stress. PMID:23834488

30 CFR 937.700 - Oregon Federal program.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Federal program. (c) The rules in this part apply to all surface coal mining operations in Oregon... more stringent environmental control and regulation of surface coal mining operations than do the... extent they provide for regulation of surface coal mining and reclamation operations which are exempt...

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...: (a) Has adopted drinking water regulations which are no less stringent than the national primary...

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...: (a) Has adopted drinking water regulations which are no less stringent than the national primary...

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...: (a) Has adopted drinking water regulations which are no less stringent than the national primary...

Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP.

PubMed

Wenderska, Iwona B; Latos, Andrew; Pruitt, Benjamin; Palmer, Sara; Spatafora, Grace; Senadheera, Dilani B; Cvitkovitch, Dennis G

2017-01-01

In the cariogenic Streptococcus mutans , competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the S. mutans transcriptome. RNA sequencing revealed that XIP induction resulted in a global change in gene expression that was consistent with a stress response. An increase in several membrane-bound regulators, including HdrRM and BrsRM, involved in bacteriocin production, and the VicRKX system, involved in acid tolerance and biofilm formation, was observed. Furthermore, global changes in gene expression corresponded to changes observed during the stringent response to amino acid starvation. Effects were also observed on genes involved in sugar transport and carbon catabolite repression and included the levQRST and levDEFG operons. Finally, our work identified a novel heat shock-responsive intergenic region, encoding a small RNA, with a potential role in competence shutoff. IMPORTANCE Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans , DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans , XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a potential role in competence shutoff. Together, our results provide further evidence that multiple stress response mechanisms are linked through the genetic competence signaling pathway in S. mutans .

State Law Approaches to Facility Regulation of Abortion and Other Office Interventions

PubMed Central

Daniel, Sara; Cloud, Lindsay K.

2018-01-01

Objectives. To compare the prevalence and characteristics of facility laws governing abortion provision specifically (targeted regulation of abortion providers [TRAP] laws); office-based surgeries, procedures, sedation or anesthesia (office interventions) generally (OBS laws); and other procedures specifically. Methods. We conducted cross-sectional legal assessments of state facility laws for office interventions in effect as of August 1, 2016. We coded characteristics for each law and compared characteristics across categories of laws. Results. TRAP laws (n = 55; in 34 states) were more prevalent than OBS laws (n = 25; in 25 states) or laws targeting other procedures (n = 1; in 1 state). TRAP laws often regulated facilities that would not be regulated under OBS laws (e.g., all TRAP laws, but only 2 OBS laws, applied regardless of sedation or anesthesia used). TRAP laws imposed more numerous and more stringent requirements than OBS laws. Conclusions. Many states regulate abortion-providing facilities differently, and more stringently, than facilities providing other office interventions. The Supreme Court’s 2016 decision in Whole Woman’s Health v Hellerstedt casts doubt on the legitimacy of that differential treatment. PMID:29470114

Insulated hsp70B' promoter: stringent heat-inducible activity in replication-deficient, but not replication-competent adenoviruses.

PubMed

Rohmer, Stanimira; Mainka, Astrid; Knippertz, Ilka; Hesse, Andrea; Nettelbeck, Dirk M

2008-04-01

Key to the realization of gene therapy is the development of efficient and targeted gene transfer vectors. Therapeutic gene transfer by replication-deficient or more recently by conditionally replication-competent/oncolytic adenoviruses has shown much promise. For specific applications, however, it will be advantageous to provide vectors that allow for external control of gene expression. The efficient cellular heat shock system in combination with available technology for focused and controlled hyperthermia suggests heat-regulated transcription control as a promising tool for this purpose. We investigated the feasibility of a short fragment of the human hsp70B' promoter, with and without upstream insulator elements, for the regulation of transgene expression by replication-deficient or oncolytic adenoviruses. Two novel adenoviral vectors with an insulated hsp70B' promoter were developed and showed stringent heat-inducible gene expression with induction ratios up to 8000-fold. In contrast, regulation of gene expression from the hsp70B' promoter without insulation was suboptimal. In replication-competent/oncolytic adenoviruses regulation of the hsp70B' promoter was lost specifically during late replication in permissive cells and could not be restored by the insulators. We developed novel adenovirus gene transfer vectors that feature improved and stringent regulation of transgene expression from the hsp70B' promoter using promoter insulation. These vectors have potential for gene therapy applications that benefit from external modulation of therapeutic gene expression or for combination therapy with hyperthermia. Furthermore, our study reveals that vector replication can deregulate inserted cellular promoters, an observation which is of relevance for the development of replication-competent/oncolytic gene transfer vectors. (c) 2008 John Wiley & Sons, Ltd.

Cosmetic Regulations: A Comparative Study.

PubMed

Suhag, Jyoti; Dureja, Harish

2015-01-01

The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

ATP-Induced IL-1β Specific Secretion: True Under Stringent Conditions.

PubMed

Stoffels, Monique; Zaal, Ruben; Kok, Nina; van der Meer, Jos W M; Dinarello, Charles A; Simon, Anna

2015-01-01

Interleukin-1β is a potent proinflammatory cytokine, of which processing and secretion are tightly regulated. After exposure to various stimuli, mononuclear phagocytes synthesize the inactive precursor (pro-IL-1β), which is then cleaved intracellularly by caspase-1 and secreted. A widely used method for in vitro secretion of IL-1β employs LPS-primed human peripheral blood monocytes. Subsequently, adenosine triphosphate (ATP) is added to the cells in order to trigger the P2X7 receptor resulting in processing and secretion of mature IL-1β. However, it is often reported that secretion is due to cytotoxic effects of ATP with P2X7 receptor-activation-related cell death. We have challenged this concept and demonstrate IL-1β specific secretion, since there is no increase in cell death and IL-1α and IL-18 are not released in the same cultures. More importantly we show that these conclusions can only be drawn under stringent experimental conditions.

Constraints and consequences of the emergence of amino acid repeats in eukaryotic proteins.

PubMed

Chavali, Sreenivas; Chavali, Pavithra L; Chalancon, Guilhem; de Groot, Natalia Sanchez; Gemayel, Rita; Latysheva, Natasha S; Ing-Simmons, Elizabeth; Verstrepen, Kevin J; Balaji, Santhanam; Babu, M Madan

2017-09-01

Proteins with amino acid homorepeats have the potential to be detrimental to cells and are often associated with human diseases. Why, then, are homorepeats prevalent in eukaryotic proteomes? In yeast, homorepeats are enriched in proteins that are essential and pleiotropic and that buffer environmental insults. The presence of homorepeats increases the functional versatility of proteins by mediating protein interactions and facilitating spatial organization in a repeat-dependent manner. During evolution, homorepeats are preferentially retained in proteins with stringent proteostasis, which might minimize repeat-associated detrimental effects such as unregulated phase separation and protein aggregation. Their presence facilitates rapid protein divergence through accumulation of amino acid substitutions, which often affect linear motifs and post-translational-modification sites. These substitutions may result in rewiring protein interaction and signaling networks. Thus, homorepeats are distinct modules that are often retained in stringently regulated proteins. Their presence facilitates rapid exploration of the genotype-phenotype landscape of a population, thereby contributing to adaptation and fitness.

Stringency and relaxation among the halobacteria.

PubMed Central

Cimmino, C; Scoarughi, G L; Donini, P

1993-01-01

Accumulation of stable RNA and production of guanosine polyphosphates (ppGpp and pppGpp) were studied during amino acid starvation in four species of halobacteria. In two of the four species, stable RNA was under stringent control, whereas one of the remaining two species was relaxed and the other gave an intermediate phenotype. The stringent reaction was reversed by anisomycin, an effect analogous to the chloroamphenicol-induced reversal of stringency in the eubacteria. During the stringent response, neither ppGpp nor pppGpp accumulation took place during starvation. In both growing and starved cells a very low basal level of the two polyphosphates appeared to be present. In the stringent species the intracellular concentration of GTP did not diminish but actually increased during the course of the stringent response. These data demonstrate that (i) wild-type halobacteria can have either the stringent or the relaxed phenotype (all wild-type eubacteria tested have been shown to be stringent); (ii) stringency in the halobacteria is dependent on the deaminoacylation of tRNA, as in the eubacteria; and (iii) in the halobacteria, ppGpp is not an effector of stringent control over stable-RNA synthesis. Images PMID:7691798

76 FR 25569 - Defense Federal Acquisition Regulation Supplement; Minimizing the Use of Materials Containing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

..., therefore, this action establishes requirements that DoD personnel must follow when making acquisitions for...) ten-fold from 52 to 5 micrograms-per-cubic-meter, making it among the most stringently regulated... officer will forward the request to the authorized approving official (DFARS 223.7305(a)) for decision...

Medical Device Regulation: A Comparison of the United States and the European Union.

PubMed

Maak, Travis G; Wylie, James D

2016-08-01

Medical device regulation is a controversial topic in both the United States and the European Union. Many physicians and innovators in the United States cite a restrictive US FDA regulatory process as the reason for earlier and more rapid clinical advances in Europe. The FDA approval process mandates that a device be proved efficacious compared with a control or be substantially equivalent to a predicate device, whereas the European Union approval process mandates that the device perform its intended function. Stringent, peer-reviewed safety data have not been reported. However, after recent high-profile device failures, political pressure in both the United States and the European Union has favored more restrictive approval processes. Substantial reforms of the European Union process within the next 5 to 10 years will result in a more stringent approach to device regulation, similar to that of the FDA. Changes in the FDA regulatory process have been suggested but are not imminent.

76 FR 44293 - Defense Acquisition Regulations System; Defense Federal Acquisition Regulation Supplement; Only...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-25

.... DFARS 215.371 states the DoD policy that adequate price competition does not exist if only one offer is... maximum practicable competition and to ensure that the price is fair and reasonable. This proposed rule applies a more stringent policy for determination of adequate price competition than is allowed by FAR 15...

SRNL Atmospheric Technologies Group

ScienceCinema

Viner, Brian; Parker, Matthew J.

2018-01-16

The Savannah River National Laboratory, Atmospheric Technologies Group, conducts a best-in class Applied Meteorology Program to ensure the Department of Energy’s Savannah River Site is operated safely and complies with stringent environmental regulations.

Integrated Analysis of Greenhouse Gas Mitigation Options and Related Impacts

EPA Science Inventory

Increased concerns over air pollution (combined with detrimental health effects) and climate change have called for more stringent emission reduction strategies for criteria air pollutants and greenhouse gas emissions. However, stringent regulatory policies can possibly have a...

The effect of environmental regulation on firms' competitive performance: the case of the building & construction sector in some EU regions.

PubMed

Testa, Francesco; Iraldo, Fabio; Frey, Marco

2011-09-01

There is a considerable debate on the effects of environmental regulation on competitive performance. Based on survey data, this paper analyzes the two main research questions, derived from literature, on the links between environmental regulation and competitiveness, by focusing on firms operating in the building and construction sector, i.e.: 1) whether environmental policy stringency affects the competitive performance of firms in the building and construction sector 2) and how a specific form of environmental regulation (direct regulation, economic instruments and soft instruments) affects this performance? By applying a regression analysis, we find that a more stringent environmental regulation, measured by inspection frequency, provides a positive impulse for increasing investments in advanced technological equipment and innovative products and on business performance. Moreover, a well-designed "direct regulation" appears to be the most effective policy instrument for prompting the positive impact of environmental policies on innovation and intangible performance while economic instruments do negatively affect business performance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Universal Industrial Solution and Industrial Sectors Module for Pulp and Paper Sector

EPA Science Inventory

Increased concerns over air pollution and its detrimental effects on health have called for more stringent emission reduction strategies in the industrial sector. However, stringent regulatory policies can potentially adversely affect domestic and international trade. Therefore E...

Air pollution from hot mix plants.

DOT National Transportation Integrated Search

1970-10-01

The Louisiana Air Control Commission adopted Regulation II, effective 1969, which sets stringent limits on suspended particulates. Because of the lack of knowledge concerning air pollution caused by hot mix plants within the Stake and because of the ...

Nitrogen stress response and stringent response are coupled in Escherichia coli

PubMed Central

Brown, Daniel R.; Barton, Geraint; Pan, Zhensheng; Buck, Martin; Wigneshweraraj, Sivaramesh

2014-01-01

Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria. PMID:24947454

Light-duty vehicle CO2 targets consistent with 450 ppm CO2 stabilization.

PubMed

Winkler, Sandra L; Wallington, Timothy J; Maas, Heiko; Hass, Heinz

2014-06-03

We present a global analysis of CO2 emission reductions from the light-duty vehicle (LDV) fleet consistent with stabilization of atmospheric CO2 concentration at 450 ppm. The CO2 emission reductions are described by g CO2/km emission targets for average new light-duty vehicles on a tank-to-wheel basis between 2010 and 2050 that we call CO2 glide paths. The analysis accounts for growth of the vehicle fleet, changing patterns in driving distance, regional availability of biofuels, and the changing composition of fossil fuels. New light-duty vehicle fuel economy and CO2 regulations in the U.S. through 2025 and in the EU through 2020 are broadly consistent with the CO2 glide paths. The glide path is at the upper end of the discussed 2025 EU range of 68-78 g CO2/km. The proposed China regulation for 2020 is more stringent than the glide path, while the 2017 Brazil regulation is less stringent. Existing regulations through 2025 are broadly consistent with the light-duty vehicle sector contributing to stabilizing CO2 at approximately 450 ppm. The glide paths provide long-term guidance for LDV powertrain/fuel development.

Public Water System Supervision Program Revision for the State of Nevada

EPA Pesticide Factsheets

Nevada revised its approved Public Water System Supervision Program under the federal Safe Drinking Water Act. EPA has determined that these revisions by the State of Nevada are no less stringent than the corresponding Federal regulations.

40 CFR 131.4 - State authority.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS... reviewing, establishing, and revising water quality standards. As recognized by section 510 of the Clean Water Act, States may develop water quality standards more stringent than required by this regulation...

Does the First Amendment Guarantee a Right to Conduct Scientific Experiments?

ERIC Educational Resources Information Center

Attanasio, John B.

1987-01-01

An analysis of first amendment guarantees focuses on the federal government's power to regulate experiments, arguing that they do not merit the stringent level of first amendment protection offered by strict scrutiny or related standards. (Author/MSE)

Ensuring the safe and effective FDA regulation of fecal microbiota transplantation

PubMed Central

Sachs, Rachel E.; Edelstein, Carolyn A.

2015-01-01

Scientists, policymakers, and medical professionals alike have become increasingly worried about the rise of antibiotic resistance, and the growing number of infections due to bacteria like Clostridium difficile, which cause a significant number of deaths and are imposing increasing costs on our health care system. However, in the last few years, fecal microbiota transplantation (FMT), the transplantation of stool from a healthy donor into the bowel of a patient, has emerged as a startlingly effective means to treat recurrent C. difficile infections. At present, the FDA is proposing to regulate FMT as a biologic drug. However, this proposed classification is both underregulatory and overregulatory. The FDA's primary goal is to ensure that patients have access to safe, effective treatments—and as such they should regulate some aspects of FMT more stringently than they propose to, and others less so. This essay will examine the nature of the regulatory challenges the FDA will face in deciding to regulate FMT as a biologic drug, and will then evaluate available policy alternatives for the FDA to pursue, ultimately concluding that the FDA ought to consider adopting a hybrid regulatory model as it has done in the case of cord blood. PMID:27774199

Food and Drug Administration regulation and evaluation of vaccines.

PubMed

Marshall, Valerie; Baylor, Norman W

2011-05-01

The vaccine-approval process in the United States is regulated by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. Throughout the life cycle of development, from preclinical studies to after licensure, vaccines are subject to rigorous testing and oversight. Manufacturers must adhere to good manufacturing practices and control procedures to ensure the quality of vaccines. As mandated by Title 21 of the Code of Regulations, licensed vaccines must meet stringent criteria for safety, efficacy, and potency.

77 FR 57524 - Stage 3 Helicopter Noise Certification Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-18

... standards of the International Civil Aviation Organization (ICAO). The proposal of these more stringent... Organization (ICAO) is the international body with the responsibility for the development of international..., organizations, and governmental jurisdictions subject to regulation.'' To achieve that principle, the RFA...

UTILIZING LOW VOLATILE ORGANIC CONTENT EXTERIOR COATINGS FOR WOOD FURNITURE

EPA Science Inventory

This report provides an evaluation of commercially viable source reduction techniques implemented by a manufacturer of wood chairs, bar stools and settees in various styles ranging from classic American to European contemporary. As federal EPA regulations became more stringent fo...

Secondary lead production in Malaysia

NASA Astrophysics Data System (ADS)

Phillips, M. J.; Lim, S. S.

The increase in the number of vehicles and, subsequently, the volume of batteries made by manufacturers in Malaysia have seen a dramatic rise in lead demand over the last five years. Without any lead mines, the only source of lead in Malaysia has been from the recycling of lead/acid batteries. Metal Reclamation (Industries) has commenced the design of a new and advanced secondary lead plant at West Port, Malaysia to meet the increasing demand for lead and the increasingly stringent environmental regulations. The plant is designed to produce up to 75 000 t of lead and lead alloys per year. The plant will also produce, as by-products: polypropylene chips, wallboard-grade gypsum, non-leachable slag for use in construction. A discussion of the process and the products from the new secondary smelter is outlined.

7 CFR 1955.103 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... convenience of the Government to facilitate sales; more stringent than terms offered under FmHA or its... terms for SFH or MFH property sales, offered for the convenience of the Government to facilitate sales...

Trade treaties and alcohol advertising policy.

PubMed

Gould, Ellen

2005-09-01

Restrictions on alcohol advertising are vulnerable to challenge under international trade agreements. As countries negotiate new trade treaties and expand the scope of existing ones, the risk of such a challenge increases. While alcohol advertising restrictions normally do not distinguish between foreign and domestic products, this neutral character does not protect them from being challenged under trade rules. The article analyzes four provisions of trade agreements--expropriation, de facto discrimination, market access, and necessity--in relation to the jeopardy they pose for alcohol advertising restrictions. Key cases are reviewed to illustrate how these provisions have been used to either overturn existing advertising restrictions or prevent new ones from coming into force. The article also reports on the mixed results governments have had in trying to justify their regulations to trade panels and the stringent criteria imposed for proving that a regulation is "necessary."

Functional impact of splice isoform diversity in individual cells

PubMed Central

Yap, Karen; Makeyev, Eugene V.

2016-01-01

Alternative pre-mRNA splicing provides an effective means for expanding coding capacity of eukaryotic genomes. Recent studies suggest that co-expression of different splice isoforms may increase diversity of RNAs and proteins at a single-cell level. A pertinent question in the field is whether such co-expression is biologically meaningful or, rather, represents insufficiently stringent splicing regulation. Here we argue that isoform co-expression may produce functional outcomes that are difficult and sometimes impossible to achieve using other regulation strategies. Far from being a ‘splicing noise’, co-expression is often established through co-ordinated activity of specific cis-elements and trans-acting factors. Further work in this area may uncover new biological functions of alternative splicing (AS) and generate important insights into mechanisms allowing different cell types to attain their unique molecular identities. PMID:27528755

Functional impact of splice isoform diversity in individual cells.

PubMed

Yap, Karen; Makeyev, Eugene V

2016-08-15

Alternative pre-mRNA splicing provides an effective means for expanding coding capacity of eukaryotic genomes. Recent studies suggest that co-expression of different splice isoforms may increase diversity of RNAs and proteins at a single-cell level. A pertinent question in the field is whether such co-expression is biologically meaningful or, rather, represents insufficiently stringent splicing regulation. Here we argue that isoform co-expression may produce functional outcomes that are difficult and sometimes impossible to achieve using other regulation strategies. Far from being a 'splicing noise', co-expression is often established through co-ordinated activity of specific cis-elements and trans-acting factors. Further work in this area may uncover new biological functions of alternative splicing (AS) and generate important insights into mechanisms allowing different cell types to attain their unique molecular identities. © 2016 The Author(s).

Rsd balances (p)ppGpp level by stimulating the hydrolase activity of SpoT during carbon source downshift in Escherichia coli.

PubMed

Lee, Jae-Woo; Park, Young-Ha; Seok, Yeong-Jae

2018-06-18

Bacteria respond to nutritional stresses by changing the cellular concentration of the alarmone (p)ppGpp. This control mechanism, called the stringent response, depends on two enzymes, the (p)ppGpp synthetase RelA and the bifunctional (p)ppGpp synthetase/hydrolase SpoT in Escherichia coli and related bacteria. Because SpoT is the only enzyme responsible for (p)ppGpp hydrolysis in these bacteria, SpoT activity needs to be tightly regulated to prevent the uncontrolled accumulation of (p)ppGpp, which is lethal. To date, however, no such regulation of SpoT (p)ppGpp hydrolase activity has been documented in E. coli In this study, we show that Rsd directly interacts with SpoT and stimulates its (p)ppGpp hydrolase activity. Dephosphorylated HPr, but not phosphorylated HPr, of the phosphoenolpyruvate-dependent sugar phosphotransferase system could antagonize the stimulatory effect of Rsd on SpoT (p)ppGpp hydrolase activity. Thus, we suggest that Rsd is a carbon source-dependent regulator of the stringent response in E. coli . Copyright © 2018 the Author(s). Published by PNAS.

Tackling the x-ray cargo inspection challenge using machine learning

NASA Astrophysics Data System (ADS)

Jaccard, Nicolas; Rogers, Thomas W.; Morton, Edward J.; Griffin, Lewis D.

2016-05-01

The current infrastructure for non-intrusive inspection of cargo containers cannot accommodate exploding com-merce volumes and increasingly stringent regulations. There is a pressing need to develop methods to automate parts of the inspection workflow, enabling expert operators to focus on a manageable number of high-risk images. To tackle this challenge, we developed a modular framework for automated X-ray cargo image inspection. Employing state-of-the-art machine learning approaches, including deep learning, we demonstrate high performance for empty container verification and specific threat detection. This work constitutes a significant step towards the partial automation of X-ray cargo image inspection.

Control of lipopolysaccharide biosynthesis and release by Escherichia coli and Salmonella typhimurium.

PubMed Central

Ishiguro, E E; Vanderwel, D; Kusser, W

1986-01-01

The influence of the relA gene on lipopolysaccharide (LPS) biosynthesis and release by Escherichia coli and Salmonella typhimurium was investigated. Similar results were obtained with both species. The incorporation of [3H]galactose into LPS by galE mutants was inhibited by at least 50% (as compared with normal growing controls) during amino acid deprivation of relA+ strains. This inhibition could be prevented by the treatment of the amino acid-deprived relA+ bacteria with chloramphenicol, a known antagonist of the stringent control mechanism. Furthermore, LPS biosynthesis was not inhibited during amino acid deprivation of isogenic relA mutant strains. These results indicate that LPS synthesis is regulated by the stringent control mechanism. Normal growing cells of both relA+ and relA strains released LPS into the culture fluid at low rates. Amino acid deprivation stimulated the rate of LPS release by relA mutants but not by relA+ bacteria. Chloramphenicol treatment markedly stimulated the release of cell-bound LPS by amino acid-deprived relA+ cells. Thus, a low rate of LPS release was characteristic of normal growth and could be increased in nongrowing cells by relaxing the control of LPS synthesis. Images PMID:3531174

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in... operator of an off-road vehicle operated on Reclamation lands shall possess a valid motor vehicle operator...

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in... operator of an off-road vehicle operated on Reclamation lands shall possess a valid motor vehicle operator...

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in... operator of an off-road vehicle operated on Reclamation lands shall possess a valid motor vehicle operator...

30 CFR 939.700 - Rhode Island Federal program.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Rhode Island Federal program. (a) This part contains all rules that are applicable to surface coal... to all surface coal mining and reclamation operations in Rhode Island conducted on non-Federal and... stringent environmental control and regulation of surface coal mining and reclamation operations than do the...

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... snowmobiles, trail bikes, and any other off road vehicle the operator shall wear safety equipment, generally... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in...

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... snowmobiles, trail bikes, and any other off road vehicle the operator shall wear safety equipment, generally... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in...

On the road to recovery: Gasoline content regulations and child health.

PubMed

Marcus, Michelle

2017-07-01

Gasoline content regulations are designed to curb pollution and improve health, but their impact on health has not been quantified. By exploiting both the timing of regulation and spatial variation in children's exposure to highways, I estimate the effect of gasoline content regulation on pollution and child health. The introduction of cleaner-burning gasoline in California in 1996 reduced asthma admissions by 8% in high exposure areas. Reductions are greatest for areas downwind from highways and heavy traffic areas. Stringent gasoline content regulations can improve child health, and may diminish existing health disparities. Copyright © 2017 Elsevier B.V. All rights reserved.

Opioid management of pain: the impact of the prescription opioid abuse epidemic.

PubMed

Rauenzahn, Sherri; Del Fabbro, Egidio

2014-09-01

The greater emphasis on pain control over the last decade has been accompanied by increased opioid prescriptions and an epidemic of opioid abuse. This review examines the financial, regulatory, and clinical practice impact of the epidemic, the factors contributing to its growth, and strategies that may counter this public health crisis. Despite the call for urgent practice change and the introduction of new initiatives such as electronic prescription monitoring and additional education programs for providers and patients, the evidence for improved outcomes are limited. There are also concerns that some patients may suffer from underprescribing as an unintended consequence of more stringent state and federal regulations. There is consensus that some form of universal precautions should be adopted for all patients, including those being treated for cancer-related pain, in order to better identify and manage those at risk of opioid abuse. The opioid prescription abuse epidemic has precipitated calls for increased regulation. Clinicians can improve patient care and diminish opioid abuse by identifying patient risk factors, increasing vigilance and structure for those at risk, and providing interdisciplinary care for any patients coping in a maladaptive manner.

The Impact of Child Support Enforcement Policy on Nonmarital Childbearing

ERIC Educational Resources Information Center

Plotnick, Robert D.; Garfinkel, Irwin; McLanahan, Sara S.; Ku, Inhoe

2007-01-01

The interaction of welfare and child support regulations has created a situation in which child support policy's incentives that discourage unwed fatherhood tend to be stronger than its incentives that encourage unwed motherhood. This suggests that more stringent child support enforcement creates incentives that reduce the likelihood of nonmarital…

78 FR 20039 - Reportable Events and Certain Other Notification Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

...'' test and four other criteria designed to measure various aspects of financial soundness. The credit... controlled group changes. Like section 4043, the reportable events regulation generally requires post-event... available for plans that could meet one of two funding tests that would be more stringent than those...

76 FR 52644 - Faucets, Showerheads, Water Closets and Urinals

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

...-0053] Faucets, Showerheads, Water Closets and Urinals AGENCY: Office of Energy Efficiency and Renewable... concerning the water use or water efficiency of faucets, showerheads, water closets and urinals that is: (1) More stringent than Federal regulation concerning the water use or water efficiency for that same type...

Heavy-Duty Vehicle Thermal Management | Transportation Research | NREL

Science.gov Websites

Heavy-Duty Vehicle Thermal Management Heavy-Duty Vehicle Thermal Management Infrared image of a and meet more stringent idling regulations. NREL's HDV thermal management program, CoolCab, focuses on thermal management technologies undergo assessment at NREL's Vehicle Testing and Integration Facility test

76 FR 45253 - Public Water Supply Supervision Program; Program Revision for the State of Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-28

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9444-8] Public Water Supply Supervision Program; Program... Water Supply Supervision Primacy Program. Alaska has adopted regulations analogous to the EPA's Ground Water Rule. The EPA has determined that these revisions are no less stringent than the corresponding...

Sex Discrimination and Intercollegiate Athletics: Putting Some Muscle on Title IX.

ERIC Educational Resources Information Center

Yale Law Journal, 1979

1979-01-01

Argues that the general language of the Title IX statute, together with certain specific features of it, strongly suggests that the Department of Health, Education, and Welfare should develop more stringent and demanding regulations based on social policy considerations concerning sex discrimination in intercollegiate sports. Available from Yale…

SpoT-Mediated Regulation and Amino Acid Prototrophy Are Essential for Pyocyanin Production During Parasitic Growth of Pseudomonas aeruginosa in a Co-culture Model System With Aeromonas hydrophila

PubMed Central

Jagmann, Nina; Philipp, Bodo

2018-01-01

The opportunistic pathogen Pseudomonas aeruginosa employs its complex quorum sensing (QS) network to regulate the expression of virulence factors such as pyocyanin. Besides cell density, QS in this bacterium is co-regulated by environmental cues. In this study, we employed a previously established co-culture model system to identify metabolic influences that are involved in the regulation of pyocyanin production in P. aeruginosa. In this co-culture consisting of P. aeruginosa and the chitinolytic bacterium Aeromonas hydrophila, parasitic growth of P. aeruginosa is strictly dependent on the production of pyocyanin. We could show that in this co-culture, pyocyanin production is likely induced by the stringent response mediated by SpoT in response to nutrient limitation. Pyocyanin production by stringent response mutants in the co-culture could not be complemented by overexpression of PqsE. Via transposon mutagenesis, several amino acid auxotrophic mutants were identified that were also unable to produce pyocyanin when PqsE was overexpressed or when complementing amino acids were present. The inability to produce pyocyanin even though PqsE was overexpressed was likely a general effect of amino acid auxotrophy. These results show the value of the co-culture approach to identify both extra- and intracellular metabolic influences on QS that might be important in infection processes as well. PMID:29720972

NOx adsorber and method of regenerating same

DOEpatents

Endicott, Dennis L [Peoria, IL; Verkiel, Maarten [Metamora, IL; Driscoll, James J [Dunlap, IL

2007-01-30

New technologies, such as NOx adsorber catalytic converters, are being used to meet increasingly stringent regulations on undesirable emissions, including NOx emissions. NOx adsorbers must be periodically regenerated, which requires an increased fuel consumption. The present disclosure includes a method of regenerating a NOx adsorber within a NOx adsorber catalytic converter. At least one sensor positioned downstream from the NOx adsorber senses, in the downstream exhaust, at least one of NOx, nitrous oxide and ammonia concentrations a plurality of times during a regeneration phase. The sensor is in communication with an electronic control module that includes a regeneration monitoring algorithm operable to end the regeneration phase when a time rate of change of the at least one of NOx, nitrous oxide and ammonia concentrations is after an expected plateau region begins.

Noise pollution is pervasive in U.S. protected areas.

PubMed

Buxton, Rachel T; McKenna, Megan F; Mennitt, Daniel; Fristrup, Kurt; Crooks, Kevin; Angeloni, Lisa; Wittemyer, George

2017-05-05

Anthropogenic noise threatens ecological systems, including the cultural and biodiversity resources in protected areas. Using continental-scale sound models, we found that anthropogenic noise doubled background sound levels in 63% of U.S. protected area units and caused a 10-fold or greater increase in 21%, surpassing levels known to interfere with human visitor experience and disrupt wildlife behavior, fitness, and community composition. Elevated noise was also found in critical habitats of endangered species, with 14% experiencing a 10-fold increase in sound levels. However, protected areas with more stringent regulations had less anthropogenic noise. Our analysis indicates that noise pollution in protected areas is closely linked with transportation, development, and extractive land use, providing insight into where mitigation efforts can be most effective. Copyright © 2017, American Association for the Advancement of Science.

Regulated and unregulated emissions from modern 2010 emissions-compliant heavy-duty on-highway diesel engines

PubMed Central

Khalek, Imad A.; Blanks, Matthew G.; Merritt, Patrick M.; Zielinska, Barbara

2015-01-01

The U.S. Environmental Protection Agency (EPA) established strict regulations for highway diesel engine exhaust emissions of particulate matter (PM) and nitrogen oxides (NOx) to aid in meeting the National Ambient Air Quality Standards. The emission standards were phased in with stringent standards for 2007 model year (MY) heavy-duty engines (HDEs), and even more stringent NOX standards for 2010 and later model years. The Health Effects Institute, in cooperation with the Coordinating Research Council, funded by government and the private sector, designed and conducted a research program, the Advanced Collaborative Emission Study (ACES), with multiple objectives, including detailed characterization of the emissions from both 2007- and 2010-compliant engines. The results from emission testing of 2007-compliant engines have already been reported in a previous publication. This paper reports the emissions testing results for three heavy-duty 2010-compliant engines intended for on-highway use. These engines were equipped with an exhaust diesel oxidation catalyst (DOC), high-efficiency catalyzed diesel particle filter (DPF), urea-based selective catalytic reduction catalyst (SCR), and ammonia slip catalyst (AMOX), and were fueled with ultra-low-sulfur diesel fuel (~6.5 ppm sulfur). Average regulated and unregulated emissions of more than 780 chemical species were characterized in engine exhaust under transient engine operation using the Federal Test Procedure cycle and a 16-hr duty cycle representing a wide dynamic range of real-world engine operation. The 2010 engines’ regulated emissions of PM, NOX, nonmethane hydrocarbons, and carbon monoxide were all well below the EPA 2010 emission standards. Moreover, the unregulated emissions of polycyclic aromatic hydrocarbons (PAHs), nitroPAHs, hopanes and steranes, alcohols and organic acids, alkanes, carbonyls, dioxins and furans, inorganic ions, metals and elements, elemental carbon, and particle number were substantially (90 to >99%) lower than pre-2007-technology engine emissions, and also substantially (46 to >99%) lower than the 2007-technology engine emissions characterized in the previous study. Implications: Heavy-duty on-highway diesel engines equipped with DOC/DPF/SCR/AMOX and fueled with ultra-low-sulfur diesel fuel produced lower emissions than the stringent 2010 emission standards established by the U.S. Environmental Protection Agency. They also resulted in significant reductions in a wide range of unregulated toxic emission compounds relative to older technology engines. The increased use of newer technology (2010+) diesel engines in the on-highway sector and the adaptation of such technology by other sectors such as nonroad, displacing older, higher emissions engines, will have a positive impact on ambient levels of PM, NOx, and volatile organic compounds, in addition to many other toxic compounds. PMID:26037832

78 FR 56267 - Article 19-A of the State of New York's Vehicle and Traffic Law

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-12

... safety benefits, how it is being enforced against interstate passenger carriers and its effect, if any, on interstate commerce. DATES: Comments are due on or before November 12, 2013. ADDRESSES: You may... interstate commerce by imposing requirements that are more stringent than Federal regulations. MCC stated...

77 FR 2741 - Draft Guidance Regarding Inspection and Certification of Vessels Under the Maritime Security Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... traditional inspection methods to newly reflagged vessels, while at the same time apply a less stringent level... any one of the following methods: (1) Federal eRulemaking Portal: http://www.regulations.gov . (2) Fax... methods. See the ``Public Participation and Request for Comments'' portion of the SUPPLEMENTARY...

Emission and distribution of fumigants as affected by soil moistures in three different textured soils

USDA-ARS?s Scientific Manuscript database

Stringent environmental regulations are being developed to control the emission of soil fumigants to reduce air pollution. Water application is a low-cost strategy for fumigant emission control and applicable for a wide range of commodity groups, especially those with low profit margins. Although it...

Dual Regulation of Bacillus subtilis kinB Gene Encoding a Sporulation Trigger by SinR through Transcription Repression and Positive Stringent Transcription Control.

PubMed

Fujita, Yasutaro; Ogura, Mitsuo; Nii, Satomi; Hirooka, Kazutake

2017-01-01

It is known that transcription of kinB encoding a trigger for Bacillus subtilis sporulation is under repression by SinR, a master repressor of biofilm formation, and under positive stringent transcription control depending on the adenine species at the transcription initiation nucleotide (nt). Deletion and base substitution analyses of the kinB promoter (P kinB ) region using lacZ fusions indicated that either a 5-nt deletion (Δ5, nt -61/-57, +1 is the transcription initiation nt) or the substitution of G at nt -45 with A (G-45A) relieved kinB repression. Thus, we found a pair of SinR-binding consensus sequences (GTTCTYT; Y is T or C) in an inverted orientation (SinR-1) between nt -57/-42, which is most likely a SinR-binding site for kinB repression. This relief from SinR repression likely requires SinI, an antagonist of SinR. Surprisingly, we found that SinR is essential for positive stringent transcription control of P kinB . Electrophoretic mobility shift assay (EMSA) analysis indicated that SinR bound not only to SinR-1 but also to SinR-2 (nt -29/-8) consisting of another pair of SinR consensus sequences in a tandem repeat arrangement; the two sequences partially overlap the '-35' and '-10' regions of P kinB . Introduction of base substitutions (T-27C C-26T) in the upstream consensus sequence of SinR-2 affected positive stringent transcription control of P kinB , suggesting that SinR binding to SinR-2 likely causes this positive control. EMSA also implied that RNA polymerase and SinR are possibly bound together to SinR-2 to form a transcription initiation complex for kinB transcription. Thus, it was suggested in this work that derepression of kinB from SinR repression by SinI induced by Spo0A∼P and occurrence of SinR-dependent positive stringent transcription control of kinB might induce effective sporulation cooperatively, implying an intimate interplay by stringent response, sporulation, and biofilm formation.

Hypermutation in derepressed operons of Escherichia coli K12

PubMed Central

Wright, Barbara E.; Longacre, Angelika; Reimers, Jacqueline M.

1999-01-01

This article presents evidence that starvation for leucine in an Escherichia coli auxotroph triggers metabolic activities that specifically target the leu operon for derepression, increased rates of transcription, and mutation. Derepression of the leu operon was a prerequisite for its activation by the signal nucleotide, guanosine tetraphosphate, which accumulates in response to nutritional stress (the stringent response). A quantitative correlation was established between leuB mRNA abundance and leuB− reversion rates. To further demonstrate that derepression increased mutation rates, the chromosomal leu operon was placed under the control of the inducible tac promoter. When the leu operon was induced by isopropyl-d-thiogalactoside, both leuB mRNA abundance and leuB− reversion rates increased. These investigations suggest that guanosine tetraphosphate may contribute as much as attenuation in regulating leu operon expression and that higher rates of mutation are specifically associated with the derepressed leu operon. PMID:10220423

Noise-Reduction Benefits Analyzed for Over-the-Wing-Mounted Advanced Turbofan Engines

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.

2000-01-01

As we look to the future, increasingly stringent civilian aviation noise regulations will require the design and manufacture of extremely quiet commercial aircraft. Also, the large fan diameters of modern engines with increasingly higher bypass ratios pose significant packaging and aircraft installation challenges. One design approach that addresses both of these challenges is to mount the engines above the wing. In addition to allowing the performance trend towards large diameters and high bypass ratio cycles to continue, this approach allows the wing to shield much of the engine noise from people on the ground. The Propulsion Systems Analysis Office at the NASA Glenn Research Center at Lewis Field conducted independent analytical research to estimate the noise reduction potential of mounting advanced turbofan engines above the wing. Certification noise predictions were made for a notional long-haul commercial quadjet transport. A large quad was chosen because, even under current regulations, such aircraft sometimes experience difficulty in complying with certification noise requirements with a substantial margin. Also, because of its long wing chords, a large airplane would receive the greatest advantage of any noise-shielding benefit.

77 FR 18477 - Energy Conservation Program: Energy Conservation Standards for Battery Chargers and External...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... Interstate Rule (CAIR, 70 FR 25162 (May 12, 2005)), but not the Clean Air Mercury Rule (CAMR, 70 FR 28606 (May 18, 2005)). Subsequent regulations, including the finalized CAIR replacement rule, the Cross-State... Air Interstate Rule (CAIR, which has a similar structure, but with less stringent budgets and less...

77 FR 59408 - Finding of Equivalence; Alternate Pressure Relief Valve Settings on Certain Vessels Carrying...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-27

... allowable stress factors for type B and type C independent cargo tanks are more stringent than the... inspections have advanced since the Coast Guard first promulgated regulations on allowable stress factors on... allowable stress factors provide a level of safety protection equivalent to the standards in 46 CFR 154.447...

40 CFR 52.675 - Control strategy: Sulfur oxides-Eastern Idaho Intrastate Air Quality Control Region.

Code of Federal Regulations, 2014 CFR

2014-07-01

... of Sulfur Oxide Emissions from Sulfuric Acid Plants) of the “Rules and Regulations for the Control of... have previously been established for certain existing acid plants in this Air Quality Control Region... apply to existing acid plants with approved or promulgated emission limits that are more stringent than...

40 CFR 52.675 - Control strategy: Sulfur oxides-Eastern Idaho Intrastate Air Quality Control Region.

Code of Federal Regulations, 2013 CFR

2013-07-01

... of Sulfur Oxide Emissions from Sulfuric Acid Plants) of the “Rules and Regulations for the Control of... have previously been established for certain existing acid plants in this Air Quality Control Region... apply to existing acid plants with approved or promulgated emission limits that are more stringent than...

40 CFR 52.675 - Control strategy: Sulfur oxides-Eastern Idaho Intrastate Air Quality Control Region.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of Sulfur Oxide Emissions from Sulfuric Acid Plants) of the “Rules and Regulations for the Control of... have previously been established for certain existing acid plants in this Air Quality Control Region... apply to existing acid plants with approved or promulgated emission limits that are more stringent than...

40 CFR 52.675 - Control strategy: Sulfur oxides-Eastern Idaho Intrastate Air Quality Control Region.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of Sulfur Oxide Emissions from Sulfuric Acid Plants) of the “Rules and Regulations for the Control of... have previously been established for certain existing acid plants in this Air Quality Control Region... apply to existing acid plants with approved or promulgated emission limits that are more stringent than...

40 CFR 52.675 - Control strategy: Sulfur oxides-Eastern Idaho Intrastate Air Quality Control Region.

Code of Federal Regulations, 2011 CFR

2011-07-01

... of Sulfur Oxide Emissions from Sulfuric Acid Plants) of the “Rules and Regulations for the Control of... have previously been established for certain existing acid plants in this Air Quality Control Region... apply to existing acid plants with approved or promulgated emission limits that are more stringent than...

32 CFR 766.5 - Conditions governing use of aviation facilities by civil aircraft.

Code of Federal Regulations, 2011 CFR

2011-07-01

... weather minimums as follows: (1) Visual Flight Operations shall be conducted in accordance with Federal Aviation Regulations (FAR), § 91.105 of this title. If more stringent visual flight rules minimums have... must be noted in § 766.5 of the license application. If a narrative report from the pilot is available...

32 CFR 766.5 - Conditions governing use of aviation facilities by civil aircraft.

Code of Federal Regulations, 2010 CFR

2010-07-01

... weather minimums as follows: (1) Visual Flight Operations shall be conducted in accordance with Federal Aviation Regulations (FAR), § 91.105 of this title. If more stringent visual flight rules minimums have... must be noted in § 766.5 of the license application. If a narrative report from the pilot is available...

40 CFR 52.970 - Identification of plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

...)(50) Section 1303.A Toxic Substances 10/20/1995 7/05/2011, 76 FR 38977 Section 1305 Control of....999(c)(50) Section 1315 More Stringent Regulations may be Prescribed if Particulates are Toxic Jun... Law 30:2060 N.6 Toxic air pollution emission control program 10/22/92 06/23/94, 59 FR 32359 Ref 52.999...

40 CFR 52.970 - Identification of plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

...)(50) Section 1303.A Toxic Substances 10/20/1995 7/05/2011, 76 FR 38977 Section 1305 Control of....999(c)(50) Section 1315 More Stringent Regulations may be Prescribed if Particulates are Toxic Jun... Law 30:2060 N.6 Toxic air pollution emission control program 10/22/92 06/23/94, 59 FR 32359 Ref 52.999...

Access to bacteriophage therapy: discouraging experiences from the human cell and tissue legal framework.

PubMed

Verbeken, G; Huys, I; De Vos, D; De Coninck, A; Roseeuw, D; Kets, E; Vanderkelen, A; Draye, J P; Rose, T; Jennes, S; Ceulemans, C; Pirnay, J P

2016-02-01

Cultures of human epithelial cells (keratinocytes) are used as an additional surgical tool to treat critically burnt patients. Initially, the production environment of keratinocyte grafts was regulated exclusively by national regulations. In 2004, the European Tissues and Cells Directive 2004/23/EC (transposed into Belgian Law) imposed requirements that resulted in increased production costs and no significant increase in quality and/or safety. In 2007, Europe published Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Overnight, cultured keratinocytes became (arguably) 'Advanced' Therapy Medicinal Products to be produced as human medicinal products. The practical impact of these amendments was (and still is) considerable. A similar development appears imminent in bacteriophage therapy. Bacteriophages are bacterial viruses that can be used for tackling the problem of bacterial resistance development to antibiotics. Therapeutic natural bacteriophages have been in clinical use for almost 100 years. Regulators today are framing the (re-)introduction of (natural) bacteriophage therapy into 'modern western' medicine as biological medicinal products, also subject to stringent regulatory medicinal products requirements. In this paper, we look back on a century of bacteriophage therapy to make the case that therapeutic natural bacteriophages should not be classified under the medicinal product regulatory frames as they exist today. It is our call to authorities to not repeat the mistake of the past. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Redox-Active Sensing by Bacterial DksA Transcription Factors Is Determined by Cysteine and Zinc Content

PubMed Central

Crawford, Matthew A.; Tapscott, Timothy; Fitzsimmons, Liam F.; Liu, Lin; Reyes, Aníbal M.; Libby, Stephen J.; Trujillo, Madia; Fang, Ferric C.; Radi, Rafael

2016-01-01

ABSTRACT The four-cysteine zinc finger motif of the bacterial RNA polymerase regulator DksA is essential for protein structure, canonical control of the stringent response to nutritional limitation, and thiol-based sensing of oxidative and nitrosative stress. This interdependent relationship has limited our understanding of DksA-mediated functions in bacterial pathogenesis. Here, we have addressed this challenge by complementing ΔdksA Salmonella with Pseudomonas aeruginosa dksA paralogues that encode proteins differing in cysteine and zinc content. We find that four-cysteine, zinc-bound (C4) and two-cysteine, zinc-free (C2) DksA proteins are able to mediate appropriate stringent control in Salmonella and that thiol-based sensing of reactive species is conserved among C2 and C4 orthologues. However, variations in cysteine and zinc content determine the threshold at which individual DksA proteins sense and respond to reactive species. In particular, zinc acts as an antioxidant, dampening cysteine reactivity and raising the threshold of posttranslational thiol modification with reactive species. Consequently, C2 DksA triggers transcriptional responses in Salmonella at levels of oxidative or nitrosative stress normally tolerated by Salmonella expressing C4 orthologues. Inappropriate transcriptional regulation by C2 DksA increases the susceptibility of Salmonella to the antimicrobial effects of hydrogen peroxide and nitric oxide, and attenuates virulence in macrophages and mice. Our findings suggest that the redox-active sensory function of DksA proteins is finely tuned to optimize bacterial fitness according to the levels of oxidative and nitrosative stress encountered by bacterial species in their natural and host environments. PMID:27094335

Characteristics of typical non-road machinery emissions in China by using portable emission measurement system.

PubMed

Fu, Mingliang; Ge, Yunshan; Tan, Jianwei; Zeng, Tao; Liang, Bin

2012-10-15

Non-road machinery, especially construction equipment could be an important pollutant source of the deterioration in air quality in Chinese urban areas due to its large quantity and to the absence of stringent emission requirements. In this study, emission tests were performed on 12 excavators and 8 wheel loaders by using portable emission measurement system (PEMS) to determine their emission characteristics. The typical operating modes were categorized as idling mode, moving mode and working mode. Compared with those during idling and moving modes, the average time-based emission factors during working mode of HC were 2.61 and 1.27 times higher, NO(x) were 3.66 and 1.36 times higher, and PM were 4.05 and 1.95 times higher, respectively. Under all conditions, categories of the measured emissions increased with the rise in engine power. Compared with those of Stage I emission standard equipment, gaseous emissions and PM emitted from Stage II emission standard equipment were lower. The results indicated that, from Stage I to Stage II, the average reductions of HC, NO(x) and PM were 56%, 37% and 29% for the working mode, respectively. Those results also demonstrated the effectiveness of emission control regulation and the improvement of emission control technology. The data and tests show that the longer the accumulated working hours, the higher HC and NO(x) average fuel-based emission factors are. The emissions measured from the construction vehicles employed in this study were higher than the data collected in previous studies, which shows that it is critical for the government to put into effect more stringent emission regulations to further improve the air quality in Chinese urban areas. Copyright © 2012 Elsevier B.V. All rights reserved.

Control of rRNA transcription in Escherichia coli.

PubMed Central

Condon, C; Squires, C; Squires, C L

1995-01-01

The control of rRNA synthesis in response to both extra- and intracellular signals has been a subject of interest to microbial physiologists for nearly four decades, beginning with the observations that Salmonella typhimurium cells grown on rich medium are larger and contain more RNA than those grown on poor medium. This was followed shortly by the discovery of the stringent response in Escherichia coli, which has continued to be the organism of choice for the study of rRNA synthesis. In this review, we summarize four general areas of E. coli rRNA transcription control: stringent control, growth rate regulation, upstream activation, and anti-termination. We also cite similar mechanisms in other bacteria and eukaryotes. The separation of growth rate-dependent control of rRNA synthesis from stringent control continues to be a subject of controversy. One model holds that the nucleotide ppGpp is the key effector for both mechanisms, while another school holds that it is unlikely that ppGpp or any other single effector is solely responsible for growth rate-dependent control. Recent studies on activation of rRNA synthesis by cis-acting upstream sequences has led to the discovery of a new class of promoters that make contact with RNA polymerase at a third position, called the UP element, in addition to the well-known -10 and -35 regions. Lastly, clues as to the role of antitermination in rRNA operons have begun to appear. Transcription complexes modified at the antiterminator site appear to elongate faster and are resistant to the inhibitory effects of ppGpp during the stringent response. PMID:8531889

Electron-processing technology: A promising application for the viscose industry

NASA Astrophysics Data System (ADS)

Stepanik, T. M.; Rajagopal, S.; Ewing, D.; Whitehouse, R.

1998-06-01

In marketing its IMPELA ® line of high power, high-throughput industrial accelerators, Atomic Energy of Canada Limited (AECL) is working with viscose (rayon) companies world-wide to integrate electron-processing technology as part of the viscose manufacturing process. The viscose industry converts cellulose wood pulp into products such as staple fiber, filament, cord, film, packaging, and non-edible sausage casings. This multibillion dollar industry is currently suffering from high production costs, and is facing increasingly stringent environmental regulations. The use of electron-treated pulp can significantly lower production costs and can provide equally significant environmental benefits. This paper describes our current understanding of the benefits of using electron-treated pulp in this process, and AECL's efforts in developing this technology.

Environmental Quality: Environmental Protection and Enhancement

DTIC Science & Technology

2002-01-17

have an adverse effect on human health . These regulations are federally enforceable. Primacy states may have more stringent requirements. Primary...includes TT requirements for filtered and unfiltered systems that are specifically designed to protect against the adverse health effects of exposure to...MTBE (20) Alachlor ESA (36) Lead- 210 (9) Nitrobenzene (21) 1,2-diphenylhydrazine (37) Polonium - 210 (10) Terbacil (22) Diazinon (11) Acetochlor (23

Counting at low concentrations: the statistical challenges of verifying ballast water discharge standards

USGS Publications Warehouse

Frazier, Melanie; Miller, A. Whitman; Lee, Henry; Reusser, Deborah A.

2013-01-01

Discharge from the ballast tanks of ships is one of the primary vectors of nonindigenous species in marine environments. To mitigate this environmental and economic threat, international, national, and state entities are establishing regulations to limit the concentration of living organisms that may be discharged from the ballast tanks of ships. The proposed discharge standards have ranged from zero detectable organisms to 3. If standard sampling methods are used, verifying whether ballast discharge complies with these stringent standards will be challenging due to the inherent stochasticity of sampling. Furthermore, at low concentrations, very large volumes of water must be sampled to find enough organisms to accurately estimate concentration. Despite these challenges, adequate sampling protocols comprise a critical aspect of establishing standards because they help define the actual risk level associated with a standard. A standard that appears very stringent may be effectively lax if it is paired with an inadequate sampling protocol. We describe some of the statistical issues associated with sampling at low concentrations to help regulators understand the uncertainties of sampling as well as to inform the development of sampling protocols that ensure discharge standards are adequately implemented.

Precision Adjustable Liquid Regulator (ALR)

NASA Astrophysics Data System (ADS)

Meinhold, R.; Parker, M.

2004-10-01

A passive mechanical regulator has been developed for the control of fuel or oxidizer flow to a 450N class bipropellant engine for use on commercial and interplanetary spacecraft. There are several potential benefits to the propulsion system, depending on mission requirements and spacecraft design. This system design enables more precise control of main engine mixture ratio and inlet pressure, and simplifies the pressurization system by transferring the function of main engine flow rate control from the pressurization/propellant tank assemblies, to a single component, the ALR. This design can also reduce the thermal control requirements on the propellant tanks, avoid costly Qualification testing of biprop engines for missions with more stringent requirements, and reduce the overall propulsion system mass and power usage. In order to realize these benefits, the ALR must meet stringent design requirements. The main advantage of this regulator over other units available in the market is that it can regulate about its nominal set point to within +/-0.85%, and change its regulation set point in flight +/-4% about that nominal point. The set point change is handled actively via a stepper motor driven actuator, which converts rotary into linear motion to affect the spring preload acting on the regulator. Once adjusted to a particular set point, the actuator remains in its final position unpowered, and the regulator passively maintains outlet pressure. The very precise outlet regulation pressure is possible due to new technology developed by Moog, Inc. which reduces typical regulator mechanical hysteresis to near zero. The ALR requirements specified an outlet pressure set point range from 225 to 255 psi, and equivalent water flow rates required were in the 0.17 lb/sec range. The regulation output pressure is maintained at +/-2 psi about the set point from a P (delta or differential pressure) of 20 to over 100 psid. Maximum upstream system pressure was specified at 320 psi. The regulator is fault tolerant in that it was purposely designed with no shutoff capability, such that the minimum flow position of the poppet still allows the subsystem to provide adequate flow to the main engine for basic operation.

Genotypic variability enhances the reproducibility of an ecological study.

PubMed

Milcu, Alexandru; Puga-Freitas, Ruben; Ellison, Aaron M; Blouin, Manuel; Scheu, Stefan; Freschet, Grégoire T; Rose, Laura; Barot, Sebastien; Cesarz, Simone; Eisenhauer, Nico; Girin, Thomas; Assandri, Davide; Bonkowski, Michael; Buchmann, Nina; Butenschoen, Olaf; Devidal, Sebastien; Gleixner, Gerd; Gessler, Arthur; Gigon, Agnès; Greiner, Anna; Grignani, Carlo; Hansart, Amandine; Kayler, Zachary; Lange, Markus; Lata, Jean-Christophe; Le Galliard, Jean-François; Lukac, Martin; Mannerheim, Neringa; Müller, Marina E H; Pando, Anne; Rotter, Paula; Scherer-Lorenzen, Michael; Seyhun, Rahme; Urban-Mead, Katherine; Weigelt, Alexandra; Zavattaro, Laura; Roy, Jacques

2018-02-01

Many scientific disciplines are currently experiencing a 'reproducibility crisis' because numerous scientific findings cannot be repeated consistently. A novel but controversial hypothesis postulates that stringent levels of environmental and biotic standardization in experimental studies reduce reproducibility by amplifying the impacts of laboratory-specific environmental factors not accounted for in study designs. A corollary to this hypothesis is that a deliberate introduction of controlled systematic variability (CSV) in experimental designs may lead to increased reproducibility. To test this hypothesis, we had 14 European laboratories run a simple microcosm experiment using grass (Brachypodium distachyon L.) monocultures and grass and legume (Medicago truncatula Gaertn.) mixtures. Each laboratory introduced environmental and genotypic CSV within and among replicated microcosms established in either growth chambers (with stringent control of environmental conditions) or glasshouses (with more variable environmental conditions). The introduction of genotypic CSV led to 18% lower among-laboratory variability in growth chambers, indicating increased reproducibility, but had no significant effect in glasshouses where reproducibility was generally lower. Environmental CSV had little effect on reproducibility. Although there are multiple causes for the 'reproducibility crisis', deliberately including genetic variability may be a simple solution for increasing the reproducibility of ecological studies performed under stringently controlled environmental conditions.

Biodesulfurization of refractory organic sulfur compounds in fossil fuels.

PubMed

Soleimani, Mehran; Bassi, Amarjeet; Margaritis, Argyrios

2007-01-01

The stringent new regulations to lower sulfur content in fossil fuels require new economic and efficient methods for desulfurization of recalcitrant organic sulfur. Hydrodesulfurization of such compounds is very costly and requires high operating temperature and pressure. Biodesulfurization is a non-invasive approach that can specifically remove sulfur from refractory hydrocarbons under mild conditions and it can be potentially used in industrial desulfurization. Intensive research has been conducted in microbiology and molecular biology of the competent strains to increase their desulfurization activity; however, even the highest activity obtained is still insufficient to fulfill the industrial requirements. To improve the biodesulfurization efficiency, more work is needed in areas such as increasing specific desulfurization activity, hydrocarbon phase tolerance, sulfur removal at higher temperature, and isolating new strains for desulfurizing a broader range of sulfur compounds. This article comprehensively reviews and discusses key issues, advances and challenges for a competitive biodesulfurization process.

Measurements of atmospheric ethene by solar absorption FTIR spectrometry

NASA Astrophysics Data System (ADS)

Toon, Geoffrey C.; Blavier, Jean-Francois L.; Sung, Keeyoon

2018-04-01

Atmospheric ethene (C2H4; ethylene) amounts have been retrieved from high-resolution solar absorption spectra measured by the Jet Propulsion Laboratory (JPL) MkIV interferometer. Data recorded from 1985 to 2016 from a dozen ground-based sites have been analyzed, mostly between 30 and 67° N. At clean-air sites such as Alaska, Sweden, New Mexico, or the mountains of California, the ethene columns were always less than 1 × 1015 molec cm-2 and therefore undetectable. In urban sites such as JPL, California, ethene was measurable with column amounts of 20 × 1015 molec cm-2 observed in the 1990s. Despite the increasing population and traffic in southern California, a factor 3 decrease in ethene column density is observed over JPL over the past 25 years, accompanied by a decrease in CO. This is likely due to southern California's increasingly stringent vehicle exhaust regulations and tighter enforcement over this period.

Noise Reduction Potential of Large, Over-the-Wing Mounted, Advanced Turbofan Engines

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.

2000-01-01

As we look to the future, increasingly stringent civilian aviation noise regulations will require the design and manufacture of extremely quiet commercial aircraft. Indeed, the noise goal for NASA's Aeronautics Enterprise calls for technologies that will help to provide a 20 EPNdB reduction relative to today's levels by the year 2022. Further, the large fan diameters of modem, increasingly higher bypass ratio engines pose a significant packaging and aircraft installation challenge. One design approach that addresses both of these challenges is to mount the engines above the wing. In addition to allowing the performance trend towards large, ultra high bypass ratio cycles to continue, this over-the-wing design is believed to offer noise shielding benefits to observers on the ground. This paper describes the analytical certification noise predictions of a notional, long haul, commercial quadjet transport with advanced, high bypass engines mounted above the wing.

The Stringent Response Is Essential for Pseudomonas aeruginosa Virulence in the Rat Lung Agar Bead and Drosophila melanogaster Feeding Models of Infection▿†

PubMed Central

Vogt, Stefanie L.; Green, Christopher; Stevens, Katarzyna M.; Day, Brad; Erickson, David L.; Woods, Donald E.; Storey, Douglas G.

2011-01-01

The stringent response is a regulatory system that allows bacteria to sense and adapt to nutrient-poor environments. The central mediator of the stringent response is the molecule guanosine 3′,5′-bispyrophosphate (ppGpp), which is synthesized by the enzymes RelA and SpoT and which is also degraded by SpoT. Our laboratory previously demonstrated that a relA mutant of Pseudomonas aeruginosa, the principal cause of lung infections in cystic fibrosis patients, was attenuated in virulence in a Drosophila melanogaster feeding model of infection. In this study, we examined the role of spoT in P. aeruginosa virulence. We generated an insertion mutation in spoT within the previously constructed relA mutant, thereby producing a ppGpp-devoid strain. The relA spoT double mutant was unable to establish a chronic infection in D. melanogaster and was also avirulent in the rat lung agar bead model of infection, a model in which the relA mutant is fully virulent. Synthesis of the virulence determinants pyocyanin, elastase, protease, and siderophores was impaired in the relA spoT double mutant. This mutant was also defective in swarming and twitching, but not in swimming motility. The relA spoT mutant and, to a lesser extent, the relA mutant were less able to withstand stresses such as heat shock and oxidative stress than the wild-type strain PAO1, which may partially account for the inability of the relA spoT mutant to successfully colonize the rat lung. Our results indicate that the stringent response, and SpoT in particular, is a crucial regulator of virulence processes in P. aeruginosa. PMID:21788391

Documentation of hazards and safety perceptions for mechanized logging operations in east central Alabama

Treesearch

R. M. Bordas; G. A. Davis; B. L. Hopkins; R. E. Thornas; Robert B. Rummer

2001-01-01

The logging industry remains one of the most hazardous in the nation. Despite more stringent safety regulations and improvements in equipment safety features, the rate of logging fatalities has decreased at a much lower rate than the decrease in the rate of illnesses and injuries in the same occupation. The objective of this research was to identify and assess the...

Welding and joining techniques.

PubMed

Chipperfield, F A; Dunkerton, S B

2001-05-01

There is a welding solution for most applications. As products must meet more stringent requirements or require more flexible processes to aid design or reduce cost, further improvements or totally new processes are likely to be developed. Quality control aspects are also becoming more important to meet regulation, and monitoring and control of welding processes and the standardised testing of joints will meet some if not all of these requirements.

40 CFR 52.970 - Identification of plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Particulate Matter Jun 1988, LR14:348 06/15/89, 54 FR 25451 Ref 52.999(c)(50) Section 1303.A Toxic Substances... Stringent Regulations may be Prescribed if Particulates are Toxic Jun 1988, LR14:348 06/15/89, 54 FR 25451... Law 30:2060 N.6 Toxic air pollution emission control program 10/22/92 06/23/94, 59 FR 32359 Ref 52.999...

Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET

PubMed Central

Swiercz, Rafal; Chiguru, Srinivas; Tahmasbi, Amir; Ramezani, Saleh M.; Hao, Guiyang; Challa, Dilip K.; Lewis, Matthew A.; Kulkarni, Padmakar V.; Sun, Xiankai; Ober, Raimund J.; Mason, Ralph P.; Ward, E. Sally

2015-01-01

Despite promise for the use of antibodies as molecular imaging agents in PET, their long in vivo half-lives result in poor contrast and radiation damage to normal tissue. This study describes an approach to overcome these limitations. Methods Mice bearing human epidermal growth factor receptor type 2 (HER2)–overexpressing tumors were injected with radiolabeled (124I, 125I) HER2-specific antibody (pertuzumab). Pertuzumab injection was followed 8 h later by the delivery of an engineered, antibody-based inhibitor of the receptor, FcRn. Biodistribution analyses and PET were performed at 24 and 48 h after pertuzumab injection. Results The delivery of the engineered, antibody-based FcRn inhibitor (or Abdeg, for antibody that enhances IgG degradation) results in improved tumor-to-blood ratios, reduced systemic exposure to radiolabel, and increased contrast during PET. Conclusion Abdegs have considerable potential as agents to stringently regulate antibody dynamics in vivo, resulting in increased contrast during molecular imaging with PET. PMID:24868106

Food poisoning as an in-flight safety hazard.

PubMed

Beers, K N; Mohler, S R

1985-06-01

The leading cause by far of airline pilot incapacitations is gastrointestinal illness resulting from "food poisoning". This potentially hazardous condition is inadequately dealt with by the airlines today and strikes equally in all pilot age groups. Sufficient incidents are occurring to justify more stringent aircrew meal standards and regulations. Aircrew heart attack and stroke concerns pale into insignificance relative to the far more common food poisoning incapacitations. Specific regulations on aircrew feeding should be promulgated by the Federal Aviation Administration and the regulatory authorities in other countries to preclude simultaneous-onset in-flight incapacitations due to common-source food poisoning.

Land-use policies and corporate investments in agriculture in the Gran Chaco and Chiquitano

PubMed Central

le Polain de Waroux, Yann; Garrett, Rachael D.; Heilmayr, Robert; Lambin, Eric F.

2016-01-01

Growing demand for agricultural commodities is causing the expansion of agricultural frontiers onto native vegetation worldwide. Agribusiness companies linking these frontiers to distant spaces of consumption through global commodity chains increasingly make zero-deforestation pledges. However, production and land conversion are often carried out by less-visible local and regional actors that are mobile and responsive to new agricultural expansion opportunities and legal constraints on land use. With more stringent deforestation regulations in some countries, we ask whether their movements are determined partly by differences in land-use policies, resulting in “deforestation havens.” We analyze the determinants of investment decisions by agricultural companies in the Gran Chaco and Chiquitano, a region that has become the new deforestation “hot spot” in South America. We test whether companies seek out less-regulated forest areas for new agricultural investments. Based on interviews with 82 companies totaling 2.5 Mha of properties, we show that, in addition to proximity to current investments and the availability of cheap forestland, lower deforestation regulations attract investments by companies that tend to clear more forest, mostly cattle ranching operations, and that lower enforcement attracts all companies. Avoiding deforestation leakage requires harmonizing deforestation regulations across regions and commodities and promoting sustainable intensification in cattle ranching. PMID:27035995

The Effect of State Regulatory Stringency on Nursing Home Quality

PubMed Central

Mukamel, Dana B; Weimer, David L; Harrington, Charlene; Spector, William D; Ladd, Heather; Li, Yue

2012-01-01

Objective To test the hypothesis that more stringent quality regulations contribute to better quality nursing home care and to assess their cost-effectiveness. Data Sources/Setting Primary and secondary data from all states and U.S. nursing homes between 2005 and 2006. Study Design We estimated seven models, regressing quality measures on the Harrington Regulation Stringency Index and control variables. To account for endogeneity between regulation and quality, we used instrumental variables techniques. Quality was measured by staffing hours by type per case-mix adjusted day, hotel expenditures, and risk-adjusted decline in activities of daily living, high-risk pressure sores, and urinary incontinence. Data Collection All states' licensing and certification offices were surveyed to obtain data about deficiencies. Secondary data included the Minimum Data Set, Medicare Cost Reports, and the Economic Freedom Index. Principal Findings Regulatory stringency was significantly associated with better quality for four of the seven measures studied. The cost-effectiveness for the activities-of-daily-living measure was estimated at about 72,000 in 2011/ Quality Adjusted Life Year. Conclusions Quality regulations lead to better quality in nursing homes along some dimensions, but not all. Our estimates of cost-effectiveness suggest that increased regulatory stringency is in the ballpark of other acceptable cost-effective practices. PMID:22946859

Land-use policies and corporate investments in agriculture in the Gran Chaco and Chiquitano.

PubMed

le Polain de Waroux, Yann; Garrett, Rachael D; Heilmayr, Robert; Lambin, Eric F

2016-04-12

Growing demand for agricultural commodities is causing the expansion of agricultural frontiers onto native vegetation worldwide. Agribusiness companies linking these frontiers to distant spaces of consumption through global commodity chains increasingly make zero-deforestation pledges. However, production and land conversion are often carried out by less-visible local and regional actors that are mobile and responsive to new agricultural expansion opportunities and legal constraints on land use. With more stringent deforestation regulations in some countries, we ask whether their movements are determined partly by differences in land-use policies, resulting in "deforestation havens." We analyze the determinants of investment decisions by agricultural companies in the Gran Chaco and Chiquitano, a region that has become the new deforestation "hot spot" in South America. We test whether companies seek out less-regulated forest areas for new agricultural investments. Based on interviews with 82 companies totaling 2.5 Mha of properties, we show that, in addition to proximity to current investments and the availability of cheap forestland, lower deforestation regulations attract investments by companies that tend to clear more forest, mostly cattle ranching operations, and that lower enforcement attracts all companies. Avoiding deforestation leakage requires harmonizing deforestation regulations across regions and commodities and promoting sustainable intensification in cattle ranching.

A review of automated image understanding within 3D baggage computed tomography security screening.

PubMed

Mouton, Andre; Breckon, Toby P

2015-01-01

Baggage inspection is the principal safeguard against the transportation of prohibited and potentially dangerous materials at airport security checkpoints. Although traditionally performed by 2D X-ray based scanning, increasingly stringent security regulations have led to a growing demand for more advanced imaging technologies. The role of X-ray Computed Tomography is thus rapidly expanding beyond the traditional materials-based detection of explosives. The development of computer vision and image processing techniques for the automated understanding of 3D baggage-CT imagery is however, complicated by poor image resolutions, image clutter and high levels of noise and artefacts. We discuss the recent and most pertinent advancements and identify topics for future research within the challenging domain of automated image understanding for baggage security screening CT.

Evaluation of implementation, compliance and acceptance of partial smoking bans among hospitality workers before and after the Swiss Tobacco Control Act.

PubMed

Rajkumar, Sarah; Hoffmann, Susanne; Röösli, Martin; Bauer, Georg F

2015-03-01

The World Health Organization recommends uniform comprehensive smoking bans in public places. In Switzerland, regulations differ between various areas and are mostly incomplete for hospitality venues. As ambiguous regulations offer more leeway for implementation, we evaluated the Swiss regulations with respect to their effects on implementation, acceptance and compliance among hospitality workers. In our longitudinal study, a standardized, self-administered questionnaire was mailed to a sample of 185 hospitality workers before and 4-6 month after the smoking ban came into effect. The matched longitudinal sample comprised 71 participants (repeated response rate 38.4%). We developed a seven-item acceptance scale. Logistic regressions were performed to explore the factors associated with acceptance. Acceptance of smoking bans was influenced by smoking status and perceived annoyance with second-hand smoke in private. Although not statistically significant (P = 0.09), we found some indications that post-ban acceptance increased in an area with strict regulations, whereas it decreased in two areas with less stringent regulations. Tobacco bans in Swiss hospitality venues are still in a period of consolidation. The incomplete nature of the law may also have had a negative impact on the development of greater acceptance. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Contact Transfer of VX from Contaminated Grass onto Army Combat Uniform

DTIC Science & Technology

2017-01-01

intervals for agricultural workers who use pesticides . The reentry intervals are based on the available toxicity data, concentrations of chemicals used...for workers using some of the more toxic organophosphate pesticides . State regulators are free to set more stringent intervals. Watson suggested...report, the RASH method that uses RPF values for pesticide exposure of agricultural workers appears to be unrealistic for extrapolating to the exposure

Advanced Conversion Coatings for Magnesium alloys

NASA Astrophysics Data System (ADS)

Nibhanupudi, Syam; Manavbasi, Alp

Magnesium and its alloys have excellent physical and mechanical properties due to their high strength-to-weight ratio and are ideal for various applications in automotive, aerospace and defense sectors. However, Mg alloys are also highly susceptible to corrosion under harsh environments. Owing to this carcinogenicity as well as environmental impact of hexavalent chromium fueled by stringent environmental regulations, an environmentally green alternative to the carcinogenic hexavalent chromium coatings on magnesium is due.

Synthetic dual-input mammalian genetic circuits enable tunable and stringent transcription control by chemical and light.

PubMed

Chen, Xianjun; Li, Ting; Wang, Xue; Du, Zengmin; Liu, Renmei; Yang, Yi

2016-04-07

Programmable transcription factors can enable precise control of gene expression triggered by a chemical inducer or light. To obtain versatile transgene system with combined benefits of a chemical inducer and light inducer, we created various chimeric promoters through the assembly of different copies of the tet operator and Gal4 operator module, which simultaneously responded to a tetracycline-responsive transcription factor and a light-switchable transactivator. The activities of these chimeric promoters can be regulated by tetracycline and blue light synergistically or antagonistically. Further studies of the antagonistic genetic circuit exhibited high spatiotemporal resolution and extremely low leaky expression, which therefore could be used to spatially and stringently control the expression of highly toxic protein Diphtheria toxin A for light regulated gene therapy. When transferring plasmids engineered for the gene switch-driven expression of a firefly luciferase (Fluc) into mice, the Fluc expression levels of the treated animals directly correlated with the tetracycline and light input program. We suggest that dual-input genetic circuits using TET and light that serve as triggers to achieve expression profiles may enable the design of robust therapeutic gene circuits for gene- and cell-based therapies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Stringent Response Controls Catalases in Pseudomonas aeruginosa and Is Required for Hydrogen Peroxide and Antibiotic Tolerance

PubMed Central

Khakimova, Malika; Ahlgren, Heather G.; Harrison, Joe J.; English, Ann M.

2013-01-01

Pseudomonas aeruginosa, a human opportunistic pathogen, possesses a number of antioxidant defense enzymes under the control of multiple regulatory systems. We recently reported that inactivation of the P. aeruginosa stringent response (SR), a starvation stress response controlled by the alarmone (p)ppGpp, caused impaired antioxidant defenses and antibiotic tolerance. Since catalases are key antioxidant enzymes in P. aeruginosa, we compared the levels of H2O2 susceptibility and catalase activity in P. aeruginosa wild-type and ΔrelA ΔspoT (ΔSR) mutant cells. We found that the SR was required for optimal catalase activity and mediated H2O2 tolerance during both planktonic and biofilm growth. Upon amino acid starvation, induction of the SR upregulated catalase activity. Full expression of katA and katB also required the SR, and this regulation occurred through both RpoS-independent and RpoS-dependent mechanisms. Furthermore, overexpression of katA was sufficient to restore H2O2 tolerance and to partially rescue the antibiotic tolerance of ΔSR cells. All together, these results suggest that the SR regulates catalases and that this is an important mechanism in protecting nutrient-starved and biofilm bacteria from H2O2- and antibiotic-mediated killing. PMID:23457248

Development of the risk-based, phased-in approach for the international harmonization of the regulation of container closure systems for drugs in Taiwan.

PubMed

Chang, Lin-Chau; Kang, Jaw-Jou; Gau, Churn-Shiouh

2016-06-01

The main concern for container closure systems of drugs is to ensure suitability for the intended use which is associated with issues regarding protection, compatibility, safety, and performance. Among various concerns, leachables may pose a safety hazard to patients, while risks might vary depending on the dosage form and the administration route. Stringent regulatory authorities such as the European Medicines Agency and the United States Food and Drug Administration have established risk-based regulatory requirements and published corresponding guidelines to facilitate implementation. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes every effort to harmonize with international regulations and to strengthen protection of public health through regulatory controls. The aim of the present study was to investigate the regulatory framework and policies set by stringent regulatory authorities. The strategy proposed for the development of an eventual guideline was sent to the Taiwan Food and Drug Administration for decision. A risk-based, phased-in approach which was extensively discussed in the expert committee was proposed. The approach proposed herein could also serve as a starting point which is worth considered by other countries in which international harmonization is in process. Copyright © 2016 Elsevier Inc. All rights reserved.

The evolution and challenges for the international harmonization of the regulation of pharmaceutical excipients in Taiwan.

PubMed

Chang, Lin-Chau; Kang, Jaw-Jou; Gau, Churn-Shiouh

2015-12-01

Excipients, once considered an inert component, have been shown to greatly influence the characteristics of the drug product, such as quality and safety. Functionality-related characteristics of excipients could affect the performance of the drug product. Moreover, the impact of globalization has complicated the issue and made the supervision of supply chain highly important. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes efforts to harmonize with international regulations and to strengthen the protection of patients through regulatory controls. In order to improve the harmonization and the transparency of regulatory requirements, the aim of the present study was to investigate the regulatory framework and considerations of stringent regulatory authorities and to propose the draft regulatory requirements to the Taiwan Food and Drug Administration for jurisdiction. The proposal which was extensively discussed in the expert committee includes the regulatory considerations to ensure the safety and quality of the excipients and may serve as a platform to facilitate the communication with industries about the current thinking on related issues. Moreover, through the review of the recent guidelines published by the stringent regulatory authorities, the trend of the regulatory considerations was revealed and discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Decision-Making and Environmental Implications under Cap-and-Trade and Take-Back Regulations

PubMed Central

Chen, Yuyu; Li, Bangyi; Liu, Zhi

2018-01-01

To reduce carbon emissions during production and realize the recycling of resources, the government has promulgated carbon cap-and-trade regulation and take-back regulation separately. This paper firstly analyses the manufacturing, remanufacturing and collection decisions of a monopoly manufacturer under cap-and-trade regulation and take-back regulation conditions, and then explores the environmental impact (i.e., carbon emissions) of both carbon regulation and more stringent take-back regulation. Finally, numerical examples are provided to illustrate the theoretical results. The results indicate that it will do good for the environment once the cap-and-trade regulation is carried out. We also conclude that government’s supervision of carbon trading price plays an important role in reducing the environmental impact. Furthermore, unexpectedly, we prove that if emissions intensity of a remanufactured (vis-á-vis new) product is sufficiently high, the improvement of collection and remanufacturing targets might lead to the deterioration of environment. PMID:29617334

A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

PubMed

Abraham, John; Davis, Courtney

2005-09-01

By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

The implementation and development of complex alcohol control policies in indigenous communities in Queensland (Australia).

PubMed

Clough, Alan R; Bird, Katrina

2015-04-01

Very high rates of injury and death during the 1990s were linked with increased alcohol availability and misuse in discrete Indigenous communities in rural and remote Queensland (Australia). To address widespread concerns about a public health crisis, from 2002, the Queensland Government implemented alcohol control strategies known as 'Alcohol Management Plans' (AMPs) in 19 of these communities. Although resources for prevention and treatment were promised, AMPs became increasingly focused on local prohibition, restricted access to alcohol and punitive measures for breaching restrictions. An examination of legislation, regulations, explanatory notes, and published documents indicates this focus evolved across four phases since 2002. The first phase, from 2002 to 2004, saw 'restricted areas' with alcohol 'carriage limits' introduced, restricting the amounts and types of liquor permitted within some communities. The second phase (2002-2007) featured evaluations and reviews by the Queensland Government bringing recommendations for more stringent controls. Additionally, beyond the 'restricted areas', licenced premises situated within the 'catchments' of the targeted communities, mainly located in the nearby regional towns, became subject to 'minimising harm' provisions. These more stringent controls were implemented widely in the third phase (2008-2011) when: the operations of seven community-managed liquor outlets were terminated; the trading arrangements of two others were modified; Police powers to search and seize were increased; and 'attempting' to take liquor into a 'restricted area' also became an offence. Some communities have seen a reduction in alcohol-related harms that have been attributed to these alcohol control strategies. This commentary maps the recent regulatory history of Queensland's alcohol controls targeting discrete Indigenous communities highlighting their increasing focus on punitive measures to reduce access to alcohol. With AMPs in Queensland currently under Government review, and with community resolve for change rising, the limits to Government controls and punitive measures may have been reached. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of material improvements to mitigate the abrasive wear mechanism of concrete crosstie rail seat deterioration (RSD).

DOT National Transportation Integrated Search

2014-11-01

To meet the increasingly stringent design and performance requirements due to increasing cumulative : gross tonnages from heavy-haul freight operations, along with increased high-speed inter-city passenger : rail development, improvements in concrete...

Bacterial Cysteine-Inducible Cysteine Resistance Systems

PubMed Central

Takumi, Kazuhiro

2016-01-01

ABSTRACT Cysteine donates sulfur to macromolecules and occurs naturally in many proteins. Because low concentrations of cysteine are cytotoxic, its intracellular concentration is stringently controlled. In bacteria, cysteine biosynthesis is regulated by feedback inhibition of the activities of serine acetyltransferase (SAT) and 3-phosphoglycerate dehydrogenase (3-PGDH) and is also regulated at the transcriptional level by inducing the cysteine regulon using the master regulator CysB. Here, we describe two novel cysteine-inducible systems that regulate the cysteine resistance of Pantoea ananatis, a member of the family Enterobacteriaceae that shows great potential for producing substances useful for biotechnological, medical, and industrial purposes. One locus, designated ccdA (formerly PAJ_0331), encodes a novel cysteine-inducible cysteine desulfhydrase (CD) that degrades cysteine, and its expression is controlled by the transcriptional regulator encoded by ccdR (formerly PAJ_0332 or ybaO), located just upstream of ccdA. The other locus, designated cefA (formerly PAJ_3026), encodes a novel cysteine-inducible cysteine efflux pump that is controlled by the transcriptional regulator cefR (formerly PAJ_3027), located just upstream of cefA. To our knowledge, this is the first example where the expression of CD and an efflux pump is regulated in response to cysteine and is directly involved in imparting resistance to excess levels of cysteine. We propose that ccdA and cefA function as safety valves that maintain homeostasis when the intra- or extracellular cysteine concentration fluctuates. Our findings contribute important insights into optimizing the production of cysteine and related biomaterials by P. ananatis. IMPORTANCE Because of its toxicity, the bacterial intracellular cysteine level is stringently regulated at biosynthesis. This work describes the identification and characterization of two novel cysteine-inducible systems that regulate, through degradation and efflux, the cysteine resistance of Pantoea ananatis, a member of the family Enterobacteriaceae that shows great potential for producing substances useful for industrial purposes. We propose that this novel mechanism for sensing and regulating cysteine levels is a safety valve enabling adaptation to sudden changes in intra- or extracellular cysteine levels in bacteria. Our findings provide important insights into optimizing the production of cysteine and related biomaterials by P. ananatis and also a deep understanding of sulfur/cysteine metabolism and regulation in this plant pathogen and related bacteria. PMID:26883827

The Cost of Conscience.

PubMed

Kennett, Jeanette

2017-01-01

The spread of demands by physicians and allied health professionals for accommodation of their private ethical, usually religiously based, objections to providing care of a particular type, or to a particular class of persons, suggests the need for a re-evaluation of conscientious objection in healthcare and how it should be regulated. I argue on Kantian grounds that respect for conscience and protection of freedom of conscience is consistent with fairly stringent limitations and regulations governing refusal of service in healthcare settings. Respect for conscience does not entail that refusal of service should be cost free to the objector. I suggest that conscientious objection in medicine should be conceptualized and treated analogously to civil disobedience.

Technology innovations and experience curves for nitrogen oxides control technologies.

PubMed

Yeh, Sonia; Rubin, Edward S; Taylor, Margaret R; Hounshell, David A

2005-12-01

This paper reviews the regulatory history for nitrogen oxides (NOx) pollutant emissions from stationary sources, primarily in coal-fired power plants. Nitrogen dioxide (NO2) is one of the six criteria pollutants regulated by the 1970 Clean Air Act where National Ambient Air Quality Standards were established to protect public health and welfare. We use patent data to show that in the cases of Japan, Germany, and the United States, innovations in NOx control technologies did not occur until stringent government regulations were in place, thus "forcing" innovation. We also demonstrate that reductions in the capital and operation and maintenance (O&M) costs of new generations of high-efficiency NOx control technologies, selective catalytic reduction (SCR), are consistently associated with the increasing adoption of the control technology: the so-called learning-by-doing phenomena. The results show that as cumulative world coal-fired SCR capacity doubles, capital costs decline to approximately 86% and O&M costs to 58% of their original values. The observed changes in SCR technology reflect the impact of technological advance as well as other factors, such as market competition and economies of scale.

Dynamic regulation of six histone H3 lysine (K) methyltransferases in response to prolonged anoxia exposure in a freshwater turtle.

PubMed

Wijenayake, Sanoji; Hawkins, Liam J; Storey, Kenneth B

2018-04-05

The importance of histone lysine methylation is well established in health, disease, early development, aging, and cancer. However, the potential role of histone H3 methylation in regulating gene expression in response to extended periods of oxygen deprivation (anoxia) in a natural, anoxia-tolerant model system is underexplored. Red-eared sliders (Trachemys scripta elegans) can tolerate and survive three months of absolute anoxia and recover without incurring detrimental cellular damage, mainly by reducing the overall metabolic rate by 90% when compared to normoxia. Stringent regulation of gene expression is a vital aspect of metabolic rate depression in red-eared sliders, and as such we examined the anoxia-responsive regulation of histone lysine methylation in the liver during 5 h and 20 h anoxia exposure. Interestingly, this is the first study to illustrate the existence of histone lysine methyltransferases (HKMTs) and corresponding histone H3 lysine methylation levels in the liver of anoxia-tolerant red-eared sliders. In brief, H3K4me1, a histone mark associated with active transcription, and two corresponding histone lysine methyltransferases that modify H3K4me1 site, significantly increased in response to anoxia. On the contrary, H3K27me1, another transcriptionally active histone mark, significantly decreased during 20 h anoxia, and a transcriptionally repressive histone mark, H3K9me3, and the corresponding KMTs, similarly increased during 20 h anoxia. Overall, the results suggest a dynamic regulation of histone H3 lysine methylation in the liver of red-eared sliders that could theoretically aid in the selective upregulation of genes that are necessary for anoxia survival, while globally suppressing others to conserve energy. Copyright © 2018 Elsevier B.V. All rights reserved.

Design and Optimisation of Electrostatic Precipitator for Diesel Exhaust

NASA Astrophysics Data System (ADS)

Srinivaas, A.; Sathian, Samanyu; Ramesh, Arjun

2018-02-01

The principle of an industrially used emission reduction technique is employed in automotive diesel exhaust to reduce the diesel particulate emission. As the Emission regulation are becoming more stringent legislations have been formulated, due to the hazardous increase in the air quality index in major cities. Initially electrostatic precipitation principle and working was investigated. The High voltage requirement in an Electrostatic precipitator is obtained by designing an appropriate circuit in MATLAB -SIMULINK. Mechanical structural design of the new model after treatment device for the specific diesel exhaust was done. Fluid flow analysis of the ESP model was carried out using ANSYS CFX for optimized fluid with a reduced back pressure. Design reconsideration was done in accordance with fluid flow analysis. Accordingly, a new design is developed by considering diesel particulate filter and catalytic converter design to ESP model.

Electron treatment of wood pulp for the viscose process

NASA Astrophysics Data System (ADS)

Stepanik, T. M.; Ewing, D. E.; Whitehouse, R.

2000-03-01

Electron processing is currently being evaluated by several viscose producers for integration into their process. The viscose industry converts dissolving wood pulp into products such as staple fibre, filament, cord, film, packaging, and non-edible sausage casings. These materials are used in the clothing, drapery, hygiene, automobile, food, and packaging industries. Viscose producers are facing increasingly high production costs and stringent environmental regulations that have forced some plants to close. Electron treatment of wood pulp can significantly reduce the amounts of chemicals used for producing viscose and the production of hazardous pollutants. Acsion Industries has worked with companies worldwide to demonstrate the benefits of using electron treated pulp for producing viscose (rayon). This paper describes the viscose process, the benefits of using electron treatment in the viscose process, and Acsion's efforts in developing this technology.

Regulatory environment and claims - limits and opportunities.

PubMed

Martin, Ambroise

2010-01-01

During the past decade, the use of claims became more and more important in many countries in relation to the increased awareness of consumer about the link between foods and health, offering to industry a valuable opportunity to differentiate and valorize their products and to promote innovation. However, more and more stringent regulations are developed, all based on the general principles adopted by the Codex Alimentarius Commission. In addition to the different regulatory processes and administrative requirements according to the country, the high level (and cost) of scientific substantiation of claims, the constraints introduced by nutrient profiles and the poor knowledge of the impact on consumer depending on the cultural contexts may limit these opportunities or, at least complicate their use. All these issues are briefly analyzed, highlighting some striking convergences and differences between countries. Copyright © 2010 S. Karger AG, Basel.

Portable pilot plant for evaluating marine biofouling growth and control in heat exchangers-condensers.

PubMed

Casanueva, J F; Sánchez, J; García-Morales, J L; Casanueva-Robles, T; López, J A; Portela, J R; Nebot, E; Sales, D

2003-01-01

Biofouling frequently involves a serious impediment to achieving optimum operating conditions in heat exchangers-condensers. The economic coat and energy losses associated with this phenomenon are significant and the environmental impact of biocides must satisfy stringent regulations. A portable pilot plant has been designed in order to carry out in-situ experimental study as biofilm is formed under thermal and hydrodynamically controlled conditions. The pilot plant has an automatic monitoring, control and data acquisition system, which automatically processes data from indirect measure of fouling in terms of increased fluid frictional and heat transfer resistances. A particular method is used and proposed for direct measuring and biofilm characterization. Once we know the actual film thickness, we can calculate the effective thermal conductivity of the layer by using the appropriate heat transfer equations.

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

Lee, J.W.; Hwang, K.J.; Shim, W.G.

Regulations on the removal of trinitrotoluene (TNT) from wastewater have become increasingly more stringent, demanding faster, less expensive, and more efficient treatment. This study focuses on the adsorption equilibrium and kinetics of TNT on powered activated carbons (PAC). Three types of PACs (i.e., wood based, coal based, and coconut-shell based) were studied as functions of temperature and pH. Thermodynamic properties including Gibbs free energy, enthalpy, and entropy, were evaluated by applying the Van't Hoff equation. In addition, the adsorption energy distribution functions which describe heterogeneous characteristics of porous solid sorbents were calculated by using the generalized nonlinear regularization method. Adsorptionmore » kinetic studies were carried out in batch adsorber under important conditions such as PAC types, temperature, pH, and concentration. We found that fast and efficient removal of TNT dissolved in water can be successfully achieved by PAC adsorption.« less

Issues of environmental compliance in developing countries.

PubMed

Singh, S; Rajamani, S

2003-01-01

Environmental laws define the scarcity of environmental resources as they affect the factor endowment of a country and therefore its position in the international division of labour. There is now also a general agreement that applying the "polluter pays" principle should solve environmental problems. As the burden of abatement increases, as measured by the ratio of abatement expenditure to sales, there is definitely an incentive for firms to either invest in cleaner technology or more efficient abatement technology. There is also evidence that taxes and charges, designed to internalise externalities, can actually affect trade. It is interesting to know if the developing countries face particular market access problems in the face of stringent environmental standards and regulations. While it is true that stringent measures impose market access restrictions and cause limitations on competitiveness, this is much more widely felt by the developing countries because of lack of infrastructure and monitoring facilities, limited technology choices, inadequate access to environment-friendly raw materials, lack of complete information, presence of small-scale exporters and emergence of environmental standards in sectors of export interest to developing countries. The small and medium enterprises often divert sales either to the domestic market or to external markets where environmental requirements are less stringent, in order to save on their costs. In developing countries, 80% of the tanning industry is comprised of small and medium enterprises (SMEs) processing raw to semi-finished leather, usually less than 2 tons per day. In Europe and other developed countries the SMEs in the leather sector have vanished due to strict environmental legislation and this will likely occur in developing countries also. The environmental legislation has not always been practical, either because the laws are too ambitious or unrealistic in certain parameters, or because they have lacked effective instrumentation and institutional support. Some environmental regulations have not succeeded as they do not match the technical requirements and economic reality of the country or region, or because they do not take the institutional capabilities of the society that has to implement them into consideration. For the survival and sustenance of the SMEs in the leather industry, it may be a viable alternative to carry out the tanning process in a decentralized fashion such that the raw to semi-finished process is carried out in the large scale sector while the semi-finished to finished process could either be reserved or open to competition as per the countries' requirements. But the issue of concern is whether it is fair that the raw to semi-finished tanning process, containing 70% of the pollution discharge should be undertaken by developing countries alone, especially if it is at the cost of their survival! However, the game analysed in the paper reveals that tanning units in developing countries would prefer to comply with the regulations and stay in the industry, the alternatives being to collude or to compete!

Systems biology of stored blood cells: can it help to extend the expiration date?

PubMed

Paglia, Giuseppe; Palsson, Bernhard Ø; Sigurjonsson, Olafur E

2012-12-05

With increasingly stringent regulations regarding deferral and elimination of blood donors it will become increasingly important to extend the expiration date of blood components beyond the current allowed storage periods. One reason for the storage time limit for blood components is that platelets and red blood cells develop a condition called storage lesions during their storage in plastic blood containers. Systems biology provides comprehensive bio-chemical descriptions of organisms through quantitative measurements and data integration in mathematical models. The biological knowledge for a target organism can be translated in a mathematical format and used to compute physiological properties. The use of systems biology represents a concrete solution in the study of blood cell storage lesions, and it may open up new avenues towards developing better storage methods and better storage media, thereby extending the storage period of blood components. This article is part of a Special Issue entitled: Integrated omics. Copyright © 2012 Elsevier B.V. All rights reserved.

A large shRNA library approach identifies lncRNA Ntep as an essential regulator of cell proliferation

PubMed Central

Beermann, Julia; Kirste, Dominique; Iwanov, Katharina; Lu, Dongchao; Kleemiß, Felix; Kumarswamy, Regalla; Schimmel, Katharina; Bär, Christian; Thum, Thomas

2018-01-01

The mammalian cell cycle is a complex and tightly controlled event. Myriads of different control mechanisms are involved in its regulation. Long non-coding RNAs (lncRNA) have emerged as important regulators of many cellular processes including cellular proliferation. However, a more global and unbiased approach to identify lncRNAs with importance for cell proliferation is missing. Here, we present a lentiviral shRNA library-based approach for functional lncRNA profiling. We validated our library approach in NIH3T3 (3T3) fibroblasts by identifying lncRNAs critically involved in cell proliferation. Using stringent selection criteria we identified lncRNA NR_015491.1 out of 3842 different RNA targets represented in our library. We termed this transcript Ntep (non-coding transcript essential for proliferation), as a bona fide lncRNA essential for cell cycle progression. Inhibition of Ntep in 3T3 and primary fibroblasts prevented normal cell growth and expression of key fibroblast markers. Mechanistically, we discovered that Ntep is important to activate P53 concomitant with increased apoptosis and cell cycle blockade in late G2/M. Our findings suggest Ntep to serve as an important regulator of fibroblast proliferation and function. In summary, our study demonstrates the applicability of an innovative shRNA library approach to identify long non-coding RNA functions in a massive parallel approach. PMID:29099486

Impact of California firearms sales laws and dealer regulations on the illegal diversion of guns.

PubMed

Pierce, Glenn L; Braga, Anthony A; Wintemute, Garen J

2015-06-01

The available evidence suggests that more restrictive state firearm sales laws can reduce criminal access to guns. California has firearm-related laws that are more stringent than many other states and regulates its retail firearms dealers to a unique degree. This research seeks to examine the effect of more restrictive state gun laws and regulations on the illegal diversion of guns to criminals. Survival analyses are used to determine whether state firearm sales laws, particularly California's legal context and regulatory regime, impact the distribution of time-to-crime of recovered firearms in that state relative to other US states. USA. 225,392 traced firearms, where the first retail purchasers and the gun possessors were different individuals, recovered by law enforcement agencies between 2003 and 2006. The increased stringency of state-level firearms laws and regulations leads to consistently older firearms being recovered. California was associated with the oldest recovered crime guns compared with guns associated with other states. These patterns persisted regardless of whether firearms were first purchased within the recovery state or in another state. These findings suggest that more restrictive gun sales laws and gun dealer regulations do make it more difficult for criminals to acquire new guns first purchased at retail outlets. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Serious Mental Illness and Nursing Home Quality of Care

PubMed Central

Rahman, Momotazur; Grabowski, David C; Intrator, Orna; Cai, Shubing; Mor, Vincent

2013-01-01

Objective To estimate the effect of a nursing home's share of residents with a serious mental illness (SMI) on the quality of care. Data Sources Secondary nursing home level data over the period 2000 through 2008 obtained from the Minimum Data Set, OSCAR, and Medicare claims. Study Design We employ an instrumental variables approach to address the potential endogeneity of the share of SMI residents in nursing homes in a model including nursing home and year fixed effects. Principal Findings An increase in the share of SMI nursing home residents positively affected the hospitalization rate among non-SMI residents and negatively affected staffing skill mix and level. We did not observe a statistically significant effect on inspection-based health deficiencies or the hospitalization rate for SMI residents. Conclusions Across the majority of indicators, a greater SMI share resulted in lower nursing home quality. Given the increased prevalence of nursing home residents with SMI, policy makers and providers will need to adjust practices in the context of this new patient population. Reforms may include more stringent preadmission screening, new regulations, reimbursement changes, and increased reporting and oversight. PMID:23278400

Avoiding Title V permitting pitfalls

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

Laswell, D.L.

1993-04-01

Title V of the 1990 Clean Air Act Amendments requires states to implement new air operating permit programs. States have a great deal of flexibility in developing their permit programs. Industry should work now to ensure that state programs contain the favorable aspects of the federal regulations and do not contain more stringent requirements that are not required under the Clean Air Act. This article outlines areas of the permit program that have the potential to handicap industry`s ability to expand.

Oral bioaccessibility testing and read-across hazard assessment of nickel compounds.

PubMed

Henderson, Rayetta G; Cappellini, Danielle; Seilkop, Steven K; Bates, Hudson K; Oller, Adriana R

2012-06-01

In vitro metal ion bioaccessibility, as a measure of bioavailability, can be used to read-across toxicity information from data-rich, source substances to data-poor, target substances. To meet the data requirements for oral systemic toxicity endpoints under the REACH Regulation in Europe, 12 nickel substances underwent bioaccessibility testing in stomach and intestinal fluids. A read-across paradigm was developed based on the correlation between gastric bioaccessibility and in vivo acute oral toxicity. The oral LD₅₀ values were well predicted by nickel release (R² = 0.91). Samples releasing <48% available nickel (mgNi released/mg available Ni × 100) are predicted to have an LD₅₀ > 2000 mg/kg; while samples releasing > 76% available nickel are expected to have an LD₅₀ between 300 and 2000 mg/kg. The hazard classifications (European Regulation on Classification, Labelling and Packaging of Chemical Substances and Mixtures) for all oral systemic endpoints were evaluated based on read-across from three source nickel compounds (sulfate, subsulfide, oxide). Samples releasing < 48% available nickel were read-across from nickel oxides and subsulfide. Samples releasing > 76% Ni were read-across from nickel sulfate. This assessment suggests that nickel chloride and dihydroxide should be less stringently classified and nickel sulfamate should receive a more stringent classification for oral systemic endpoints than currently assigned. Copyright © 2012 Elsevier Inc. All rights reserved.

Serine phosphorylation by SYK is critical for nuclear localization and transcription factor function of Ikaros

PubMed Central

Uckun, Fatih M.; Ma, Hong; Zhang, Jian; Ozer, Zahide; Dovat, Sinisa; Mao, Cheney; Ishkhanian, Rita; Goodman, Patricia; Qazi, Sanjive

2012-01-01

Ikaros is a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis through transcriptional regulation of the earliest stages of lymphocyte ontogeny and differentiation. Functional deficiency of Ikaros has been implicated in the pathogenesis of acute lymphoblastic leukemia, the most common form of childhood cancer. Therefore, a stringent regulation of Ikaros activity is considered of paramount importance, but the operative molecular mechanisms responsible for its regulation remain largely unknown. Here we provide multifaceted genetic and biochemical evidence for a previously unknown function of spleen tyrosine kinase (SYK) as a partner and posttranslational regulator of Ikaros. We demonstrate that SYK phoshorylates Ikaros at unique C-terminal serine phosphorylation sites S358 and S361, thereby augmenting its nuclear localization and sequence-specific DNA binding activity. Mechanistically, we establish that SYK-induced Ikaros activation is essential for its nuclear localization and optimal transcription factor function. PMID:23071339

Integration of multiple stimuli-sensing systems to regulate HrpS and type III secretion system in Erwinia amylovora.

PubMed

Lee, Jae Hoon; Zhao, Youfu

2018-02-01

The bacterial enhancer binding protein (bEBP) HrpS is essential for Erwinia amylovora virulence by activating the type III secretion system (T3SS). However, how the hrpS gene is regulated remains poorly understood in E. amylovora. In this study, 5' rapid amplification of cDNA ends and promoter deletion analyses showed that the hrpS gene contains two promoters driven by HrpX/HrpY and the Rcs phosphorelay system, respectively. Electrophoretic mobility shift and gene expression assays demonstrated that integration host factor IHF positively regulates hrpS expression through directly binding the hrpX promoter and positively regulating hrpX/hrpY expression. Moreover, hrpX expression was down-regulated in the relA/spoT ((p)ppGpp-deficient) mutant and the dksA mutant, but up-regulated when the wild-type strain was treated with serine hydroxamate, which induced (p)ppGpp-mediated stringent response. Furthermore, the csrA mutant showed significantly reduced transcripts of major hrpS activators, including the hrpX/hrpY, rcsA and rcsB genes, indicating that CsrA is required for full hrpS expression. On the other hand, the csrB mutant exhibited up-regulation of the rcsA and rcsB genes, and hrpS expression was largely diminished in the csrB/rcsB mutant, indicating that the Rcs system is mainly responsible for the increased hrpS expression in the csrB mutant. These findings suggest that E. amylovora recruits multiple stimuli-sensing systems, including HrpX/HrpY, the Rcs phosphorelay system and the Gac-Csr system, to regulate hrpS and T3SS gene expression.

Environmental Life Cycle Assessment and Cost Analysis of Bath, NY Wastewater Treatment Plant: Potential Upgrade Implications

EPA Science Inventory

Many communities across the U.S. are required to upgrade wastewater treatment plants (WWTP) to meet increasingly stringent nutrient effluent standards. However, increased capital, energy and chemical requirements of upgrades create potential trade-offs between eutrophication pot...

Environmental policy constraints for acidic exhaust gas scrubber discharges from ships.

PubMed

Ülpre, H; Eames, I

2014-11-15

Increasingly stringent environmental legislation on sulphur oxide emissions from the combustion of fossil fuels onboard ships (International Maritime Organization (IMO) Regulation 14) can be met by either refining the fuel to reduce sulphur content or by scrubbing the exhaust gases. Commonly used open loop marine scrubbers discharge warm acidic exhaust gas wash water into the sea, depressing its pH. The focus on this paper is on the physics and chemistry behind the disposal of acidic discharges in seawater. The IMO Marine Environment Protection Committee (MEPC 59/24/Add.1 Annex 9) requires the wash water to reach a pH greater than 6.5 at a distance of 4m from the point of discharge. We examine the engineering constraints, specifically size and number of ports, to identify the challenges of meeting regulatory compliance. Copyright © 2014. Published by Elsevier Ltd.

Microbiological and biochemical spoilage of smoke-dried fishes sold in West African open markets.

PubMed

Ikutegbe, Victoria; Sikoki, Francis

2014-10-15

Proximate composition and microbiological characteristics of pre-dried Chrysichthys nigrodigitatus and Pseudotolithus typus were studied over a period of 4weeks to determine the health risks associated with delayed consumption. All analyses were conducted using standard microbiological and chemical methods. Results showed a general decline in microbiological safety and nutritive characteristics of both fish species over time, with an observed increase in microbial loads over time. Aspergillus flavus was also present on both species which makes consumption of the fishes hazardous to the health of consumers due to its ability to produce carcinogenic aflatoxins. In order to minimise the health risks to consumers, it is recommended that smoke-dried fishes be consumed with minimal delay and cooked properly before consumption. The findings of this study will prove important in the development of more stringent regulations regarding food safety in Nigeria. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nutrient Removal and Resource Recovery: Effect on Life Cycle Cost and Environmental Impacts of Small Scale Wastewater Treatment

EPA Science Inventory

Many communities across the U.S. are required to upgrade wastewater treatment plants (WWTP) to meet increasingly stringent nutrient effluent standards. However, increased capital, energy and chemical requirements of upgrades create potential trade-offs between eutrophication pote...

Gene-Editing: Interpretation of Current Law and Legal Policy.

PubMed

Kim, Na-Kyoung

2017-09-01

With the development of the third-generation gene scissors, CRISPR-Cas9, concerns are being raised about ethical and social repercussions of the new gene-editing technology. In this situation, this article explores the legislation and interpretation of the positive laws in South Korea. The BioAct does not specify and regulate 'gene editing' itself. However, assuming that genetic editing is used in the process of research and treatment, we can look to the specific details of the regulations for research on humans as well as gene therapy research in order to see how genetic editing is regulated under the BioAct. BioAct differentiates the regulation between (born) humans and embryos etc. and the regulation differ entirely in the manner and scope. Moreover, due to the fact that gene therapy products are regarded as drugs, they fall under different regulations. The Korean Pharmacopoeia Act put stringent sanctions on clinical trials for gene therapy products and the official Notification "Approval and Examination Regulations for Biological Products, etc." by Food and Drug Safety Administration may be applied to gene editing for gene therapy purposes.

cGMP Signaling in the Cardiovascular System—The Role of Compartmentation and Its Live Cell Imaging

PubMed Central

Bork, Nadja I.; Nikolaev, Viacheslav O.

2018-01-01

The ubiquitous second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time cGMP measurements with a specific focus on live cell imaging methods. We will also discuss currently accepted and emerging mechanisms of cGMP compartmentation in the cardiovascular system. PMID:29534460

Structural integrity and containment aspects of small gas turbine engines

NASA Astrophysics Data System (ADS)

Gupta, S. S.; Gomuc, R.

1994-03-01

Structural integrity of rotating components in gas turbine engines is very crucial since their failure implies high impact energy, which, if uncontained, could mean damage to aircraft structures, controls, and so forth, and, in the worst scenario, even loss of lives. This final consequence has led to very stringent airworthiness regulations for engine/aircraft certifications. This paper discusses the historical statistics of noncontainment events in turbofans, turboprops, and turboshafts and shows how the damage severity varies between different applications and how changes to regulations are continuing in order to improve the reliability of aircraft/rotorcraft. The paper also presents design challenges resulting from the analysis complexity of containment/noncontainment event and the way Pratt & Whitney Canada design/analysis/test system caters to all the requirements. The weight and cost impact of possible changes to current regulations are also presented.

Influence of the stringent control system on the transcription of ribosomal ribonucleic acid and ribosomal protein genes in Escherichia coli.

PubMed Central

Dennis, P P

1977-01-01

The fraction of the total ribonucleic acid (RNA) synthesis rate that is messenger RNA (mRNA) for ribosomal protein (r-protein) and ribosomal RNA (rRNA) has been estimated in valS(Ts) rel+ stringent and valS(Ts) relA1 relaxed strains of Escherichia coli during a partial inhibition of valyl-transfer RNA aminoacylation. The partial inhibition was accomplished by shifting the strains from the permissive growth temperature of 29.5 degrees C to the semipermissive temperature of 35.5 degrees C. The RNA synthesized at the elevated temperature was pulse labeled with [3H]uracil. The fraction of the total incorpoarted 3H radioactivity in r-protein mRNA or in rRNA was estimated by specific hybridization to the transducing phages gammaspc1, which carries about 15 r-protein genes and lambdailv5, which carries an rRNA transcription unit. The results clearly demonstrate that the rel gene influences the fraction of the total RNA synthesis rate that is r protein mRNA and rRNA; in the rel+ strain they are significantly increased relative to control cultures. This indicates that the expression of the genes coding for the RNA and protein component of the ribosome are most likely regulated at the level of transcription. Furthermore, it appears that the distribution of functioning RNA polymerase between rRNA genes, r-protein genes, and other types of genes is influenced by the rel gene control system; presumably this influence is mediated through the unusual nucleotide guanosine tetraphosphate. PMID:320185

Regulated and unregulated emissions from modern 2010 emissions-compliant heavy-duty on-highway diesel engines.

PubMed

Khalek, Imad A; Blanks, Matthew G; Merritt, Patrick M; Zielinska, Barbara

2015-08-01

The U.S. Environmental Protection Agency (EPA) established strict regulations for highway diesel engine exhaust emissions of particulate matter (PM) and nitrogen oxides (NOx) to aid in meeting the National Ambient Air Quality Standards. The emission standards were phased in with stringent standards for 2007 model year (MY) heavy-duty engines (HDEs), and even more stringent NOX standards for 2010 and later model years. The Health Effects Institute, in cooperation with the Coordinating Research Council, funded by government and the private sector, designed and conducted a research program, the Advanced Collaborative Emission Study (ACES), with multiple objectives, including detailed characterization of the emissions from both 2007- and 2010-compliant engines. The results from emission testing of 2007-compliant engines have already been reported in a previous publication. This paper reports the emissions testing results for three heavy-duty 2010-compliant engines intended for on-highway use. These engines were equipped with an exhaust diesel oxidation catalyst (DOC), high-efficiency catalyzed diesel particle filter (DPF), urea-based selective catalytic reduction catalyst (SCR), and ammonia slip catalyst (AMOX), and were fueled with ultra-low-sulfur diesel fuel (~6.5 ppm sulfur). Average regulated and unregulated emissions of more than 780 chemical species were characterized in engine exhaust under transient engine operation using the Federal Test Procedure cycle and a 16-hr duty cycle representing a wide dynamic range of real-world engine operation. The 2010 engines' regulated emissions of PM, NOX, nonmethane hydrocarbons, and carbon monoxide were all well below the EPA 2010 emission standards. Moreover, the unregulated emissions of polycyclic aromatic hydrocarbons (PAHs), nitroPAHs, hopanes and steranes, alcohols and organic acids, alkanes, carbonyls, dioxins and furans, inorganic ions, metals and elements, elemental carbon, and particle number were substantially (90 to >99%) lower than pre-2007-technology engine emissions, and also substantially (46 to >99%) lower than the 2007-technology engine emissions characterized in the previous study.

US major crops’ uncertain climate change risks and greenhouse gas mitigation benefits

DOE PAGES

Wing, Ian Sue; Monier, Erwan; Stern, Ari; ...

2015-10-28

In this study, we estimate the costs of climate change to US agriculture, and associated potential benefits of abating greenhouse gas emissions. Five major crops' yield responses to climatic variation are modeled empirically, and the results combined with climate projections for a no-policy, high-warming future, as well as moderate and stringent mitigation scenarios. Unabated warming reduces yields of wheat and soybeans by 2050, and cotton by 2100, but moderate warming increases yields of all crops except wheat. Yield changes are monetized using the results of economic simulations within an integrated climate-economy modeling framework. Uncontrolled warming's economic effects on major cropsmore » are slightly positive—annual benefits <$4 B. These are amplified by emission reductions, but subject to diminishing returns—by 2100 reaching $17 B under moderate mitigation, but only $7 B with stringent mitigation. Costs and benefits are sensitive to irreducible uncertainty about the fertilization effects of elevated atmospheric carbon dioxide, without which unabated warming incurs net costs of up to $18 B, generating benefits to moderate (stringent) mitigation as large as $26 B ($20 B).« less

US major crops’ uncertain climate change risks and greenhouse gas mitigation benefits

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

Wing, Ian Sue; Monier, Erwan; Stern, Ari

In this study, we estimate the costs of climate change to US agriculture, and associated potential benefits of abating greenhouse gas emissions. Five major crops' yield responses to climatic variation are modeled empirically, and the results combined with climate projections for a no-policy, high-warming future, as well as moderate and stringent mitigation scenarios. Unabated warming reduces yields of wheat and soybeans by 2050, and cotton by 2100, but moderate warming increases yields of all crops except wheat. Yield changes are monetized using the results of economic simulations within an integrated climate-economy modeling framework. Uncontrolled warming's economic effects on major cropsmore » are slightly positive—annual benefits <$4 B. These are amplified by emission reductions, but subject to diminishing returns—by 2100 reaching $17 B under moderate mitigation, but only $7 B with stringent mitigation. Costs and benefits are sensitive to irreducible uncertainty about the fertilization effects of elevated atmospheric carbon dioxide, without which unabated warming incurs net costs of up to $18 B, generating benefits to moderate (stringent) mitigation as large as $26 B ($20 B).« less

Modeling determinants of growth: evidence for a community-based target in height?

PubMed

Aßmann, Christian; Hermanussen, Michael

2013-07-01

Human growth is traditionally envisaged as a target-seeking process regulated by genes, nutrition, health, and the state of an individual's social and economic environment; it is believed that under optimal physical conditions, an individual will achieve his or her full genetic potential. Using a panel data set on individual height increments, we suggest a statistical modeling approach that characterizes growth as first-order trend stationary and allows for controlling individual growth tempo via observable measures of individual maturity. A Bayesian framework and corresponding Markov-chain Monte Carlo techniques allowing for a conceptually stringent treatment of missing values are adapted for parameter estimation. The model provides evidence for the adjustment of the individual growth rate toward average height of the population. The increase in adult body height during the past 150 y has been explained by the steady improvement of living conditions that are now being considered to have reached an optimum in Western societies. The current investigation questions the notion that the traditional concept in the understanding of this target-seeking process is sufficient. We consider an additional regulator that possibly points at community-based target seeking in growth.

Evaluating the effectiveness of air quality interventions.

PubMed

van Erp, Annemoon M M; O'Keefe, Robert; Cohen, Aaron J; Warren, Jane

2008-01-01

Evaluating the extent to which air quality regulations improve public health--sometimes referred to as accountability--is part of an emerging effort to assess the effectiveness of environmental regulatory policies. Air quality has improved substantially in the United States and Western Europe in recent decades, with far less visible pollution and decreasing concentrations of several major pollutants. In large part, these gains were achieved through increasingly stringent air quality regulations. The costs associated with compliance and, importantly, the need to ensure that the regulations are achieving the intended public health benefits underscore the importance of accountability research. To date, accountability research has emphasized measuring the effects of actions already taken to improve air quality. Such research may also contribute to estimating the burden of disease that might be avoided in the future if certain actions are taken. The Health Effects Institute (HEI) currently funds eight ongoing studies on accountability, which cover near-term interventions to improve air quality including (1) a ban on the sale of coal, (2) replacing old wood stoves with cleaner ones, (3) decreasing sulfur content in fuel, (4) measures to reduce traffic, and (5) longer term, wide-ranging actions or events (such as complex changes associated with the reunification of Germany). HEI is also funding the development of methods and research to assess regulations that are implemented incrementally over extended periods of time, such as Title IV of the 1990 Clean Air Act Amendments, which reduces sulfur dioxide emissions from power plants in the eastern United States.

Toward a workable biosafety system for regulating genetically modified organisms in Ethiopia: balancing conservation and competitiveness.

PubMed

Abraham, Adane

2013-01-01

On September 9, 2009, Ethiopia enacted a highly restrictive biosafety law firmly based on precautionary principles as a foundation for its GMO regulation system. Its drafting process, led by the country's Environmental Protection Authority, was judged as biased, focusing only on protecting the environment from perceived risks, giving little attention to potential benefits of GMOs. Many of its provisions are very stringent, exceeding those of Cartagena Protocol on Biosafety, while others cannot be fulfilled by applicants, collectively rendering the emerged biosafety system unworkable. These provisions include requirements for advance informed agreement and rigorous socioeconomic assessment in risk evaluation for all GMO transactions, including contained research use-which requires the head of the competent national authority of the exporting country to take full responsibility for GMO-related information provided-and stringent labeling, insurance and monitoring requirements for all GMO activities. Furthermore, there is no provision to establish an independent national biosafety decision-making body(ies). As a result, foreign technology owners that provide highly demanded technologies like Bt cotton declined to work with Ethiopia. There is a fear that the emerged biosafety system might also continue to suppress domestic genetic engineering research and development. Thus, to benefit from GMOs, Ethiopia has to revise its biosafety system, primarily by making changes to some provisions of the law in a way that balances its diverse interests of conserving biodiversity, protecting the environment and enhancing competition in agricultural and other economic sectors.

Roles of relSpn in Stringent Response, Global Regulation, and Virulence of Serotype 2 Streptococcus pneumoniae D39

PubMed Central

Kazmierczak, Krystyna M.; Wayne, Kyle J.; Rechtsteiner, Andreas; Winkler, Malcolm E.

2009-01-01

Summary RelA/ SpoT homolog (RSH) proteins have (p)ppGpp synthetase and hydrolase activities that mediate major global responses to nutrient limitation and other stresses. RSH proteins are conserved in most bacteria and play diverse roles in bacterial pathogenesis. We report here that the RSH protein of S. pneumoniae, RelSpn, can be deleted and is the primary source of (p)ppGpp synthesis in virulent strain D39 under some conditions. A D39 ΔrelSpn mutant grew well in complex medium, but did not grow in chemically defined medium unless supplemented with the metals copper and manganese. Transcriptome analysis of D39 rel+Spn and ΔreSpn strains treated with mupirocin revealed relSpn-independent (translation stress), relSpn-dependent (stringent response), and ΔrelSpn-dependent changes suggesting that relSpn and (p)ppGpp amount play wide-ranging homeostatic roles in pneumococcal physiology, besides adjusting macromolecular synthesis and transport in response to nutrient availability. Notably, the relSpn-dependent response included significant up-regulation of the ply operon encoding pneumolysin toxin, whereas the ΔrelSpn-dependent response affected expression linked to the VicRK and CiaRH two component systems. Finally, a D39 ΔrelSpn mutant was severely attenuated and displayed a significantly altered course of disease progression in a mouse model of infection, which was restored to normal by an ectopic copy of rel+Spn. PMID:19426208

A predictive analysis of CO2 emissions, environmental policy stringency, and economic growth in China.

PubMed

Ahmed, Khalid; Ahmed, Sidrah

2018-03-28

This study takes environmental policy stringency and economic activity as the controlling variables and forecasts the CO 2 emissions in China up to 2022. In doing so, an application of corrected grey model with convolution is used over the annual time series data between 1990 and 2012. The simulation results show that (1) between 2012 and 2022, CO 2 emissions in China is expected to increase at an average rate of 17.46% annually, raising the emissions intensity from 7.04 in 2012 to 25.461 metric tons per capita by 2022; (2) stringent environmental policies reduce CO 2 emissions-whereas, GDP tends to increase the emissions intensity in China; (3) stringent environmental policies are found to have a negative impact on GDP in China. Based on the empirical findings, the study also provides some policy suggestions to reduce emissions intensity in China.

Irrigation Water Quality for Leafy Crops: A Perspective of Risks and Potential Solutions

PubMed Central

Allende, Ana; Monaghan, James

2015-01-01

There is increasing evidence of the contribution of irrigation water in the contamination of produce leading to subsequent outbreaks of foodborne illness. This is a particular risk in the production of leafy vegetables that will be eaten raw without cooking. Retailers selling leafy vegetables are increasingly targeting zero-risk production systems and the associated requirements for irrigation water quality have become more stringent in regulations and quality assurance schemes (QAS) followed by growers. Growers can identify water sources that are contaminated with potential pathogens through a monitoring regime and only use water free of pathogens, but the low prevalence of pathogens makes the use of faecal indicators, particularly E. coli, a more practical approach. Where growers have to utilise water sources of moderate quality, they can reduce the risk of contamination of the edible portion of the crop (i.e., the leaves) by treating irrigation water before use through physical or chemical disinfection systems, or avoid contact between the leaves and irrigation water through the use of drip or furrow irrigation, or the use of hydroponic growing systems. This study gives an overview of the main problems in the production of leafy vegetables associated with irrigation water, including microbial risk and difficulties in water monitoring, compliance with evolving regulations and quality standards, and summarises the current alternatives available for growers to reduce microbial risks. PMID:26151764

Irrigation Water Quality for Leafy Crops: A Perspective of Risks and Potential Solutions.

PubMed

Allende, Ana; Monaghan, James

2015-07-03

There is increasing evidence of the contribution of irrigation water in the contamination of produce leading to subsequent outbreaks of foodborne illness. This is a particular risk in the production of leafy vegetables that will be eaten raw without cooking. Retailers selling leafy vegetables are increasingly targeting zero-risk production systems and the associated requirements for irrigation water quality have become more stringent in regulations and quality assurance schemes (QAS) followed by growers. Growers can identify water sources that are contaminated with potential pathogens through a monitoring regime and only use water free of pathogens, but the low prevalence of pathogens makes the use of faecal indicators, particularly E. coli, a more practical approach. Where growers have to utilise water sources of moderate quality, they can reduce the risk of contamination of the edible portion of the crop (i.e., the leaves) by treating irrigation water before use through physical or chemical disinfection systems, or avoid contact between the leaves and irrigation water through the use of drip or furrow irrigation, or the use of hydroponic growing systems. This study gives an overview of the main problems in the production of leafy vegetables associated with irrigation water, including microbial risk and difficulties in water monitoring, compliance with evolving regulations and quality standards, and summarises the current alternatives available for growers to reduce microbial risks.

Contribution of Wastewater Treatment Plant Effluents to Nutrient Dynamics in Aquatic Systems: A Review

NASA Astrophysics Data System (ADS)

Carey, Richard O.; Migliaccio, Kati W.

2009-08-01

Excessive nutrient loading (considering nitrogen and phosphorus) is a major ongoing threat to water quality and here we review the impact of nutrient discharges from wastewater treatment plants (WWTPs) to United States (U.S.) freshwater systems. While urban and agricultural land uses are significant nonpoint nutrient contributors, effluent from point sources such as WWTPs can overwhelm receiving waters, effectively dominating hydrological characteristics and regulating instream nutrient processes. Population growth, increased wastewater volumes, and sustainability of critical water resources have all been key factors influencing the extent of wastewater treatment. Reducing nutrient concentrations in wastewater is an important aspect of water quality management because excessive nutrient concentrations often prevent water bodies from meeting designated uses. WWTPs employ numerous physical, chemical, and biological methods to improve effluent water quality but nutrient removal requires advanced treatment and infrastructure that may be economically prohibitive. Therefore, effluent nutrient concentrations vary depending on the particular processes used to treat influent wastewater. Increasingly stringent regulations regarding nutrient concentrations in discharged effluent, along with greater freshwater demand in populous areas, have led to the development of extensive water recycling programs within many U.S. regions. Reuse programs provide an opportunity to reduce or eliminate direct nutrient discharges to receiving waters while allowing for the beneficial use of reclaimed water. However, nutrients in reclaimed water can still be a concern for reuse applications, such as agricultural and landscape irrigation.

Review of the state-of-the-art of exhaust particulate filter technology in internal combustion engines.

PubMed

Guan, Bin; Zhan, Reggie; Lin, He; Huang, Zhen

2015-05-01

The increasingly stringent emission regulations, such as US 2010, Tier 2 Bin 5 and beyond, off-road Tier 4 final, and Euro V/5 for particulate matter (PM) reduction applications, will mandate the use of the diesel particulate filters (DPFs) technology, which is proven to be the only way that can effectively control the particulate emissions. This paper covers a comprehensive overview of the state-of-the-art DPF technologies, including the advanced filter substrate materials, the novel catalyst formulations, the highly sophisticated regeneration control strategies, the DPF uncontrolled regenerations and their control methodologies, the DPF soot loading prediction, and the soot sensor for the PM on-board diagnostics (OBD) legislations. Furthermore, the progress of the highly optimized hybrid approaches, which involves the integration of diesel oxidation catalyst (DOC) + (DPF, NOx reduction catalyst), the selective catalytic reduction (SCR) catalyst coated on DPF, as well as DPF in the high-pressure exhaust gas recirculation (EGR) loop systems, is well discussed. Besides, the impacts of the quality of fuel and lubricant on the DPF performance and the maintenance and retrofit of DPF are fully elaborated. Meanwhile, the high efficiency gasoline particulate filter (GPF) technology is being required to effectively reduce the PM and particulate number (PN) emissions from the gasoline direct injection (GDI) engines to comply with the future increasingly stricter emissions regulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Orphan Toxin OrtT (YdcX) of Escherichia coli Reduces Growth during the Stringent Response

DTIC Science & Technology

2015-01-29

antimicrobials trimethoprim and sulfamethoxazole; these antimicrobials induce the stringent response by inhibiting tetrahydrofolate synthesis...in the presence of both antimicrobials trimethoprim and sulfamethoxazole; these antimicrobials induce the stringent response by inhibiting...level [20]. Toxins 2015, 7 301 Despite these difficulties in determining physiological roles, TA systems are clearly phage inhibition systems

Virulence gene regulation by CvfA, a putative RNase: the CvfA-enolase complex in Streptococcus pyogenes links nutritional stress, growth-phase control, and virulence gene expression.

PubMed

Kang, Song Ok; Caparon, Michael G; Cho, Kyu Hong

2010-06-01

Streptococcus pyogenes, a multiple-auxotrophic human pathogen, regulates virulence gene expression according to nutritional availability during various stages in the infection process or in different infection sites. We discovered that CvfA influenced the expression of virulence genes according to growth phase and nutritional status. The influence of CvfA in C medium, rich in peptides and poor in carbohydrates, was most pronounced at the stationary phase. Under these conditions, up to 30% of the transcriptome exhibited altered expression; the levels of expression of multiple virulence genes were altered, including the genes encoding streptokinase, CAMP factor, streptolysin O, M protein (more abundant in the CvfA(-) mutant), SpeB, mitogenic factor, and streptolysin S (less abundant). The increase of carbohydrates or peptides in media restored the levels of expression of the virulence genes in the CvfA(-) mutant to wild-type levels (emm, ska, and cfa by carbohydrates; speB by peptides). Even though the regulation of gene expression dependent on nutritional stress is commonly linked to the stringent response, the levels of ppGpp were not altered by deletion of cvfA. Instead, CvfA interacted with enolase, implying that CvfA, a putative RNase, controls the transcript decay rates of virulence factors or their regulators according to nutritional status. The virulence of CvfA(-) mutants was highly attenuated in murine models, indicating that CvfA-mediated gene regulation is necessary for the pathogenesis of S. pyogenes. Taken together, the CvfA-enolase complex in S. pyogenes is involved in the regulation of virulence gene expression by controlling RNA degradation according to nutritional stress.

An overview of the recovery of acid from spent acidic solutions from steel and electroplating industries.

PubMed

Agrawal, Archana; Sahu, K K

2009-11-15

Every metal and metallurgical industry is associated with the generation of waste, which may be a solid, liquid or gaseous in nature. Their impacts on the ecological bodies are noticeable due to their complex and hazardous nature affecting the living and non-living environment which is an alarming issue to the environmentalist. The increasingly stringent regulations regarding the discharge of acid and metal into the environment, and the increasing stress upon the recycling/reuse of these effluents after proper treatment have focused the interest of the research community on the development of new approaches for the recovery of acid and metals from industrial wastes. This paper is a critical review on the acidic waste streams generated from steel and electroplating industries particularly from waste pickle liquor and spent bleed streams. Various aspects on the generation of these streams and the methods used for their treatment either for the recovery of acid for reuse or disposal are being dealt with. Major stress is laid upon the hydrometallurgical methods such as solvent extraction.

Signal-mediated nuclear transport in the amoeba.

PubMed

Feldherr, C M; Akin, D

1999-06-01

The evolutionary changes that occur in signal-mediated nuclear transport would be expected to reflect an increasing need to regulate nucleocytoplasmic exchanges as the complexity of organisms increases. This could involve changes in both the composition and structure of the pore complex, as well as the cytosolic factors that mediate transport. In this regard, we investigated the transport process in amoebae (Amoeba proteus and Chaos carolinensis), primitive cells that would be expected to have less stringent regulatory requirements than more complex organisms. Colloidal gold particles, coated with bovine serum albumin (BSA) conjugated with simple (large T) nuclear localization signals (NLSs), bipartite (nucleoplasmin) NLSs or mutant NLSs, were used to assay nuclear import. It was found that in amoebae (1) the diameter of the particles that are able to enter the nucleoplasm is significantly less than in vertebrate cells, (2) the simple NLS is more effective in mediating nuclear import than the bipartite NLS, and (3) the nucleoporins do not appear to be glycosylated. Evidence was also obtained suggesting that, in amoebae, the simple NLS can mediate nuclear export.

Technological change, depletion and environmental policy in the offshore oil and gas industry

NASA Astrophysics Data System (ADS)

Managi, Shunsuke

Technological change is central to maintaining standards of living in modern economies with finite resources and increasingly stringent environmental goals. Successful environmental policies can contribute to efficiency by encouraging, rather than inhibiting, technological innovation. However, little research to date has focused on the design and implementation of environmental regulations that encourage technological progress, or in insuring productivity improvements in the face of depletion of natural resources and increasing stringency of environmental regulations. This study models and measures productivity change, with an application to offshore oil and gas production in the Gulf of Mexico using Data Envelopment Analysis. This is an important application because energy resources are central to sustaining our economy. The net effects of technological progress and depletion on productivity of offshore oil and gas production are measured using a unique field-level set of data of production from all wells in the Gulf of Mexico over the time period from 1946--1998. Results are consistent with the hypothesis that technological progress has mitigated depletion effects over the study period, but the pattern differs from the conventional wisdom for nonrenewable resource industries. The Porter Hypothesis was recast, and revised version was tested. The Porter Hypothesis states that well designed environmental regulations can potentially contribute to productive efficiency in the long run by encouraging innovation. The Porter Hypothesis was recast to include market and nonmarket outputs. Our results support the recast version of Porter hypothesis, which examine productivity of joint production of market and environmental outputs. But we find no evidence for the standard formulation of the Porter hypothesis, that increased stringency of environmental regulation lead to increased productivity of market outputs and therefore increased industry profits. The model is used to forecast market and environmental outputs under alternative policy scenarios. Reliable baseline forecast and response to different policy actions of production and pollution are critical to the formation of sound energy and environmental policy. Forecast of production and pollution until year 2050 are generated from the model. Detailed policy scenarios provide quantitative assessments of potential benefits that indicate the significance of potential benefits of technological change and well-designed environmental policy.

Fuel prices, emission standards, and generation costs for coal vs natural gas power plants.

PubMed

Pratson, Lincoln F; Haerer, Drew; Patiño-Echeverri, Dalia

2013-05-07

Low natural gas prices and stricter, federal emission regulations are promoting a shift away from coal power plants and toward natural gas plants as the lowest-cost means of generating electricity in the United States. By estimating the cost of electricity generation (COE) for 304 coal and 358 natural gas plants, we show that the economic viability of 9% of current coal capacity is challenged by low natural gas prices, while another 56% would be challenged by the stricter emission regulations. Under the current regulations, coal plants would again become the dominant least-cost generation option should the ratio of average natural gas to coal prices (NG2CP) rise to 1.8 (it was 1.42 in February 2012). If the more stringent emission standards are enforced, however, natural gas plants would remain cost competitive with a majority of coal plants for NG2CPs up to 4.3.

A mire of highly subjective and ineffective voluntary guidelines: tobacco industry efforts to thwart tobacco control in Malaysia.

PubMed

Assunta, M; Chapman, S

2004-12-01

To describe tobacco industry efforts in Malaysia to thwart government efforts to regulate tobacco promotion and health warnings. Systematic keyword and opportunistic website searches of formerly private tobacco industry internal documents made available through the Master Settlement Agreement and secondary websites; relevant information from news articles and financial reports. Commencing in the 1970s, the industry began to systematically thwart government tobacco control. Guidelines were successfully promoted in the place of legislation for over two decades. Even when the government succeeded in implementing regulations such as health warnings and advertising bans they were compromised and acted effectively to retard further progress for years to come. Counter-measures to delay or thwart government efforts to regulate tobacco were initiated by the industry. Though not unique to Malaysia, the main difference lies in the degree to which strategies were used to successfully counter stringent tobacco control measures between 1970 and 1995.

High-throughput sequencing methods to study neuronal RNA-protein interactions.

PubMed

Ule, Jernej

2009-12-01

UV-cross-linking and RNase protection, combined with high-throughput sequencing, have provided global maps of RNA sites bound by individual proteins or ribosomes. Using a stringent purification protocol, UV-CLIP (UV-cross-linking and immunoprecipitation) was able to identify intronic and exonic sites bound by splicing regulators in mouse brain tissue. Ribosome profiling has been used to quantify ribosome density on budding yeast mRNAs under different environmental conditions. Post-transcriptional regulation in neurons requires high spatial and temporal precision, as is evident from the role of localized translational control in synaptic plasticity. It remains to be seen if the high-throughput methods can be applied quantitatively to study the dynamics of RNP (ribonucleoprotein) remodelling in specific neuronal populations during the neurodegenerative process. It is certain, however, that applications of new biochemical techniques followed by high-throughput sequencing will continue to provide important insights into the mechanisms of neuronal post-transcriptional regulation.

A 0.18 μm CMOS LDO Regulator for an On-Chip Sensor Array Impedance Measurement System.

PubMed

Pérez-Bailón, Jorge; Márquez, Alejandro; Calvo, Belén; Medrano, Nicolás

2018-05-02

This paper presents a fully integrated 0.18 μm CMOS Low-Dropout (LDO) Voltage Regulator specifically designed to meet the stringent requirements of a battery-operated impedance spectrometry multichannel CMOS micro-instrument. The proposed LDO provides a regulated 1.8 V voltage from a 3.6 V to 1.94 V battery voltage over a −40 °C to 100 °C temperature range, with a compact topology (<0.10 mm² area) and a constant quiescent current of only 7.45 μA with 99.985% current efficiency, achieving remarkable state-of-art Figures of Merit (FoMs) for the regulating⁻transient performance. Experimental measurements validate its suitability for the target application, paving the way towards the future achievement of a truly portable System on Chip (SoC) platform for impedance sensors.

Iron acquisition in Pasteurella haemolytica: expression and identification of a bovine-specific transferrin receptor.

PubMed Central

Ogunnariwo, J A; Schryvers, A B

1990-01-01

Seven type 1 field isolates of Pasteurella haemolytica were screened for their ability to use different transferrins as a source of iron for growth. All seven strains were capable of using bovine but not human, porcine, avian, or equine transferrin. A screening assay failed to detect siderophore production in any of the strains tested. Iron-deficient cells from these strains expressed a binding activity, specific for bovine transferrin, that was regulated by the level of iron in the medium. Inhibition of expression by translation and transcription inhibitors suggested that iron regulation was occurring at the gene level. Affinity isolation of receptor proteins from all seven strains with biotinylated bovine transferrin identified a 100-kilodalton iron-regulated outer membrane protein as the bovine transferrin receptor. Iron-regulated outer membrane proteins of 71 and 77 kilodaltons were isolated along with the 100-kilodalton protein when less stringent washing procedures were employed in the affinity isolation procedure. Images PMID:2365453

[Mechanical Shimming Method and Implementation for Permanent Magnet of MRI System].

PubMed

Xue, Tingqiang; Chen, Jinjun

2015-03-01

A mechanical shimming method and device for permanent magnet of MRI system has been developed to meet its stringent homogeneity requirement without time-consuming passive shimming on site, installation and adjustment efficiency has been increased.

After 'dieselgate': Regulations or economic incentives for a successful environmental policy?

NASA Astrophysics Data System (ADS)

Zachariadis, Theodoros

2016-08-01

In September 2015 the U.S. Environmental Protection Agency announced that it started investigations against the automaker Volkswagen for illegally installing software that allowed some diesel-powered vehicle models to pass stringent emission tests for type-approval. Although generally prohibited, modern software makes it feasible for vehicles to detect an emission test and modulate engine operation or emission control accordingly. It has also been well known to experts worldwide - and readers of this Journal - that emission tests for motor vehicles are conducted with outdated test procedures which do not reflect today's actual driving conditions and enable automakers to exploit 'flexibilities' so as to yield artificially low emission results. For example, on-road carbon dioxide (CO2) emissions of cars that entered the European market in 2014 were reportedly 40% higher than their formal test emissions, while this gap was less than 10% in the early 2000s (Tietge et al., 2015). In the case of health-related pollutant nitrogen oxides (NOx), this gap seems to be markedly higher, in particular for diesel-powered cars (Weiss et al., 2012) - whereas this does not seem to be a serious problem for other air pollutants. In internal combustion engines of motor vehicles there is still a trade-off between NOx emissions and fuel efficiency (and hence CO2 emissions): a fast combustion with high temperatures is optimal for maximum fuel efficiency and minimum CO2 emissions, whereas these conditions give rise to higher NOx emissions. Conversely, NOx control techniques such as exhaust gas recirculation reduce combustion temperature and often lead to lower fuel efficiency. In short, it becomes ever more difficult for internal combustion engines to meet the increasingly stringent legislated standards for some air pollutants and carbon dioxide at the same time. This increases the probability of applying legal and illegal defeat strategies.

Modules for estimating solid waste from fossil-fuel technologies

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

Crowther, M.A.; Thode, H.C. Jr.; Morris, S.C.

1980-10-01

Solid waste has become a subject of increasing concern to energy industries for several reasons. Increasingly stringent air and water pollution regulations result in a larger fraction of residuals in the form of solid wastes. Control technologies, particularly flue gas desulfurization, can multiply the amount of waste. With the renewed emphasis on coal utilization and the likelihood of oil shale development, increased amounts of solid waste will be produced. In the past, solid waste residuals used for environmental assessment have tended only to include total quantities generated. To look at environmental impacts, however, data on the composition of the solidmore » wastes are required. Computer modules for calculating the quantities and composition of solid waste from major fossil fuel technologies were therefore developed and are described in this report. Six modules have been produced covering physical coal cleaning, conventional coal combustion with flue gas desulfurization, atmospheric fluidized-bed combustion, coal gasification using the Lurgi process, coal liquefaction using the SRC-II process, and oil shale retorting. Total quantities of each solid waste stream are computed together with the major components and a number of trace elements and radionuclides.« less

Proceedings: Workshop on Environmental Considerations in the Life-Cycle of Paints and Coatings Held in Champaign, Illinois on September 9-10, 1986

DTIC Science & Technology

1988-07-01

MSDS or Material Safety Data Sheets from our suppliers and we are required to provide the same for our customers . We are required to train our personnel...non-sparking tools. Labels We protect our customers by labeling our materials in accordance with the NPCA Labeling Guide which is at least as...stringent as any federal or local regulations, by providing Material Safety Data Sheets and by providing customer assistance O when requested regarding safe

Sensors and regulators of intracellular pH.

PubMed

Casey, Joseph R; Grinstein, Sergio; Orlowski, John

2010-01-01

Protons dictate the charge and structure of macromolecules and are used as energy currency by eukaryotic cells. The unique function of individual organelles therefore depends on the establishment and stringent maintenance of a distinct pH. This, in turn, requires a means to sense the prevailing pH and to respond to deviations from the norm with effective mechanisms to transport, produce or consume proton equivalents. A dynamic, finely tuned balance between proton-extruding and proton-importing processes underlies pH homeostasis not only in the cytosol, but in other cellular compartments as well.

Transnational Dynamics Amid Poor Regulations: Taiwan's Asbestos Ban Actions and Experiences.

PubMed

Wu, Harry Yi-Jui; Lin, Ro-Ting; Wang, Jung-Der; Cheng, Yawen

2017-10-17

This article describes the history of the asbestos use regulation process in Taiwan and the associated factors leading to its total ban in 2018. Despite the long history of asbestos mining and manufacturing since the Japanese colonial period, attempts to understand the impact of asbestos on the health of the population and to control its use did not emerge until the early 1980s. We attempted to investigate the driving forces and obstructions involved in asbestos regulations by reviewing available public sources and scientific journal articles and conducting interviews with key propagators of the asbestos regulation and ban. Correlation between asbestos exposure and asbestos-related diseases has already been established; however, authorities have been unable to effectively regulate the extensive application of asbestos in various light industries that support economic growth since the 1960s. More stringent regulations on asbestos use in industries and an eventual ban were caused indirectly by appeals made by visionary scholars and healthcare professionals but also due to the subsidence of asbestos-related industries. With the elucidation of factors that affect asbestos regulation and ban, a thorough long-term healthcare plan for the neglected victims of asbestos-related diseases and upstream measures for policy change must be developed.

Development and fabrication of the Virginia skid-resistance measurement vehicle (model 2).

DOT National Transportation Integrated Search

1970-01-01

The inefficiency of the Virginia Highway Research Council, Model 1, skid measurement trailer, and the increasing effort expended by the American Society for Testing and Materials toward the development of more stringent specifications for pavement sk...

Assessment of wastewater treatment facility compliance with decreasing ammonia discharge limits using a regression tree model.

PubMed

Suchetana, Bihu; Rajagopalan, Balaji; Silverstein, JoAnn

2017-11-15

A regression tree-based diagnostic approach is developed to evaluate factors affecting US wastewater treatment plant compliance with ammonia discharge permit limits using Discharge Monthly Report (DMR) data from a sample of 106 municipal treatment plants for the period of 2004-2008. Predictor variables used to fit the regression tree are selected using random forests, and consist of the previous month's effluent ammonia, influent flow rates and plant capacity utilization. The tree models are first used to evaluate compliance with existing ammonia discharge standards at each facility and then applied assuming more stringent discharge limits, under consideration in many states. The model predicts that the ability to meet both current and future limits depends primarily on the previous month's treatment performance. With more stringent discharge limits predicted ammonia concentration relative to the discharge limit, increases. In-sample validation shows that the regression trees can provide a median classification accuracy of >70%. The regression tree model is validated using ammonia discharge data from an operating wastewater treatment plant and is able to accurately predict the observed ammonia discharge category approximately 80% of the time, indicating that the regression tree model can be applied to predict compliance for individual treatment plants providing practical guidance for utilities and regulators with an interest in controlling ammonia discharges. The proposed methodology is also used to demonstrate how to delineate reliable sources of demand and supply in a point source-to-point source nutrient credit trading scheme, as well as how planners and decision makers can set reasonable discharge limits in future. Copyright © 2017 Elsevier B.V. All rights reserved.

A systematic review of US state environmental legislation and regulation with regards to the prevention of neurodevelopmental disabilities and asthma

PubMed Central

2009-01-01

Background While much attention is focused on national policies intended to protect human health from environmental hazards, states can also prevent environmentally mediated disease through legislation and regulation. However, relatively few analyses have examined the extent to which states protect children from chemical factors in the environment. Methods Using Lexis Nexis and other secondary sources, we systematically reviewed environmental regulation and legislation in the fifty states and the District of Columbia as of July 2007 intended to protect children against neurodevelopmental disabilities and asthma. Results States rarely address children specifically in environmental regulation and legislation, though many state regulations go far to limit children's exposures to environmental hazards. Northeast and Midwest states have implemented model regulation of mercury emissions, and regulations in five states set exposure limits to volatile organic compound emissions that are more stringent than US Environmental Protection Agency standards. Discussion Differences in state environmental regulation and legislation are likely to lead to differences in exposure, and thus to impacts on children's health. The need for further study should not inhibit other states and the federal government from pursuing the model regulation and legislation we identified to prevent diseases of environmental origin in children. PMID:19323818

Synthetic (p)ppGpp Analogue Is an Inhibitor of Stringent Response in Mycobacteria

PubMed Central

Syal, Kirtimaan; Flentie, Kelly; Bhardwaj, Neerupma; Maiti, Krishnagopal; Jayaraman, Narayanaswamy; Stallings, Christina L.

2017-01-01

ABSTRACT Bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. Their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppGpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for stress response and persistence inside a host. Our aim was to design an inhibitor of (p)ppGpp synthesis, monitor its efficiency using enzyme kinetics, and assess its phenotypic effects in mycobacteria. As such, new sets of inhibitors targeting (p)ppGpp synthesis were synthesized and characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. We observed significant inhibition of (p)ppGpp synthesis by RelMsm in the presence of designed inhibitors in a dose-dependent manner, which we further confirmed by monitoring the enzyme kinetics. The Rel enzyme inhibitor binding kinetics were investigated by isothermal titration calorimetry. Subsequently, the effects of the compounds on long-term persistence, biofilm formation, and biofilm disruption were assayed in Mycobacterium smegmatis, where inhibition in each case was observed. In vivo, (p)ppGpp levels were found to be downregulated in M. smegmatis treated with the synthetic inhibitors. The compounds reported here also inhibited biofilm formation by the pathogen Mycobacterium tuberculosis. The compounds were tested for toxicity by using an MTT assay with H460 cells and a hemolysis assay with human red blood cells, for which they were found to be nontoxic. The permeability of compounds across the cell membrane of human lung epithelial cells was also confirmed by mass spectrometry. PMID:28396544

Synthetic (p)ppGpp Analogue Is an Inhibitor of Stringent Response in Mycobacteria.

PubMed

Syal, Kirtimaan; Flentie, Kelly; Bhardwaj, Neerupma; Maiti, Krishnagopal; Jayaraman, Narayanaswamy; Stallings, Christina L; Chatterji, Dipankar

2017-06-01

Bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. Their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppGpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for stress response and persistence inside a host. Our aim was to design an inhibitor of (p)ppGpp synthesis, monitor its efficiency using enzyme kinetics, and assess its phenotypic effects in mycobacteria. As such, new sets of inhibitors targeting (p)ppGpp synthesis were synthesized and characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. We observed significant inhibition of (p)ppGpp synthesis by Rel Msm in the presence of designed inhibitors in a dose-dependent manner, which we further confirmed by monitoring the enzyme kinetics. The Rel enzyme inhibitor binding kinetics were investigated by isothermal titration calorimetry. Subsequently, the effects of the compounds on long-term persistence, biofilm formation, and biofilm disruption were assayed in Mycobacterium smegmatis , where inhibition in each case was observed. In vivo , (p)ppGpp levels were found to be downregulated in M. smegmatis treated with the synthetic inhibitors. The compounds reported here also inhibited biofilm formation by the pathogen Mycobacterium tuberculosis The compounds were tested for toxicity by using an MTT assay with H460 cells and a hemolysis assay with human red blood cells, for which they were found to be nontoxic. The permeability of compounds across the cell membrane of human lung epithelial cells was also confirmed by mass spectrometry. Copyright © 2017 American Society for Microbiology.

Highly accessible AU-rich regions in 3' untranslated regions are hotspots for binding of regulatory factors.

PubMed

Plass, Mireya; Rasmussen, Simon H; Krogh, Anders

2017-04-01

Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3'UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing "free" target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer of regulation of post-transcriptional regulatory networks.

Highly accessible AU-rich regions in 3’ untranslated regions are hotspots for binding of regulatory factors

PubMed Central

2017-01-01

Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3’UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing “free” target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer of regulation of post-transcriptional regulatory networks. PMID:28410363

Registering medicines for low-income countries: how suitable are the stringent review procedures of the World Health Organisation, the US Food and Drug Administration and the European Medicines Agency?

PubMed

Doua, Joachim Y; Van Geertruyden, Jean-Pierre

2014-01-01

New medicines are registered after a resource-demanding process. Unfortunately, in low-income countries (LICs), demand outweighs resources. To facilitate registration in LICs, stringent review procedures of the European Medicines Agency (EMA Article-58), Food and Drug Administration (FDA PEPFAR-linked review) and WHO Prequalification programme have been established. Only the PEPFAR-linked review gives approval, while the others make recommendations for approval. This study assessed the performance and discussed the challenges of these three stringent review procedures. Data from WHO, FDA, EMA, Medline and Internet were analysed. Over 60% of medicines reviewed by stringent review procedures are manufactured in India. Until 2012, WHO prequalified 400 medicines (211 vaccines, 130 antiretrovirals, 29 tuberculostatics, 15 antimalarials and 15 others). PEPFAR-linked review approved 156 antiretrovirals, while EMA Article 58 recommended approval of 3 antiretrovirals, 1 vaccine and 1 antimalarial. WHO Prequalification and PEPFAR-linked review are free of charge and as a result have accelerated access to antiretrovirals. They both built capacity in sub-Saharan Africa, although WHO prequalification relies technically on stringent regulatory authorities and financially on donors. Article-58 offers the largest disease coverage and strongest technical capacities, is costly and involves fewer LICs. To meet the high demand for quality medicines in LICs, these stringent review procedures need to enlarge their disease coverage. To improve registration, EMA Article 58 should actively involve LICs. Furthermore, LIC regulatory activities must not be fully resigned to stringent review procedure. © 2013 John Wiley & Sons Ltd.

Trapped strontium ion optical clock

NASA Astrophysics Data System (ADS)

Barwood, G. P.; Gill, P.; Klein, H. A.; Hosaka, K.; Huang, G.; Lea, S. N.; Margolis, H. S.; Szymaniec, K.; Walton, B. R.

2017-11-01

Increasingly stringent demands on atomic timekeeping, driven by applications such as global navigation satellite systems (GNSS), communications, and very-long baseline interferometry (VBLI) radio astronomy, have motivated the development of improved time and frequency standards. There are many scientific applications of such devices in space.

Can re-regulation reservoirs and batteries cost-effectively mitigate sub-daily hydropeaking?

NASA Astrophysics Data System (ADS)

Haas, J.; Nowak, W.; Anindito, Y.; Olivares, M. A.

2017-12-01

To compensate for mismatches between generation and load, hydropower plants frequently operate in strong hydropeaking schemes, which is harmful to the downstream ecosystem. Furthermore, new power market structures and variable renewable systems may exacerbate this behavior. Ecological constraints (minimum flows, maximum ramps) are frequently used to mitigate hydropeaking, but these stand in direct tradeoff with the operational flexibility required for integrating renewable technologies. Fortunately, there are also physical methods (i.e. re-regulation reservoirs and batteries) but to date, there are no studies about their cost-effectiveness for hydropeaking mitigation. This study aims to fill that gap. For this, we formulate an hourly mixed-integer linear optimization model to plan the weekly operation of a hydro-thermal-renewable power system from southern Chile. The opportunity cost of water (needed for this weekly scheduling) is obtained from a mid-term programming solved with dynamic programming. We compare the current (unconstrained) hydropower operation with an ecologically constrained operation. The resulting cost increase is then contrasted with the annual payments necessary for the physical hydropeaking mitigation options. For highly constrained operations, both re-regulation reservoirs and batteries show to be economically attractive for hydropeaking mitigation. For intermediate constrained scenarios, re-regulation reservoirs are still economic, whereas batteries can be a viable solution only if they become cheaper in future. Given current cost projections, their break-even point (for hydropeaking mitigation) is expected within the next ten years. Finally, less stringent hydropeaking constraints do not justify physical mitigation measures, as the necessary flexibility can be provided by other power plants of the system.

Gene expression profiling in the adult Down syndrome brain.

PubMed

Lockstone, H E; Harris, L W; Swatton, J E; Wayland, M T; Holland, A J; Bahn, S

2007-12-01

The mechanisms by which trisomy 21 leads to the characteristic Down syndrome (DS) phenotype are unclear. We used whole genome microarrays to characterize for the first time the transcriptome of human adult brain tissue (dorsolateral prefrontal cortex) from seven DS subjects and eight controls. These data were coanalyzed with a publicly available dataset from fetal DS tissue and functional profiling was performed to identify the biological processes central to DS and those that may be related to late onset pathologies, particularly Alzheimer disease neuropathology. A total of 685 probe sets were differentially expressed between adult DS and control brains at a stringent significance threshold (adjusted p value (q) < 0.005), 70% of these being up-regulated in DS. Over 25% of genes on chromosome 21 were differentially expressed in comparison to a median of 4.4% for all chromosomes. The unique profile of up-regulation on chromosome 21, consistent with primary dosage effects, was accompanied by widespread transcriptional disruption. The critical Alzheimer disease gene, APP, located on chromosome 21, was not found to be up-regulated in adult brain by microarray or QPCR analysis. However, numerous other genes functionally linked to APP processing were dysregulated. Functional profiling of genes dysregulated in both fetal and adult datasets identified categories including development (notably Notch signaling and Dlx family genes), lipid transport, and cellular proliferation. In the adult brain these processes were concomitant with cytoskeletal regulation and vesicle trafficking categories, and increased immune response and oxidative stress response, which are likely linked to the development of Alzheimer pathology in individuals with DS.

[Biosimilars--opportunity or threat?].

PubMed

Swierkot, Jerzy

2013-01-01

Strong interest in biosimilars dates back several years. In the coming years the patent protection ends for subsequent biological drugs, including monoclonal antibodies. This paper organizes the most important facts related to the issue of biosimilars. A biosimilar is a biotherapeutic product which is similar in terms of quality, efficacy and safety to an already licensed reference biotherapeutic product'. It should be noted that biosimilars approved underthe current regulations of the European Medicines Agency (EMA) meet the stringent standards of safety, efficacy and immunogenicity. It is also important to realize that the biosimilar has the right to that name, if it is registered by regulatory authorities like EMA or FDA. One should not confuse biosimilar drugs with those which counterfeit or imitate. Clinical trials on the convertibility of innovative and biosimilar drugs are ongoing. Nevertheless,there is no regulatory framework and clear guidelines of conduct in this regard. In the near future, thanks to the registration of the first biosimilar monoclonal antibodies in rheumatology and gastroenterology the availability of biological treatment for patients should increase.

Motion control of multi-actuator hydraulic systems for mobile machineries: Recent advancements and future trends

NASA Astrophysics Data System (ADS)

Xu, Bing; Cheng, Min

2018-06-01

This paper presents a survey of recent advancements and upcoming trends in motion control technologies employed in designing multi-actuator hydraulic systems for mobile machineries. Hydraulic systems have been extensively used in mobile machineries due to their superior power density and robustness. However, motion control technologies of multi-actuator hydraulic systems have faced increasing challenges due to stringent emission regulations. In this study, an overview of the evolution of existing throttling control technologies is presented, including open-center and load sensing controls. Recent advancements in energy-saving hydraulic technologies, such as individual metering, displacement, and hybrid controls, are briefly summarized. The impact of energy-saving hydraulic technologies on dynamic performance and control solutions are also discussed. Then, the advanced operation methods of multi-actuator mobile machineries are reviewed, including coordinated and haptic controls. Finally, challenges and opportunities of advanced motion control technologies are presented by providing an overall consideration of energy efficiency, controllability, cost, reliability, and other aspects.

Environmental externalities: Thinking globally, taxing locally

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

Trisko, E.M.

1993-03-01

Assigning monetary externality values to the airborne emissions of electric power plants is gaining the attention of state utility commissions as a means to measure the social costs of alternative energy investments. Some commissions are using environmental externalities to encourage utility investments in energy conservation and renewable energy technologies such as solar, wind, and biomass. However, the monetization of externalities through so-called adders to direct generation costs can lead to inefficient resource allocation and expose consumers to electric rate increases without corresponding environmental benefits. The addition of externality values to direct electric generation costs distorts the economics of power supplymore » planning by creating artificial subsidies for generation sources that are not currently competitive in the market. Businesses and consumers will be forced to support higher-cost sources of electric generation as a consequence. Because pollutant emissions of all new sources of electric generation are stringently regulated, and generally are well below those of existing fossil-fired sources, little demonstrable environmental benefit would result from the expanded use of externality valuation.« less

Spinal Locomotor Circuits Develop Using Hierarchical Rules Based on Motorneuron Position and Identity.

PubMed

Hinckley, Christopher A; Alaynick, William A; Gallarda, Benjamin W; Hayashi, Marito; Hilde, Kathryn L; Driscoll, Shawn P; Dekker, Joseph D; Tucker, Haley O; Sharpee, Tatyana O; Pfaff, Samuel L

2015-09-02

The coordination of multi-muscle movements originates in the circuitry that regulates the firing patterns of spinal motorneurons. Sensory neurons rely on the musculotopic organization of motorneurons to establish orderly connections, prompting us to examine whether the intraspinal circuitry that coordinates motor activity likewise uses cell position as an internal wiring reference. We generated a motorneuron-specific GCaMP6f mouse line and employed two-photon imaging to monitor the activity of lumbar motorneurons. We show that the central pattern generator neural network coordinately drives rhythmic columnar-specific motorneuron bursts at distinct phases of the locomotor cycle. Using multiple genetic strategies to perturb the subtype identity and orderly position of motorneurons, we found that neurons retained their rhythmic activity-but cell position was decoupled from the normal phasing pattern underlying flexion and extension. These findings suggest a hierarchical basis of motor circuit formation that relies on increasingly stringent matching of neuronal identity and position. Copyright © 2015 Elsevier Inc. All rights reserved.

Potential of activated sludge disintegration.

PubMed

Boehler, M; Siegrist, H

2006-01-01

The disposal of sewage sludge and the agricultural use of stabilised sludge are decreasing due to more stringent regulations in Europe. An increasing fraction of sewage sludge must therefore be dewatered, dried, incinerated and the ashes disposed of in landfills. These processes are cost-intensive and also lead to the loss of valuable phosphate resources incorporated in the sludge ash. The implementation of processes that could reduce excess sludge production and recycle phosphate is therefore recommended. Disintegration of biological sludge by mechanical, thermal and physical methods could significantly reduce excess sludge production, improve the settling properties of the sludge and reduce bulking and scumming. The solubilised COD could also improve denitrification if the treated sludge is recycled to the anoxic zone. However, disintegration partly inhibits and kills nitrifiers and could therefore shorten their effective solid retention time, thus reducing the safety of the nitrification. This paper discusses the potential of disintegration on sludge reduction, the operating stability of nitrification, the improvement of denitrification and also presents an energy and cost evaluation.

Why small and medium chemical companies continue to pose severe environmental risks in rural China.

PubMed

He, Guizhen; Zhang, Lei; Mol, Arthur P J; Wang, Tieyu; Lu, Yonglong

2014-02-01

In China, rural chemical SMEs are often believed to still largely operate below the sustainability radar. This paper investigates to what extent and how chemical SMEs are already experiencing pressure to improve their environmental performance, using an in-depth case study in Jasmine County, Hebei province. The results show that local residents had rather low trust in the environmental improvement promises made by the enterprises and the local government, and disagreed with the proposed improvement plans. Although the power of local residents to influence decision making remained limited, the chemical SMEs started to feel increasing pressures to clean up their business, from governments, local communities and civil society, and international value chain stakeholders. Notwithstanding these mounting pressures chemical SME's environmental behavior and performance has not changed radically for the better. The strong economic ties between local county governments and chemical SMEs continue to be a major barrier for stringent environmental regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Health risks by bromomethane and other toxic gases in import cargo ship containers.

PubMed

Baur, Xaver; Yu, Fang; Poschadel, Bernd; Veldman, Wim; Vos, Tosca Knol-de

2006-01-01

Containers are increasingly used for the worldwide transport of all kinds of goods. Consistent with national and international regulations on pest controls, a growing proportion of these containers undergoes fumigation. Frequently, the prescribed labelling is missing. According to literature, this situation may lead to accidents and represents a significant health risk to dock workers, inspectors and custom workers. Furthermore, warehouse workers and even consumers may come in contact with these toxic fumigants. Presented measurement data underline this health risks due to bromomethane but also due to other fumigants and, surprisingly, due to further noxious gases. So far, no routine method for sensitive and specific measurements on the spot has been available. The consequences of container fumigation should always be carefully weighed up, and alternatives to pesticides, e.g. heat treatment or atmospheres with reduced oxygen and for high CO2 concentrations should be considered. In addition, stringent international controls as well as sanctions if IMO's "Recommendations on the safe use of pesticides in ships" are disregarded are required.

The pluralization of the international: Resistance and alter-standardization in regenerative stem cell medicine

PubMed Central

Rosemann, Achim; Chaisinthop, Nattaka

2016-01-01

The article explores the formation of an international politics of resistance and ‘alter-standardization’ in regenerative stem cell medicine. The absence of internationally harmonized regulatory frameworks in the clinical stem cell field and the presence of lucrative business opportunities have resulted in the formation of transnational networks adopting alternative research standards and practices. These oppose, as a universal global standard, strict evidence-based medicine clinical research protocols as defined by scientists and regulatory agencies in highly developed countries. The emergence of transnational spaces of alter-standardization is closely linked to scientific advances in rapidly developing countries such as China and India, but calls for more flexible regulatory frameworks, and the legitimization of experimental for-profit applications outside of evidence-based medical care, are emerging increasingly also within more stringently regulated countries, such as the United States and countries in the European Union. We can observe, then, a trend toward the pluralization of the standards, practices, and concepts in the stem cell field. PMID:26983174

A transdisciplinary approach to understanding the health effects of wildfire and prescribed fire smoke regimes

NASA Astrophysics Data System (ADS)

Williamson, G. J.; Bowman, D. M. J. S.; Price, O. F.; Henderson, S. B.; Johnston, F. H.

2016-12-01

Prescribed burning is used to reduce the occurrence, extent and severity of uncontrolled fires in many flammable landscapes. However, epidemiologic evidence of the human health impacts of landscape fire smoke emissions is shaping fire management practice through increasingly stringent environmental regulation and public health policy. An unresolved question, critical for sustainable fire management, concerns the comparative human health effects of smoke from wild and prescribed fires. Here we review current knowledge of the health effects of landscape fire emissions and consider the similarities and differences in smoke from wild and prescribed fires with respect to the typical combustion conditions and fuel properties, the quality and magnitude of air pollution emissions, and the potential for dispersion to large populations. We further examine the interactions between these considerations, and how they may shape the longer term smoke regimes to which populations are exposed. We identify numerous knowledge gaps and propose a conceptual framework that describes pathways to better understanding of the health trade-offs of prescribed and wildfire smoke regimes.

Economics of oversized cyclones in the cotton ginning industry

USDA-ARS?s Scientific Manuscript database

Cost of reducing pollution to meet increasingly stringent air quality standards particularly for the U.S. cotton ginning industry is rising overtime. Most industry participants use cyclones to control air pollutants. These cyclones have no moving parts and their initial investment costs are relative...

Treated Wastewater Effluent as a Source of Microbial Pollution of Surface Water Resources

PubMed Central

Naidoo, Shalinee; Olaniran, Ademola O.

2013-01-01

Since 1990, more than 1.8 billion people have gained access to potable water and improved sanitation worldwide. Whilst this represents a vital step towards improving global health and well-being, accelerated population growth coupled with rapid urbanization has further strained existing water supplies. Whilst South Africa aims at spending 0.5% of its GDP on improving sanitation, additional factors such as hydrological variability and growing agricultural needs have further increased dependence on this finite resource. Increasing pressure on existing wastewater treatment plants has led to the discharge of inadequately treated effluent, reinforcing the need to improve and adopt more stringent methods for monitoring discharged effluent and surrounding water sources. This review provides an overview of the relative efficiencies of the different steps involved in wastewater treatment as well as the commonly detected microbial indicators with their associated health implications. In addition, it highlights the need to enforce more stringent measures to ensure compliance of treated effluent quality to the existing guidelines. PMID:24366046

The RpoB H481Y Rifampicin Resistance Mutation and an Active Stringent Response Reduce Virulence and Increase Resistance to Innate Immune Responses in Staphylococcus aureus

PubMed Central

Gao, Wei; Cameron, David R.; Davies, John K.; Kostoulias, Xenia; Stepnell, Justin; Tuck, Kellie L.; Yeaman, Michael R.; Peleg, Anton Y.; Stinear, Timothy P.; Howden, Benjamin P.

2013-01-01

The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H481Y, which is linked to rifampicin resistance, and RelA F128Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure. PMID:23255563

Gene network-based analysis identifies two potential subtypes of small intestinal neuroendocrine tumors.

PubMed

Kidd, Mark; Modlin, Irvin M; Drozdov, Ignat

2014-07-15

Tumor transcriptomes contain information of critical value to understanding the different capacities of a cell at both a physiological and pathological level. In terms of clinical relevance, they provide information regarding the cellular "toolbox" e.g., pathways associated with malignancy and metastasis or drug dependency. Exploration of this resource can therefore be leveraged as a translational tool to better manage and assess neoplastic behavior. The availability of public genome-wide expression datasets, provide an opportunity to reassess neuroendocrine tumors at a more fundamental level. We hypothesized that stringent analysis of expression profiles as well as regulatory networks of the neoplastic cell would provide novel information that facilitates further delineation of the genomic basis of small intestinal neuroendocrine tumors. We re-analyzed two publically available small intestinal tumor transcriptomes using stringent quality control parameters and network-based approaches and validated expression of core secretory regulatory elements e.g., CPE, PCSK1, secretogranins, including genes involved in depolarization e.g., SCN3A, as well as transcription factors associated with neurodevelopment (NKX2-2, NeuroD1, INSM1) and glucose homeostasis (APLP1). The candidate metastasis-associated transcription factor, ST18, was highly expressed (>14-fold, p < 0.004). Genes previously associated with neoplasia, CEBPA and SDHD, were decreased in expression (-1.5 - -2, p < 0.02). Genomic interrogation indicated that intestinal tumors may consist of two different subtypes, serotonin-producing neoplasms and serotonin/substance P/tachykinin lesions. QPCR validation in an independent dataset (n = 13 neuroendocrine tumors), confirmed up-regulated expression of 87% of genes (13/15). An integrated cellular transcriptomic analysis of small intestinal neuroendocrine tumors identified that they are regulated at a developmental level, have key activation of hypoxic pathways (a known regulator of malignant stem cell phenotypes) as well as activation of genes involved in apoptosis and proliferation. Further refinement of these analyses by RNAseq studies of large-scale databases will enable definition of individual master regulators and facilitate the development of novel tissue and blood-based tools to better understand diagnose and treat tumors.

Hydrologic analysis of the challenges facing water resources and sustainable development of Wadi Feiran basin, southern Sinai, Egypt

NASA Astrophysics Data System (ADS)

Ahmed, Ayman A.; Diab, Maghawri S.

2018-04-01

Wadi Feiran basin is one of the most promising areas in southern Sinai (Egypt) for establishing new communities and for growth in agriculture, tourism, and industry. The present challenges against development include water runoff hazards (flash flooding), the increasing water demand, and water scarcity and contamination. These challenges could be mitigated by efficient use of runoff and rainwater through appropriate management, thereby promoting sustainable development. Strategies include the mitigation of runoff hazards and promoting the natural and artificial recharge of aquifers. This study uses a watershed modeling system, geographic information system, and classification scheme to predict the effects of various mitigation options on the basin's water resources. Rainwater-harvesting techniques could save more than 77% of the basin's runoff (by volume), which could be used for storage and aquifer recharge. A guide map is provided that shows possible locations for the proposed mitigation options in the study basin. Appropriate measures should be undertaken urgently: mitigation of groundwater contamination (including effective sewage effluent management); regular monitoring of the municipal, industrial and agricultural processes that release contaminants; rationalization and regulation of the application of agro-chemicals to farmland; and regular monitoring of contaminants in groundwater. Stringent regulations should be implemented to prevent wastewater disposal to the aquifers in the study area.

The role of the food industry in health: lessons from tobacco?

PubMed

Capewell, Simon; Lloyd-Williams, Ffion

2018-03-01

In this review, we highlight poor diet as the biggest risk factor for non-communicable diseases. We examine the denial tactics used by the food industry, how they reflect the tactics previously used by the tobacco industry, and how campaigners can use this knowledge to achieve future public health successes. Data sources are wide ranging, notably publications relating to public health, obesity and processed food, the effectiveness hierarchy and food industry denialism tactics. Global burden of disease analyses consistently demonstrate that poor diet produces a bigger burden of non-communicable disease than tobacco, alcohol and inactivity put together. The lessons learnt from the tobacco control experience of successfully fighting the tobacco industry can be applied to other industries including processed food and sugary drinks. Tackling obesity and poor diet is a more complex issue than tobacco. Food industries continue to promote weak or ineffective policies such as voluntary reformulation, and resist regulation and taxation. However, the UK food industry now faces increasing pressure from professionals, public and politicians to accept reformulation and taxes, or face more stringent measures. The rise in childhood and adult obesity needs to be arrested and then reversed. Unhealthy processed food and sugary drinks are a major contributing factor. There is increasing interest in the tactics being used by the food industry to resist change. Advocacy and activism will be essential to counter these denialism tactics and ensure that scientific evidence is translated into effective regulation and taxation.

Low-dose γ-radiation-induced oxidative stress response in mouse brain and gut: regulation by NFκB-MnSOD cross-signaling.

PubMed

Veeraraghavan, Jamunarani; Natarajan, Mohan; Herman, Terence S; Aravindan, Natarajan

2011-01-10

Radiation-induced amplification of reactive oxygen species (ROS) may be a sensing mechanism for activation of signaling cascades that influence cell fate. However, the regulated intrinsic mechanisms and targets of low-dose ionizing radiation (LDIR) are still unclear. Accordingly, we investigated the effects of LDIR on NFκB signal transduction and manganese superoxide dismutase (SOD2) activity in mice brain and gut. LDIR resulted in both dose-dependent and persistent NFκB activation in gut and brain. QPCR displayed a dose- and tissue-dependent differential modulation of 88 signaling molecules. With stringent criteria, a total of 15 (2cGy), 43 (10cGy) and 19 (50cGy) genes were found to be commonly upregulated between brain and gut. SOD2 immunostaining showed a LDIR-dose dependent increase. Consistent with the NFκB results, we observed a persistent increase in SOD2 activity after LDIR. Moreover, muting of LDIR-induced NFκB attenuated SOD2 transactivation and cellular localization. These results imply that exposure of healthy tissues to LDIR results in induced NFκB and SOD2 activity and transcriptional activation of NFκB-signal transduction/target molecules. More importantly, the results suggest that NFκB initiates a feedback response through transcriptional activation of SOD2 that may play a key role in the LDIR-induced oxidative stress response and may control the switch that directs cell fate. 2010 Elsevier B.V. All rights reserved.

Transplanting Sensitized Kidney Transplant Patients With Equivalent Outcomes Utilizing Stringent HLA Crossmatching.

PubMed

Rohan, Vinayak S; Taber, David J; Moussa, Omar; Pilch, Nicole A; Denmark, Signe; Meadows, Holly B; McGillicuddy, John W; Chavin, Kenneth D; Baliga, Prabhakar K; Bratton, Charles F

2017-02-01

Elevated panel reactive antibody levels have been traditionally associated with increased acute rejection rate and decreased long-term graft survival after kidney transplant. In this study, our objective was to determine patient and allograft outcomes in sensitized kidney transplant recipients with advanced HLA antibody detection and stringent protein sequence epitope analyses. This was a subanalysis of a prospective, risk-stratified randomized controlled trial that compared interleukin 2 receptor antagonist to rabbit antithymocyte globulin induction in 200 kidney transplant recipients, examining outcomes based on panel reactive antibody levels of < 20% (low) versus ≥ 20% (high, sensitized). The study was conducted between February 2009 and July 2011. All patients underwent solid-phase single antigen bead assays to detect HLA antibodies and stringent HLA epitope analyses with protein sequence alignment for virtual crossmatching. Delayed graft function, acute rejection rates, and graft loss were the main outcomes measured. Both the low (134 patients) and high (66 patients) panel reactive antibody level cohorts had equivalent induction and maintenance immunosuppression. Patients in the high-level group were more likely to be female (P < .001), African American (P < .001), and received a kidney from a deceased donor (P = .004). Acute rejection rates were similar between the low (rate of 8%) and high (rate of 9%) panel reactive antibody groups (P = .783). Delayed graft function, borderline rejection, graft loss, and death were not different between groups. Multivariate analyses demonstrated delayed graft function to be the strongest predictor of acute rejection (odds ratio, 5.7; P = .005); panel reactive antibody level, as a continuous variable, had no significant correlation with acute rejection (C statistic, 0.48; P = .771). Appropriate biologic matching with single antigen bead assays and stringent epitope analyses provided excellent outcomes in sensitized patients regardless of the induction therapy choice.

Lubricity of biobased diesel fuels and additives

USDA-ARS?s Scientific Manuscript database

Modern diesel engines rely on the fuel itself to lubricate moving parts in the fuel and engine systems. Prior to the late 1990s, diesel fuel from petroleum provided sufficient lubricity to effectively reduce wear in injectors and fuel pumps. Increasingly stringent limitations on the sulfur content o...

Using Common Planning Time to Foster Professional Learning

ERIC Educational Resources Information Center

Dever, Robin; Lash, Martha J.

2013-01-01

Increased emphasis on meeting state standards, more stringent requirements for designation as highly qualified, and intensified accountability for student performance have foisted new expectations upon teachers and stimulated changes in professional development models in which the greater urgency is clearly to attend to the teacher's role as…

Accuracy of Surgery Clerkship Performance Raters.

ERIC Educational Resources Information Center

Littlefield, John H.; And Others

1991-01-01

Interrater reliability in numerical ratings of clerkship performance (n=1,482 students) in five surgery programs was studied. Raters were classified as accurate or moderately or significantly stringent or lenient. Results indicate that increasing the proportion of accurate raters would substantially improve the precision of class rankings. (MSE)

The Installation of a P.E.T. Pharmacy at Washington University

NASA Astrophysics Data System (ADS)

Gaehle, G.; Schwarz, S.; Mueller, M.; Margenau, B.; Welch, M. J.

2003-08-01

Washington University has produced radioisotopes for medical application since the early 1960s. In order to serve seven PET scanners and to meet more stringent government regulations we have installed a new PET pharmacy based on our past years of experiences. The new pharmacy was installed at the site of the 3.7 MeV tandem cascade accelerator that was decommissioned in April of 2001. The pharmacy consists of a production lab, quality control lab, reagent preparation lab, shipping and storage area and an office. Security and safety was a main consideration in the design of this PET pharmacy.

Integrins in bone metastasis formation and potential therapeutic implications.

PubMed

Clëzardin, P

2009-11-01

Integrins constitute a family of cell surface receptors that are heterodimers composed of noncovalently associated alpha and beta subunits. Integrins bind to extracellular matrix proteins and immunogobulin superfamily molecules. They exert a stringent control on cell migration, survival and proliferation. However, their expression and functions are often deregulated in cancer, and many lines of evidence implicate them as key regulators during progression from primary tumor growth to metastasis. Here, we review the role of integrins in bone metastasis formation and present evidence that the use of integrin-targeted therapeutic agents may be an efficient strategy to block tumor metastasis.

The right to know and the duty to disclose hazard information.

PubMed

Baram, M S

1984-04-01

In late 1983, the Occupational Safety and Health Administration (OSHA) promulgated its final rule on "hazard communication," establishing the right of workers in manufacturing industries to information about chemical hazards, and the duty of importers and manufacturers to disclose such information. Baram reviews areas where the new, limited OSHA regulation conflicts with existing local, state, and federal laws, many of which are more stringent and more protective of worker and community health. He suggests steps that could be taken to avoid the extensive litigation that might result from the potential preemptive effect of the new OSHA rule.

The Installation of a P.E.T. Pharmacy at Washington University

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

Gaehle, G.; Schwarz, S.; Mueller, M.

2003-08-26

Washington University has produced radioisotopes for medical application since the early 1960s. In order to serve seven PET scanners and to meet more stringent government regulations we have installed a new PET pharmacy based on our past years of experiences. The new pharmacy was installed at the site of the 3.7 MeV tandem cascade accelerator that was decommissioned in April of 2001. The pharmacy consists of a production lab, quality control lab, reagent preparation lab, shipping and storage area and an office. Security and safety was a main consideration in the design of this PET pharmacy.

Applications of fuzzy ranking methods to risk-management decisions

NASA Astrophysics Data System (ADS)

Mitchell, Harold A.; Carter, James C., III

1993-12-01

The Department of Energy is making significant improvements to its nuclear facilities as a result of more stringent regulation, internal audits, and recommendations from external review groups. A large backlog of upgrades has resulted. Currently, a prioritization method is being utilized which relies on a matrix of potential consequence and probability of occurrence. The attributes of the potential consequences considered include likelihood, exposure, public health and safety, environmental impact, site personnel safety, public relations, legal liability, and business loss. This paper describes an improved method which utilizes fuzzy multiple attribute decision methods to rank proposed improvement projects.

Transnational Dynamics Amid Poor Regulations: Taiwan’s Asbestos Ban Actions and Experiences

PubMed Central

Wu, Harry Yi-Jui; Wang, Jung-Der; Cheng, Yawen

2017-01-01

This article describes the history of the asbestos use regulation process in Taiwan and the associated factors leading to its total ban in 2018. Despite the long history of asbestos mining and manufacturing since the Japanese colonial period, attempts to understand the impact of asbestos on the health of the population and to control its use did not emerge until the early 1980s. We attempted to investigate the driving forces and obstructions involved in asbestos regulations by reviewing available public sources and scientific journal articles and conducting interviews with key propagators of the asbestos regulation and ban. Correlation between asbestos exposure and asbestos-related diseases has already been established; however, authorities have been unable to effectively regulate the extensive application of asbestos in various light industries that support economic growth since the 1960s. More stringent regulations on asbestos use in industries and an eventual ban were caused indirectly by appeals made by visionary scholars and healthcare professionals but also due to the subsidence of asbestos-related industries. With the elucidation of factors that affect asbestos regulation and ban, a thorough long-term healthcare plan for the neglected victims of asbestos-related diseases and upstream measures for policy change must be developed. PMID:29039774

Public Support for Electronic Cigarette Regulation in Hong Kong: A Population-Based Cross-Sectional Study.

PubMed

Cheung, Yee Tak Derek; Wang, Man Ping; Ho, Sai Yin; Jiang, Nan; Kwong, Antonio; Lai, Vienna; Lam, Tai Hing

2017-06-30

This study aimed to gauge the Hong Kong's public support towards new e-cigarette regulation, and examine the associated factors of the support. We conducted a two-stage, randomized cross-sectional telephone-based survey to assess the public support towards the banning of e-cigarette promotion and advertisement, its use in smoke-free venues, the sale to people aged under 18, and regulating the sale of nicotine-free e-cigarettes. Adults (aged 15 years or above) who were never smoking ( n = 1706), ex-smoking ( n = 1712) or currently smoking ( n = 1834) were included. Over half (57.8%) supported all the four regulations. Banning of e-cigarette promotion and advertisement (71.7%) received slightly less support than the other three regulations (banning of e-cigarette use in smoke-free venues (81.5%); banning of e-cigarette sale to minors (93.9%); sale restriction of nicotine-free e-cigarettes (80.9%)). Current smokers, and perceiving e-cigarettes as less harmful than traditional cigarettes or not knowing the harmfulness, were associated with a lower level of support. Our findings showed a strong public support for further regulation of e-cigarettes in Hong Kong. Current stringent measures on tobacco and e-cigarettes, and media reports on the harmfulness of e-cigarettes may underpin the strong support for the regulation.

Regulation of stem cell therapies under attack in Europe: for whom the bell tolls

PubMed Central

Bianco, Paolo; Barker, Roger; Brüstle, Oliver; Cattaneo, Elena; Clevers, Hans; Daley, George Q; De Luca, Michele; Goldstein, Lawrence; Lindvall, Olle; Mummery, Christine; Robey, Pamela G; Sattler de Sousa e Brito, Clara; Smith, Austin

2013-01-01

At the time of writing, the Italian Parliament is debating a new law that would make it legal to practice an unproven stem cell treatment in public hospitals. The treatment, offered by a private non-medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulations. This case raises multiple concerns, most prominently the urgent need to protect patients who are severely ill, exposed to significant risks, and vulnerable to exploitation. The scientific community must consider the context—social, financial, medical, legal—in which stem cell science is currently situated and the need for stringent regulation. Additional concerns are emerging. These emanate from the novel climate, created within science itself, and stem cell science in particular, by the currently prevailing model of ‘translational medicine'. Only rigorous science and rigorous regulation can ensure translation of science into effective therapies rather than into ineffective market products, and mark, at the same time, the sharp distinction between the striving for new therapies and the deceit of patients. PMID:23644381

Securing Safety - Spaceflight Standards for the Mass Market

NASA Astrophysics Data System (ADS)

Goh, G.

The projected total revenue of the space tourism industry is expected to exceed USD $1 billion by 2021. The vast economic potential of space tourism has fuelled ambitious plans for commercial orbital and suborbital flights, in addition to longer- duration spaceflights on board the International Space Station (ISS) and other planned orbiting habitats. International and national legal frameworks are challenged to provide regulations to ensure minimum standards of spaceflight safety for a high risk activity that aims to enter the mainstream tourism market. Thrown into the mix are various considerations of the number of spaceflight participants per flight, the economic viability of stringent safety standards, the plethora of possible flight vehicles and the compensation mechanism in case of violations of safety regulations. This paper surveys the legal challenges in the regulation of safety in commercial manned spaceflight, including issues of jurisdiction, authorization, licensing and liability. Drawing on analogous developments in other fields of law related to international carriage, a safety regulation framework with minimum international standards is proposed. This proposed framework considers both accident avoidance and emergency response in light of international legal, policy and economic perspectives.

Investigation into the use of cement kiln dust in high density sludge (HDS) treatment of acid mine water.

PubMed

Mackie, Allison L; Walsh, Margaret E

2015-11-15

The purpose of this study was to investigate the potential to replace lime with cement kiln dust (CKD) in high density sludge (HDS) treatment of acid mine drainage (AMD). The bench-scale study used two water samples: AMD sampled from a lead-zinc mine with high concentrations of iron (Fe), zinc (Zn), and arsenic (As) (Fe/Zn-AMD) and a synthetic AMD solution (Syn-AMD) spiked with ferric sulfate (Fe2(SO4)3). Arsenic was found to be significantly reduced with CKD-HDS treatment of Fe/Zn-AMD compared to lime-HDS treatment, to concentrations below the stringent mine effluent discharge regulation of 0.10 mg As/L (i.e., 0.04 ± 0.02 mg/L). Both CKD- and lime-HDS treatment of the two AMD samples resulted in settled water Fe concentrations above the stringent discharge guideline of 0.3 mg Fe/L. CKD addition in the HDS process also resulted in high settled water turbidity, above typical discharge guidelines of 15 mg TSS/L. CKD-HDS treatment was found to result in significantly improved settled solids (i.e., sludge) quality compared to that generated in the lime-HDS process. HDS treatment with CKD resulted in 25-88% lower sludge volume indices, 2 to 9 times higher % wet solids, and 10 to 20 times higher % dry solids compared to lime addition. XRD and XPS testing indicated that CKD-HDS sludge consisted of mainly CaCO3 and SiO2 with Fe(3+) precipitates attached at particle surfaces. XRD and XPS testing of the lime-HDS generated sludge showed that it consisted of non-crystalline Fe oxides typical of sludge formed from precipitates with a high water concentration. Increased sedimentation rates were also found for CKD (1.3 cm/s) compared to lime (0.3 cm/s). The increased solids loading with CKD addition compared to lime addition in the HDS process was suggested to both promote surface complexation of metal precipitates with insoluble CKD particles and increase compression effects during Type IV sedimentation. These mechanisms collectively contributed to the reduced water content of CKD-HDS sludge. The results of this study suggest that solids loading is a significant factor in increased sludge density found with the HDS process compared to conventional lime precipitation-sedimentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The impact of multiple show-ups on eyewitness decision-making and innocence risk.

PubMed

Smith, Andrew M; Bertrand, Michelle; Lindsay, R C L; Kalmet, Natalie; Grossman, Deborah; Provenzano, Daniel

2014-09-01

If an eyewitness rejects a show-up, police may respond by finding a new suspect and conducting a second show-up with the same eyewitness. Police may continue finding suspects and conducting show-ups until the eyewitness makes an identification (Study 1). Relatively low criterion-setting eyewitnesses filter themselves out of the multiple show-ups procedure by choosing the first suspect with whom they are presented (Studies 2 and 3). Accordingly, response bias was more stringent on the second show-up when compared with the first, but became no more stringent with additional show-ups. Despite this stringent shift in response bias, innocence risk increased with additional show-ups, as false alarms cumulate (Studies 2 and 3). Although unbiased show-up instructions decreased innocent suspect identifications, the numbers were still discouraging (Study 4). Given the high number of innocent suspects who would be mistakenly identified through the use of multiple show-up procedures, using such identifications as evidence of guilt is questionable. Although evidence of guilt is limited to identifications from a single show-up, practical constraints might sometimes require police to use additional show-ups. Accordingly, we propose a stronger partition between evidentiary and investigative procedures. PsycINFO Database Record (c) 2014 APA, all rights reserved.

A mire of highly subjective and ineffective voluntary guidelines: tobacco industry efforts to thwart tobacco control in Malaysia

PubMed Central

Assunta, M; Chapman, S

2004-01-01

Objective: To describe tobacco industry efforts in Malaysia to thwart government efforts to regulate tobacco promotion and health warnings. Methods: Systematic keyword and opportunistic website searches of formerly private tobacco industry internal documents made available through the Master Settlement Agreement and secondary websites; relevant information from news articles and financial reports. Results: Commencing in the 1970s, the industry began to systematically thwart government tobacco control. Guidelines were successfully promoted in the place of legislation for over two decades. Even when the government succeeded in implementing regulations such as health warnings and advertising bans they were compromised and acted effectively to retard further progress for years to come. Conclusion: Counter-measures to delay or thwart government efforts to regulate tobacco were initiated by the industry. Though not unique to Malaysia, the main difference lies in the degree to which strategies were used to successfully counter stringent tobacco control measures between 1970 and 1995. PMID:15564220

Regulatory Phosphorylation of Ikaros by Bruton's Tyrosine Kinase

PubMed Central

Zhang, Jian; Ishkhanian, Rita; Uckun, Fatih M.

2013-01-01

Diminished Ikaros function has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. Therefore, a stringent regulation of Ikaros is of paramount importance for normal lymphocyte ontogeny. Here we provide genetic and biochemical evidence for a previously unknown function of Bruton's tyrosine kinase (BTK) as a partner and posttranslational regulator of Ikaros, a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis. We demonstrate that BTK phosphorylates Ikaros at unique phosphorylation sites S214 and S215 in the close vicinity of its zinc finger 4 (ZF4) within the DNA binding domain, thereby augmenting its nuclear localization and sequence-specific DNA binding activity. Our results further demonstrate that BTK-induced activating phosphorylation is critical for the optimal transcription factor function of Ikaros. PMID:23977012

Multilevel DC Link Inverter for Brushless Permanent Magnet Motors with Very Low Inductance

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

Su, G.J.

2001-10-29

Due to their long effective air gaps, permanent magnet motors tend to have low inductance. The use of ironless stator structure in present high power PM motors (several tens of kWs) reduces the inductance even further (< 100 {micro}H). This low inductance imposes stringent current regulation demands for the inverter to obtain acceptable current ripple. An analysis of the current ripple for these low inductance brushless PM motors shows that a standard inverter with the most commonly used IGBT switching devices cannot meet the current regulation demands and will produce unacceptable current ripples due to the IGBT's limited switching frequency.more » This paper introduces a new multilevel dc link inverter, which can dramatically reduce the current ripple for brushless PM motor drives. The operating principle and design guidelines are included.« less

40 CFR 63.503 - Emissions averaging provisions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... used in conjunction with other controls for a Group 1 storage vessel, batch front-end process vent... will be allowed only for the increase in control after November 15, 1990. (2) Group 1 emission points... Group 1 emission points that are controlled to a level less stringent than the reference control...

40 CFR 63.503 - Emissions averaging provisions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... used in conjunction with other controls for a Group 1 storage vessel, batch front-end process vent... will be allowed only for the increase in control after November 15, 1990. (2) Group 1 emission points... Group 1 emission points that are controlled to a level less stringent than the reference control...

40 CFR 63.503 - Emissions averaging provisions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... used in conjunction with other controls for a Group 1 storage vessel, batch front-end process vent... will be allowed only for the increase in control after November 15, 1990. (2) Group 1 emission points... Group 1 emission points that are controlled to a level less stringent than the reference control...

40 CFR 63.503 - Emissions averaging provisions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... used in conjunction with other controls for a Group 1 storage vessel, batch front-end process vent... will be allowed only for the increase in control after November 15, 1990. (2) Group 1 emission points... Group 1 emission points that are controlled to a level less stringent than the reference control...

40 CFR 63.503 - Emissions averaging provisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... used in conjunction with other controls for a Group 1 storage vessel, batch front-end process vent... will be allowed only for the increase in control after November 15, 1990. (2) Group 1 emission points... Group 1 emission points that are controlled to a level less stringent than the reference control...

Plural Societies and the Possibility of Shared Citizenship

ERIC Educational Resources Information Center

Merry, Michael S.

2012-01-01

As civilization pushes headlong into the twenty-first century, increasingly stringent demands for citizenship issue forth from governments around the world faced with a formidable assortment of challenges. Faced with these challenges, states are exploring ways to elicit civic attachments from their heterogeneous populations, but doing so is…

Opportunities for improving risk communication during the permitting process for entomophagous biological control agents: A review of current systems

USDA-ARS?s Scientific Manuscript database

Concerns about potentially irreversible non-target impacts from the importation and release of entomophagous biological control agents (BCAs) have resulted in increasingly stringent import requirements by National Plant Protection Organizations. Despite numerous scientific publications on the poten...

Television, Censorship and South Africa.

ERIC Educational Resources Information Center

Giffard, C. Anthony; Cohen, Lisa

Network television news has often been accused of inciting and prolonging incidents of public violence, whether riots or terrorism, and in South Africa this type of thinking has led to increasingly stringent restrictions on both domestic and foreign media covering the violent unrest there. A study determined a chronology of events and analyzed the…

Stringent DDI-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions.

PubMed

Zhou, Hufeng; Rezaei, Javad; Hugo, Willy; Gao, Shangzhi; Jin, Jingjing; Fan, Mengyuan; Yong, Chern-Han; Wozniak, Michal; Wong, Limsoon

2013-01-01

H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are very important information to illuminate the infection mechanism of M. tuberculosis H37Rv. But current H. sapiens-M. tuberculosis H37Rv PPI data are very scarce. This seriously limits the study of the interaction between this important pathogen and its host H. sapiens. Computational prediction of H. sapiens-M. tuberculosis H37Rv PPIs is an important strategy to fill in the gap. Domain-domain interaction (DDI) based prediction is one of the frequently used computational approaches in predicting both intra-species and inter-species PPIs. However, the performance of DDI-based host-pathogen PPI prediction has been rather limited. We develop a stringent DDI-based prediction approach with emphasis on (i) differences between the specific domain sequences on annotated regions of proteins under the same domain ID and (ii) calculation of the interaction strength of predicted PPIs based on the interacting residues in their interaction interfaces. We compare our stringent DDI-based approach to a conventional DDI-based approach for predicting PPIs based on gold standard intra-species PPIs and coherent informative Gene Ontology terms assessment. The assessment results show that our stringent DDI-based approach achieves much better performance in predicting PPIs than the conventional approach. Using our stringent DDI-based approach, we have predicted a small set of reliable H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies. We also analyze the H. sapiens-M. tuberculosis H37Rv PPIs predicted by our stringent DDI-based approach using cellular compartment distribution analysis, functional category enrichment analysis and pathway enrichment analysis. The analyses support the validity of our prediction result. Also, based on an analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent DDI-based approach, we have discovered some important properties of domains involved in host-pathogen PPIs. We find that both host and pathogen proteins involved in host-pathogen PPIs tend to have more domains than proteins involved in intra-species PPIs, and these domains have more interaction partners than domains on proteins involved in intra-species PPI. The stringent DDI-based prediction approach reported in this work provides a stringent strategy for predicting host-pathogen PPIs. It also performs better than a conventional DDI-based approach in predicting PPIs. We have predicted a small set of accurate H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies.

Dummy and injury criteria for aircraft crashworthiness.

DOT National Transportation Integrated Search

1996-04-01

Since 1988, newly type-certificated aircraft are required to comply with stringent crashworthiness requirements. Central to these more stringent requirements is a dynamic test that assesses the potential for injury for someone exposed to similar cond...

Metrological traceability and harmonization of medical tests: a quantum leap forward is needed to keep pace with globalization and stringent IVD-regulations in the 21st century!

PubMed

Cobbaert, Christa; Smit, Nico; Gillery, Philippe

2018-05-07

In our efforts to advance the profession and practice of clinical laboratory medicine, strong coordination and collaboration are needed more than ever before. At the dawn of the 21st century, medical laboratories are facing many unmet clinical needs, a technological revolution promising a plethora of better biomarkers, financial constraints, a growing scarcity of well-trained laboratory technicians and a sharply increasing number of International Organization for Standardization guidelines and new regulations to which medical laboratories should comply in order to guarantee safety and effectiveness of medical test results. Although this is a global trend, medical laboratories across continents and countries are in distinct phases and experience various situations. A universal underlying requirement for safe and global use of medical test results is the standardization and harmonization of test results. Since two decades and after a number of endeavors on standardization/harmonization of medical tests, it is time to reflect on the effectiveness of the approaches used. To keep laboratory medicine sustainable, viable and affordable, clarification of the promises of metrological traceability of test results for improving sick and health care, realization of formal commitment among all stakeholders of the metrological traceability chain and preparation of a joint and global plan for action are essential prerequisites. Policy makers and regulators should not only overwhelm the diagnostic sector with oversight and regulations but should also create the conditions by establishing a global professional forum for anchoring the metrological traceability concept in the medical test domain. Even so, professional societies should have a strong voice in their (inter-) national governments to negotiate long-lasting public policy commitment and funds for global standardization of medical tests.

Applications of Probabilistic Combiners on Linear Feedback Shift Register Sequences

DTIC Science & Technology

2016-12-01

on the resulting output strings show a drastic increase in complexity, while simultaneously passing the stringent randomness tests required by the...a three-variable function. Our tests on the resulting output strings show a drastic increase in complex- ity, while simultaneously passing the...10001101 01000010 11101001 Decryption of a message that has been encrypted using bitwise XOR is quite simple. Since each bit is its own additive inverse

Differential transcriptional control of the two tRNA(fMet) genes of Escherichia coli K-12.

PubMed

Nagase, T; Ishii, S; Imamoto, F

1988-07-15

The metZ gene of Escherichia coli, which encodes the tRNA(f1Met), was cloned. Using the nucleotide sequence, in vitro transcription, and S1 nuclease mapping analyses, we identified the promoter region, transcriptional start point, the two tandem tRNA(f1Met) structural genes separated by an intergenic space of 33 bp, and the two Rho-independent transcriptional termination sites, in that order. We compared the promoter region of the metZ gene with that of the metY gene, which encodes the tRNA(f2Met) and is located in the promoter-proximal portion of the nusA operon. A G + C-rich sequence (5'-GCGCATCCAC-3'), similar to the corresponding sequence of the rrn promoters that are under stringent control, was found between the Pribnow box and the transcriptional start point of the metZ promoter, but not in the metY promoter region. We therefore examined the effect of guanosine 3'-diphosphate, 5'-diphosphate (ppGpp), the chemical mediator of stringent control, and found that ppGpp inhibited the transcription of the metZ gene, but not that of the metY gene. These data suggested that the promoters for metZ and metY have different physiological functions and are regulated by different mechanisms.

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

Sparn, Bethany; Hunsberger, Randolph

Water and wastewater treatment plants and distribution systems use significant amounts of energy, around 2 - 4% of the total electricity used in the US, and their energy use is projected to increase as populations increase and regulations become more stringent. Water and wastewater systems have largely been disconnected from the electric utilities' efforts to improve energy efficiency and provide energy efficiency and provide grid services, likely because their core mission is to provide clean water and treated wastewater. Energy efficiency has slowly crept into the water and wastewater industry as the economic benefit has become more apparent, but theremore » is still potential for significant improvement. Some of the larger, more progressive water utilities are starting to consider providing grid services; however, it remains a foreign concept to many. This report explores intrinsic mechanisms by which the water and wastewater industries can provide exchangeable services, the benefit to the parties involved, and the barriers to implementation. It also highlights relevant case studies and next steps. Although opportunities for increasing process efficiencies are certainly available, this report focuses on the exchangeable services that water and wastewater loads can provide to help maintain grid reliability, keep overall costs down, and increase the penetration of distributed renewables on the electric grid. These services have potential to provide water utilities additional value streams, using existing equipment with modest or negligible upgrade cost.« less

Undertaking Experiments in Social Sciences: Sequential, Multiple Time Series Designs for Consideration

ERIC Educational Resources Information Center

Phan, Huy P.; Ngu, Bing H.

2017-01-01

In social sciences, the use of stringent methodological approaches is gaining increasing emphasis. Researchers have recognized the limitations of cross-sectional, non-manipulative data in the study of causality. True experimental designs, in contrast, are preferred as they represent rigorous standards for achieving causal flows between variables.…

Cybersecurity Education: Bridging the Gap between Hardware and Software Domains

ERIC Educational Resources Information Center

Lukowiak, Marcin; Radziszowski, Stanislaw; Vallino, James; Wood, Christopher

2014-01-01

With the continuous growth of cyberinfrastructure throughout modern society, the need for secure computing and communication is more important than ever before. As a result, there is also an increasing need for entry-level developers who are capable of designing and building practical solutions for systems with stringent security requirements.…

The RpoB H₄₈₁Y rifampicin resistance mutation and an active stringent response reduce virulence and increase resistance to innate immune responses in Staphylococcus aureus.

PubMed

Gao, Wei; Cameron, David R; Davies, John K; Kostoulias, Xenia; Stepnell, Justin; Tuck, Kellie L; Yeaman, Michael R; Peleg, Anton Y; Stinear, Timothy P; Howden, Benjamin P

2013-03-15

The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H₄₈₁Y, which is linked to rifampicin resistance, and RelA F₁₂₈Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure.

Performance of a peroxide-based cetane improvement additive in different diesel fuels

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

Nandi, M.K.; Jacobs, D.C.; Liotta, F.J. Jr.

The implementation of stringent diesel engine emissions regulations is growing worldwide. The use of high cetane diesel fuels is a cost-effective option that can be used to reduce engine emissions. A direct comparison of heavy-duty diesel engine emissions for three different low sulfur diesel fuels treated with di-t-butyl peroxide and 2-ethylhexyl nitrate, at the same cetane level, was evaluated. Both the peroxide and the nitrate cetane improvement additive significantly reduced all regulated and unregulated emissions including the oxides of nitrogen (NOx) emission. Di-t-butyl peroxide shows a small advantage over ethylhexyl nitrate in reducing NOx in all the three fuels. Compatibilitymore » of the peroxide and the nitrate additives, when mixed in a fuel blend, has been demonstrated by cetane response and engine emissions for the fuel blend. 13 refs., 2 figs., 9 tabs.« less

Mobile phones: time to rethink and limit usage.

PubMed

Paul, Bobby; Saha, Indranil; Kumar, Sanjay; Samim Ferdows, S K; Ghose, Gautam

2015-01-01

Radiofrequency waves generated from mobile phones cause potential public health problems. Short-term effects like changes in sleep, heart rate, and blood pressure, and long-term effects like carcinoma are well documented. The Government of India's efforts in laying down regulations regarding the safety limits, manufacture, marketing, and mobile use are still in nascent stage. The need for stringent enforcement of laws for prevention of phone usage while driving and guidelines of medical regulatory bodies regarding rules and regulations of phone usage while at class or attending patients is of utmost importance. This should be supplemented by mass media to raise awareness among people regarding the possible health effects of radiofrequency emissions from mobile phones and the guidelines to minimize its exposure. It is the need of the hour to teach young people to be structured, to know when to have the cell phone on, and to avoid becoming the slave of technology instead of its mastery.

Ban on advertising promoting energy usage violates First Amendment

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

Cohen, J.C.

In reversing the New York Court of Appeals in the Central Hudson Gas suit, the Supreme Court expanded the protection afforded commercial speech. The result could have a major impact on means used to achieve policy objectives of national and state energy conservation. Public utility commissions attempting to limit the growth of energy usage may have to devise stringent economic regulations that directly affect the marketplace and consumer alternatives. This might require an expansion of the statutory powers of public utility commissions. The Court's decision will require public utility commissions to either adopt regulations that restrict the content and formatmore » of utility speech or allocate costs to utility shareholders of impermissible advertising. Otherwise, a utility's unbridled ability to speak, given the economic power of such enterprises and their economic interest, could totally undermine the credibility of national and state energy-conservation policy. 12 references.« less

Coagulant Recovery from Water Treatment Residuals: A Review of Applicable Technologies

PubMed Central

Keeley, J.; Jarvis, P.; Judd, S. J.

2014-01-01

Conventional water treatment consumes large quantities of coagulant and produces even greater volumes of sludge. Coagulant recovery (CR) presents an opportunity to reduce both the sludge quantities and the costs they incur, by regenerating and purifying coagulant before reuse. Recovery and purification must satisfy stringent potable regulations for harmful contaminants, while remaining competitive with commercial coagulants. These challenges have restricted uptake and lead research towards lower-gain, lower-risk alternatives. This review documents the context in which CR must be considered, before comparing the relative efficacies and bottlenecks of potential technologies, expediting identification of the major knowledge gaps and future research requirements. PMID:26064036

Label-free proteome of water buffalo (Bubalus bubalis) seminal plasma.

PubMed

Brito, Mayara F; Auler, Patrícia A; Tavares, Guilherme C; Rezende, Cristiana P; Almeida, Gabriel M F; Pereira, Felipe L; Leal, Carlos A G; Moura, Arlindo de Alencar; Figueiredo, Henrique C P; Henry, Marc

2018-06-11

The study aimed to describe the Bubalus bubalis seminal plasma proteome using a label-free shotgun UDMS E approach. A total of 859 nonredundant proteins were identified across five biological replicates with stringent identification. Proteins specifically related to sperm maturation and protection, capacitation, fertilization and metabolic activity were detected in the buffalo seminal fluid. In conclusion, we provide a comprehensive proteomic profile of buffalo seminal plasma, which establishes a foundation for further studies designed to understand regulation of sperm function and discovery of novel biomarkers for fertility. MS data are available in the ProteomeXchange with identifier PXD003728. © 2018 Blackwell Verlag GmbH.

ppGpp Conjures Bacterial Virulence

PubMed Central

Dalebroux, Zachary D.; Svensson, Sarah L.; Gaynor, Erin C.; Swanson, Michele S.

2010-01-01

Summary: Like for all microbes, the goal of every pathogen is to survive and replicate. However, to overcome the formidable defenses of their hosts, pathogens are also endowed with traits commonly associated with virulence, such as surface attachment, cell or tissue invasion, and transmission. Numerous pathogens couple their specific virulence pathways with more general adaptations, like stress resistance, by integrating dedicated regulators with global signaling networks. In particular, many of nature's most dreaded bacteria rely on nucleotide alarmones to cue metabolic disturbances and coordinate survival and virulence programs. Here we discuss how components of the stringent response contribute to the virulence of a wide variety of pathogenic bacteria. PMID:20508246

Stringent DDI-based Prediction of H. sapiens-M. tuberculosis H37Rv Protein-Protein Interactions

PubMed Central

2013-01-01

Background H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are very important information to illuminate the infection mechanism of M. tuberculosis H37Rv. But current H. sapiens-M. tuberculosis H37Rv PPI data are very scarce. This seriously limits the study of the interaction between this important pathogen and its host H. sapiens. Computational prediction of H. sapiens-M. tuberculosis H37Rv PPIs is an important strategy to fill in the gap. Domain-domain interaction (DDI) based prediction is one of the frequently used computational approaches in predicting both intra-species and inter-species PPIs. However, the performance of DDI-based host-pathogen PPI prediction has been rather limited. Results We develop a stringent DDI-based prediction approach with emphasis on (i) differences between the specific domain sequences on annotated regions of proteins under the same domain ID and (ii) calculation of the interaction strength of predicted PPIs based on the interacting residues in their interaction interfaces. We compare our stringent DDI-based approach to a conventional DDI-based approach for predicting PPIs based on gold standard intra-species PPIs and coherent informative Gene Ontology terms assessment. The assessment results show that our stringent DDI-based approach achieves much better performance in predicting PPIs than the conventional approach. Using our stringent DDI-based approach, we have predicted a small set of reliable H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies. We also analyze the H. sapiens-M. tuberculosis H37Rv PPIs predicted by our stringent DDI-based approach using cellular compartment distribution analysis, functional category enrichment analysis and pathway enrichment analysis. The analyses support the validity of our prediction result. Also, based on an analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent DDI-based approach, we have discovered some important properties of domains involved in host-pathogen PPIs. We find that both host and pathogen proteins involved in host-pathogen PPIs tend to have more domains than proteins involved in intra-species PPIs, and these domains have more interaction partners than domains on proteins involved in intra-species PPI. Conclusions The stringent DDI-based prediction approach reported in this work provides a stringent strategy for predicting host-pathogen PPIs. It also performs better than a conventional DDI-based approach in predicting PPIs. We have predicted a small set of accurate H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies. PMID:24564941

The control of inositol lipid hydrolysis.

PubMed

Katan, M

1996-01-01

Hydrolysis of PIP2 by specific PLC enzymes is involved in the regulation of different cellular processes by many extracellular signals. The need stringently to control this reaction is reflected by the fact that there are many PLC isozymes and multiple mechanisms linking these isozymes to various receptors. For two of the three PLC families found in mammalian cells (PLC beta and gamma), the components of the main regulatory pathways have been identified. PLC beta isozymes are regulated through G protein coupled receptors. Their activity is stimulated by interaction with alpha subunit from the Gq family and interaction with G protein beta gamma subunits. PLC gamma isozymes are regulated through receptor and non-receptor tyrosine kinases. The combination of SH2 dependent complex formation with phosphorylated tyrosine kinases and the subsequent phosphorylation of PLC gamma leads to stimulation of its activity. Although components that stimulate PLC beta and gamma isozymes have been identified, the molecular mechanism of stimulation remains largely unknown. Each signalling component operating within this general framework represents a family of related proteins. It is not clear what all the functional differences between members of the same family may be and to what extent they could determine specificity of individual signalling pathways. Similarly, it is not known to what extent alterations in PLC function/expression contribute to human pathologies. In the context of oncology, there is evidence for upregulation of PLC gamma in parallel with increased expression of the EGF receptor (Artega et al. 1991). However, it is not clear yet whether this is causally involved or a bystander effect.

Global parameter estimation for thermodynamic models of transcriptional regulation.

PubMed

Suleimenov, Yerzhan; Ay, Ahmet; Samee, Md Abul Hassan; Dresch, Jacqueline M; Sinha, Saurabh; Arnosti, David N

2013-07-15

Deciphering the mechanisms involved in gene regulation holds the key to understanding the control of central biological processes, including human disease, population variation, and the evolution of morphological innovations. New experimental techniques including whole genome sequencing and transcriptome analysis have enabled comprehensive modeling approaches to study gene regulation. In many cases, it is useful to be able to assign biological significance to the inferred model parameters, but such interpretation should take into account features that affect these parameters, including model construction and sensitivity, the type of fitness calculation, and the effectiveness of parameter estimation. This last point is often neglected, as estimation methods are often selected for historical reasons or for computational ease. Here, we compare the performance of two parameter estimation techniques broadly representative of local and global approaches, namely, a quasi-Newton/Nelder-Mead simplex (QN/NMS) method and a covariance matrix adaptation-evolutionary strategy (CMA-ES) method. The estimation methods were applied to a set of thermodynamic models of gene transcription applied to regulatory elements active in the Drosophila embryo. Measuring overall fit, the global CMA-ES method performed significantly better than the local QN/NMS method on high quality data sets, but this difference was negligible on lower quality data sets with increased noise or on data sets simplified by stringent thresholding. Our results suggest that the choice of parameter estimation technique for evaluation of gene expression models depends both on quality of data, the nature of the models [again, remains to be established] and the aims of the modeling effort. Copyright © 2013 Elsevier Inc. All rights reserved.

On-road vehicle emissions and their control in China: A review and outlook.

PubMed

Wu, Ye; Zhang, Shaojun; Hao, Jiming; Liu, Huan; Wu, Xiaomeng; Hu, Jingnan; Walsh, Michael P; Wallington, Timothy J; Zhang, K Max; Stevanovic, Svetlana

2017-01-01

The large (26-fold over the past 25years) increase in the on-road vehicle fleet in China has raised sustainability concerns regarding air pollution prevention, energy conservation, and climate change mitigation. China has established integrated emission control policies and measures since the 1990s, including implementation of emission standards for new vehicles, inspection and maintenance programs for in-use vehicles, improvement in fuel quality, promotion of sustainable transportation and alternative fuel vehicles, and traffic management programs. As a result, emissions of major air pollutants from on-road vehicles in China have peaked and are now declining despite increasing vehicle population. As might be expected, progress in addressing vehicle emissions has not always been smooth and challenges such as the lack of low sulfur fuels, frauds over production conformity and in-use inspection tests, and unreliable retrofit programs have been encountered. Considering the high emission density from vehicles in East China, enhanced vehicle, fuel and transportation strategies will be required to address vehicle emissions in China. We project the total vehicle population in China to reach 400-500 million by 2030. Serious air pollution problems in many cities of China, in particular high ambient PM 2.5 concentration, have led to pressure to accelerate the progress on vehicle emission reduction. A notable example is the draft China 6 emission standard released in May 2016, which contains more stringent emission limits than those in the Euro 6 regulations, and adds a real world emission testing protocol and a 48-h evaporation testing procedure including diurnal and hot soak emissions. A scenario (PC[1]) considered in this study suggests that increasingly stringent standards for vehicle emissions could mitigate total vehicle emissions of HC, CO, NO X and PM 2.5 in 2030 by approximately 39%, 57%, 59% and 79%, respectively, compared with 2013 levels. With additional actions to control the future light-duty passenger vehicle population growth and use, and introduce alternative fuels and new energy vehicles, the China total vehicle emissions of HC, CO, NO X and PM 2.5 in 2030 could be reduced by approximately 57%, 71%, 67% and 84%, respectively, (the PC[2] scenario) relative to 2013. This paper provides detailed policy roadmaps and technical options related to these future emission reductions for governmental stakeholders. Copyright © 2016 Elsevier B.V. All rights reserved.

New frontier, new power: the retail environment in Australia's dark market.

PubMed

Carter, S M

2003-12-01

To investigate the role of the retail environment in cigarette marketing in Australia, one of the "darkest" markets in the world. Analysis of 172 tobacco industry documents; and articles and advertisements found by hand searching Australia's three leading retail trade journals. As Australian cigarette marketing was increasingly restricted, the retail environment became the primary communication vehicle for building cigarette brands. When retail marketing was restricted, the industry conceded only incrementally and under duress, and at times continues to break the law. The tobacco industry targets retailers via trade promotional expenditure, financial and practical assistance with point of sale marketing, alliance building, brand advertising, and distribution. Cigarette brand advertising in retail magazines are designed to build brand identities. Philip Morris and British American Tobacco are now competing to control distribution of all products to retailers, placing themselves at the heart of retail business. Cigarette companies prize retail marketing in Australia's dark market. Stringent point of sale marketing restrictions should be included in any comprehensive tobacco control measures. Relationships between retailers and the industry will be more difficult to regulate. Retail press advertising and trade promotional expenditure could be banned. In-store marketing assistance, retail-tobacco industry alliance building, and new electronic retail distribution systems may be less amenable to regulation. Alliances between the health and retail sectors and financial support for a move away from retail dependence on tobacco may be necessary to effect cultural change.

Legal harvest and illegal trade: Trends, challenges, and options in khat production in Ethiopia.

PubMed

Cochrane, Logan; O'Regan, Davin

2016-04-01

The production of khat in Ethiopia has boomed over the last two decades, making the country the world's leading source. Khat is now one of Ethiopia's largest crops by area of cultivation, the country's second largest export earner, and an essential source of income for millions of Ethiopian farmers. Consumption has also spread from the traditional khat heartlands in the eastern and southern regions of Ethiopia to most major cities. This steady growth in production and use has unfolded under negligible government support or regulation. Meanwhile, khat, which releases a stimulant when chewed, is considered an illicit drug in an increasing number of countries. Drawing on government data on khat production, trade, and seizures as well as research on the political, socioeconomic, and development effects of plant-based illicit narcotics industries, this commentary identifies possible considerations and scenarios for Ethiopia as the country begins to manage rising khat production, domestic consumption, and criminalization abroad. Deeply embedded in social and cultural practices and a major source of government and agricultural revenue, Ethiopian policymakers have few enviable choices. Criminalization abroad raises a small but not insignificant possibility that previously nonexistent linkages between khat and transnational organized crime and trafficking networks will emerge. Likewise, more stringent regulation of khat in Ethiopia could merge with lingering political cleavages and anti-government sentiments, exacerbating low-level domestic conflicts. Copyright © 2016 Elsevier B.V. All rights reserved.

Best Practices for Gauging Evidence of Causality in Air Pollution Epidemiology.

PubMed

Dominici, Francesca; Zigler, Corwin

2017-12-15

The contentious political climate surrounding air pollution regulations has brought some researchers and policy-makers to argue that evidence of causality is necessary before implementing more stringent regulations. Recently, investigators in an increasing number of air pollution studies have purported to have used "causal analysis," generating the impression that studies not explicitly labeled as such are merely "associational" and therefore less rigorous. Using 3 prominent air pollution studies as examples, we review good practices for how to critically evaluate the extent to which an air pollution study provides evidence of causality. We argue that evidence of causality should be gauged by a critical evaluation of design decisions such as 1) what actions or exposure levels are being compared, 2) whether an adequate comparison group was constructed, and 3) how closely these design decisions approximate an idealized randomized study. We argue that air pollution studies that are more scientifically rigorous in terms of the decisions made to approximate a randomized experiment are more likely to provide evidence of causality and should be prioritized among the body of evidence for regulatory review accordingly. Our considerations, although presented in the context of air pollution epidemiology, can be broadly applied to other fields of epidemiology. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Emissions of metals and polychlorinated dibenzo(p)dioxins and furans (PCDD/Fs) from Portland cement manufacturing plants: inter-kiln variability and dependence on fuel-types.

PubMed

Zemba, Stephen; Ames, Michael; Green, Laura; Botelho, Maria João; Gossman, David; Linkov, Igor; Palma-Oliveira, José

2011-09-15

Emissions from Portland cement manufacturing facilities may increase health risks in nearby populations and are thus subject to stringent regulations. Direct testing of pollutant concentrations in exhaust gases provides the best basis for assessing the extent of these risks. However, these tests (i) are often conducted under stressed, rather than typical, operating conditions, (ii) may be limited in number and duration, and (iii) may be influenced by specific fuel-types and attributes of individual kilns. We report here on the results of more than 150 emissions-tests conducted of two kilns at a Portland cement manufacturing plant in Portugal. The tests measured various regulated metals and polychlorinated dibenzo(p)dioxins and furans (PCDD/Fs). Stack-gas concentrations of pollutants were found to be highly variable, with standard deviations on the order of mean values. Emission rates of many pollutants were higher when coal was used as the main kiln fuel (instead of petroleum coke). Use of various supplemental fuels, however, had little effect on stack emissions, and few statistically significant differences were observed when hazardous waste was included in the fuel mix. Significant differences in emissions for some pollutants were observed between the two kilns despite their similar designs and uses of similar fuels. All measured values were found to be within applicable regulatory limits. Published by Elsevier B.V.

Role of the Stringent Stress Response in the Antibiotic Resistance Phenotype of Methicillin-Resistant Staphylococcus aureus

PubMed Central

Aedo, Sandra

2016-01-01

Resistance to beta-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) requires the presence of an acquired genetic determinant, mecA or mecC, which encode penicillin-binding protein PBP2A or PBP2A′, respectively. Although all MRSA strains share a mechanism of resistance, the phenotypic expression of beta-lactam resistance shows considerable strain-to-strain variation. The stringent stress response, a stress response that results from nutrient limitation, was shown to play a key role in determining the resistance level of an MRSA strain. In the present study, we validated the impact of the stringent stress response on transcription and translation of mecA in the MRSA clinical isolate strain N315, which also carries known regulatory genes (mecI/mecR1/mecR2 and blaI/blaR1) for mecA transcription. We showed that the impact of the stringent stress response on the resistance level may be restricted to beta-lactam resistance based on a “foreign” determinant such as mecA, as opposed to resistance based on mutations in the native S. aureus determinant pbpB (encoding PBP2). Our observations demonstrate that high-level resistance mediated by the stringent stress response follows the current model of beta-lactam resistance in which the native PBP2 protein is also essential for expression of the resistance phenotype. We also show that the Staphylococcus sciuri pbpD gene (also called mecAI), the putative evolutionary precursor of mecA, confers oxacillin resistance in an S. aureus strain, generating a heterogeneous phenotype that can be converted to high and homogenous resistance by induction of the stringent stress response in the bacteria. PMID:26833147

Context-Aware Reviewer Assignment for Trust Enhanced Peer Review

PubMed Central

Li, Lei; Wang, Yan; Liu, Guanfeng; Wang, Meng; Wu, Xindong

2015-01-01

Reviewer assignment is critical to peer review systems, such as peer-reviewed research conferences or peer-reviewed funding applications, and its effectiveness is a deep concern of all academics. However, there are some problems in existing peer review systems during reviewer assignment. For example, some of the reviewers are much more stringent than others, leading to an unfair final decision, i.e., some submissions (i.e., papers or applications) with better quality are rejected. In this paper, we propose a context-aware reviewer assignment for trust enhanced peer review. More specifically, in our approach, we first consider the research area specific expertise of reviewers, and the institution relevance and co-authorship between reviewers and authors, so that reviewers with the right expertise are assigned to the corresponding submissions without potential conflict of interest. In addition, we propose a novel cross-assignment paradigm, and reviewers are cross-assigned in order to avoid assigning a group of stringent reviewers or a group of lenient reviewers to the same submission. More importantly, on top of them, we propose an academic CONtext-aware expertise relevanCe oriEnted Reviewer cross-assignmenT approach (CONCERT), which aims to effectively estimate the “true” ratings of submissions based on the ratings from all reviewers, even though no prior knowledge exists about the distribution of stringent reviewers and lenient reviewers. The experiments illustrate that compared with existing approaches, our proposed CONCERT approach can less likely assign more than one stringent reviewers or lenient reviewers to a submission simultaneously and significantly reduce the influence of ratings from stringent reviewers and lenient reviewers, leading to trust enhanced peer review and selection, no matter what kind of distributions of stringent reviewers and lenient reviewers are. PMID:26090849

Comparison of International Regulations for Written Medicine Information (WMI) on Prescription Medicines.

PubMed

Yuan, Hsiu-Chun Tony; Raynor, David K; Aslani, Parisa

2018-01-01

This paper presents a review of the literature, including government legislations, policies, guidelines, and recommendations available in the European Union, the United States of America, and Australia pertaining to the availability, development, and distribution of written medicine information (WMI) for prescription medicines. The online databases searched were Embase, International Pharmaceutical Abstracts, Medline, and PubMed, together with Google as the Internet search engine. The design and content of WMI documents have similarities and differences across all the 3 geographical regions. All the 3 regions have legislations in place to evaluate and regulate WMI documents for health care professionals (HCPs) and, to some degree, for patients; however, the degree of regulation varies between the 3 regions. The regulations around the content and information design of WMI impacts how well the WMI performs and consequently influences patients' knowledge and medication-taking behavior. Legislation in certain areas could be seen as more beneficial and can be implemented across the 3 regions. Furthermore, the required legislation on the evaluation of the content of WMIs can be seen in some areas to be more stringent and comprehensive, which when taken onboard across the 3 regions can be valuable when creating WMIs for both patients and HCPs.

Introduction to Exide Corporations`s high temperature metals recovery system

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

Rozelle, P.L.; Baranski, J.P.; Bitler, J.A.

1995-12-31

Environmental strategies concerning the processing and ultimate fate of wastes and byproducts are of ever increasing importance to the public and business sectors in the world today. Recycling materials and reusing energy from wastes and byproducts results in a reduction of environmental impacts and the cost of disposal. These are the key steps in reaching the ultimate goal of waste minimization. In response to these needs, Exide Corporation, in its vision to develop waste minimization programs, has developed the Exide High Temperature Metals Recovery (EHTMR) process. This process can treat a variety of wastes and byproducts where metals contents aremore » an issue, recover the metal values for reuse, and produce a metals-depleted slag that can be marketable under the most stringent proposed EPA regulations for leachability of contaminants. The central feature of the EHTMR process is the exposure of treated materials to a transferred arc plasma generated in an electric furnace. The process achieves a reduction in costs and liability by recovering portions of a waste that can be recycled or reclaimed and produces a slag that has beneficial use to society.« less

Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.

PubMed

Verstraeten, Natalie; Knapen, Wouter Joris; Kint, Cyrielle Ines; Liebens, Veerle; Van den Bergh, Bram; Dewachter, Liselot; Michiels, Joran Elie; Fu, Qiang; David, Charlotte Claudia; Fierro, Ana Carolina; Marchal, Kathleen; Beirlant, Jan; Versées, Wim; Hofkens, Johan; Jansen, Maarten; Fauvart, Maarten; Michiels, Jan

2015-07-02

Within bacterial populations, a small fraction of persister cells is transiently capable of surviving exposure to lethal doses of antibiotics. As a bet-hedging strategy, persistence levels are determined both by stochastic induction and by environmental stimuli called responsive diversification. Little is known about the mechanisms that link the low frequency of persisters to environmental signals. Our results support a central role for the conserved GTPase Obg in determining persistence in Escherichia coli in response to nutrient starvation. Obg-mediated persistence requires the stringent response alarmone (p)ppGpp and proceeds through transcriptional control of the hokB-sokB type I toxin-antitoxin module. In individual cells, increased Obg levels induce HokB expression, which in turn results in a collapse of the membrane potential, leading to dormancy. Obg also controls persistence in Pseudomonas aeruginosa and thus constitutes a conserved regulator of antibiotic tolerance. Combined, our findings signify an important step toward unraveling shared genetic mechanisms underlying persistence. Copyright © 2015 Elsevier Inc. All rights reserved.

Performance characteristics and typical industrial applications of Selfshield® electron accelerators (< 300 kV)

NASA Astrophysics Data System (ADS)

Aaronson, Judith N.; Nablo, Sam V.

1985-05-01

Selfshielded electron accelerators have been successfully used in industry for more than ten years. One of the important advantages of these machines is their compactness for easy adaptation to conventional coating and product finishing machinery. It is equally important that these machines qualify for use under "unrestricted" conditions as specified by OSHA. The shielding and product handling configurations which make this unrestricted designation possible for operating voltages under 300 kV are discussed. Thin film dosimetry techniques used for the determination of the machine performance parameters are discussed along with the rotary scanner techniques employed for the dose rate studies which are important in the application of these processors. Paper and wood coatings, which are important industrial applications involving electron initiated polymerization, are reviewed. The sterilization and disinfestation applications are also discussed. The increasing concern of these industries for the more efficient use of energy and for compliance with more stringent pollution regulations, coupled with the novel processes this energy source makes possible, assure a bright future for this developing technology.

SOx removal by calcined MgAlFe hydrotalcite-like materials: effect of the chemical composition and the cerium incorporation method.

PubMed

Cantú, Manuel; López-Salinas, Esteban; Valente, Jaime S; Montiel, Ramon

2005-12-15

Sulfur oxides are one of the most hazardous atmospheric pollutants since they contribute directly to acid rain formation. Consequently, stringent environmental regulations limit atmospheric SOx emissions, motivating research on efficient ways to reduce them. To supply an alternative to reduce these emissions in fluid catalytic cracking units, this study discloses efficient SOx reducing materials based on calcined MgAlFe hydrotalcite-like compounds (HT's). Thus, HT materials were synthesized by several methods including cerium addition. The adsorption of SO2 was carried out by contacting the calcined solid with a mixture of SO2 (1%) in air at 650 degrees C. It was demonstrated that the isomorphic incorporation of iron increased its reduction capability which was reflected in higher reduction rates and metal sulfate reduction grade at 550 degrees C. Moreover, when cerium was present in the iron-containing materials the saturation rate was improved, because cerium oxide promotes the oxidation of SO2 to SO3. The way cerium is incorporated influences the SO2 adsorption capacity.

Recent Progress on the Conversion of Surplus Picric Acid/Explosive D to Higher Value Products

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

R.Mitchell, A; Hsu, P C; Coburn, M D

2004-07-06

The global demilitarization of nuclear and conventional munitions is producing millions of pounds of surplus energetic materials. Historically, energetic materials (high explosives, propellants, and pyrotechnics) have been disposed of by open burning/open detonation (OB/OD). The use of OB/OD is becoming unacceptable due to public concerns and increasingly stringent environmental regulations. Clearly, there is a great need to develop environmentally sound and cost-effective alternatives to OB/OD. The conversion of surplus picric acid and/or ammonium picrate (Explosive D) to1,3,5-triamino-2,4,6- trinitrobenzene (TATB) has been subject of extensive process development studies at Lawrence Livermore National Laboratory (LLNL). LLNL, under the direction and sponsorship ofmore » the U.S. Army Defense Ammunition Center (DAC), is developing a process for the conversion of picric acid to TATB on a larger scale. In FY 03, a 10 g per batch process was developed with good results. Development for a one pound per batch system is required as part of overall scale up process for producing TATB from the surplus feedstocks.« less

Benefits of advanced software techniques for mission planning systems

NASA Technical Reports Server (NTRS)

Gasquet, A.; Parrod, Y.; Desaintvincent, A.

1994-01-01

The increasing complexity of modern spacecraft, and the stringent requirement for maximizing their mission return, call for a new generation of Mission Planning Systems (MPS). In this paper, we discuss the requirements for the Space Mission Planning and the benefits which can be expected from Artificial Intelligence techniques through examples of applications developed by Matra Marconi Space.

Diving into Data: Developing the Capacity for Data Literacy in Teacher Education

ERIC Educational Resources Information Center

Dunlap, Karen; Piro, Jody S.

2016-01-01

Educators by definition are now required to utilize a variety of student data to shape the decisions they make and design the lessons they teach. As accountability standards become more stringent and as teachers face increasingly diverse student populations within their classrooms, they often struggle to adequately meet the needs of all learners.…

Benefits of advanced software techniques for mission planning systems

NASA Astrophysics Data System (ADS)

Gasquet, A.; Parrod, Y.; Desaintvincent, A.

1994-10-01

The increasing complexity of modern spacecraft, and the stringent requirement for maximizing their mission return, call for a new generation of Mission Planning Systems (MPS). In this paper, we discuss the requirements for the Space Mission Planning and the benefits which can be expected from Artificial Intelligence techniques through examples of applications developed by Matra Marconi Space.

Design and Evaluation of Energy Efficient Modular Classroom Structures.

ERIC Educational Resources Information Center

Brown, G. Z.; And Others

This paper describes a study that developed innovations that would enable modular builders to improve the energy performance of their classrooms without increasing their first cost. The Modern Building Systems' classroom building conforms to the stringent Oregon and Washington energy codes, and, at $18 per square foot, it is at the low end of the…

Incorporating Knowledge of Legal and Ethical Aspects into Computing Curricula of South African Universities

ERIC Educational Resources Information Center

Wayman, Ian; Kyobe, Michael

2012-01-01

As students in computing disciplines are introduced to modern information technologies, numerous unethical practices also escalate. With the increase in stringent legislations on use of IT, users of technology could easily be held liable for violation of this legislation. There is however lack of understanding of social aspects of computing, and…

U. S. light duty vehicle fleet emissions performance and the emissions impact of technology changes

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

Sabourin, M.; Platte, L

1988-01-01

This paper determines the level of improvement in Federal Test Procedure (FTP) exhaust emissions realized by typical in-use vehicles over the last twenty years as emission standards have become increasingly stringent. Furthermore, this paper explores the likelihood that in-use emission performance improvements will continue now that emission standards have stabilized.

Circuitry linking the global Csr and σE-dependent cell envelope stress response systems.

PubMed

Yakhnin, Helen; Aichele, Robert; Ades, Sarah E; Romeo, Tony; Babitzke, Paul

2017-09-18

CsrA of Escherichia coli is an RNA-binding protein that globally regulates a wide variety of cellular processes and behaviors including carbon metabolism, motility, biofilm formation, and the stringent response. CsrB and CsrC are sRNAs that sequester CsrA, thereby preventing CsrA-mRNA interaction. RpoE (σ E ) is the extracytoplasmic stress response sigma factor of E. coli Previous RNA-seq studies identified rpoE mRNA as a CsrA target. Here we explored the regulation of rpoE by CsrA and found that CsrA represses rpoE translation. Gel mobility shift, footprint and toeprint studies identified three CsrA binding sites in the rpoE leader transcript, one of which overlaps the rpoE Shine-Dalgarno (SD) sequence, while another overlaps the rpoE translation initiation codon. Coupled in vitro transcription-translation experiments showed that CsrA represses rpoE translation by binding to these sites. We further demonstrate that σ E indirectly activates transcription of csrB and csrC , leading to increased sequestration of CsrA such that repression of rpoE by CsrA is reduced. We propose that the Csr system fine-tunes the σ E -dependent cell envelope stress response. We also identified a 51 amino acid coding sequence whose stop codon overlaps the rpoE start codon, and demonstrate that rpoE is translationally coupled with this upstream open reading frame (ORF51). Loss of coupling reduces rpoE translation by more than 50%. Identification of a translationally coupled ORF upstream of rpoE suggests that this previously unannotated protein may participate in the cell envelope stress response. In keeping with existing nomenclature, we name ORF51 as rseD , resulting in an operon arrangement of rseD-rpoE-rseA-rseB-rseC IMPORTANCE CsrA posttranscriptionally represses genes required for bacterial stress responses, including the stringent response, catabolite repression, and the RpoS (σ S )-mediated general stress response. We show that CsrA represses translation of rpoE , encoding the extracytoplasmic stress response sigma factor and that σ E indirectly activates transcription of csrB and csrC , resulting in reciprocal regulation of these two global regulatory systems. These findings suggest that extracytoplasmic stress leads to derepression of rpoE translation by CsrA, and CsrA-mediated repression helps to reset RpoE abundance to pre-stress levels once envelope damage is repaired. The discovery of an ORF, RseD, translationally coupled with rpoE adds further complexity to translational control of rpoE . Copyright © 2017 American Society for Microbiology.

Fluoride content in table salt distributed in Mexico City, Mexico.

PubMed

Hernández-Guerrero, Juan Carlos; de la Fuente-Hernández, Javier; Jiménez-Farfán, Maria Dolores; Ledesma-Montes, Constantino; Castañeda-Castaneira, Enrique; Molina-Frechero, Nelly; Jacinto-Alemán, Luís Fernando; Juárez-Lopez, Lilia Adriana; Moreno-Altamirano, Alejandra

2008-01-01

The aim of this study was to analyze table salt available in Mexico City's market to identify the fluoride concentrations and to compare these with the Mexican regulations. We analyzed 44 different brands of table salt. All samples were purchased at random in different stores, supermarkets, and groceries from Mexico City's metropolitan area and analyzed in triplicate in three different laboratories (nine determinations per sample) with an Orion 720 A potentiometer and an Orion 9609 BN ion-specific electrode. Fluoride concentration in the samples varied from 0 ppm to 485 ppm. It was found that fluoride concentration varied widely among the analyzed brands. Also, we found that fluoride concentration in 92 percent of the analyzed samples did not match with that printed on the label. Only 6.8 percent of the analyzed samples contained fluoride concentrations that meet Mexican and WHO regulations. The broad variation in the analyzed samples suggests that Mexican Public Health authorities must implement more stringent regulation guidelines and procedures for controlling the distribution of salt and its fluoride concentration for human consumption.

Characterizing dilute combustion instabilities in a multi-cylinder spark-ignited engine using symbolic analysis

DOE PAGES

Daw, C. Stuart; Finney, Charles E. A.; Kaul, Brian C.; ...

2014-12-29

Spark-ignited internal combustion engines have evolved considerably in recent years in response to increasingly stringent regulations for emissions and fuel-economy. One new advanced engine strategy utilizes high levels of exhaust gas recirculation (EGR) to reduce combustion temperatures, thereby increasing thermodynamic efficiency and reducing nitrogen oxide emissions. While this strategy can be highly effective, it also poses major control and design challenges due to the large combustion oscillations that develop at sufficiently high EGR levels. Previous research has documented that combustion instabilities can propagate between successive engine cycles in individual cylinders via self-generated feedback of reactive species and thermal energy inmore » the retained residual exhaust gases. In this work, we use symbolic analysis to characterize multi-cylinder combustion oscillations in an experimental engine operating with external EGR. At low levels of EGR, intra-cylinder oscillations are clearly visible and appear to be associated with brief, intermittent coupling among cylinders. As EGR is increased further, a point is reached where all four cylinders lock almost completely in phase and alternate simultaneously between two distinct bi-stable combustion states. From a practical perspective, it is important to understand the causes of this phenomenon and develop diagnostics that might be applied to ameliorate its effects. We demonstrate here that two approaches for symbolizing the engine combustion measurements can provide useful probes for characterizing these instabilities.« less

Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes.

PubMed

Ong, Huan Ting; Redmond, Sharon L; Marano, Robert J; Atlas, Marcus D; von Unge, Magnus; Aabel, Peder; Dilley, Rodney J

2017-03-15

Stem cell therapies for tympanic membrane repair have shown initial experimental success using mesenchymal stem cells in rat models to promote healing; however, the mechanisms providing this benefit are not known. We investigated in vitro the paracrine effects of human adipose-derived stem cells (ADSCs) on wound healing mechanisms for human tympanic membrane-derived keratinocytes (hTM) and immortalized human keratinocytes (HaCaT). ADSC conditioned media (CM ADSC ) were assessed for paracrine activity on keratinocyte proliferation and migration, with hypoxic conditions for ADSC culture used to generate contrasting effects on cytokine gene expression. Keratinocytes cultured in CM ADSC showed a significant increase in cell number compared to serum-free cultures and further significant increases in hypoxic CM ADSC . Assessment of ADSC gene expression on a cytokine array showed a range of wound healing cytokines expressed and under stringent hypoxic and serum-free conditions was upregulated (VEGF A, MMP9, Tissue Factor, PAI-1) or downregulated (CXCL5, CCL7, TNF-α). Several of these may contribute to the activity of conditioned media on the keratinocytes with potential applications in TM perforation repair. VEGFA protein was confirmed by immunoassay to be increased in conditioned media. Together with gene regulation associated with hypoxia in ADSCs, this study has provided several strong leads for a stem cell-derived approach to TM wound healing.

40 CFR 281.37 - Financial responsibility for UST systems containing petroleum.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Financial responsibility for UST... for No-Less-Stringent § 281.37 Financial responsibility for UST systems containing petroleum. (a) In order to be considered no less stringent than the federal requirements for financial responsibility for...

40 CFR 503.5 - Additional or more stringent requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... requirements. 503.5 Section 503.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STANDARDS FOR THE USE OR DISPOSAL OF SEWAGE SLUDGE General Provisions § 503.5 Additional or more... the use or disposal of sewage sludge in addition to or more stringent than the requirements in this...

Successful performance of a refinery with Eureka unit

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

Hirotani, Y.; Takeuchi, T.; Miyabuchi, Y.

1981-03-01

Since starting in February, 1976, 3,400,000 Kl of vacuum residue (13,000,000 Kl of crude oil equivalent) has been successfully processed in the Eureka unit of Fuji Oil refinery complex and more than 2,500,000 Kl of cracked oil and 1,000,000 tons of pitch have been produced. The operation rate has been 94 to 98% except for the annual shutdown period for inspection. The cracked oil is easily desulfurized to make naphta, diesel oil and a large amount of gas oil (low sulfur fuel oil, 0.1 wt % sulfur). As for the desulfurization of cracked oil, the increase in H/sub 2/ consumptionmore » and the decline of catalyst life are observed. However, the operation conditions do not differ much from those for straight run fractions. Processing both hydrotreated and untreated cracked heavy oil (CHO) with FCC unit has proved to be possible. In case of untreated CHO, however, it causes a slight increase in make up catalyst and coke yield. It is demonstrated that heavy crude oils, such as Bachaquero, can effectively be processed in this system. No additional pollution problems have occurred by introducing an Eureka unit to the refinery, although it is located in the district where the most stringent environmental regulations are urged.« less

Analysis of the holistic impact of the Hydrogen Economy on the coal industry

NASA Astrophysics Data System (ADS)

Lusk, Shannon Perry

As gas prices soar and energy demand continues to grow amidst increasingly stringent environmental regulations and an assortment of global pressures, implementing alternative energy sources while considering their linked economic, environmental and societal impacts becomes a more pressing matter. The Hydrogen Economy has been proposed as an answer to meeting the increasing energy demand for electric power generation and transportation in an environmentally benign way. Based on current hydrogen technology development, the most practical feedstock to fuel the Hydrogen Economy may prove to be coal via hydrogen production at FutureGen plants. The planned growth of the currently conceived Hydrogen Economy will cause dramatic impacts, some good and some bad, on the economy, the environment, and society, which are interlinked. The goal of this research is to provide tools to inform public policy makers in sorting out policy options related to coal and the Hydrogen Economy. This study examines the impact of a transition to a Hydrogen Economy on the coal industry by creating FutureGen penetration models, forecasting coal MFA's which clearly provide the impact on coal production and associated environmental impacts, and finally formulating a goal programming model that seeks the maximum benefit to society while analyzing the trade-offs between environmental, social, and economical concerns related to coal and the Hydrogen Economy.

Effect of reductive treatments on Pt behavior and NOx storage in lean NOx trap catalysts

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

Wang, Xianqin; Kim, Do Heui; Kwak, Ja Hun

2011-10-01

Lean NOx trap (LNT) catalysts represent a promising approach to meet increasingly stringent NOx emission regulations on diesel and other lean-burn engines. Pt material properties, including dispersion and particle size, are known to be important factors in determining NOx uptake performance, since Pt provides active sites for NO oxidation to NO2 necessary for storing NOx as nitrates, and for the reduction of nitrates to N2. In this work, the physicochemical properties of Pt in Pt-BaO/Al2O3 LNT catalysts, such as the Pt accessible surface area and particle size, were investigated by using various tools, such as irreversible volumetric H2 chemisorption, highmore » resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD), following successive reductive treatments at elevated temperatures. NOx uptake activities were also measured to establish a relationship between the properties of Pt and NOx storage following identical high-temperature reductive treatments. We find that the reductive treatments of Pt-BaO/Al2O3 lean NOx trap catalysts at temperatures up to 500 ºC promote a significant increase in NOx uptake explained, in part, by an induced close interaction between Pt and BaO phases in the catalyst, thus enabling facilitation of the NOx storage process.« less

78 FR 29815 - Control of Air Pollution From Motor Vehicles: Tier 3 Motor Vehicle Emission and Fuel Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-21

...This action would establish more stringent vehicle emissions standards and reduce the sulfur content of gasoline beginning in 2017, as part of a systems approach to addressing the impacts of motor vehicles and fuels on air quality and public health. The proposed gasoline sulfur standard would make emission control systems more effective for both existing and new vehicles, and would enable more stringent vehicle emissions standards. The proposed vehicle standards would reduce both tailpipe and evaporative emissions from passenger cars, light-duty trucks, medium-duty passenger vehicles, and some heavy-duty vehicles. This would result in significant reductions in pollutants such as ozone, particulate matter, and air toxics across the country and help state and local agencies in their efforts to attain and maintain health-based National Ambient Air Quality Standards. Motor vehicles are an important source of exposure to air pollution both regionally and near roads. These proposed vehicle standards are intended to harmonize with California's Low Emission Vehicle program, thus creating a federal vehicle emissions program that would allow automakers to sell the same vehicles in all 50 states. The proposed vehicle standards would be implemented over the same timeframe as the greenhouse gas/fuel efficiency standards for light-duty vehicles, as part of a comprehensive approach toward regulating emissions from motor vehicles.

Evaluating the fate of mercury and other metals across the life-cycle stages from the use of FGD gypsum for wallboard production

EPA Science Inventory

In 2007, 12.3 million tons of flue gas desulfurization (FGD) gypsum was produced due to air emission controls at coal-fired power plants. With increasing use of wet scrubbers in response to more stringent air pollution control requirements, FGD gypsum production is expected to in...

Novel pppGpp binding site at the C-terminal region of the Rel enzyme from Mycobacterium smegmatis.

PubMed

Syal, Kirtimaan; Joshi, Himanshu; Chatterji, Dipankar; Jain, Vikas

2015-10-01

Mycobacterium tuberculosis elicits the stringent response under unfavorable growth conditions, such as those encountered by the pathogen inside the host. The hallmark of this response is production of guanosine tetra- and pentaphosphates, collectively termed (p)ppGpp, which have pleiotropic effects on the bacterial physiology. As the stringent response is connected to survival under stress, it is now being targeted for developing inhibitors against bacterial persistence. The Rel enzyme in mycobacteria has two catalytic domains at its N-terminus that are involved in the synthesis and hydrolysis of (p)ppGpp, respectively. However, the function of the C-terminal region of the protein remained unknown. Here, we have identified a binding site for pppGpp in the C-terminal region of Rel. The binding affinity of pppGpp was quantified by isothermal titration calorimetry. The binding site was determined by crosslinking using the nucleotide analog azido-pppGpp, and examining the crosslink product by mass spectrometry. Additionally, mutations in the Rel protein were created to confirm the site of pppGpp binding by isothermal titration calorimetry. These mutants showed increased pppGpp synthesis and reduced hydrolytic activity. We believe that binding of pppGpp to Rel provides a feedback mechanism that allows the protein to detect and adjust the (p)ppGpp level in the cell. Our work suggests that such sites should also be considered while designing inhibitors to target the stringent response. © 2015 FEBS.

Critical needs for piston engine overhaul centre in Malaysia

NASA Astrophysics Data System (ADS)

Khairuddin, M. H.; Yahya, M. Y.; Johari, M. K.

2017-12-01

Piston engine overhaul centre (PEOC) is the branch of aviation Maintenance, Repair and Overhaul (MRO) providers, which plays a pivotal role in maintaining the fleet of business and commercial aircraft in the world. The centre typically offers three main MRO capabilities: airframe, engine and component services. Companies holding a PEOC(s) are all subjected to stringent procedures and conditions regulated and audited by the International Civil Aviation Organization. Currently, piston engine maintenance and repair for Asian countries is conducted only in Singapore. The focus of this study is to establish the needs for a PEOC in Malaysia, which will cater almost all small local aircraft companies such as transport and flying school companies.

A response to Dodds and Jones.

PubMed

Purdy, Laura M

1989-01-01

In response to "Surrogacy and Autonomy," by Susan Dodds and Karen Jones in this issue of Bioethics, the author concedes that only a surrogacy practice stringently regulated by good counseling, escape clauses for pregnant women, and the prohibition of profit-making agencies will save women from exploitation, but she objects to singling out women for paternalistic "protection against themselves," and to defending women's autonomy to the extent of their right to behave in ways known to harm a fetus. Dodds and Jones' concerns about attitudes toward women, genetic bias, the concept of children as property, and the harm principle generated by surrogacy contracts are answered with arguments for why surrogacy should not be illegal.

Chevron v Echazabal: Protection, Opportunity, and Paternalism

PubMed Central

Daniels, Norman

2003-01-01

The Supreme Court, in Chevron v Echazabal, ruled that risks to a disabled worker, if established by an individualized medical assessment, can disqualify the worker from protections offered by the Americans with Disabilities Act (ADA). This decision rejected the antipaternalist position of ADA advocates that workers with disabilities should be able to determine, through their own consent, the risks they will take. Such strong antipaternalism may not be compatible with the underlying justification for the protection of workers against health hazards. Stringent regulation of workplace hazards involves restricting the scope of consent to risk. Resolution of this conflict will depend on more careful examination of the degree to which individualized medical assessments avoid stereotyping and bias. PMID:12660194

Student Research and Ethics: Contributing to the Debate

ERIC Educational Resources Information Center

Winder, Belinda; Brunsden, Vivienne; Farnsworth, Bill

2007-01-01

In this article, the authors comment on Hugh Foot's article on student research and ethics ["Psychology Teaching Review," 12(1), 82-86 (2006)] The authors agree with Foot that there is no case for accepting less stringent ethical criteria when the researcher is a student. However, they argue that greater attention and more stringent measures…

40 CFR 35.910-7 - Fiscal Year 1977 Supplemental Appropriations Act allotments.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (secondary treatment, more stringent treatment required to meet water quality standards, and interceptor..., and V (secondary treatment, more stringent treatment required to meet water quality standards... Mexico 3,272,000 New York 105,294,000 North Carolina 20,722,000 North Dakota 3,272,000 Ohio 55,522,000...

76 FR 74057 - Clean Water Act Section 303(d): Availability of List Decisions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-30

... for which existing technology-based pollution controls are not stringent enough to attain or maintain... marine criterion for dissolved oxygen was not attained in these segments. EPA is providing the public the... which existing technology-based pollution controls are not stringent enough to attain or maintain State...

Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic Escherichia coli.

PubMed

Molina-Quiroz, Roberto C; Silva-Valenzuela, Cecilia; Brewster, Jennifer; Castro-Nallar, Eduardo; Levy, Stuart B; Camilli, Andrew

2018-01-09

Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli , as measured by survival after exposure to a β-lactam antibiotic. This phenotype is regulated by a set of genes leading to an oxidative stress response and SOS-dependent DNA repair. Thus, persister cells tolerant to cell wall-acting antibiotics must cope with oxidative stress and DNA damage and these processes are regulated by cyclic AMP in uropathogenic E. coli IMPORTANCE Bacterial persister cells are important in relapsing infections in patients treated with antibiotics and also in the emergence of antibiotic resistance. Our results show that in uropathogenic E. coli , the second messenger cyclic AMP negatively regulates persister cell formation, since in its absence much more persister cells form that are tolerant to β-lactams antibiotics. We reveal the mechanism to be decreased levels of reactive oxygen species, specifically hydroxyl radicals, and SOS-dependent DNA repair. Our findings suggest that the oxidative stress response and DNA repair are relevant pathways to target in the design of persister-specific antibiotic compounds. Copyright © 2018 Molina-Quiroz et al.

Environmentally regulated aerospace coatings

NASA Technical Reports Server (NTRS)

Morris, Virginia L.

1995-01-01

Aerospace coatings represent a complex technology which must meet stringent performance requirements in the protection of aerospace vehicles. Topcoats and primers are used, primarily, to protect the structural elements of the air vehicle from exposure to and subsequent degradation by environmental elements. There are also many coatings which perform special functions, i.e., chafing resistance, rain erosion resistance, radiation and electric effects, fuel tank coatings, maskants, wire and fastener coatings. The scheduled promulgation of federal environmental regulations for aerospace manufacture and rework materials and processes will regulate the emissions of photochemically reactive precursors to smog and air toxics. Aerospace organizations will be required to identify, qualify and implement less polluting materials. The elimination of ozone depleting chemicals (ODC's) and implementation of pollution prevention requirements are added constraints which must be addressed concurrently. The broad categories of operations affected are the manufacture, operation, maintenance, and repair of military, commercial, general aviation, and space vehicles. The federal aerospace regulations were developed around the precept that technology had to be available to support the reduction of organic and air toxic emissions, i.e., the regulations cannot be technology forcing. In many cases, the regulations which are currently in effect in the South Coast Air Quality Management District (SCAQMD), located in Southern California, were used as the baseline for the federal regulations. This paper addresses strategies used by Southern California aerospace organizations to cope with these regulatory impacts on aerospace productions programs. All of these regulatory changes are scheduled for implementation in 1993 and 1994, with varying compliance dates established.

Animal experimentation in snake venom research and in vitro alternatives.

PubMed

Sells, Paula G

2003-08-01

Current experimental techniques used in snake venom research (with and without the use of animals) are reviewed. The emphasis is on the reduction of the use of animals in the development of antivenoms for the clinical treatment of snakebite. Diagnostic and research techniques for the major pathologies of envenoming are described and those using animals are contrasted with non-sentient methods where possible. In particular, LD50 and ED50 assays using animals (in vivo) and fertilised eggs (in vivo, non-sentient) are compared as well as in vitro procedures (ELISA and haemolytic test) for ED50 estimations. The social context of antivenom production, supply and demand is outlined together with the consequent tension between the benefits derived and the increase in opposition to experiments on animals. Stringent regulations governing the use of animals, limited research funds and public pressure all focus the need for progress towards non-animal, or non-sentient, research methods. Some achievements are noted but success is hampered by lack of detailed knowledge of the many constituents of venom which have to be assessed as a whole rather than individually. The only way to evaluate the net pathological effect of venom is to use a living system, usually a rodent, and similarly, the efficacy of antivenoms is also measured in vivo. The pre-clinical testing of antivenoms in animals is therefore a legal requirement in many countries and is strictly monitored by government authorities. New technologies applied to the characterisation of individual venom proteins should enable novel in vitro assays to be designed thus reducing the number of animals required. In the meantime, the principles of Reduce, Refine and Replace relating to animals in research are increasingly endorsed by those working in the field and the many agencies regulating ethical and research policy.

Air quality and respiratory health in Delhi.

PubMed

Nidhi; Jayaraman, Girija

2007-12-01

Delhi is an instructive location for studying the impact of air pollution since it is a rapidly expanding centre of government, trade commerce and industry. We have made an attempt to (1) determine the association between environmental pollution and respiratory morbidity in Delhi for the period 1998-2004, (2) assess the impact on hospital admission of the implementation of recent governmental regulations and (3) calculate the relative risk of hospitalization due to respiratory ailments caused by air pollutants. Seven hospitals from different parts of Delhi were selected. The pollution profiles of these areas were assessed and subsequently Poisson regression model was performed for the patient population. There was a remarkable decrease in monthly average concentration of sulphur dioxide (from 17.9 to 11.1 microg m(-3)) and increase in monthly average concentration of nitrogen dioxide (from 34.2 to 49.1 microg m(-3)) after the newly introduced regulations. Particulates were observed to have marginal fall in their concentration but still remained above the permissible limits. Gaseous pollutants, in spite of being at a level lower than the permissible level, showed more consistent significant association with respiratory admissions. The relative risks of hospitalization due to respiratory diseases were in the range of 1.07-2.82 in residential cum commercial areas. Comparative study of pre and post new stringent governmental regulation showed significant positive association of NO(2) with respiratory disorders in southern (RR: 1.10; CI: 1.09-1.12) and northern regions (RR: 1.33; CI: 1.27-1.39), both mixed use areas. In spite of the improvement in the air quality, the associated health effects were found to be substantial.

Sorbent Nanotechnologies for Water Cleaning

NASA Astrophysics Data System (ADS)

Ahmed, Snober

Despite decades of regulatory efforts to mitigate water pollution, many chemicals, particularly heavy metals, still present risks to human health. In addition to direct exposure, certain metals such as mercury threaten public health due to its persistence, bioaccumulation and bioamplification throughout the food chain. A number of U.S. Federal and State regulations have been established to reduce the levels of mercury in water. Activated carbon (AC) has been widely explored for the removal of mercury. However, AC suffers from many limitations inherent to its chemical properties, and it becomes increasingly challenging to meet current and future regulations by simply modifying AC to enhance its performance. Recently, the performance of nanosorbents have been studied in order to removal pollutants. Nanosorbents utilize the ultra-high reactive surface of nanoparticles for rapid, effective and even permanent sequestration of heavy metals from water and air, thus showed promising results as compared to AC. The goal of this thesis research is to develop nanomaterial-based sorbents for the removal of mercury from water. It describes the development of a new solid-support assisted growth of selenium nanoparticles, their use for water remediation, and the development of a new nanoselenium-based sorbent sponge for fast and efficient mercury removal. The nanoselenium sorbent not only shows irreversible interaction with mercury but also exhibits remarkable properties by overcoming the limitations of AC. The nanoselenium sponge was shown to remove mercury to undetectable levels within one minute. This new sponge technology would have an impact on inspiring new stringent regulations and lowering costs to help industries meet regulatory requirements, which will ultimately help improve air and water quality, aquatic life and public health.

Analysis of multiuser mixed RF/FSO relay networks for performance improvements in Cloud Computing-Based Radio Access Networks (CC-RANs)

NASA Astrophysics Data System (ADS)

Alimi, Isiaka A.; Monteiro, Paulo P.; Teixeira, António L.

2017-11-01

The key paths toward the fifth generation (5G) network requirements are towards centralized processing and small-cell densification systems that are implemented on the cloud computing-based radio access networks (CC-RANs). The increasing recognitions of the CC-RANs can be attributed to their valuable features regarding system performance optimization and cost-effectiveness. Nevertheless, realization of the stringent requirements of the fronthaul that connects the network elements is highly demanding. In this paper, considering the small-cell network architectures, we present multiuser mixed radio-frequency/free-space optical (RF/FSO) relay networks as feasible technologies for the alleviation of the stringent requirements in the CC-RANs. In this study, we use the end-to-end (e2e) outage probability, average symbol error probability (ASEP), and ergodic channel capacity as the performance metrics in our analysis. Simulation results show the suitability of deployment of mixed RF/FSO schemes in the real-life scenarios.

Integrated assessment of health, crop, and climate impacts of mitigating excess diesel NOx emissions in 11 major vehicle markets

NASA Astrophysics Data System (ADS)

Henze, D. K.; Anenberg, S.; Miller, J.; Vicente, F.; Du, L.; Emberson, L.; Lacey, F.; Malley, C.; Minjares, R. J.

2016-12-01

Vehicle emissions contribute to tropospheric ozone and fine particulate matter (PM2.5), impacting human health, crop yields, and climate worldwide. Diesel cars, trucks, and buses produce 70% of global land transportation emissions of nitrogen oxides (NOx), a key PM2.5 and ozone precursor. Despite progressive tightening of regulated NOx emission limits in leading markets, current diesel vehicles emit far more NOx under real-world operating conditions than during laboratory certification testing. Here we show that real-world diesel NOx emissions in 11 markets representing 80% of global diesel vehicle sales are on average 24% higher than certification limits indicate. This excess NOx contributed an estimated 33,000 additional ozone- and PM2.5-related premature deaths globally in 2015, including 6% of all EU-28 ozone- and PM2.5-related premature deaths. Next-generation diesel NOx standards and in-use compliance (more stringent than Euro 6/VI standards) could avoid 358,000 (5%) of global PM2.5- and ozone-related premature deaths in 2040 and up to 4% of ozone-related crop production loss regionally. Impacts of NOx-induced changes in aerosols, methane, and ozone on the global climate are found to present a small net positive radiative forcing (i.e., climate disbenefit), likely outweighed by the climate benefits of reductions to co-emitted black carbon aerosol. In some markets (Australia, Brazil, China, Mexico, and Russia), Euro 6/VI standards alone can achieve most (72-98%) of these health benefits. In India and the EU-28, reducing Euro 6 real-world NOx emissions through strengthened type-approval and in-use emissions testing programs (including market surveillance and expanded emissions test procedure boundaries) would achieve one-third of the health benefits from adopting next generation standards. Our results indicate that implementing stringent and technically feasible NOx emission regulations for diesel vehicles can substantially improve public health.

Cellular manganese content is developmentally regulated in human dopaminergic neurons

NASA Astrophysics Data System (ADS)

Kumar, Kevin K.; Lowe, Edward W., Jr.; Aboud, Asad A.; Neely, M. Diana; Redha, Rey; Bauer, Joshua A.; Odak, Mihir; Weaver, C. David; Meiler, Jens; Aschner, Michael; Bowman, Aaron B.

2014-10-01

Manganese (Mn) is both an essential biological cofactor and neurotoxicant. Disruption of Mn biology in the basal ganglia has been implicated in the pathogenesis of neurodegenerative disorders, such as parkinsonism and Huntington's disease. Handling of other essential metals (e.g. iron and zinc) occurs via complex intracellular signaling networks that link metal detection and transport systems. However, beyond several non-selective transporters, little is known about the intracellular processes regulating neuronal Mn homeostasis. We hypothesized that small molecules that modulate intracellular Mn could provide insight into cell-level Mn regulatory mechanisms. We performed a high throughput screen of 40,167 small molecules for modifiers of cellular Mn content in a mouse striatal neuron cell line. Following stringent validation assays and chemical informatics, we obtained a chemical `toolbox' of 41 small molecules with diverse structure-activity relationships that can alter intracellular Mn levels under biologically relevant Mn exposures. We utilized this toolbox to test for differential regulation of Mn handling in human floor-plate lineage dopaminergic neurons, a lineage especially vulnerable to environmental Mn exposure. We report differential Mn accumulation between developmental stages and stage-specific differences in the Mn-altering activity of individual small molecules. This work demonstrates cell-level regulation of Mn content across neuronal differentiation.

Genome-wide mRNA processing in methanogenic archaea reveals post-transcriptional regulation of ribosomal protein synthesis

PubMed Central

Qi, Lei; Yue, Lei; Feng, Deqin; Qi, Fengxia

2017-01-01

Abstract Unlike stable RNAs that require processing for maturation, prokaryotic cellular mRNAs generally follow an ‘all-or-none’ pattern. Herein, we used a 5΄ monophosphate transcript sequencing (5΄P-seq) that specifically captured the 5΄-end of processed transcripts and mapped the genome-wide RNA processing sites (PSSs) in a methanogenic archaeon. Following statistical analysis and stringent filtration, we identified 1429 PSSs, among which 23.5% and 5.4% were located in 5΄ untranslated region (uPSS) and intergenic region (iPSS), respectively. A predominant uridine downstream PSSs served as a processing signature. Remarkably, 5΄P-seq detected overrepresented uPSS and iPSS in the polycistronic operons encoding ribosomal proteins, and the majority upstream and proximal ribosome binding sites, suggesting a regulatory role of processing on translation initiation. The processed transcripts showed increased stability and translation efficiency. Particularly, processing within the tricistronic transcript of rplA-rplJ-rplL enhanced the translation of rplL, which can provide a driving force for the 1:4 stoichiometry of L10 to L12 in the ribosome. Growth-associated mRNA processing intensities were also correlated with the cellular ribosomal protein levels, thereby suggesting that mRNA processing is involved in tuning growth-dependent ribosome synthesis. In conclusion, our findings suggest that mRNA processing-mediated post-transcriptional regulation is a potential mechanism of ribosomal protein synthesis and stoichiometry. PMID:28520982

New frontier, new power: the retail environment in Australia's dark market

PubMed Central

Carter, S

2003-01-01

Objective: To investigate the role of the retail environment in cigarette marketing in Australia, one of the "darkest" markets in the world. Design: Analysis of 172 tobacco industry documents; and articles and advertisements found by hand searching Australia's three leading retail trade journals. Results: As Australian cigarette marketing was increasingly restricted, the retail environment became the primary communication vehicle for building cigarette brands. When retail marketing was restricted, the industry conceded only incrementally and under duress, and at times continues to break the law. The tobacco industry targets retailers via trade promotional expenditure, financial and practical assistance with point of sale marketing, alliance building, brand advertising, and distribution. Cigarette brand advertising in retail magazines are designed to build brand identities. Philip Morris and British American Tobacco are now competing to control distribution of all products to retailers, placing themselves at the heart of retail business. Conclusions: Cigarette companies prize retail marketing in Australia's dark market. Stringent point of sale marketing restrictions should be included in any comprehensive tobacco control measures. Relationships between retailers and the industry will be more difficult to regulate. Retail press advertising and trade promotional expenditure could be banned. In-store marketing assistance, retail–tobacco industry alliance building, and new electronic retail distribution systems may be less amenable to regulation. Alliances between the health and retail sectors and financial support for a move away from retail dependence on tobacco may be necessary to effect cultural change. PMID:14645954

A genome-wide survey of maternal and embryonic transcripts during Xenopus tropicalis development.

PubMed

Paranjpe, Sarita S; Jacobi, Ulrike G; van Heeringen, Simon J; Veenstra, Gert Jan C

2013-11-06

Dynamics of polyadenylation vs. deadenylation determine the fate of several developmentally regulated genes. Decay of a subset of maternal mRNAs and new transcription define the maternal-to-zygotic transition, but the full complement of polyadenylated and deadenylated coding and non-coding transcripts has not yet been assessed in Xenopus embryos. To analyze the dynamics and diversity of coding and non-coding transcripts during development, both polyadenylated mRNA and ribosomal RNA-depleted total RNA were harvested across six developmental stages and subjected to high throughput sequencing. The maternally loaded transcriptome is highly diverse and consists of both polyadenylated and deadenylated transcripts. Many maternal genes show peak expression in the oocyte and include genes which are known to be the key regulators of events like oocyte maturation and fertilization. Of all the transcripts that increase in abundance between early blastula and larval stages, about 30% of the embryonic genes are induced by fourfold or more by the late blastula stage and another 35% by late gastrulation. Using a gene model validation and discovery pipeline, we identified novel transcripts and putative long non-coding RNAs (lncRNA). These lncRNA transcripts were stringently selected as spliced transcripts generated from independent promoters, with limited coding potential and a codon bias characteristic of noncoding sequences. Many lncRNAs are conserved and expressed in a developmental stage-specific fashion. These data reveal dynamics of transcriptome polyadenylation and abundance and provides a high-confidence catalogue of novel and long non-coding RNAs.

Tourists' attitudes towards ban on smoking in air-conditioned hotel lobbies in Thailand.

PubMed

Viriyachaiyo, V; Lim, A

2009-06-01

Thailand is internationally renowned for its stringent tobacco control measures. In Thailand, a regulation banning smoking in air-conditioned hotel lobbies was issued in late 2006, causing substantial apprehension within the hospitality industry. A survey of tourists' attitudes toward the ban was conducted. A cross-sectional survey of 5550 travellers staying in various hotels in Bangkok, Surat Thani, Phuket, Krabi and Songkhla provinces, October 2005 to December 2006. Travellers aged 15 years or older with a check-in duration of at least one day and willing to complete the questionnaire were requested by hotel staff to fill in the 5-minute questionnaire at check-in or later at their convenience. Secondhand cigarette smoke was recognised as harmful to health by 89.7% of respondents. 47.8% of travellers were aware of the Thai regulation banning smoking in air-conditioned restaurants. 80.9% of the respondents agreed with the ban, particularly female non-smokers. 38.6% of survey respondents indicated that they would be more likely to visit Thailand again because of the regulation, 53.4% that the regulation would not affect their decision and 7.9% that they would be less likely to visit Thailand again. Banning smoking in air-conditioned hotel lobbies in Thailand is widely supported by tourists. Enforcement of the regulation is more likely to attract tourists than dissuade them from holidaying in Thailand.

Tourists’ attitudes towards ban on smoking in air-conditioned hotel lobbies in Thailand

PubMed Central

Viriyachaiyo, V; Lim, A

2009-01-01

Background: Thailand is internationally renowned for its stringent tobacco control measures. In Thailand, a regulation banning smoking in air-conditioned hotel lobbies was issued in late 2006, causing substantial apprehension within the hospitality industry. A survey of tourists’ attitudes toward the ban was conducted. Methods: A cross-sectional survey of 5550 travellers staying in various hotels in Bangkok, Surat Thani, Phuket, Krabi and Songkhla provinces, October 2005 to December 2006. Travellers aged 15 years or older with a check-in duration of at least one day and willing to complete the questionnaire were requested by hotel staff to fill in the 5-minute questionnaire at check-in or later at their convenience. Results: Secondhand cigarette smoke was recognised as harmful to health by 89.7% of respondents. 47.8% of travellers were aware of the Thai regulation banning smoking in air-conditioned restaurants. 80.9% of the respondents agreed with the ban, particularly female non-smokers. 38.6% of survey respondents indicated that they would be more likely to visit Thailand again because of the regulation, 53.4% that the regulation would not affect their decision and 7.9% that they would be less likely to visit Thailand again. Conclusion: Banning smoking in air-conditioned hotel lobbies in Thailand is widely supported by tourists. Enforcement of the regulation is more likely to attract tourists than dissuade them from holidaying in Thailand. PMID:19364754

State of play in direct-to-consumer genetic testing for lifestyle-related diseases: market, marketing content, user experiences and regulation.

PubMed

Saukko, Paula

2013-02-01

Direct-to-consumer (DTC) genetic tests have aroused controversy. Critics have argued many of the tests are not backed by scientific evidence, misguide their customers and should be regulated more stringently. Proponents suggest that finding out genetic susceptibilities for diseases could encourage healthier behaviours and makes the results of genetics research available to the public. This paper reviews the state of play in DTC genetic testing, focusing on tests identifying susceptibilities for lifestyle-related diseases. It will start with mapping the market for the tests. The paper will review (1) research on the content of the online marketing of DTC tests, (2) studies on the effects of DTC genetic tests on customers and (3) academic and policy proposals on how to regulate the tests. Current studies suggest that the marketing of DTC genetic tests often exaggerates their predictive powers, which could misguide consumers. However, research indicates that the tests do not seem to have major negative effects (worry and confusion) but neither do they engender positive effects (lifestyle change) on current users. Research on regulation of the tests has most commonly suggested regulating the marketing claims of the companies. In conclusion, the risks and benefits of DTC genetic tests are less significant than what has been predicted by critics and proponents, which will be argued reflects broader historical trends transforming health and medicine.

A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly

PubMed Central

Vavassori, Stefano; Cortini, Margherita; Masui, Shoji; Sannino, Sara; Anelli, Tiziana; Caserta, Imma R.; Fagioli, Claudio; Mossuto, Maria F.; Fornili, Arianna; van Anken, Eelco; Degano, Massimo; Inaba, Kenji; Sitia, Roberto

2013-01-01

Summary To warrant the quality of the secretory proteome, stringent control systems operate at the endoplasmic reticulum (ER)-Golgi interface, preventing the release of nonnative products. Incompletely assembled oligomeric proteins that are deemed correctly folded must rely on additional quality control mechanisms dedicated to proper assembly. Here we unveil how ERp44 cycles between cisGolgi and ER in a pH-regulated manner, patrolling assembly of disulfide-linked oligomers such as IgM and adiponectin. At neutral, ER-equivalent pH, the ERp44 carboxy-terminal tail occludes the substrate-binding site. At the lower pH of the cisGolgi, conformational rearrangements of this peptide, likely involving protonation of ERp44’s active cysteine, simultaneously unmask the substrate binding site and −RDEL motif, allowing capture of orphan secretory protein subunits and ER retrieval via KDEL receptors. The ERp44 assembly control cycle couples secretion fidelity and efficiency downstream of the calnexin/calreticulin and BiP-dependent quality control cycles. PMID:23685074

The role of passive sampling in monitoring the environmental impacts of produced water discharges from the Norwegian oil and gas industry.

PubMed

Hale, Sarah E; Oen, Amy M P; Cornelissen, Gerard; Jonker, Michiel T O; Waarum, Ivar-Kristian; Eek, Espen

2016-10-15

Stringent and periodic iteration of regulations related to the monitoring of chemical releases from the offshore oil and gas industry requires the use of ever changing, rapidly developing and technologically advancing techniques. Passive samplers play an important role in water column monitoring of produced water (PW) discharge to seawater under Norwegian regulation, where they are used to; i) measure aqueous concentrations of pollutants, ii) quantify the exposure of caged organisms and investigate PW dispersal, and iii) validate dispersal models. This article summarises current Norwegian water column monitoring practice and identifies research and methodological gaps for the use of passive samplers in monitoring. The main gaps are; i) the range of passive samplers used should be extended, ii) differences observed in absolute concentrations accumulated by passive samplers and organisms should be understood, and iii) the link between PW discharge concentrations and observed acute and sub-lethal ecotoxicological end points in organisms should be investigated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Downsizing Antenna Technologies for Mobile and Satellite Communications

NASA Technical Reports Server (NTRS)

Huang, J.; Densmore, A.; Tulintseff, A.; Jamnejad, V.

1993-01-01

Due to the increasing and stringent functional requirements (larger capacity, longer distances, etc.) of modern day communication systems, higher antenna gains are generally needed. This higher gain implies larger antenna size and mass which are undesirable to many systems. Consequently, downsizing antenna technology becomes one of the most critical areas for research and development efforts. Techniques to reduce antenna size can be categorized and are briefly discussed.

Lightweight Solar Photovoltaic Blankets

NASA Technical Reports Server (NTRS)

Ceragioli, R.; Himmler, R.; Nath, P.; Vogeli, C.; Guha, S.

1995-01-01

Lightweight, flexible sheets containing arrays of stacked solar photovoltaic cells developed to supply electric power aboard spacecraft. Solar batteries satisfying stringent requirements for operation in outer space also adaptable to terrestrial environment. Attractive for use as long-lived, portable photovoltaic power sources. Cells based on amorphous silicon which offers potential for order-of-magnitude increases in power per unit weight, power per unit volume, and endurance in presence of ionizing radiation.

Low Impact Development for Industrial Areas

DTIC Science & Technology

2015-07-01

Stormwater program managers are faced with increasingly stringent stormwater discharge limits for heavy metals such as copper, zinc , nutrients, total...limits for heavy metals such as copper, zinc , nutrients, total suspended solids (TSS), oil and grease. These limits are required to reduce...U.S. EPA), state agencies, and local agencies set permit limits as part of the total mass daily loading regulatory framework. Copper, zinc , lead

National Strategy for Homeland Security

DTIC Science & Technology

2007-10-01

biometrics, including in passports and visas, has made it increasingly diffi- cult to counterfeit travel docu- ments, and we must encourage those... counterfeiting , altera- tion, and misuse of identifica- tion and travel documents, and to report lost and stolen passports in a timely manner. These efforts...in medicine , agriculture, and industry. We will stringently enforce our export control laws as a means of denying rogue actors – including

Comparison of CpG island methylator phenotype (CIMP) frequency in colon cancer using different probe- and gene-specific scoring alternatives on recommended multi-gene panels.

PubMed

Berg, Marianne; Hagland, Hanne R; Søreide, Kjetil

2014-01-01

In colorectal cancer a distinct subgroup of tumours demonstrate the CpG island methylator phenotype (CIMP). However, a consensus of how to score CIMP is not reached, and variation in definition may influence the reported CIMP prevalence in tumours. Thus, we sought to compare currently suggested definitions and cut-offs for methylation markers and how they influence CIMP classification in colon cancer. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), with subsequent fragment analysis, was used to investigate methylation of tumour samples. In total, 31 CpG sites, located in 8 different genes (RUNX3, MLH1, NEUROG1, CDKN2A, IGF2, CRABP1, SOCS1 and CACNA1G) were investigated in 64 distinct colon cancers and 2 colon cancer cell lines. The Ogino gene panel includes all 8 genes, in addition to the Weisenberger panel of which only 5 of the 8 genes included were investigated. In total, 18 alternative combinations of scoring of CIMP positivity on probe-, gene-, and panel-level were analysed and compared. For 47 samples (71%), the CIMP status was constant and independent of criteria used for scoring; 34 samples were constantly scored as CIMP negative, and 13 (20%) consistently scored as CIMP positive. Only four of 31 probes (13%) investigated showed no difference in the numbers of positive samples using the different cut-offs. Within the panels a trend was observed that increasing the gene-level stringency resulted in a larger difference in CIMP positive samples than increasing the probe-level stringency. A significant difference between positive samples using 'the most stringent' as compared to 'the least stringent' criteria (20% vs 46%, respectively; p<0.005) was demonstrated. A statistical significant variation in the frequency of CIMP depending on the cut-offs and genes included in a panel was found, with twice as many positives samples by least compared to most stringent definition used.

Best performing definition of accelerated knee osteoarthritis: data from the Osteoarthritis Initiative

PubMed Central

Driban, Jeffrey B.; Stout, Alina C.; Lo, Grace H.; Eaton, Charles B.; Price, Lori Lyn; Lu, Bing; Barbe, Mary F.; McAlindon, Timothy E.

2016-01-01

Background: We evaluated agreement among several definitions of accelerated knee osteoarthritis (AKOA) and construct validity by comparing their individual associations with injury, age, obesity, and knee pain. Methods: We selected knees from the Osteoarthritis Initiative that had no radiographic knee osteoarthritis [Kellgren–Lawrence (KL) 0 or 1] at baseline and had high-quality quantitative medial joint space width (JSW) measures on two or more consecutive visits (n = 1655 knees, 1143 participants). Quantitative medial JSW was based on a semi-automated method and was location specific (x = 0.25). We compared six definitions of AKOA: stringent JSW (averaged): average JSW loss greater than 1.05 mm/year over 4 years; stringent JSW (consistent): JSW loss greater than 1.05 mm/year for at least 2 years; lenient JSW (averaged): average JSW loss greater than 0.25 mm/year over 4 years; lenient JSW (consistent): JSW loss greater than 0.25 mm/year for at least 2 years; comprehensive KL based: progression from no radiographic osteoarthritis to advance-stage osteoarthritis (KL 3 or 4; development of definite osteophyte and joint space narrowing) within 4 years; and lenient KL based: an increase of at least two KL grades within 4 years. Results: Over 4 years the incidence rate of AKOA was 0.4%, 0.8%, 15.5%, 22.1%, 12.4%, and 7.2% based on the stringent JSW (averaged and consistent), lenient JSW (averaged and consistent), lenient KL-based definition, and comprehensive KL-based definition. All but one knee that met the stringent JSW definition also met the comprehensive KL-based definition. There was fair substantial agreement between the lenient JSW (averaged), lenient KL-based, and comprehensive KL-based definitions. A comprehensive KL-based definition led to larger effect sizes for injury, age, body mass index, and average pain over 4 years. Conclusions: A comprehensive KL-based definition of AKOA may be ideal because it represents a broader definition of joint deterioration compared with those focused on just joint space or osteophytes alone. PMID:27721902

33 CFR 154.1045 - Response plan development and evaluation criteria for facilities that handle, store, or transport...

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Reclassifications may be to— (i) A more stringent operating environment if the prevailing wave conditions exceed the significant wave height criteria during more than 35 percent of the year; or (ii) A less stringent operating environment if the prevailing wave conditions do not exceed the significant wave height criteria for the less...

Environmental projects. Volume 2: Underground storage tanks compliance program

NASA Technical Reports Server (NTRS)

Kushner, L.

1987-01-01

Six large parabolic dish antennas are located at the Goldstone Deep Space Communications Complex north of Barstow, California. As a large-scale facility located in a remote, isolated desert region, the GDSCC operations require numerous on-site storage facilities for gasoline, diesel and hydraulic oil. These essential fluids are stored in underground storage tanks (USTs). Because USTs may develop leaks with the resultant seepage of their hazardous contents into the surrounding soil, local, State and Federal authorities have adopted stringent regulations for the testing and maintenance of USTs. Under the supervision of JPL's Office of Telecommunications and Data Acquisition, a year-long program has brought 27 USTs at the Goldstone Complex into compliance with Federal, State of California and County of San Bernadino regulations. Of these 27 USTs, 15 are operating today, 11 have been temporary closed down, and 1 abandoned in place. In 1989, the 15 USTs now operating at the Goldstone DSCC will be replaced either by modern, double-walled USTs equipped with automatic sensors for leak detection, or by above ground storage tanks. The 11 inactivated USTs are to be excavated, removed and disposed of according to regulation.

Bee guide to complying with the Safe Drinking Water Act. Final report

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

Garland, J.G.; Acker, A.M.

This report provides current information on the Safe Drinking Water Act and recent amendments. The report describes the evolution of the Safe Drinking Water Act and the responsibilities of base personnel involved in compliance with the Act. It also describes the monitoring requirements, analytical requirements, best available technology for controlling contaminants, and public notification requirements for regulated contaminants. The appendixes include proposed contaminants and state water quality agencies. Each Air Force public water distribution system (PWDS) must comply with the SDWA, and the National Primary Drinking Water Regulations (NPDWRs). In the United States and its territories, the provisions of themore » SDWA and the NPDWRs are enforced by the states except in the few instances in which the state has not been delegated primary enforcement responsibility (primacy) by the EPA. States that have primacy may establish drinking water regulations, monitoring schedules, and reporting requirements more stringent than, or in addition to, those in the NPDWRs. Air Force public water systems in these states are required to comply with these additional requirements as well as federal enforcement actions as carried out by the EPA Regional Office.« less

Suppressor of cytokine signaling 1 (SOCS1) mitigates anterior uveitis and confers protection against ocular HSV-1 infection.

PubMed

Yu, Cheng-Rong; Hayashi, Kozaburo; Lee, Yun Sang; Mahdi, Rashid M; Shen, De Fen; Chan, Chi-Chao; Egwuagu, Charles E

2015-04-01

Immunological responses to pathogens are stringently regulated in the eye to prevent excessive inflammation that damage ocular tissues and compromise vision. Suppressors of cytokine signaling (SOCS) regulate intensity/duration of inflammatory responses. We have used SOCS1-deficient mice and retina-specific SOCS1 transgenic rats to investigate roles of SOCS1 in ocular herpes simplex virus (HSV-1) infection and non-infectious uveitis. We also genetically engineered cell-penetrating SOCS proteins (membrane-translocating sequence (MTS)-SOCS1, MTS-SOCS3) and examined whether they can be used to inhibit inflammatory cytokines. Overexpression of SOCS1 in transgenic rat eyes attenuated ocular HSV-1 infection while SOCS1-deficient mice developed severe non-infectious anterior uveitis, suggesting that SOCS1 may contribute to mechanism of ocular immune privilege by regulating trafficking of inflammatory cells into ocular tissues. Furthermore, MTS-SOCS1 inhibited IFN-γ-induced signal transducers and activators of transcription 1 (STAT1) activation by macrophages while MTS-SOCS3 suppressed expansion of pathogenic Th17 cells that mediate uveitis, indicating that MTS-SOCS proteins maybe used to treat ocular inflammatory diseases of infectious or autoimmune etiology.

What should health insurance cover? A comparison of Israeli and US approaches to benefit design under national health reform.

PubMed

Nissanholtz Gannot, Rachel; Chinitz, David P; Rosenbaum, Sara

2018-04-01

What health insurance should cover and pay for represents one of the most complex questions in national health policy. Israel shares with the US reliance on a regulated insurance market and we compare the approaches of the two countries regarding determining health benefits. Based on review and analysis of literature, laws and policy in the United States and Israel. The Israeli experience consists of selection of a starting point for defining coverage; calculating the expected cost of covered benefits; and creating a mechanism for updating covered benefits within a defined budget. In implementing the Affordable Care Act, the US rejected a comprehensive and detailed approach to essential health benefits. Instead, federal regulators established broadly worded minimum standards that can be supplemented through more stringent state laws and insurer discretion. Notwithstanding differences between the two systems, the elements of the Israeli approach to coverage, which has stood the test of time, may provide a basis for the United States as it renews its health reform debate and considers delegating decisions about coverage to the states. Israel can learn to emulate the more forceful regulation of supplemental and private insurance that characterizes health policy in the United States.

Managing conflicts of interest in clinical care: the "race to the middle" at U.S. medical schools.

PubMed

Chimonas, Susan; Evarts, Susanna D; Littlehale, Sarah K; Rothman, David J

2013-10-01

National recommendations specify how medical schools should manage clinical conflicts of interest (CCOIs), including gifts and payments to physicians from pharmaceutical companies. A 2008 study showed that few schools had policies in keeping with the recommendations. The authors conducted a follow-up study in 2011 to assess possible improvements. To obtain policies in 12 areas of CCOI, the authors searched the Web sites of all 133 medical schools existing in July 2011 and contacted schools that had no online policies. Policies were scored as no policy, permissive, moderate, or stringent, based on published recommendations; each school's scores were averaged to assess overall policy strength. Changes since 2008 were evaluated. The authors also collected information on schools' public/private status, hospital ownership/affiliation, and National Institutes of Health (NIH) funding to determine whether these characteristics were associated with differences in policy strength. Policies were obtained for a representative sample of 127 (95%) medical schools. The frequency of stringent policies increased from 2008 to 2011 in all CCOI areas, and medical schools' overall policy strength more than doubled. However, less than stringent policies remained the norm for all areas except ghostwriting. Greater NIH funding was associated with stronger policies in five areas and with higher overall policy strength. Schools have made great progress toward national standards, yet room for improvement remains: The data reveal not a race to the top but a shift from the bottom to the middle. Follow-up research should explore whether stronger policies emerge in the future.

Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients

PubMed Central

Yang, Ju-Yeh; Lee, Tsung-Chun; Montez-Rath, Maria E.; Paik, Jane; Chertow, Glenn M.; Desai, Manisha

2012-01-01

Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial. PMID:22266666

Overview of differences between microbial feed additives and probiotics for food regarding regulation, growth promotion effects and health properties and consequences for extrapolation of farm animal results to humans.

PubMed

Bernardeau, M; Vernoux, J-P

2013-04-01

For many years, microbial adjuncts have been used to supplement the diets of farm animals and humans. They have evolved since the 1990s to become known as probiotics, i.e. functional food with health benefits. After the discovery of a possible link between manipulation of gut microflora in mice and obesity, a focus on the use of these beneficial microbes that act on gut microflora in animal farming was undertaken and compared with the use of probiotics for food. Beneficial microbes added to feed are classified at a regulatory level as zootechnical additives, in the category of gut flora stabilizers for healthy animals and are regulated up to strain level in Europe. Intended effects are improvement of performance characteristics, which are strain dependent and growth enhancement is not a prerequisite. In fact, increase of body weight is not commonly reported and its frequency is around 25% of the published data examined here. However, when a Body Weight Gain (BWG) was found in the literature, it was generally moderate (lower than or close to 10%) and this over a reduced period of their short industrial life. When it was higher than 10%, it could be explained as an indirect consequence of the alleviation of the weight losses linked to stressful intensive rearing conditions or health deficiency. However, regulations on feed do not consider the health effects because animals are supposed to be healthy, so there is no requirement for reporting healthy effects in the standard European dossier. The regulations governing the addition of beneficial microorganisms to food are less stringent than for feed and no dossier is required if a species has a Qualified Presumption of Safety status. The microbial strain marketed is not submitted to any regulation and its properties (including BWG) do not need to be studied. Only claims for functional or healthy properties are regulated and again growth effect is not included. However, recent studies on probiotic effects showed that BWG could also be observed in humans, or not, according to species and strains. Determining the significance of farm animal results for extrapolation to humans, especially regarding body weight improvement, was not easy because they do not use the same microbial strains nor always the same species. Furthermore, the framework for the management of microbials added to feed or to food differ, especially with regard to goal, timescale and lifestyle. So no one can exclude the possibility that beneficial microorganisms having probiotic effects may have long-term effects in humans that cannot be seen to date in animals, where short-term use is the rule. A possible link to obesity cannot be excluded in relation to timescale, species and strain specificity. To conclude, beneficial microorganisms added in feed are key factors stringently regulated for short-term improvement of zootechnical performances in animals and their use does not entirely parallel that of human probiotics. So extrapolation of farm animal results to humans is biased and not sufficient to be conclusive regarding the existence or not of a link between probiotics and obesity. From a toxicological and nutritional point of view and considering recent findings on a link between antibiotic use in early life and excessive risk of becoming overweight, one suggestion is to study the at-risk population in Europe, pregnant women and their babies before and after birth and during early childhood, in an epidemiological long-term cohort survey. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Hoisting and Rigging (Formerly Hoisting and Rigging Manual)

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

NONE

1995-06-01

This standard is intended as a reference document to be used by supervisors, line managers, safety personnel, equipment operators, and any other personnel responsible for safety of hoisting and rigging operations at DOE sites. It quotes or paraphrases the US OSHA and ANSI requirements. It also encompasses, under one cover,hoisting and rigging requirements, codes, standards, and regulations, eliminating the need to maintain extensive (and often incomplete) libraries of hoisting and rigging standards throughout DOE. The standard occasionally goes beyond the minimum general industry standards established by OSHA and ANSI, and also delineates the more stringent requirements necessary to accomplish themore » complex, diversified, critical, and often hazardous hoisting and rigging work found with the DOE complex.« less

Single molecule Raman spectroscopic assay to detect transgene from GM plants.

PubMed

Kadam, Ulhas S; Chavhan, Rahul L; Schulz, Burkhard; Irudayaraj, Joseph

2017-09-01

Substantial concerns have been raised for the safety of transgenics on human health and environment. Many organizations, consumer groups, and environmental agencies advocate for stringent regulations to avoid transgene products' contamination in food cycle or in nature. Here we demonstrate a novel approach using surface enhanced Raman spectroscopy (SERS) to detect and quantify transgene from GM plants. We show a highly sensitive and accurate quantification of transgene DNA from multiple transgenic lines of Arabidopsis. The assay allows us to detect and quantify the transgenes as low as 0.10 pg without need for PCR-amplification. This technology is relatively cheap, quick, simple, and suitable for detection at low target concentration. Copyright © 2017 Elsevier Inc. All rights reserved.

Cryogenic Evaluation of an Advanced DC/DC Converter Module for Deep Space Applications

NASA Technical Reports Server (NTRS)

Elbuluk, Malik E.; Hammoud, Ahmad; Gerber, Scott S.; Patterson, Richard

2003-01-01

DC/DC converters are widely used in power management, conditioning, and control of space power systems. Deep space applications require electronics that withstand cryogenic temperature and meet a stringent radiation tolerance. In this work, the performance of an advanced, radiation-hardened (rad-hard) commercial DC/DC converter module was investigated at cryogenic temperatures. The converter was investigated in terms of its steady state and dynamic operations. The output voltage regulation, efficiency, terminal current ripple characteristics, and output voltage response to load changes were determined in the temperature range of 20 to -140 C. These parameters were obtained at various load levels and at different input voltages. The experimental procedures along with the results obtained on the investigated converter are presented and discussed.

Friends Turned Foes: Angiogenic Growth Factors beyond Angiogenesis.

PubMed

Matkar, Pratiek N; Ariyagunarajah, Ramya; Leong-Poi, Howard; Singh, Krishna K

2017-10-02

Angiogenesis, the formation of new blood vessels from pre-existing ones is a biological process that ensures an adequate blood flow is maintained to provide the cells with a sufficient supply of nutrients and oxygen within the body. Numerous soluble growth factors and inhibitors, cytokines, proteases as well as extracellular matrix proteins and adhesion molecules stringently regulate the multi-factorial process of angiogenesis. The properties and interactions of key angiogenic molecules such as vascular endothelial growth factors (VEGFs), fibroblast growth factors (FGFs) and angiopoietins have been investigated in great detail with respect to their molecular impact on angiogenesis. Since the discovery of angiogenic growth factors, much research has been focused on their biological actions and their potential use as therapeutic targets for angiogenic or anti-angiogenic strategies in a context-dependent manner depending on the pathologies. It is generally accepted that these factors play an indispensable role in angiogenesis. However, it is becoming increasingly evident that this is not their only role and it is likely that the angiogenic factors have important functions in a wider range of biological and pathological processes. The additional roles played by these molecules in numerous pathologies and biological processes beyond angiogenesis are discussed in this review.

Friends Turned Foes: Angiogenic Growth Factors beyond Angiogenesis

PubMed Central

Matkar, Pratiek N.; Ariyagunarajah, Ramya; Leong-Poi, Howard; Singh, Krishna K.

2017-01-01

Angiogenesis, the formation of new blood vessels from pre-existing ones is a biological process that ensures an adequate blood flow is maintained to provide the cells with a sufficient supply of nutrients and oxygen within the body. Numerous soluble growth factors and inhibitors, cytokines, proteases as well as extracellular matrix proteins and adhesion molecules stringently regulate the multi-factorial process of angiogenesis. The properties and interactions of key angiogenic molecules such as vascular endothelial growth factors (VEGFs), fibroblast growth factors (FGFs) and angiopoietins have been investigated in great detail with respect to their molecular impact on angiogenesis. Since the discovery of angiogenic growth factors, much research has been focused on their biological actions and their potential use as therapeutic targets for angiogenic or anti-angiogenic strategies in a context-dependent manner depending on the pathologies. It is generally accepted that these factors play an indispensable role in angiogenesis. However, it is becoming increasingly evident that this is not their only role and it is likely that the angiogenic factors have important functions in a wider range of biological and pathological processes. The additional roles played by these molecules in numerous pathologies and biological processes beyond angiogenesis are discussed in this review. PMID:28974056

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

Matusik, Katarzyna E.; Duke, Daniel J.; Kastengren, Alan L.

The sparking behavior in an internal combustion engine affects the fuel efficiency, engine-out emissions, and general drivability of a vehicle. As emissions regulations become progressively stringent, combustion strategies, including exhaust gas recirculation (EGR), lean-burn, and turbocharging are receiving increasing attention as models of higher efficiency advanced combustion engines with reduced emissions levels. Because these new strategies affect the working environment of the spark plug, ongoing research strives to understand the influence of external factors on the spark ignition process. Due to the short time and length scales involved and the harsh environment, experimental quantification of the deposited energy from themore » sparking event is difficult to obtain. We present the results of x-ray radiography measurements of spark ignition plasma generated by a conventional spark plug. Our measurements were performed at the 7-BM beamline of the Advanced Photon Source at Argonne National Laboratory. The synchrotron x-ray source enables time-resolved measurements of the density change due to glow discharge in the spark gap with 153 ns temporal and 5 μm spatial resolutions. We also explore the effects of charging time, EGR-relevant gas compositions, and gas pressure on the sparking behavior. We also quantify the influence of the measurement technique on the obtained results.« less

Phenol wastewater remediation: advanced oxidation processes coupled to a biological treatment.

PubMed

Rubalcaba, A; Suárez-Ojeda, M E; Stüber, F; Fortuny, A; Bengoa, C; Metcalfe, I; Font, J; Carrera, J; Fabregat, A

2007-01-01

Nowadays, there are increasingly stringent regulations requiring more and more treatment of industrial effluents to generate product waters which could be easily reused or disposed of to the environment without any harmful effects. Therefore, different advanced oxidation processes were investigated as suitable precursors for the biological treatment of industrial effluents containing phenol. Wet air oxidation and Fenton process were tested batch wise, while catalytic wet air oxidation and H2O2-promoted catalytic wet air oxidation processes were studied in a trickle bed reactor, the last two using over activated carbon as catalyst. Effluent characterisation was made by means of substrate conversion (using high liquid performance chromatography), chemical oxygen demand and total organic carbon. Biodegradation parameters (i.e. maximum oxygen uptake rate and oxygen consumption) were obtained from respirometric tests using activated sludge from an urban biological wastewater treatment plant (WWTP). The main goal was to find the proper conditions in terms of biodegradability enhancement, so that these phenolic effluents could be successfully treated in an urban biological WWTP. Results show promising research ways for the development of efficient coupled processes for the treatment of wastewater containing toxic or biologically non-degradable compounds.

Recent advances in microbial fermentation for dairy and health

PubMed Central

Arendt, Elke; Hill, Colin; Stanton, Catherine; Ross, R Paul

2017-01-01

Microbial fermentation has been used historically for the preservation of foods, the health benefits of which have since come to light. Early dairy fermentations depended on the spontaneous activity of the indigenous microbiota of the milk. Modern fermentations rely on defined starter cultures with desirable characteristics to ensure consistency and commercial viability. The selection of defined starters depends on specific phenotypes that benefit the product by guaranteeing shelf life and ensuring safety, texture, and flavour. Lactic acid bacteria can produce a number of bioactive metabolites during fermentation, such as bacteriocins, biogenic amines, exopolysaccharides, and proteolytically released peptides, among others. Prebiotics are added to food fermentations to improve the performance of probiotics. It has also been found that prebiotics fermented in the gut can have benefits that go beyond helping probiotic growth. Studies are now looking at how the fermentation of prebiotics such as fructo-oligosaccharides can help in the prevention of diseases such as osteoporosis, obesity, and colorectal cancer. The potential to prevent or even treat disease through the fermentation of food is a medically and commercially attractive goal and is showing increasing promise. However, the stringent regulation of probiotics is beginning to detrimentally affect the field and limit their application. PMID:28649371

The international electronics industry.

PubMed

LaDou, J; Rohm, T

1998-01-01

High-technology microelectronics has a major presence in countries such as China, India, Indonesia, and Malaysia, now the third-largest manufacturer of semiconductor chips. The migration of European, Japanese, and American companies accommodates regional markets. Low wage rates and limited enforcement of environmental regulations in developing countries also serve as incentives for the dramatic global migration of this industry. The manufacture of microelectonics products is accompanied by a high incidence of occupational illnesses, which may reflect the widespread use of toxic materials. Metals, photoactive chemicals, solvents, acids, and toxic gases are used in a wide variety of combinations and workplace settings. The industry also presents problems of radiation exposure and various occupational stressors, including some unresolved ergonomic issues. The fast-paced changes of the technology underlying this industry, as well as the stringent security precautions, have added to the difficulty of instituting proper health and safety measures. Epidemiologic studies reveal an alarming increase in spontaneous abortions among cleanroom manufacturing workers; no definitive study has yet identified its cause. Other health issues, including occupational cancer, are yet to be studied. The microelectronics industry is a good example of an industry that is exported to many areas of the world before health and safety problems are properly addressed and resolved.

Distillery spent wash: treatment technologies and potential applications.

PubMed

Mohana, Sarayu; Acharya, Bhavik K; Madamwar, Datta

2009-04-15

Distillery spent wash is the unwanted residual liquid waste generated during alcohol production and pollution caused by it is one of the most critical environmental issue. Despite standards imposed on effluent quality, untreated or partially treated effluent very often finds access to watercourses. The distillery wastewater with its characteristic unpleasant odor poses a serious threat to the water quality in several regions around the globe. The ever-increasing generation of distillery spent wash on the one hand and stringent legislative regulations of its disposal on the other has stimulated the need for developing new technologies to process this effluent efficiently and economically. A number of clean up technologies have been put into practice and novel bioremediation approaches for treatment of distillery spent wash are being worked out. Potential microbial (anaerobic and aerobic) as well as physicochemical processes as feasible remediation technologies to combat environmental pollution are being explored. An emerging field in distillery waste management is exploiting its nutritive potential for production of various high value compounds. This review presents an overview of the pollution problems caused by distillery spent wash, the technologies employed globally for its treatment and its alternative use in various biotechnological sectors.

Cosmetic surgery in Australia: a risky business?

PubMed

Parker, Rhian

2007-08-01

Cosmetic surgery is increasing in popularity in Australia and New Zealand, as it is across other Western countries. However, there is no systematic mechanism for gathering data about cosmetic surgery, nor about the outcomes of that surgery. This column argues that the business of cosmetic surgery in Australia has questionable marketing standards, is conducted with little scrutiny or accountability and offers patients imperfect knowledge about cosmetic procedures. It also argues that while medical practitioners debate among themselves over who should carry out cosmetic procedures, little attention has been paid to questionable advertising in the industry and even less to highlighting the real risks of undergoing cosmetic surgery. While consumers are led to believe that cosmetic surgery is accessible, affordable and safe, they are sheltered from the reality of invasive and risky surgery and from the ability to clearly discern that all cosmetic procedures carry risk. While doctors continue to undertake advertising and engage in a territorial war, they fail to address the really important issues in cosmetic surgery. These are: providing real evidence about what happens in the industry, developing stringent regulations under which the industry should operate and ensuring that all patients considering cosmetic surgery are fully informed as to the risks of that surgery.

A novel multiplex poliovirus binding inhibition assay applicable for large serosurveillance and vaccine studies, without the use of live poliovirus.

PubMed

Schepp, Rutger M; Berbers, Guy A M; Ferreira, José A; Reimerink, Johan H; van der Klis, Fiona R

2017-03-01

Large-scale serosurveillance or vaccine studies for poliovirus using the "gold standard" WHO neutralisation test (NT) are very laborious and time consuming. With the polio eradication at hand and with the removal of live attenuated Sabin strains from the oral poliovirus vaccine (OPV), starting with type 2 (as of April 2016), laboratories will need to conform to much more stringent laboratory biosafety regulations when handling live poliovirus strains. In this study, a poliovirus binding inhibition multiplex immunoassay (polio MIA) using inactivated poliovirus vaccine (IPV-Salk) was developed for simultaneous quantification of serum antibodies directed to all three poliovirus types. Our assay shows a good correlation with the NT and an excellent correlation with the ELISA-based binding inhibition assay (POBI). The assay is highly type-specific and reproducible. Additionally, serum sample throughput increases about fivefold relative to NT and POBI and the amount of serum needed is reduced by more than 90%. In conclusion, the polio MIA can be used as a safe and high throughput application, especially for large-scale surveillance and vaccine studies, reducing laboratory time and serum amounts needed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Toward environmentally-benign utilization of nonmetallic fraction of waste printed circuit boards as modifier and precursor.

PubMed

Hadi, Pejman; Ning, Chao; Ouyang, Weiyi; Xu, Meng; Lin, Carol S K; McKay, Gordon

2015-01-01

Electronic waste, including printed circuit boards, is growing at an alarming rate due to the accelerated technological progress and the shorter lifespan of the electronic equipment. In the past decades, due to the lack of proper economic and environmentally-benign recycling technologies, a major fraction of e-waste generated was either destined to landfills or incinerated with the sole intention of its disposal disregarding the toxic nature of this waste. Recently, with the increasing public awareness over their environment and health issues and with the enaction of more stringent regulations, environmentally-benign recycling has been driven to be an alternative option partially replacing the traditional eco-unfriendly disposal methods. One of the most favorable green technologies has been the mechanical separation of the metallic and nonmetallic fraction of the waste printed circuit boards. Although metallic fraction, as the most profitable component, is used to generate the revenue of the separation process, the nonmetallic fraction (NMF) has been left isolated. Herein, the recent developments in the application of NMF have been comprehensively reviewed and an eco-friendly emerging usage of NMF as a value-added material for sustainable remediation has been introduced. Copyright © 2014 Elsevier Ltd. All rights reserved.

Medical physics is alive and well and growing in South East Asia.

PubMed

Ng, K; Pirabul, R; Peralta, A; Soejoko, D

1997-03-01

In recent years there has been a significant economic growth in South East Asia, along with it a concurrent development of medical physics. The status of four countries--Malaysia, Thailand, the Philippines and Indonesia are presented. Medical physicists in these countries have been experiencing the usual problems of lack of recognition, low salaries, and insufficient facilities for education and training opportunities. However the situation has improved recently through the initiative of local enthusiastic medical physicists who have started MS graduate programs in medical physics and begun organizing professional activities to raise the profile of medical physics. The tremendous support and catalytic roles of the American Association of Physicists in Medicine (AAPM) and international organizations such as International Organization for Medical Physics (IOMP), International Atomic Energy Agency (IAEA), World Health Organization (WHO), and International Center for Theoretical Physics (ICTP) have been instrumental in achieving progress. Contributions by these organizations include co-sponsorship of workshops and conferences, travel grants, medical physics libraries programs, and providing experts and educators. The demand for medical physicists is expected to rise in tandem with the increased emphasis on innovative technology for health care, stringent governmental regulation, and acceptance by the medical community of the important role of medical physicists.

The dual role of microbes in corrosion

PubMed Central

Kip, Nardy; van Veen, Johannes A

2015-01-01

Corrosion is the result of a series of chemical, physical and (micro) biological processes leading to the deterioration of materials such as steel and stone. It is a world-wide problem with great societal and economic consequences. Current corrosion control strategies based on chemically produced products are under increasing pressure of stringent environmental regulations. Furthermore, they are rather inefficient. Therefore, there is an urgent need for environmentally friendly and sustainable corrosion control strategies. The mechanisms of microbially influenced corrosion and microbially influenced corrosion inhibition are not completely understood, because they cannot be linked to a single biochemical reaction or specific microbial species or groups. Corrosion is influenced by the complex processes of different microorganisms performing different electrochemical reactions and secreting proteins and metabolites that can have secondary effects. Information on the identity and role of microbial communities that are related to corrosion and corrosion inhibition in different materials and in different environments is scarce. As some microorganisms are able to both cause and inhibit corrosion, we pay particular interest to their potential role as corrosion-controlling agents. We show interesting interfaces in which scientists from different disciplines such as microbiology, engineering and art conservation can collaborate to find solutions to the problems caused by corrosion. PMID:25259571

Mycotoxin contamination of animal feedingstuff: detoxification by gamma-irradiation and reduction of aflatoxins and ochratoxin A concentrations.

PubMed

Di Stefano, Vita; Pitonzo, Rosa; Cicero, Nicola; D'Oca, Maria Cristina

2014-01-01

Mycotoxins are fungal secondary metabolites identified in many agricultural products screened for toxigenic moulds. They have been reported to be carcinogenic, teratogenic, tremorogenic, haemorrhagic and dermatitic to a wide range of organisms. With the increasing stringent regulations for mycotoxins imposed by importing countries such as those of the European Union, many cereals that are not safe for human consumption are used in formulations intended for animal feed. Gamma-rays are reported in the scientific literature to destroy ochratoxin A and aflatoxin in food crops and feed. The present study provides preliminary data for establishing the effect of dose of gamma-irradiation, ranging from 0 to 15 kGy, on aflatoxins and ochratoxin A reduction in commercial animal feed. The mycotoxin levels were determined by means of immunoaffinity clean-up (IAC) and HPLC with fluorescence detection (HPLC-FLD). The maximum reductions found at 15 kGy were 23.9%, 18.2%, 11.0%, 21.1% and 13.6% for ochratoxin A, aflatoxin B₁, aflatoxin B₂, aflatoxin G₁ and aflatoxin G₂, respectively. Results showed that the gamma-rays even at 15 kGy were not effective in the complete destruction of ochratoxin A and aflatoxins in the tested feed.

The dual role of microbes in corrosion.

PubMed

Kip, Nardy; van Veen, Johannes A

2015-03-01

Corrosion is the result of a series of chemical, physical and (micro) biological processes leading to the deterioration of materials such as steel and stone. It is a world-wide problem with great societal and economic consequences. Current corrosion control strategies based on chemically produced products are under increasing pressure of stringent environmental regulations. Furthermore, they are rather inefficient. Therefore, there is an urgent need for environmentally friendly and sustainable corrosion control strategies. The mechanisms of microbially influenced corrosion and microbially influenced corrosion inhibition are not completely understood, because they cannot be linked to a single biochemical reaction or specific microbial species or groups. Corrosion is influenced by the complex processes of different microorganisms performing different electrochemical reactions and secreting proteins and metabolites that can have secondary effects. Information on the identity and role of microbial communities that are related to corrosion and corrosion inhibition in different materials and in different environments is scarce. As some microorganisms are able to both cause and inhibit corrosion, we pay particular interest to their potential role as corrosion-controlling agents. We show interesting interfaces in which scientists from different disciplines such as microbiology, engineering and art conservation can collaborate to find solutions to the problems caused by corrosion.

Endogenous ω-3 Polyunsaturated Fatty Acid Production Confers Resistance to Obesity, Dyslipidemia, and Diabetes in Mice

PubMed Central

Li, Jie; Li, Fanghong R.; Wei, Dong; Jia, Wei; Kang, Jing X.; Stefanovic-Racic, Maja

2014-01-01

Despite the well-documented health benefits of ω-3 polyunsaturated fatty acids (PUFAs), their use in clinical management of hyperglycemia and obesity has shown little success. To better define the mechanisms of ω-3 PUFAs in regulating energy balance and insulin sensitivity, we deployed a transgenic mouse model capable of endogenously producing ω-3 PUFAs while reducing ω-6 PUFAs owing to the expression of a Caenorhabditis elegans fat-1 gene encoding an ω-3 fatty acid desaturase. When challenged with high-fat diets, fat-1 mice strongly resisted obesity, diabetes, hypercholesterolemia, and hepatic steatosis. Endogenous elevation of ω-3 PUFAs and reduction of ω-6 PUFAs did not alter the amount of food intake but led to increased energy expenditure in the fat-1 mice. The requirements for the levels of ω-3 PUFAs as well as the ω-6/ω-3 ratios in controlling blood glucose and obesity are much more stringent than those in lipid metabolism. These metabolic phenotypes were accompanied by attenuation of the inflammatory state because tissue levels of prostaglandin E2, leukotriene B4, monocyte chemoattractant protein-1, and TNF-α were significantly decreased. TNF-α–induced nuclear factor-κB signaling was almost completely abolished. Consistent with the reduction in chronic inflammation and a significant increase in peroxisome proliferator–activated receptor-γ activity in the fat-1 liver tissue, hepatic insulin signaling was sharply elevated. The activities of prolipogenic regulators, such as liver X receptor, stearoyl-CoA desaturase-1, and sterol regulatory element binding protein-1 were sharply decreased, whereas the activity of peroxisome proliferator–activated receptor-α, a nuclear receptor that facilitates lipid β-oxidation, was markedly increased. Thus, endogenous conversion of ω-6 to ω-3 PUFAs via fat-1 strongly protects against obesity, diabetes, inflammation, and dyslipidemia and may represent a novel therapeutic modality to treat these prevalent disorders. PMID:24978197

Characterizing dilute combustion instabilities in a multi-cylinder spark-ignited engine using symbolic analysis.

PubMed

Daw, C S; Finney, C E A; Kaul, B C; Edwards, K D; Wagner, R M

2015-02-13

Spark-ignited internal combustion engines have evolved considerably in recent years in response to increasingly stringent regulations for emissions and fuel economy. One new advanced engine strategy ustilizes high levels of exhaust gas recirculation (EGR) to reduce combustion temperatures, thereby increasing thermodynamic efficiency and reducing nitrogen oxide emissions. While this strategy can be highly effective, it also poses major control and design challenges due to the large combustion oscillations that develop at sufficiently high EGR levels. Previous research has documented that combustion instabilities can propagate between successive engine cycles in individual cylinders via self-generated feedback of reactive species and thermal energy in the retained residual exhaust gases. In this work, we use symbolic analysis to characterize multi-cylinder combustion oscillations in an experimental engine operating with external EGR. At low levels of EGR, intra-cylinder oscillations are clearly visible and appear to be associated with brief, intermittent coupling among cylinders. As EGR is increased further, a point is reached where all four cylinders lock almost completely in phase and alternate simultaneously between two distinct bi-stable combustion states. From a practical perspective, it is important to understand the causes of this phenomenon and develop diagnostics that might be applied to ameliorate its effects. We demonstrate here that two approaches for symbolizing the engine combustion measurements can provide useful probes for characterizing these instabilities. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

San Francisco Biofuel Program: Brown Grease to Biodiesel Demonstration

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

Jolis, Domènec; Martis, Mary; Jones, Bonnie

2013-03-01

Municipal wastewater treatment facilities have typically been limited to the role of accepting wastewater, treating it to required levels, and disposing of its treatment residuals. However, a new view is emerging which includes wastewater treatment facilities as regional resource recovery centers. This view is a direct result of increasingly stringent regulations, concerns over energy use, carbon footprint, and worldwide depletion of fossil fuel resources. Resources in wastewater include chemical and thermal energy, as well as nutrients, and water. A waste stream such as residual grease, which concentrates in the drainage from restaurants (referred to as Trap Waste), is a goodmore » example of a resource with an energy content that can be recovered for beneficial reuse. If left in wastewater, grease accumulates inside of the wastewater collection system and can lead to increased corrosion and pipe blockages that can cause wastewater overflows. Also, grease in wastewater that arrives at the treatment facility can impair the operation of preliminary treatment equipment and is only partly removed in the primary treatment process. In addition, residual grease increases the demand in treatment materials such as oxygen in the secondary treatment process. When disposed of in landfills, grease is likely to undergo anaerobic decay prior to landfill capping, resulting in the atmospheric release of methane, a greenhouse gas (GHG). This research project was therefore conceptualized and implemented by the San Francisco Public Utilities Commission (SFPUC) to test the feasibility of energy recovery from Trap Waste in the form of Biodiesel or Methane gas.« less

The large-scale structure of the asteroid belt

NASA Technical Reports Server (NTRS)

Zellner, B.; Thirunagari, A.; Bender, D.

1985-01-01

The distributions of 2888 numbered minor planets over orbital inclination, eccentricity, and semimajor axis are examined, and 19 zones believed to adequately isolate the selection biases in survey programs of the physical properties of minor planets are defined. Six numbered asteroids have exceptional orbits and fall into no zone. Attention is called to rather sharp upper limits, which become increasingly stringent at larger heliocentric distances, on orbital inclinations and eccentricity.

Role of the standard deviation in the estimation of benchmark doses with continuous data.

PubMed

Gaylor, David W; Slikker, William

2004-12-01

For continuous data, risk is defined here as the proportion of animals with values above a large percentile, e.g., the 99th percentile or below the 1st percentile, for the distribution of values among control animals. It is known that reducing the standard deviation of measurements through improved experimental techniques will result in less stringent (higher) doses for the lower confidence limit on the benchmark dose that is estimated to produce a specified risk of animals with abnormal levels for a biological effect. Thus, a somewhat larger (less stringent) lower confidence limit is obtained that may be used as a point of departure for low-dose risk assessment. It is shown in this article that it is important for the benchmark dose to be based primarily on the standard deviation among animals, s(a), apart from the standard deviation of measurement errors, s(m), within animals. If the benchmark dose is incorrectly based on the overall standard deviation among average values for animals, which includes measurement error variation, the benchmark dose will be overestimated and the risk will be underestimated. The bias increases as s(m) increases relative to s(a). The bias is relatively small if s(m) is less than one-third of s(a), a condition achieved in most experimental designs.

Terbium(III) Modified Fluorescent Carbon Dots for Highly Selective and Sensitive Ratiometry of Stringent.

PubMed

Chen, Bin Bin; Liu, Meng Li; Zhan, Lei; Li, Chun Mei; Huang, Cheng Zhi

2018-03-20

Highly selective and sensitive detection of guanosine 3'-diphosphate-5'-diphosphate (ppGpp), namely, the stringent in plants or microorganisms responding to strict or extreme environmental conditions such as stress and starvation, which plays an important role in gene expression, rRNA and antibiotics production, regulations of virulence of bacteria, and growth of plants, faces a great challenge owing to its extreme similarity to normal nucleotides. By modifying the surface groups of a facile two-step hydrothermal route prepared carbon dots (CDs) with terbium ions (Tb 3+ ) in this contribution, a novel fluorescent probe with excellent properties such as highly physical and chemical stability, narrow emission and excitation wavelength-independent emission was prepared. The Tb 3+ ions on the surface of CDs cannot only preserve the intrinsic fluorescence (FL) of CDs but also keep its own coordination capacity with rare earth complex, and thus the clamp structure (four phosphate groups) of ppGpp can specific binding with Tb 3+ ions on the surface of CDs to produce antenna effect. Therefore, a highly selective and sensitive fluorescent ratiometry of ppGpp was developed by terbium-modified carbon dots (CDs-Tb) with the limit of detection as low as 50 nM based on the synergistic effect of antenna effect of Tb 3+ ions and specific recognition capacity of CDs. The applicability of this assay was demonstrated by CDs-Tb-based paper sensor for high distinguishing ppGpp from other nucleotides with similar structure.

Canada's Patented Medicine Notice of Compliance regulations: balancing the scales or tipping them?

PubMed Central

2011-01-01

Background In order to comply with the provisions of the North American Free Trade Agreement, in 1993 the Canadian federal government introduced the Patented Medicine Notice of Compliance Linkage Regulations. These regulations were meant to achieve a balance between the timely entry of generic medicines and the rights of patent holders. The regulations tied the regulatory approval of generic medicines to the patent status of the original brand-name product. Discussion Since their introduction the regulations have been a source of contention between the generic and the brand-name industry. While the regulations have generated a considerable amount of work for the Federal Court of Canada both sides dispute the interpretation of the "win rate" in the court cases. Similarly, there is no agreement on whether multiple patents on single drugs represent a legitimate activity by the brand-name industry or an "evergreening" tactic. The generic industry's position is that the regulations are being abused leading to the delay in the introduction of lower cost generic products by as much as 8 years. The brand-name companies counter that the regulations are necessary because injunctions against the introduction of generic products are frequently unavailable to them. The regulations were amended in 2006 and again in 2008 but both sides continue to claim that the regulations favour the other party. The battle around the regulations also has an international dimension with interventions by PhRMA, the trade association representing the United States based multinational companies, arguing that the regulations are not stringent enough and that Canada needs to be placed on the U.S. Priority Watch List of countries. Finally, there are multiple costs to Canadian society as a result of the NOC regulations. Summary Despite the rhetoric there has been almost no empiric academic research done into the effect of the regulations. In order to develop rational policy in this area a number of key research questions have been formulated. PMID:21435247

Future automotive materials: Evolution or revolution

NASA Technical Reports Server (NTRS)

Beardmore, P.

1990-01-01

An exciting era is evolving in the application of new materials technologies to automotive applications. The desire on the part of the automobile industry to completely satisfy the customers while concurrently meeting increasing demands and regulations for stringent emission control and fuel efficiency is opening a plethora of opportunities for new materials. In many cases, materials solutions are the only mechanisms for resolving some of the upcoming issues. The materials scientist and engineer will therefore have a primary role to play and will assume a position of significance hithertofore unseen in the automobile industry. The nature of the industry dictates that changes are primarily evolutionary with respect to chronology but nevertheless some of the future material changes will be revolutionary in nature. This presentation will treat three primary systems of the vehicle separately, based on the different materials approaches which will be adopted. These areas are: (1) skin panels, (2) structures, and (3) powertrains. The competition between a variety of new materials in these 3 systems will be discussed in detail with the various tradeoffs being outlined. Amongst the more prominent of the new breed of materials will be new steel technologies, structural plastics (FRP), aluminum alloys (conventional and rapidly solidified), titanium alloys, metal matrix composites and smart materials (electrorheological fluids, etc.). The pace of development and application is accelerating rapidly and the impetus is likely to increase.

Evolution of Mycolic Acid Biosynthesis Genes and Their Regulation during Starvation in Mycobacterium tuberculosis

PubMed Central

Jamet, Stevie; Quentin, Yves; Coudray, Coralie; Texier, Pauline; Laval, Françoise; Daffé, Mamadou

2015-01-01

ABSTRACT Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a Gram-positive bacterium with a unique cell envelope composed of an essential outer membrane. Mycolic acids, which are very-long-chain (up to C100) fatty acids, are the major components of this mycomembrane. The enzymatic pathways involved in the biosynthesis and transport of mycolates are fairly well documented and are the targets of the major antituberculous drugs. In contrast, only fragmented information is available on the expression and regulation of the biosynthesis genes. In this study, we report that the hadA, hadB, and hadC genes, which code for the mycolate biosynthesis dehydratase enzymes, are coexpressed with three genes that encode proteins of the translational apparatus. Consistent with the well-established control of the translation potential by nutrient availability, starvation leads to downregulation of the hadABC genes along with most of the genes required for the synthesis, modification, and transport of mycolates. The downregulation of a subset of the biosynthesis genes is partially dependent on RelMtb, the key enzyme of the stringent response. We also report the phylogenetic evolution scenario that has shaped the current genetic organization, characterized by the coregulation of the hadABC operon with genes of the translational apparatus and with genes required for the modification of the mycolates. IMPORTANCE Mycobacterium tuberculosis infects one-third of the human population worldwide, and despite the available therapeutic arsenal, it continues to kill millions of people each year. There is therefore an urgent need to identify new targets and develop a better understanding of how the bacterium is adapting itself to host defenses during infection. A prerequisite of this understanding is knowledge of how this adaptive skill has been implanted by evolution. Nutrient scarcity is an environmental condition the bacterium has to cope with during infection. In many bacteria, adaptation to starvation relies partly on the stringent response. M. tuberculosis's unique outer membrane layer, the mycomembrane, is crucial for its viability and virulence. Despite its being the target of the major antituberculosis drugs, only scattered information exists on how the genes required for biosynthesis of the mycomembrane are expressed and regulated during starvation. This work has addressed this issue as a step toward the identification of new targets in the fight against M. tuberculosis. PMID:26416833

Worrying about the Future: An Episodic Specificity Induction Impacts Problem Solving, Reappraisal, and Well-Being

PubMed Central

Jing, Helen G.; Madore, Kevin P.; Schacter, Daniel L.

2015-01-01

Previous research has demonstrated that an episodic specificity induction – brief training in recollecting details of a recent experience – enhances performance on various subsequent tasks thought to draw upon episodic memory processes. Existing work has also shown that mental simulation can be beneficial for emotion regulation and coping with stressors. Here we focus on understanding how episodic detail can affect problem solving, reappraisal, and psychological well-being regarding worrisome future events. In Experiment 1, an episodic specificity induction significantly improved participants’ performance on a subsequent means-end problem solving task (i.e., more relevant steps) and an episodic reappraisal task (i.e., more episodic details) involving personally worrisome future events compared with a control induction not focused on episodic specificity. Imagining constructive behaviors with increased episodic detail via the specificity induction was also related to significantly larger decreases in anxiety, perceived likelihood of a bad outcome, and perceived difficulty to cope with a bad outcome, as well as larger increases in perceived likelihood of a good outcome and indicated use of active coping behaviors compared with the control. In Experiment 2, we extended these findings using a more stringent control induction, and found preliminary evidence that the specificity induction was related to an increase in positive affect and decrease in negative affect compared with the control. Our findings support the idea that episodic memory processes are involved in means-end problem solving and episodic reappraisal, and that increasing the episodic specificity of imagining constructive behaviors regarding worrisome events may be related to improved psychological well-being. PMID:26820166

Furfural Inhibits Growth by Limiting Sulfur Assimilation in Ethanologenic Escherichia coli Strain LY180▿

PubMed Central

Miller, Elliot N.; Jarboe, Laura R.; Turner, Peter C.; Pharkya, Priti; Yomano, Lorraine P.; York, Sean W.; Nunn, David; Shanmugam, K. T.; Ingram, Lonnie O.

2009-01-01

A wide variety of commercial products can be potentially made from monomeric sugars produced by the dilute acid hydrolysis of lignocellulosic biomass. However, this process is accompanied by side products such as furfural that hinder microbial growth and fermentation. To investigate the mechanism of furfural inhibition, mRNA microarrays of an ethanologenic strain of Escherichia coli (LY180) were compared immediately prior to and 15 min after a moderate furfural challenge. Expression of genes and regulators associated with the biosynthesis of cysteine and methionine was increased by furfural, consistent with a limitation of these critical metabolites. This was in contrast to a general stringent response and decreased expression of many other biosynthetic genes. Of the 20 amino acids individually tested as supplements (100 μM each), cysteine and methionine were the most effective in increasing furfural tolerance with serine (precursor of cysteine), histidine, and arginine of lesser benefit. Supplementation with other reduced sulfur sources such as d-cysteine and thiosulfate also increased furfural tolerance. In contrast, supplementation with taurine, a sulfur source that requires 3 molecules of NADPH for sulfur assimilation, was of no benefit. Furfural tolerance was also increased by inserting a plasmid encoding pntAB, a cytoplasmic NADH/NADPH transhydrogenase. Based on these results, a model is proposed for the inhibition of growth in which the reduction of furfural by YqhD, an enzyme with a low Km for NADPH, depletes NADPH sufficiently to limit the assimilation of sulfur into amino acids (cysteine and methionine) by CysIJ (sulfite reductase). PMID:19684179

Update on clinical attire requirements in dental hygiene programs.

PubMed

Foley, E S

1994-01-01

Many changes have occurred in the clinical appearance of dental hygienists in the past few years because of increased emphasis on infection control and disease prevention. The purpose of this study was to assess dental hygiene program clinical attire requirements in 1993 and to compare them with requirements as described by a 1988 survey. Checklist questionnaires were mailed to the directors of all 211 dental hygiene programs in the United States and Puerto Rico in October 1993. Questions were asked regarding clinical attire requirements for students and faculty, including uniforms, gowns, lab coats, masks, protective eyewear, shoes, hair coverings, laundry management, and changes under consideration. Percentages were calculated by region and for all responding programs. Of 211 questionnaires mailed, 178 were returned, for a response rate of 84%. Results indicated that students and faculty are currently wearing more colorful uniforms and scrubs than in 1988. Long-sleeved lab coats, disposable gowns, and washable surgical gowns are increasing in use. Glasses and face masks were required for all students and faculty in both surveys, but chin-length face shields are increasing in use as optional face protection. In most instances, face shields are worn with face masks. Laundry services are being provided for faculty (employees); however, most students continue to be responsible for their own laundry after being instructed to follow stringent guidelines taught by the faculty. Increasing emphasis on personal and patient protection is moving clinical attire requirements toward a more surgical appearance. Dental hygiene educators continue to monitor and to stay current with federal infection control recommendations, regulations, and guidelines.

Comparison of Gasoline Direct-Injection (GDI) and Port Fuel Injection (PFI) Vehicle Emissions: Emission Certification Standards, Cold-Start, Secondary Organic Aerosol Formation Potential, and Potential Climate Impacts.

PubMed

Saliba, Georges; Saleh, Rawad; Zhao, Yunliang; Presto, Albert A; Lambe, Andrew T; Frodin, Bruce; Sardar, Satya; Maldonado, Hector; Maddox, Christine; May, Andrew A; Drozd, Greg T; Goldstein, Allen H; Russell, Lynn M; Hagen, Fabian; Robinson, Allen L

2017-06-06

Recent increases in the Corporate Average Fuel Economy standards have led to widespread adoption of vehicles equipped with gasoline direct-injection (GDI) engines. Changes in engine technologies can alter emissions. To quantify these effects, we measured gas- and particle-phase emissions from 82 light-duty gasoline vehicles recruited from the California in-use fleet tested on a chassis dynamometer using the cold-start unified cycle. The fleet included 15 GDI vehicles, including 8 GDIs certified to the most-stringent emissions standard, superultra-low-emission vehicles (SULEV). We quantified the effects of engine technology, emission certification standards, and cold-start on emissions. For vehicles certified to the same emissions standard, there is no statistical difference of regulated gas-phase pollutant emissions between PFIs and GDIs. However, GDIs had, on average, a factor of 2 higher particulate matter (PM) mass emissions than PFIs due to higher elemental carbon (EC) emissions. SULEV certified GDIs have a factor of 2 lower PM mass emissions than GDIs certified as ultralow-emission vehicles (3.0 ± 1.1 versus 6.3 ± 1.1 mg/mi), suggesting improvements in engine design and calibration. Comprehensive organic speciation revealed no statistically significant differences in the composition of the volatile organic compounds emissions between PFI and GDIs, including benzene, toluene, ethylbenzene, and xylenes (BTEX). Therefore, the secondary organic aerosol and ozone formation potential of the exhaust does not depend on engine technology. Cold-start contributes a larger fraction of the total unified cycle emissions for vehicles meeting more-stringent emission standards. Organic gas emissions were the most sensitive to cold-start compared to the other pollutants tested here. There were no statistically significant differences in the effects of cold-start on GDIs and PFIs. For our test fleet, the measured 14.5% decrease in CO 2 emissions from GDIs was much greater than the potential climate forcing associated with higher black carbon emissions. Thus, switching from PFI to GDI vehicles will likely lead to a reduction in net global warming.

Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle.

PubMed

Chao, Hui Xiao; Poovey, Cere E; Privette, Ashley A; Grant, Gavin D; Chao, Hui Yan; Cook, Jeanette G; Purvis, Jeremy E

2017-11-22

Although molecular mechanisms that prompt cell-cycle arrest in response to DNA damage have been elucidated, the systems-level properties of DNA damage checkpoints are not understood. Here, using time-lapse microscopy and simulations that model the cell cycle as a series of Poisson processes, we characterize DNA damage checkpoints in individual, asynchronously proliferating cells. We demonstrate that, within early G1 and G2, checkpoints are stringent: DNA damage triggers an abrupt, all-or-none cell-cycle arrest. The duration of this arrest correlates with the severity of DNA damage. After the cell passes commitment points within G1 and G2, checkpoint stringency is relaxed. By contrast, all of S phase is comparatively insensitive to DNA damage. This checkpoint is graded: instead of halting the cell cycle, increasing DNA damage leads to slower S phase progression. In sum, we show that a cell's response to DNA damage depends on its exact cell-cycle position and that checkpoints are phase-dependent, stringent or relaxed, and graded or all-or-none. Copyright © 2017 Elsevier Inc. All rights reserved.

Particulate matter emissions from combustion of wood in district heating applications

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

Ghafghazi, S.; Sowlati, T.; Sokhansanj, Shahabaddine

2011-01-01

The utilization of wood biomass to generate district heat and power in communities that have access to this energy source is increasing. In this paper the effect of wood fuel properties, combustion condition, and flue gas cleaning system on variation in the amount and formation of particles in the flue gas of typical district heating wood boilers are discussed based on the literature survey. Direct measurements of particulate matter (PM) emissions from wood boilers with district heating applications are reviewed and presented. Finally, recommendations are given regarding the selection of wood fuel, combustion system condition, and flue gas cleaning systemmore » in district heating systems in order to meet stringent air quality standards. It is concluded that utilization of high quality wood fuel, such as wood pellets produced from natural, uncontaminated stem wood, would generate the least PM emissions compared to other wood fuel types. Particulate matter emissions from grate burners equipped with electrostatic precipitators when using wood pellets can be well below stringent regulatory emission limit such as particulate emission limit of Metro Vancouver, Canada.« less

Technological options for the management of biosolids.

PubMed

Wang, Hailong; Brown, Sally L; Magesan, Guna N; Slade, Alison H; Quintern, Michael; Clinton, Peter W; Payn, Tim W

2008-06-01

Large quantities of biosolids (sewage sludge), which are produced from municipal wastewater treatment, are ever-increasing because of the commissioning of new treatment plants and continuous upgrades of the existing facilities. A large proportion of biosolids are currently landfilled. With increasing pressure from regulators and the general public, landfilling of biosolids is being phased out in many countries because of potential secondary pollution caused by leachate and the emission of methane, a potent greenhouse gas. Biosolids contain nutrients and energy that can be used beneficially. Significant efforts have been made recently to develop new technologies to manage biosolids and make useful products from them. In this paper, we provide a review of the technologies in biosolids management. A survey of literature was conducted. At present, the most common beneficial use of biosolids is agricultural land application because of inherent fertilizer values found in biosolids. Expansion of land application, however, may be limited in the future because of more stringent regulatory requirements and public concern about food chain contamination in some countries. Perceived as a green energy source, the combustion of biosolids has received renewed interest. Anaerobic digestion is generally a more effective method than incineration for energy recovery, and digested biosolids are suitable for further beneficial use through land application. Although conventional incineration systems for biosolid management generally consume more energy than they produce because of the high moisture content in the biosolids, it is expected that more combustion systems, either monocombustion or cocombustion, will be built to cope with the increasing quantity of biosolids. Under the increasingly popular low-carbon economy policy, biosolids may be recognized as a renewable fuel and be eligible for 'carbon credits'. Because ash can be used to manufacture construction materials, combustion can provide a complete management for biosolids. A number of advanced thermal conversion technologies (e.g., supercritical water oxidation process and pyrolysis) are under development for biosolids management with a goal to generate useful products, such as higher quality fuels and recovery of phosphorus. With an ever-increasing demand for renewable energy, growing bioenergy crops and forests using biosolids as a fertilizer and soil amendment can not only contribute to the low-carbon economy but also maximize the nutrient and carbon value of the biosolids. Land application of biosolids achieves a complete reuse of its nutrients and organic carbon at a relatively low cost. Therefore, land application should become a preferred management option where there is available land, the quality of biosolids meet regulatory requirements, and it is socially acceptable. Intensive energy cropping and forest production using biosolids can help us meet the ever-increasing demand for renewable energy, which can eliminate the contamination potential for food sources, a common social concern about land application of biosolids. In recent years, increasing numbers of national and local governments have adopted more stringent regulations toward biosolid management. Under such a political climate, biosolids producers will have to develop multireuse strategies for biosolids to avoid being caught because a single route management practice might be under pressure at a short notice. Conventional incineration systems for biosolids management generally consume more energy than they produce and, although by-products may be used in manufacturing, this process cannot be regarded as a beneficial use of biosolids. However, biosolids are likely to become a source of renewable energy and produce 'carbon credits' under the increasingly popular, low-carbon economy policy. To manage biosolids in a sustainable manner, there is a need for further research in the following areas: achieving a higher degree of public understanding and acceptance for the beneficial use of biosolids, developing cost-efficient and effective thermal conversions for direct energy recovery from biosolids, advancing technology for phosphorus recovery, and selecting or breeding crops for efficient biofuel production.

Differences in innate immune response gene regulation in the middle ear of children who are otitis prone and in those not otitis prone

PubMed Central

Casey, Janet; Pichichero, Michael

2016-01-01

Objective: Acute otitis media (AOM) causes an inflammatory response in the middle ear. We assessed differences in innate immune responses involved in bacterial defense at onset of AOM in children who were stringently defined as otitis prone (sOP) and children not otitis prone (NOP). Study Design: Innate immune genes analysis from middle ear fluid (MEF) samples of children. Methods: Genes of toll-like receptors (TLR), nod-like and retinoic acid-inducible gene-I-like receptors, downstream effectors important for inflammation and apoptosis, including cytokines and chemokines, were studied from MEF samples by using a real-time polymerase chain reaction array. Protein levels of differentially regulated genes were measured by Luminex. Results: Gene expression in MEF among children who were sOP was significantly different in upregulation of interleukin 8, secretory leukocyte peptidase inhibitor, and chemokine (C-C motif) ligand 3, and in downregulation of interferon regulatory factor 7 and its related signaling molecules interferon alpha, Toll-like receptor adaptor molecule 2, chemokine (C-C motif) ligand 5, and mitogen-activated protein kinase 8 compared with children who were NOP. Differences in innate gene regulation were similar when AOM was caused by Streptococcus pneumoniae or nontypeable Haemophilus influenzae. Conclusion: Innate-immune response genes are differentially regulated in children who were sOP compared with children with NOP. PMID:28124644

Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers.

PubMed

Lopez, Juan Pablo; Fiori, Laura M; Gross, Jeffrey A; Labonte, Benoit; Yerko, Volodymyr; Mechawar, Naguib; Turecki, Gustavo

2014-01-01

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in the post-transcriptional regulation of mRNA. These molecules have been the subject of growing interest as they are believed to control the regulation of a large number of genes, including those expressed in the brain. Evidence suggests that miRNAs could be involved in the pathogenesis of neuropsychiatric disorders. Alterations in metabolic enzymes of the polyamine system have been reported to play a role in predisposition to suicidal behaviour. We have previously shown the expression of the polyamine genes SAT1 and SMOX to be down-regulated in the brains of suicide completers. In this study, we hypothesized that the dysregulation of these genes in depressed suicide completers could be influenced by miRNA post-transcriptional regulation. Using a stringent target prediction analysis, we identified several miRNAs that target the 3'UTR of SAT1 and SMOX. We profiled the expression of 10 miRNAs in the prefrontal cortex (BA44) of suicide completers (N = 15) and controls (N = 16) using qRT-PCR. We found that several miRNAs showed significant up-regulation in the prefrontal cortex of suicide completers compared to psychiatric healthy controls. Furthermore, we demonstrated a significant correlation between these miRNAs and the expression levels of both SAT1 and SMOX. Our results suggest a relationship between miRNAs and polyamine gene expression in the suicide brain, and postulate a mechanism for SAT1 and SMOX down-regulation by post-transcriptional activity of miRNAs.

Evolutionary stability concepts in a stochastic environment

NASA Astrophysics Data System (ADS)

Zheng, Xiu-Deng; Li, Cong; Lessard, Sabin; Tao, Yi

2017-09-01

Over the past 30 years, evolutionary game theory and the concept of an evolutionarily stable strategy have been not only extensively developed and successfully applied to explain the evolution of animal behaviors, but also widely used in economics and social sciences. Nonetheless, the stochastic dynamical properties of evolutionary games in randomly fluctuating environments are still unclear. In this study, we investigate conditions for stochastic local stability of fixation states and constant interior equilibria in a two-phenotype model with random payoffs following pairwise interactions. Based on this model, we develop the concepts of stochastic evolutionary stability (SES) and stochastic convergence stability (SCS). We show that the condition for a pure strategy to be SES and SCS is more stringent than in a constant environment, while the condition for a constant mixed strategy to be SES is less stringent than the condition to be SCS, which is less stringent than the condition in a constant environment.

Probiotics: an update.

PubMed

Vandenplas, Yvan; Huys, Geert; Daube, Georges

2015-01-01

Triggered by the growing knowledge on the link between the intestinal microbiome and human health, the interest in probiotics is ever increasing. The authors aimed to review the recent literature on probiotics, from definitions to clinical benefits, with emphasis on children. Relevant literature from searches of PubMed, CINAHL, and recent consensus statements were reviewed. While a balanced microbiome is related to health, an imbalanced microbiome or dysbiosis is related to many health problems both within the gastro-intestinal tract, such as diarrhea and inflammatory bowel disease, and outside the gastro-intestinal tract such as obesity and allergy. In this context, a strict regulation of probiotics with health claims is urgent, because the vast majority of these products are commercialized as food (supplements), claiming health benefits that are often not substantiated with clinically relevant evidence. The major indications of probiotics are in the area of the prevention and treatment of gastro-intestinal related disorders, but more data has become available on extra-intestinal indications. At least two published randomized controlled trials with the commercialized probiotic product in the claimed indication are a minimal condition before a claim can be sustained. Today, Lactobacillus rhamnosus GG and Saccharomyces boulardii are the best-studied strains. Although adverse effects have sporadically been reported, these probiotics can be considered as safe. Although regulation is improving, more stringent definitions are still required. Evidence of clinical benefit is accumulating, although still missing in many areas. Misuse and use of products that have not been validated constitute potential drawbacks. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Cellular reprogramming through mitogen-activated protein kinases.

PubMed

Lee, Justin; Eschen-Lippold, Lennart; Lassowskat, Ines; Böttcher, Christoph; Scheel, Dierk

2015-01-01

Mitogen-activated protein kinase (MAPK) cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554) in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins) as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression-including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding, and degradation) steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes.

Exogenous nitric oxide improves salt tolerance during establishment of Jatropha curcas seedlings by ameliorating oxidative damage and toxic ion accumulation.

PubMed

Gadelha, Cibelle Gomes; Miranda, Rafael de Souza; Alencar, Nara Lídia M; Costa, José Hélio; Prisco, José Tarquinio; Gomes-Filho, Enéas

2017-05-01

Jatropha curcas is an oilseed species that is considered an excellent alternative energy source for fossil-based fuels for growing in arid and semiarid regions, where salinity is becoming a stringent problem to crop production. Our working hypothesis was that nitric oxide (NO) priming enhances salt tolerance of J. curcas during early seedling development. Under NaCl stress, seedlings arising from NO-treated seeds showed lower accumulation of Na + and Cl - than those salinized seedlings only, which was consistent with a better growth for all analyzed time points. Also, although salinity promoted a significant increase in hydrogen peroxide (H 2 O 2 ) content and membrane damage, the harmful effects were less aggressive in NO-primed seedlings. The lower oxidative damage in NO-primed stressed seedlings was attributed to operation of a powerful antioxidant system, including greater glutathione (GSH) and ascorbate (AsA) contents as well as catalase (CAT) and glutathione reductase (GR) enzyme activities in both endosperm and embryo axis. Priming with NO also was found to rapidly up-regulate the JcCAT1, JcCAT2, JcGR1 and JcGR2 gene expression in embryo axis, suggesting that NO-induced salt responses include functional and transcriptional regulations. Thus, NO almost completely abolished the deleterious salinity effects on reserve mobilization and seedling growth. In conclusion, NO priming improves salt tolerance of J. curcas during seedling establishment by inducing an effective antioxidant system and limiting toxic ion and reactive oxygen species (ROS) accumulation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Is bigger better? Driving factors of POTW performance in New York.

PubMed

Rahm, Brian G; Morse, Natalie; Bowen, Michelle; Choi, Jun; Mehta, Dhaval; Vedachalam, Sridhar

2018-05-15

Like many regions around the world, New York State, USA, faces challenges in meeting wastewater treatment quality standards because of aging infrastructure, limited funding, shifting demographics and increasingly stringent environmental regulations. In recent decades construction of new wastewater treatment and distribution infrastructure in NY has most often occurred in exurban communities and suburban developments that are less dense than traditional urban cores. Here, we examine the role of size and capacity utilization on wastewater treatment effectiveness with respect to critical effluent parameters, and additionally explore which common facility engineering controls influence water quality treatment using a unique dataset of descriptive information. Our results challenge conventional wisdom, suggesting that the largest facilities (>30,000 m 3 /d), not the smallest (<300 m 3 /d), discharge TSS, BOD, and coliform at significantly higher relative effluent concentrations (i.e., the ratio of discharged concentrations to allowable limits). Capacity utilization was also positively correlated to higher concentrations of TSS, BOD, and coliform effluent concentrations in larger facilities, though those concentrations were often within regulated limits. This implies that smaller-sized facilities may perform better in terms of environmental quality, but that the largest facilities demonstrate efficiency in the sense that they are not "over-treating" wastewater while avoiding violations. Results from NY suggest that medium sized facilities (300-30,000 m 3 /d) are sophisticated enough to incorporate appropriate unit processes, and employ operators with sufficient training and oversight, to reach treatment outcomes that are both reliable and of high quality. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genome-wide mRNA processing in methanogenic archaea reveals post-transcriptional regulation of ribosomal protein synthesis.

PubMed

Qi, Lei; Yue, Lei; Feng, Deqin; Qi, Fengxia; Li, Jie; Dong, Xiuzhu

2017-07-07

Unlike stable RNAs that require processing for maturation, prokaryotic cellular mRNAs generally follow an 'all-or-none' pattern. Herein, we used a 5΄ monophosphate transcript sequencing (5΄P-seq) that specifically captured the 5΄-end of processed transcripts and mapped the genome-wide RNA processing sites (PSSs) in a methanogenic archaeon. Following statistical analysis and stringent filtration, we identified 1429 PSSs, among which 23.5% and 5.4% were located in 5΄ untranslated region (uPSS) and intergenic region (iPSS), respectively. A predominant uridine downstream PSSs served as a processing signature. Remarkably, 5΄P-seq detected overrepresented uPSS and iPSS in the polycistronic operons encoding ribosomal proteins, and the majority upstream and proximal ribosome binding sites, suggesting a regulatory role of processing on translation initiation. The processed transcripts showed increased stability and translation efficiency. Particularly, processing within the tricistronic transcript of rplA-rplJ-rplL enhanced the translation of rplL, which can provide a driving force for the 1:4 stoichiometry of L10 to L12 in the ribosome. Growth-associated mRNA processing intensities were also correlated with the cellular ribosomal protein levels, thereby suggesting that mRNA processing is involved in tuning growth-dependent ribosome synthesis. In conclusion, our findings suggest that mRNA processing-mediated post-transcriptional regulation is a potential mechanism of ribosomal protein synthesis and stoichiometry. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Plants as models for the study of human pathogenesis.

PubMed

Guttman, David S

2004-05-01

There are many common disease mechanisms used by bacterial pathogens of plants and humans. They use common means of attachment, secretion and genetic regulation. They share many virulence factors, such as extracellular polysaccharides and some type III secreted effectors. Plant and human innate immune systems also share many similarities. Many of these shared bacterial virulence mechanisms are homologous, but even more appear to have independently converged on a common function. This combination of homologous and analogous systems reveals conserved and critical steps in the disease process. Given these similarities, and the many experimental advantages of plant biology, including ease of replication, stringent genetic and reproductive control, and high throughput with low cost, it is proposed that plants would make excellent models for the study of human pathogenesis.

Analysis of Energy Intensive Enterprises under EU Emission Trading System in Latvia

NASA Astrophysics Data System (ADS)

Zahare, Dace; Rosa, Marika

2011-01-01

Climate change and global warming has become one of the main topics worldwide. The European Union Emission Trading System (EU ETS) was established to limit climate change, providing regulations which encourage companies to invest in cleaner production and more energy efficient production. Latvian energy intensive enterprises are operating under the EU ETS from the year 2005. The main goal of this paper is to provide an analysis of energy intensive installations in terms of their energy efficiency. Additionally, an analysis of EU ETS phase III which will start to operate in 2013 under new, more stringent rules has been conducted by modelling three Latvian energy intensive enterprise operations under this phase and estimating the barriers to meet the goal of the EU ETS phase III.

Airport baggage handling--where do human factors fit in the challenges that airports put on a baggage system?

PubMed

Lenior, O N M

2012-01-01

The challenges put on large baggage systems by airports can be summarized as: handling a high number of bags in a short period of time, in a limited space, with all sorts of disruptions, whilst complying with stringent regulation upon security, sustainability and health and safety. The aim of this company case study is to show in the different project phases--as indicated in the system ergonomic approach--how the human factors specialist can play a major part in tackling these challenges. By describing different projects in terms of scope, organization, human factors topics covered, phases and lessons learned, the importance of Human-Computer Interaction, automation as well as manual handling and work organization in baggage is addressed.

SH3 interactome conserves general function over specific form

PubMed Central

Xin, Xiaofeng; Gfeller, David; Cheng, Jackie; Tonikian, Raffi; Sun, Lin; Guo, Ailan; Lopez, Lianet; Pavlenco, Alevtina; Akintobi, Adenrele; Zhang, Yingnan; Rual, Jean-François; Currell, Bridget; Seshagiri, Somasekar; Hao, Tong; Yang, Xinping; Shen, Yun A; Salehi-Ashtiani, Kourosh; Li, Jingjing; Cheng, Aaron T; Bouamalay, Dryden; Lugari, Adrien; Hill, David E; Grimes, Mark L; Drubin, David G; Grant, Barth D; Vidal, Marc; Boone, Charles; Sidhu, Sachdev S; Bader, Gary D

2013-01-01

Src homology 3 (SH3) domains bind peptides to mediate protein–protein interactions that assemble and regulate dynamic biological processes. We surveyed the repertoire of SH3 binding specificity using peptide phage display in a metazoan, the worm Caenorhabditis elegans, and discovered that it structurally mirrors that of the budding yeast Saccharomyces cerevisiae. We then mapped the worm SH3 interactome using stringent yeast two-hybrid and compared it with the equivalent map for yeast. We found that the worm SH3 interactome resembles the analogous yeast network because it is significantly enriched for proteins with roles in endocytosis. Nevertheless, orthologous SH3 domain-mediated interactions are highly rewired. Our results suggest a model of network evolution where general function of the SH3 domain network is conserved over its specific form. PMID:23549480

Modernizing the automatic temperature-regulating systems for electric resistor furnaces

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

Anchevskii, I.V.; Afanasiadi, N.G.; Demin, V.P.

An analysis of the technical level of heat-treating equipment at the sector's plants showed that automation was either insufficient or completely lacking. Modern heat-treating technology makes stringent demands on heat-treating equipment, including electric resistor furnaces. Therefore, it became necessary to modernize these furnaces and equip them with modern automatic temperature control systems (ATCSs). This is most urgent for furnaces which handle nuclear-power-station parts, which must not only be held at a certain temperature for a definite time, but which also require a complex process with established heating rates in each time period. The heat-treatment data are recorded in the part'smore » passport certificate, and the temperatures of both the heatingzone atmosphere and the heat-treated part are monitored.« less

[Homeostasis and Disorder of Musculoskeletal System.Molecular mechanism of bone metabolism and future therapeutic strategies.

PubMed

Nakashima, Tomoki

Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells. An imbalance of this process is often linked to various bone diseases. Thus, the elucidation of the molecular mechanisms involved in bone remodeling is critical for a deeper understanding of the maintenance of healthy skeleton and bone disease.

AID targeting: old mysteries and new challenges.

PubMed

Chandra, Vivek; Bortnick, Alexandra; Murre, Cornelis

2015-09-01

Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and thus stringent checks are in place to constrain and restrict its activity. Recent findings have provided new insights into the mechanisms that target AID activity to specific genomic regions, revealing an involvement for noncoding RNAs associated with polymerase pausing and with enhancer transcription as well as genomic architecture. We review these findings and integrate them into a model for multilevel regulation of AID expression and targeting in immunoglobulin and non-immunoglobulin loci. Within this framework we discuss gaps in understanding, and outline important areas of further research. Copyright © 2015 Elsevier Ltd. All rights reserved.

The etiology and determinants of hospital closure.

PubMed

Longo, D R; Sohn, M W; Shortell, S M

1996-01-01

This article examines the etiology of hospital closure and the correlates of hospital closure and the extent of similarity in this organizational outcome between pre- and post-Prospective Payment System (PPS) implementation. It also replicates a study from an earlier time period. Findings support the study's main hypotheses: in more stringent and turbulent markets, institutional and strategic variables are more important determinants of hospital closure. Merger acquisitions are found to be similar to both system acquisitions and autonomous hospitals. Standard Metropolitan Statistical Area (SMSA) status and regulation show an effect on hospital closure and merger acquisition. While many similarities exist when compared to the replicated study and findings prior to PPS implementation, it appears that sufficient differences exist to support the hypothesis that the PPS has an impact upon hospital organizational outcome.

AID Targeting: Old Mysteries and New Challenges

PubMed Central

Chandra, Vivek; Bortnick, Alexandra; Murre, Cornelis

2015-01-01

Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and thus, stringent checks are in place to constrain and restrict its activity. Recent findings have provided new insights into the mechanisms that target AID activity to specific genomic regions, revealing an involvement for non-coding RNAs associated with polymerase pausing and with enhancer transcription as well as genomic architecture. We review these findings and integrate them into a model for multi-level regulation of AID expression and targeting in immunoglobulin and non-immunoglobulin loci. Within this framework we discuss gaps in understanding, and outline important areas of further research. PMID:26254147

Genetic Mapping of Fixed Phenotypes: Disease Frequency as a Breed Characteristic

PubMed Central

Jones, Paul; Martin, Alan; Ostrander, Elaine A.; Lark, Karl G.

2009-01-01

Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pacreatitis. PMID:19321632

Ultrasound-assisted oxidative desulfurization and denitrogenation of liquid hydrocarbon fuels: A critical review.

PubMed

Ja'fari, Mahsa; Ebrahimi, Seyedeh Leila; Khosravi-Nikou, Mohammad Reza

2018-01-01

Nowadays, a continuously worldwide concern for development of process to produce ultra-low sulfur and nitrogen fuels have been emerged. Typical hydrodesulfurization and hydrodenitrogenation technology deals with important difficulties such as high pressure and temperature operating condition, failure to treat some recalcitrant compounds and limitations to meet the stringent environmental regulations. In contrary an advanced oxidation process that is ultrasound assisted oxidative desulfurization and denitrogenation satisfies latest environmental regulations in much milder conditions with more efficiency. The present work deals with a comprehensive review on findings and development in the ultrasound assisted oxidative desulfurization and denitrogenation (UAOD) during the last decades. The role of individual parameters namely temperature, residence time, ultrasound power and frequency, pH, initial concentration and types of sulfur and nitrogen compounds on the efficiency are described. What's more another treatment properties that is role of phase transfer agent (PTA) and solvents of extraction step, reaction kinetics, mechanism of the ultrasound, fuel properties and recovery in UAOD are reviewed. Finally, the required future works to mature this technology are suggested. Copyright © 2017 Elsevier B.V. All rights reserved.

Modulation of Pantothenate Kinase 3 Activity by Small Molecules that Interact with the Substrate/Allosteric Regulatory Domain

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

Leonardi, Roberta; Zhang, Yong-Mei; Yun, Mi-Kyung

2010-09-27

Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a tunnel adjacent to the active site that is occupied by the pantothenate moiety of the acetyl-CoA regulator in the PanK3 acetyl-CoA binary complex. A high-throughput screen for PanK3 inhibitors and activators was applied to a bioactive compound library. Thiazolidinediones, sulfonylureas and steroids were inhibitors, and fatty acyl-amides and tamoxifen were activators. The PanK3 activators and inhibitors either stimulated ormore » repressed CoA biosynthesis in HepG2/C3A cells. The flexible allosteric acetyl-CoA regulatory domain of PanK3 also binds the substrates, pantothenate and pantetheine, and small molecule inhibitors and activators to modulate PanK3 activity.« less

Quality control of bottled and vended water in California: A review and comparison to tap water

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

Darby, J.L.; Allen, L.

1994-04-01

Current regulations and compliance for quality control of bottled and vended water in California are compared with that of the tap water industry in this research. Over 35% of the bottled water sold in the US is consumed in California where a third of the residents use such water as a primary source of drinking water. California is one of several states that regulates bottled water more rigorously than the federal government. In California, water quality standards for the two industries are comparable except that many of the organic standards for bottled water are applicable only to the source water,more » a concern due to potential organic contamination during processing. Reporting requirements, significantly less stringent for bottled water, allow considerable latitude in assessing risks and make assessment of compliance difficult. Based on available statistics, compliance for the two industries is comparable; the majority of violations posed no health risks. For both industries, small systems comprised the majority of violations whereas large systems had excellent compliance rates.« less

KU HAPLOINSUFFIENCY CAUSES A LYMPHOPROLIFERATIVE DISORDER OF IMMATURE T-CELL PRECURSORS DUE TO IKAROS MALFUNCTION

PubMed Central

Ozer, Zahide; Qazi, Sanjive; Ishkhanian, Rita; Hasty, Paul; Ma, Hong; Uckun, Fatih M.

2013-01-01

Ikaros (IK) malfunction has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. Therefore, a stringent regulation of IK activity is very important. Here we provide unique genetic and biochemical evidence that the Ku protein components Ku70 and Ku80 act as positive regulators of IK function via formation of IK-Ku70 and IK-Ku80 heterodimers with augmented sequence-specific DNA binding activity. siRNA-mediated depletion of Ku70 or Ku80 reduced the sequence-specific DNA binding activity of IK in EMSA as well as the RT-PCR measured IK target gene expression levels in human cells. The interaction of Ku components with IK likely contributes to the anti-leukemic effects of IK as a tumor suppressor, because Ku70 as well as Ku80 haploinsuffiency in mice caused development of a lymphoproliferative disorder (LPD) involving CD2+CD4+CD8+CD1+IL7R+ thymic T-cell precursors with functional IK deficiency. PMID:24478815

Conditioned taste aversion dependent regulation of amygdala gene expression.

PubMed

Panguluri, Siva K; Kuwabara, Nobuyuki; Kang, Yi; Cooper, Nigel; Lundy, Robert F

2012-02-28

The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning. Copyright © 2011 Elsevier Inc. All rights reserved.

Cancer growth and its inhibition in terms of coherence.

PubMed

Popp, Fritz-Albert

2009-01-01

It is shown that a molecular origin for growth inhibition is rather unlikely because the cross-sectional area of inhibitory forces in a cell population cannot exceed more than about 10(-8) Dalton. A model of the time dependence of cell number N(t), where t is the time, is based on biophotons and explains without any contradiction to known experimental results growth regulation in terms of the factor a = 1/T, which stimulates the cell division rate dN/dt and the factor b = dT/dN(1/T(2)), which inhibits cell division. It accounts for the total cell division rate dN/dt = aN(t) - bN(2)(t). For adults, T is the coherence time of about 10(6) s, corresponding to the longest lifetime of cell organelles in men, while dT/dN = 10(-7) s corresponds to the resolution time of the cell population which is always the average time interval between two cell loss events. Our model follows a stringently holistic approach to describing a cell population as an entity, regulated by a fully coherent (biophoton) field.

Genetic mapping of fixed phenotypes: disease frequency as a breed characteristic.

PubMed

Chase, Kevin; Jones, Paul; Martin, Alan; Ostrander, Elaine A; Lark, Karl G

2009-01-01

Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pancreatitis.

Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes

PubMed Central

Jones, Paul; Chase, Kevin; Martin, Alan; Davern, Pluis; Ostrander, Elaine A.; Lark, Karl G.

2008-01-01

Phenotypic stereotypes are traits, often polygenic, that have been stringently selected to conform to specific criteria. In dogs, Canis familiaris, stereotypes result from breed standards set for conformation, performance (behaviors), etc. As a consequence, phenotypic values measured on a few individuals are representative of the breed stereotype. We used DNA samples isolated from 148 dog breeds to associate SNP markers with breed stereotypes. Using size as a trait to test the method, we identified six significant quantitative trait loci (QTL) on five chromosomes that include candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Less well-documented data for behavioral stereotypes tentatively identified loci for herding, pointing, boldness, and trainability. Four significant loci were identified for longevity, a breed characteristic not under direct selection, but inversely correlated with breed size. The strengths and limitations of the approach are discussed as well as its potential to identify loci regulating the within-breed incidence of specific polygenic diseases. PMID:18505865

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions.

PubMed

Zhou, Hufeng; Gao, Shangzhi; Nguyen, Nam Ninh; Fan, Mengyuan; Jin, Jingjing; Liu, Bing; Zhao, Liang; Xiong, Geng; Tan, Min; Li, Shijun; Wong, Limsoon

2014-04-08

H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies.

Irradiation of northwest agricultural products

NASA Astrophysics Data System (ADS)

Eakin, D. E.; Tingey, G. I.

1985-02-01

Irradiation of food for disinfestation and preservation is increasing in importance because of increasing restrictions on various chemical treatments. Irradiation treatment is of particular interest in the Northwest because of a growing supply of agricultural products and the need to develop new export markets. Several products have, or could potentially have, significant export markets if stringent insect ocntrol procedures are developed and followed. Due to the recognized potential benefits of irradiation, this program was conducted to evaluate the benefits of using irradiation on Northwest agricultural products. Commodities currently included in the program are cherries, apples, asparagus, spices, hay, and hides.

RelA Mutant Enterococcus faecium with Multiantibiotic Tolerance Arising in an Immunocompromised Host.

PubMed

Honsa, Erin S; Cooper, Vaughn S; Mhaissen, Mohammed N; Frank, Matthew; Shaker, Jessica; Iverson, Amy; Rubnitz, Jeffrey; Hayden, Randall T; Lee, Richard E; Rock, Charles O; Tuomanen, Elaine I; Wolf, Joshua; Rosch, Jason W

2017-01-03

Serious bacterial infections in immunocompromised patients require highly effective antibacterial therapy for cure, and thus, this setting may reveal novel mechanisms by which bacteria circumvent antibiotics in the absence of immune pressure. Here, an infant with leukemia developed vancomycin-resistant Enterococcus faecium (VRE) bacteremia that persisted for 26 days despite appropriate antibiotic therapy. Sequencing of 22 consecutive VRE isolates identified the emergence of a single missense mutation (L152F) in relA, which constitutively activated the stringent response, resulting in elevated baseline levels of the alarmone guanosine tetraphosphate (ppGpp). Although the mutant remained susceptible to both linezolid and daptomycin in clinical MIC testing and during planktonic growth, it demonstrated tolerance to high doses of both antibiotics when growing in a biofilm. This biofilm-specific gain in resistance was reflected in the broad shift in transcript levels caused by the mutation. Only an experimental biofilm-targeting ClpP-activating antibiotic was able to kill the mutant strain in an established biofilm. The relA mutation was associated with a fitness trade-off, forming smaller and less-well-populated biofilms on biological surfaces. We conclude that clinically relevant relA mutations can emerge during prolonged VRE infection, causing baseline activation of the stringent response, subsequent antibiotic tolerance, and delayed eradication in an immunocompromised state. The increasing prevalence of antibiotic-resistant bacterial pathogens is a major challenge currently facing the medical community. Such pathogens are of particular importance in immunocompromised patients as these individuals may favor emergence of novel resistance determinants due to lack of innate immune defenses and intensive antibiotic exposure. During the course of chemotherapy, a patient developed prolonged bacteremia with vancomycin-resistant Enterococcus faecium that failed to clear despite multiple front-line antibiotics. The consecutive bloodstream isolates were sequenced, and a single missense mutation identified in the relA gene, the mediator of the stringent response. Strains harboring the mutation had elevated baseline levels of the alarmone and displayed heightened resistance to the bactericidal activity of multiple antibiotics, particularly in a biofilm. Using a new class of compounds that modulate ClpP activity, the biofilms were successfully eradicated. These data represent the first clinical emergence of mutations in the stringent response in vancomycin-resistant entereococci. Copyright © 2017 Honsa et al.

The Myb-domain protein ULTRAPETALA1 INTERACTING FACTOR 1 controls floral meristem activities in Arabidopsis.

PubMed

Moreau, Fanny; Thévenon, Emmanuel; Blanvillain, Robert; Lopez-Vidriero, Irene; Franco-Zorrilla, Jose Manuel; Dumas, Renaud; Parcy, François; Morel, Patrice; Trehin, Christophe; Carles, Cristel C

2016-04-01

Higher plants continuously and iteratively produce new above-ground organs in the form of leaves, stems and flowers. These organs arise from shoot apical meristems whose homeostasis depends on coordination between self-renewal of stem cells and their differentiation into organ founder cells. This coordination is stringently controlled by the central transcription factor WUSCHEL (WUS), which is both necessary and sufficient for stem cell specification in Arabidopsis thaliana ULTRAPETALA1 (ULT1) was previously identified as a plant-specific, negative regulator of WUS expression. However, molecular mechanisms underlying this regulation remain unknown. ULT1 protein contains a SAND putative DNA-binding domain and a B-box, previously proposed as a protein interaction domain in eukaryotes. Here, we characterise a novel partner of ULT1, named ULT1 INTERACTING FACTOR 1 (UIF1), which contains a Myb domain and an EAR motif. UIF1 and ULT1 function in the same pathway for regulation of organ number in the flower. Moreover, UIF1 displays DNA-binding activity and specifically binds to WUS regulatory elements. We thus provide genetic and molecular evidence that UIF1 and ULT1 work together in floral meristem homeostasis, probably by direct repression of WUS expression. © 2016. Published by The Company of Biologists Ltd.

Proteins involved in neuronal differentiation of neuroblastoma cell line N1E-115.

PubMed

Oh, Ji-Eun; Freilinger, Angelika; Gelpi, Ellen; Pollak, Arnold; Hengstschläger, Markus; Lubec, Gert

2007-06-01

Neuronal differentiation (ND) represents a well-defined phenomenon in biological terms but proteins involved have not been studied systematically. We therefore aimed to study ND by retinoic acid (RA) in a widely used neuroblastoma cell line by comparative proteomics. The ND was induced in the N1E-115 cell line by serum deprivation and RA treatment. Undifferentiated cells and cells undergoing serum deprivation served as controls. Protein extracts were run on 2-DE followed by MALDI-TOF or MALDI-TOF-TOF analysis. Quantification was carried out using specific software and stringent statistical analysis was performed. Tubulin beta 5, cat eye syndrome critical region protein 5 homolog, putative GTP-binding protein PTD004 homolog, and the metabolic proteins glyceraldehyde-3-phosphate dehydrogenase and transketolase were differentially regulated. Differential protein levels of cytoskeleton proteins including tubulins and metabolic proteins have been reported to be regulated by ND. Herein, specific signaling differences as reflected by putative GTP-binding protein PTD004 changes in differentiated cells are shown and a possible role for the Cat eye syndrome critical region protein 5 homolog is proposed. The protein disulfide isomerase associated 3 protein fits the already proposed findings of chaperon regulation by ND. The study forms the molecular basis for further evaluation of the functional roles of the differentially expressed proteins in ND.

Interaction of the Lyme disease spirochete with its tick vector.

PubMed

Caimano, Melissa J; Drecktrah, Dan; Kung, Faith; Samuels, D Scott

2016-07-01

Borrelia burgdorferi, the causative agent of Lyme disease (along with closely related genospecies), is in the deeply branching spirochete phylum. The bacterium is maintained in nature in an enzootic cycle that involves transmission from a tick vector to a vertebrate host and acquisition from a vertebrate host to a tick vector. During its arthropod sojourn, B. burgdorferi faces a variety of stresses, including nutrient deprivation. Here, we review some of the spirochetal factors that promote persistence, maintenance and dissemination of B. burgdorferi in the tick, and then focus on the utilization of available carbohydrates as well as the exquisite regulatory systems invoked to adapt to the austere environment between blood meals and to signal species transitions as the bacteria traverse their enzootic cycle. The spirochetes shift their source of carbon and energy from glucose in the vertebrate to glycerol in the tick. Regulation of survival under limiting nutrients requires the classic stringent response in which RelBbu controls the levels of the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), while regulation at the tick-vertebrate interface as well as regulation of protective responses to the blood meal require the two-component system Hk1/Rrp1 to activate production of the second messenger cyclic-dimeric-GMP (c-di-GMP). © 2016 John Wiley & Sons Ltd.

Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

PubMed

Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

2018-06-06

Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

Alterations in the nuclear proteome of HIV-1 infected T-cells

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

DeBoer, Jason; Jagadish, Teena; Haverland, Nicole A.

Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified fourmore » clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines.« less

The role of tramadol in pain management in Latin America: a report by the Change Pain Latin America Advisory Panel.

PubMed

Santos Garcia, Joäo Batista; Lech, Osvandré; Campos Kraychete, Durval; Rico, María Antonieta; Hernández-Castro, John Jairo; Colimon, Frantz; Guerrero, Carlos; Sempértegui Gallegos, Manuel; Lara-Solares, Argelia; Flores Cantisani, José Alberto; Amescua-Garcia, César; Guillén Núñez, María Del Rocío; Berenguel Cook, María Del Rosario; Jreige Iskandar, Aziza; Bonilla Sierra, Patricia

2017-09-01

Change Pain Latin America (CPLA) was created to enhance chronic pain understanding and develop pain management improving strategies in this region. During its seventh meeting (August 2016), the main objective was to discuss tramadol's role in treating pain in Latin America. Furthermore, potential pain management consequences were considered, if tramadol was to become more stringently controlled. Key topics discussed were: main indications for prescribing tramadol, its pharmacological characteristics, safety and tolerability, effects of restrictions on its availability and use, and consequent impact on pain care quality. The experts agreed that tramadol is used to treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical, musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer pain. Its relevance when treating special patient groups (e.g. the elderly) is recognized. The main reasons for tramadol's high significance as a treatment option are: its broad efficacy, an inconspicuous safety profile and its availability, considering that access to strong analgesics - mainly controlled drugs (classical opioids) - is highly restricted in some countries. The CPLA also agreed that tramadol is well tolerated, without the safety issues associated with long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like side effects than classical opioids and lower abuse risk. In Latin America, tramadol is a valuable and frequently used medication for treating moderate to severe pain. More stringent regulations would have significant impact on its availability, especially for outpatients. This could cause regression to older and frequently inadequate pain management methods, resulting in unnecessary suffering for many Latin American patients.

Lube oil-dependent ash chemistry on soot oxidation reactivity in a gasoline direct-injection engine

DOE PAGES

Choi, Seungmok; Seong, Heeje

2016-09-30

Gasoline particulate filters (GPF) are considered an enabling technology to meet stringent particulate matter (PM) regulations for gasoline direct-injection (GDI) engines, which are known to produce significant PM emissions. While ash loading in filters has been recognized to be detrimental in filter performance by increasing back pressure, increased ash fractions in soot were observed to enhance soot oxidation. In this study, GDI soot samples derived from different gasoline/lube oil blends were evaluated to identify potential promoting factors when formulated lube oils were dosed into gasoline fuel. Ca-derived ash enhanced soot oxidation remarkably, while P- and ZDDP-derived ash deteriorated soot oxidation.more » It is apparent that the promoting effect of lube oil-derived ash is due mainly to the Ca component that is the most abundant among additive components in lube oil. Bulk and surface analyses of these ash compounds indicate that Ca-derived ash would be complex compounds, while the contribution of CaSO 4, which is one of the most abundant ash compounds from diesel engines, is almost negligible. For the validation of the ash promoting impact in filters, the regeneration experiments were compared for a TWC-coated GPF in a GDI engine before and after ash loading was performed. The pressure drop of the ash-loaded GPF decreased noticeably in the initial regeneration stage and it increased gradually, whereas that of no ash-loaded GPF increased gradually without any reduction. So, it is concluded that the ash layer in the GPF assisted soot oxidation in the early regeneration stage when it was in close contact with soot.« less

A novel role for GSK3β as a modulator of Drosha microprocessor activity and MicroRNA biogenesis.

PubMed

Fletcher, Claire E; Godfrey, Jack D; Shibakawa, Akifumi; Bushell, Martin; Bevan, Charlotte L

2016-10-23

Regulation of microRNA (miR) biogenesis is complex and stringently controlled. Here, we identify the kinase GSK3β as an important modulator of miR biogenesis at Microprocessor level. Repression of GSK3β activity reduces Drosha activity toward pri-miRs, leading to accumulation of unprocessed pri-miRs and reduction of pre-miRs and mature miRs without altering levels or cellular localisation of miR biogenesis proteins. Conversely, GSK3β activation increases Drosha activity and mature miR accumulation. GSK3β achieves this through promoting Drosha:cofactor and Drosha:pri-miR interactions: it binds to DGCR8 and p72 in the Microprocessor, an effect dependent upon presence of RNA. Indeed, GSK3β itself can immunoprecipitate pri-miRs, suggesting possible RNA-binding capacity. Kinase assays identify the mechanism for GSK3β-enhanced Drosha activity, which requires GSK3β nuclear localisation, as phosphorylation of Drosha at S 300 and/or S 302 ; confirmed by enhanced Drosha activity and association with cofactors, and increased abundance of mature miRs in the presence of phospho-mimic Drosha. Functional implications of GSK3β-enhanced miR biogenesis are illustrated by increased levels of GSK3β-upregulated miR targets following GSK3β inhibition. These data, the first to link GSK3β with the miR cascade in humans, highlight a novel pro-biogenesis role for GSK3β in increasing miR biogenesis as a component of the Microprocessor complex with wide-ranging functional consequences. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

An observational pre-post study of re-structuring Medicine inpatient teaching service: Improved continuity of care within constraint of 2011 duty hours.

PubMed

Cheung, Joseph Y; Mueller, Daniel; Blum, Marissa; Ravreby, Hannah; Williams, Paul; Moyer, Darilyn; Caroline, Malka; Zack, Chad; Fisher, Susan G; Feldman, Arthur M

2015-09-01

Implementation of more stringent regulations on duty hours and supervision by the Accreditation Council for Graduate Medical Education in July 2011 makes it challenging to design inpatient Medicine teaching service that complies with the duty hour restrictions while optimizing continuity of patient care. To prospectively compare two inpatient Medicine teaching service structures with respect to residents' impression of continuity of patient care (primary outcome), time available for teaching, resident satisfaction and length-of-stay (secondary endpoints). Observational pre-post study. Surveys were conducted both before and after Conventional Medicine teaching service was changed to a novel model (MegaTeam). Academic General Medicine inpatient teaching service. Surveys before and after MegaTeam implementation were completed by 68.5% and 72.2% of internal medicine residents, respectively. Comparing conventional with MegaTeam, the % of residents who agreed or strongly agreed that the (i) ability to care for majority of patients from admission to discharge increased from 29.7% to 86.6% (p<0.01); (ii) the concern that number of handoffs was too many decreased from 91.9% to 18.2% (p<0.01); (iii) ability to provide appropriate supervision to interns increased from 38.1% to 70.7% (p<0.01); (iv) overall resident satisfaction with inpatient Medicine teaching service increased from 24.7% to 56.4% (p<0.01); and (v) length-of-stay on inpatient Medicine service decreased from 5.3±6.2 to 4.9±6.8 days (p<0.03). According to our residents, the MegaTeam structure promotes continuity of patient care, decreases number of handoffs, provides adequate supervision and teaching of interns and medical students, increases resident overall satisfaction and decreases length-of-stay. Copyright © 2015 Elsevier Inc. All rights reserved.

Lube oil-dependent ash chemistry on soot oxidation reactivity in a gasoline direct-injection engine

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

Choi, Seungmok; Seong, Heeje

Gasoline particulate filters (GPF) are considered an enabling technology to meet stringent particulate matter (PM) regulations for gasoline direct-injection (GDI) engines, which are known to produce significant PM emissions. While ash loading in filters has been recognized to be detrimental in filter performance by increasing back pressure, increased ash fractions in soot were observed to enhance soot oxidation. In this study, GDI soot samples derived from different gasoline/lube oil blends were evaluated to identify potential promoting factors when formulated lube oils were dosed into gasoline fuel. Ca-derived ash enhanced soot oxidation remarkably, while P- and ZDDP-derived ash deteriorated soot oxidation.more » It is apparent that the promoting effect of lube oil-derived ash is due mainly to the Ca component that is the most abundant among additive components in lube oil. Bulk and surface analyses of these ash compounds indicate that Ca-derived ash would be complex compounds, while the contribution of CaSO 4, which is one of the most abundant ash compounds from diesel engines, is almost negligible. For the validation of the ash promoting impact in filters, the regeneration experiments were compared for a TWC-coated GPF in a GDI engine before and after ash loading was performed. The pressure drop of the ash-loaded GPF decreased noticeably in the initial regeneration stage and it increased gradually, whereas that of no ash-loaded GPF increased gradually without any reduction. So, it is concluded that the ash layer in the GPF assisted soot oxidation in the early regeneration stage when it was in close contact with soot.« less

The role of guanosine-3',5'-bis-pyrophosphate in mediating antimicrobial activity of the antibiotic 3,5-dihydroxy-4-ethyl-trans-stilbene.

PubMed Central

Sundar, L; Chang, F N

1992-01-01

The mode of action of 3,5-dihydroxy-4-ethyl-trans-stilbene (ES), an antibiotic produced by Xenorhabdus luminescens symbiotically associated with an entomopathogenic nematode, was investigated. ES was active against gram-positive and a number of gram-negative bacteria. In susceptible bacteria this antibiotic caused the inhibition of total RNA synthesis and, to a lesser extent, protein synthesis. At or above MICs, ES triggered a substantial accumulation of an intracellular regulatory compound, guanosine-3',5'-bis-pyrophosphate (ppGpp). This response was also noticed in species of bacteria which have previously not been shown to use ppGpp as a regulatory molecule. The involvement of ppGpp in antibiotic action was confirmed by using an isogenic stringent and a relaxed pair of Escherichia coli strains. The fact that the accumulation of ppGpp was correlated with the susceptibility of various gram-positive and gram-negative bacteria to ES suggests that this nucleotide is involved in the regulation of RNA synthesis and growth in all these microorganisms. Thus, inhibition of RNA synthesis via an increase in ppGpp concentrations may represent a mechanism that is prevalent among most bacteria and one that could be exploited for achieving a rapid inhibition of bacterial growth. Images PMID:1282791

A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y1 activation.

PubMed

Purvis, Jeremy E; Chatterjee, Manash S; Brass, Lawrence F; Diamond, Scott L

2008-11-15

To quantify how various molecular mechanisms are integrated to maintain platelet homeostasis and allow responsiveness to adenosine diphosphate (ADP), we developed a computational model of the human platelet. Existing kinetic information for 77 reactions, 132 fixed kinetic rate constants, and 70 species was combined with electrochemical calculations, measurements of platelet ultrastructure, novel experimental results, and published single-cell data. The model accurately predicted: (1) steady-state resting concentrations for intracellular calcium, inositol 1,4,5-trisphosphate, diacylglycerol, phosphatidic acid, phosphatidylinositol, phosphatidylinositol phosphate, and phosphatidylinositol 4,5-bisphosphate; (2) transient increases in intracellular calcium, inositol 1,4,5-trisphosphate, and G(q)-GTP in response to ADP; and (3) the volume of the platelet dense tubular system. A more stringent test of the model involved stochastic simulation of individual platelets, which display an asynchronous calcium spiking behavior in response to ADP. Simulations accurately reproduced the broad frequency distribution of measured spiking events and demonstrated that asynchronous spiking was a consequence of stochastic fluctuations resulting from the small volume of the platelet. The model also provided insights into possible mechanisms of negative-feedback signaling, the relative potency of platelet agonists, and cell-to-cell variation across platelet populations. This integrative approach to platelet biology offers a novel and complementary strategy to traditional reductionist methods.

X-Ray Radiography Measurements of the Thermal Energy in Spark Ignition Plasma at Variable Ambient Conditions

DOE PAGES

Matusik, Katarzyna E.; Duke, Daniel J.; Kastengren, Alan L.; ...

2017-04-09

The sparking behavior in an internal combustion engine affects the fuel efficiency, engine-out emissions, and general drivability of a vehicle. As emissions regulations become progressively stringent, combustion strategies, including exhaust gas recirculation (EGR), lean-burn, and turbocharging are receiving increasing attention as models of higher efficiency advanced combustion engines with reduced emissions levels. Because these new strategies affect the working environment of the spark plug, ongoing research strives to understand the influence of external factors on the spark ignition process. Due to the short time and length scales involved and the harsh environment, experimental quantification of the deposited energy from themore » sparking event is difficult to obtain. We present the results of x-ray radiography measurements of spark ignition plasma generated by a conventional spark plug. Our measurements were performed at the 7-BM beamline of the Advanced Photon Source at Argonne National Laboratory. The synchrotron x-ray source enables time-resolved measurements of the density change due to glow discharge in the spark gap with 153 ns temporal and 5 μm spatial resolutions. We also explore the effects of charging time, EGR-relevant gas compositions, and gas pressure on the sparking behavior. We also quantify the influence of the measurement technique on the obtained results.« less

Weather Typing-Based Flood Frequency Analysis Verified for Exceptional Historical Events of Past 500 Years Along the Meuse River

NASA Astrophysics Data System (ADS)

De Niel, J.; Demarée, G.; Willems, P.

2017-10-01

Governments, policy makers, and water managers are pushed by recent socioeconomic developments such as population growth and increased urbanization inclusive of occupation of floodplains to impose very stringent regulations on the design of hydrological structures. These structures need to withstand storms with return periods typically ranging between 1,250 and 10,000 years. Such quantification involves extrapolations of systematically measured instrumental data, possibly complemented by quantitative and/or qualitative historical data and paleoflood data. The accuracy of the extrapolations is, however, highly unclear in practice. In order to evaluate extreme river peak flow extrapolation and accuracy, we studied historical and instrumental data of the past 500 years along the Meuse River. We moreover propose an alternative method for the estimation of the extreme value distribution of river peak flows, based on weather types derived by sea level pressure reconstructions. This approach results in a more accurate estimation of the tail of the distribution, where current methods are underestimating the design levels related to extreme high return periods. The design flood for a 1,250 year return period is estimated at 4,800 m3 s-1 for the proposed method, compared with 3,450 and 3,900 m3 s-1 for a traditional method and a previous study.

Structured Development and Promotion of a Research Field: Hormesis in Biology, Toxicology, and Environmental Regulatory Science.

PubMed

Mushak, Paul; Elliott, Kevin C

2015-12-01

The ability of powerful and well-funded interest groups to steer scientific research in ways that advance their goals has become a significant social concern. This steering ability is increasingly being recognized in the peer-reviewed scientific literature and in findings of deliberative scientific bodies. This paper provides a case study that illustrates some of the major strategies that can be used to structure and advance a controversial research field. It focuses on hormesis, described as a type of dose-response relationship in toxicology and biology showing low-dose stimulation but high-dose inhibition, or the reverse. Hormesis proponents tout its significance, arguing that substances toxic at high doses and beneficial at lower doses should be regulated less stringently. We identify five strategies employed by hormesis proponents to foster its acceptance: (1) creating institutions focused on supporting hormesis; (2) developing terminology, study designs, and data interpretations that cast it in a favorable light; (3) using bibliometric techniques and surveys to attract attention; (4) aggressively advocating for the phenomenon and challenging critics; and (5) working with outside interest groups to apply the hormesis phenomenon in the economic and political spheres. We also suggest a number of oversight strategies that can be implemented to help promote credible and socially responsible research in cases like this one.

The Potential of Sequential Extraction in the Characterisation and Management of Wastes from Steel Processing: A Prospective Review

PubMed Central

Rodgers, Kiri J.; Hursthouse, Andrew; Cuthbert, Simon

2015-01-01

As waste management regulations become more stringent, yet demand for resources continues to increase, there is a pressing need for innovative management techniques and more sophisticated supporting analysis techniques. Sequential extraction (SE) analysis, a technique previously applied to soils and sediments, offers the potential to gain a better understanding of the composition of solid wastes. SE attempts to classify potentially toxic elements (PTEs) by their associations with phases or fractions in waste, with the aim of improving resource use and reducing negative environmental impacts. In this review we explain how SE can be applied to steel wastes. These present challenges due to differences in sample characteristics compared with materials to which SE has been traditionally applied, specifically chemical composition, particle size and pH buffering capacity, which are critical when identifying a suitable SE method. We highlight the importance of delineating iron-rich phases, and find that the commonly applied BCR (The community Bureau of reference) extraction method is problematic due to difficulties with zinc speciation (a critical steel waste constituent), hence a substantially modified SEP is necessary to deal with particular characteristics of steel wastes. Successful development of SE for steel wastes could have wider implications, e.g., for the sustainable management of fly ash and mining wastes. PMID:26393631

Evaluation of a model training program for respiratory-protection preparedness at local health departments.

PubMed

Alfano-Sobsey, Edie; Kennedy, Bobby; Beck, Frank; Combs, Brian; Kady, Wendy; Ramsey, Steven; Stockweather, Allison; Service, Will

2006-04-01

Respiratory-protection programs have had limited application in local health departments and have mostly focused on protecting employees against exposure to tuberculosis (TB). The need to provide the public health workforce with effective respiratory protection has, however, been underscored by recent concerns about emerging infectious diseases, bioterrorism attacks, drug-resistant microbes, and environmental exposures to microbial allergens (as in recent hurricane flood waters). Furthermore, OSHA has revoked the TB standard traditionally followed by local health departments, replacing it with a more stringent regulation. The additional OSHA requirements may place increased burdens on health departments with limited resources and time. For these reasons, the North Carolina Office of Public Health Preparedness and Response and industrial hygienists of the Public Health Regional Surveillance Teams have developed a training program to facilitate implementation of respiratory protection programs at local health departments. To date, more than 1,400 North Carolina health department employees have been properly fit-tested for respirator use and have received training in all aspects of respiratory protection. This article gives an overview of the development and evaluation of the program. The training approach presented here can serve as a model that other health departments and organizations can use in implementing similar respiratory-protection programs.

Food labeling issues in patients with severe food allergies: solving a hamlet-like doubt.

PubMed

Fierro, Vincenzo; Di Girolamo, Francesco; Marzano, Valeria; Dahdah, Lamia; Mennini, Maurizio

2017-06-01

We review the laws on labeling in the international community, the difficulties they pose to the food manufacturers to prepare the food labels and the methodologies to determine the concentration of potential allergens in foods. European Food Safety Authority and International Life Sciences Institute Europe are evaluating strategies to identify the threshold level of allergen that can trigger a reaction in individuals. The most used techniques to detect the presence of protein in food are Enzyme-linked immunosorbent assay, polymerase chain reaction and real time polymerase chain reaction. Researchers are now trying to apply proteomics to estimate the amount of protein within the food.In order to protect the health of consumers, the Codex Alimentarius Commission updates constantly the list of allergens. In response to these regulations, some industries have also added some precautionary allergen labeling (PAL). It was generally agreed that PAL statements needed to be visible, simple, and safe. It was suggested that PAL be standardized, an action that would occur if the 'Voluntary Incidental Trace Allergen Labelling' process was made mandatory. So far, no laboratory technique is able to reassure the consumers about the composition of foods found on the packaging. International authorities produced increasingly stringent laws, but more is still to do.

The Potential of Sequential Extraction in the Characterisation and Management of Wastes from Steel Processing: A Prospective Review.

PubMed

Rodgers, Kiri J; Hursthouse, Andrew; Cuthbert, Simon

2015-09-18

As waste management regulations become more stringent, yet demand for resources continues to increase, there is a pressing need for innovative management techniques and more sophisticated supporting analysis techniques. Sequential extraction (SE) analysis, a technique previously applied to soils and sediments, offers the potential to gain a better understanding of the composition of solid wastes. SE attempts to classify potentially toxic elements (PTEs) by their associations with phases or fractions in waste, with the aim of improving resource use and reducing negative environmental impacts. In this review we explain how SE can be applied to steel wastes. These present challenges due to differences in sample characteristics compared with materials to which SE has been traditionally applied, specifically chemical composition, particle size and pH buffering capacity, which are critical when identifying a suitable SE method. We highlight the importance of delineating iron-rich phases, and find that the commonly applied BCR (The community Bureau of reference) extraction method is problematic due to difficulties with zinc speciation (a critical steel waste constituent), hence a substantially modified SEP is necessary to deal with particular characteristics of steel wastes. Successful development of SE for steel wastes could have wider implications, e.g., for the sustainable management of fly ash and mining wastes.

Cognitive and personality factors in the delay of gratification of hemodialysis patients.

PubMed

Rosenbaum, M; Ben-Ari Smira, K

1986-08-01

On the basis of Mischel's (1984) social learning analysis of the process of delay of gratification in children and in line with Bandura's (1977) self-efficacy theory, we developed a model of delay of gratification in adults and tested it on dialysis patients who were continuously required to comply with a stringent regimen of fluid-intake to keep alive. We hypothesized that patients' self-evaluations of their past compliance and their efficacy expectations would be associated with their actual delay behavior. Underlying these process-regulating cognitions would be stable competencies, such as learned resourcefulness (i.e., one's self-control skills). Fifty-three dialysis patients self-evaluated their fluid intake compliance, their efficacy expectations, and their health beliefs. Resourcefulness was assessed by Rosenbaum's Self-Control Schedule. Actual fluid-intake compliance was reliably assessed by the mean body weight increase between dialyses during the 3-month period prior to the study and during two follow-up periods. The results supported the model. On the one hand, self-efficacy expectations were related to persistence with the fluid diet and on the other hand to subjects' self-evaluation of their past adherence behavior as well as to their resourcefulness. Although the path model suggested a causal pattern, the correlational nature of the study precluded any conclusions on cause-effect relationship.

Use of immobilised biocatalysts in the processing of cheese whey.

PubMed

Kosseva, Maria R; Panesar, Parmjit S; Kaur, Gurpreet; Kennedy, John F

2009-12-01

Food processing industry operations need to comply with increasingly more stringent environmental regulations related to the disposal or utilisation of by-products and wastes. These include growing restrictions on land spraying with agro-industrial wastes, and on disposal within landfill operations, and the requirements to produce end products that are stabilised and hygienic. Much of the material generated as wastes by the dairy processing industries contains components that could be utilised as substrates and nutrients in a variety of microbial/enzymatic processes, to give rise to added-value products. A good example of a waste that has received considerable attention as a source of added-value products is cheese whey. The carbohydrate reservoir of lactose (4-5%) in whey and the presence of other essential nutrients make it a good natural medium for the growth of microorganisms and a potential substrate for bioprocessing through microbial fermentation. Immobilised cell and enzyme technology has also been applied to whey bioconversion processes to improve the economics of such processes. This review focuses upon the elaboration of a range of immobilisation techniques that have been applied to produce valuable whey-based products. A comprehensive literature survey is also provided to illustrate numerous immobilisation procedures with particular emphasis upon lactose hydrolysis, and ethanol and lactic acid production using immobilised biocatalysts.

DESALINATION AND WATER TREATMENT RESEARCH AT SANDIA NATIONAL LABORATORIES.

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

Rigali, Mark J.; Miller, James E.; Altman, Susan J.

Water is the backbone of our economy - safe and adequate supplies of water are vital for agriculture, industry, recreation, and human consumption. While our supply of water today is largely safe and adequate, we as a nation face increasing water supply challenges in the form of extended droughts, demand growth due to population increase, more stringent health-based regulation, and competing demands from a variety of users. To meet these challenges in the coming decades, water treatment technologies, including desalination, will contribute substantially to ensuring a safe, sustainable, affordable, and adequate water supply for the United States. This overview documentsmore » Sandia National Laboratories' (SNL, or Sandia) Water Treatment Program which focused on the development and demonstration of advanced water purification technologies as part of the larger Sandia Water Initiative. Projects under the Water Treatment Program include: (1) the development of desalination research roadmaps (2) our efforts to accelerate the commercialization of new desalination and water treatment technologies (known as the 'Jump-Start Program),' (3) long range (high risk, early stage) desalination research (known as the 'Long Range Research Program'), (4) treatment research projects under the Joint Water Reuse & Desalination Task Force, (5) the Arsenic Water Technology Partnership Program, (6) water treatment projects funded under the New Mexico Small Business Administration, (7) water treatment projects for the National Energy Technology Laboratory (NETL) and the National Renewable Energy Laboratory (NREL), (8) Sandia- developed contaminant-selective treatment technologies, and finally (9) current Laboratory Directed Research and Development (LDRD) funded desalination projects.« less

Linkages Between Ozone-depleting Substances, Tropospheric Oxidation and Aerosols

NASA Technical Reports Server (NTRS)

Voulgarakis, A.; Shindell, D. T.; Faluvegi, G.

2013-01-01

Coupling between the stratosphere and the troposphere allows changes in stratospheric ozone abundances to affect tropospheric chemistry. Large-scale effects from such changes on chemically produced tropospheric aerosols have not been systematically examined in past studies. We use a composition-climate model to investigate potential past and future impacts of changes in stratospheric ozone depleting substances (ODS) on tropospheric oxidants and sulfate aerosols. In most experiments, we find significant responses in tropospheric photolysis and oxidants, with small but significant effects on methane radiative forcing. The response of sulfate aerosols is sizeable when examining the effect of increasing future nitrous oxide (N2O) emissions. We also find that without the regulation of chlorofluorocarbons (CFCs) through the Montreal Protocol, sulfate aerosols could have increased by 2050 by a comparable amount to the decreases predicted due to relatively stringent sulfur emissions controls. The individual historical radiative forcings of CFCs and N2O through their indirect effects on methane (-22.6mW/sq. m for CFCs and -6.7mW/sq. m for N2O) and sulfate aerosols (-3.0mW/sq. m for CFCs and +6.5mW/sq. m for N2O when considering the direct aerosol effect) discussed here are non-negligible when compared to known historical ODS forcing. Our results stress the importance of accounting for stratosphere-troposphere, gas-aerosol and composition-climate interactions when investigating the effects of changing emissions on atmospheric composition and climate.

Energy Market and Economic Impacts of S. 280, the Climate Stewardship and Innovation Act of 2007

EIA Publications

2007-01-01

This report responds to a request from Senators Joseph Lieberman and John McCain for an estimate of the economic impacts of S.280, the Climate Stewardship and Innovation Act of 2007. S. 280 would establish a series of caps on greenhouse gas emissions starting in 2012 followed by increasingly stringent caps beginning in 2020, 2030 and 2050. The report provides estimates of the effects of S. 280 on energy markets and the economy through 2030.

Reinventing Superfund means de-inventing'' superfund

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

McFarland, C.J.

The White House claims there are some things the federal government does that it could do better and other things it should not do at all. It is in this light that the federal government should delegate responsibility for Superfund to the states. Various factors that drove the federalization of many environmental programs in the 1970s and 1980s no longer apply for Superfund. Air and water pollution programs were federalized partly because states feared businesses would relocate to friendlier'', less environmentally stringent areas. States would not impose sufficiently stringent environmental controls, because pursuing tougher standards meant committing economic suicide. Thus,more » uniform air and water pollution standards were implemented on a federal level to eliminate business flight. Superfund, by contrast, imposes costs based wholly on past activities. One state's determination to rededicate its waste sites quickly and more stringently than another state has little effect on a business's location decisions. Relocating a plant does not change where the waste previously was disposed.« less

Anogenital warts contain several distinct species of human papillomavirus.

PubMed Central

Krzyzek, R A; Watts, S L; Anderson, D L; Faras, A J; Pass, F

1980-01-01

Anogenital warts from 26 patients were examined for the presence of human papillomavirus (HPV). Although no whole, intact virus could be identified, varying amounts of nonintegrated HPV DNA were detected in 18 tissue specimens (70%) by employing both an agarose gel-ethidium bromide staining method and the Southern blot hybridization procedure. When hybridization analysis was performed under stringent conditions, six anogenital warts were observed to contain HPV genomic sequences related to either of the cutaneous viruses HPV type 1 (HPV-1) or HPV-2. In 12 tissue samples lacking sequence homology to either HPV-1 or HPV-2 under stringent conditions, HPV-related sequences were detected when the hybridization was performed under less stringent conditions, indicating that an HPV distinct from both HPV-1 and HPV-2 is also associated with these lesions. This anogenital HPV also appeared to be distinct from the other characterized types of HPV. These data indicate that at least three HPVs are associated with anogenital wart disease. Images PMID:6255208

Ten Year Study of the Stringently Defined Otitis Prone Child in Rochester, NY

PubMed Central

Pichichero, Michael E.

2016-01-01

This review summarizes a prospective, longitudinal 10-year study in Rochester NY with virtually every clinically diagnosed acute otitis media (AOM) confirmed by bacterial culture of middle ear fluid. Children experiencing 3 episodes within 6 months or 4 episodes in 12 months were considered stringently-defined otitis prone (sOP). We found stringent diagnosis compared with clinical diagnosis reduced the frequency of children meeting the OP definition from 27% to 6% resulting in 14.8% and 2.4% receiving tympanostomy tubes, respectively. Significantly more often RSV infection led to AOM in sOP than non-otitis prone (NOP) children that correlated with diminished total RSV-specific serum IgG. sOP children produced low levels of antibody to Streptococcus pneumoniae and Haemophilus influenzae candidate vaccine protein antigens and to routine pediatric vaccines. sOP children generated significantly fewer memory B cells, functional and memory T cells to otopathogens following NP colonization and AOM than NOP children and they had defects in antigen presenting cells. PMID:27273691

Fraudsters operate and officialdom turns a blind eye: a proposal for controlling stem cell therapy in China.

PubMed

Jiang, Li; Dong, Bing He

2016-09-01

Stem cell tourism-the flow of patients from home countries to destination countries to obtain stem cell treatment-is a growing business in China. Many concerns have been raised regarding fraudsters that operate unsafe stem cell therapies and an officialdom that turns a blind eye to the questionable technology. The Chinese regulatory approach to stem cell research is based on Guidelines and Administrative Measures, rather than legislation, and may have no binding force on certain institutions, such as military hospitals. There is no liability and traceability system and no visible set of penalties for non-compliance in the stem cell legal framework. In addition to the lack of safety and efficacy systems in the regulations, no specific expert authority has been established to monitor stem cell therapy to date. Recognizing the global nature of stem cell tourism, this article argues that resolving stem cell tourism issues may require not only the Chinese government but also an international mechanism for transparency and ethical oversight. A stringent set of international regulations that govern stem cell therapies can encourage China to improve stem cell regulation and enforcement to fulfill its obligations. Through an international consensus, a minimum standard for clinical stem cell research and a central enforcement system will be provided. As a result, rogue clinics that conduct unauthorized stem cell therapies can be penalized, and countries that are reluctant to implement the reconciled regulations should be sanctioned.

Building a comprehensive mill-level database for the Industrial Sectors Integrated Solutions (ISIS) model of the U.S. pulp and paper sector.

PubMed

Modak, Nabanita; Spence, Kelley; Sood, Saloni; Rosati, Jacky Ann

2015-01-01

Air emissions from the U.S. pulp and paper sector have been federally regulated since 1978; however, regulations are periodically reviewed and revised to improve efficiency and effectiveness of existing emission standards. The Industrial Sectors Integrated Solutions (ISIS) model for the pulp and paper sector is currently under development at the U.S. Environmental Protection Agency (EPA), and can be utilized to facilitate multi-pollutant, sector-based analyses that are performed in conjunction with regulatory development. The model utilizes a multi-sector, multi-product dynamic linear modeling framework that evaluates the economic impact of emission reduction strategies for multiple air pollutants. The ISIS model considers facility-level economic, environmental, and technical parameters, as well as sector-level market data, to estimate the impacts of environmental regulations on the pulp and paper industry. Specifically, the model can be used to estimate U.S. and global market impacts of new or more stringent air regulations, such as impacts on product price, exports and imports, market demands, capital investment, and mill closures. One major challenge to developing a representative model is the need for an extensive amount of data. This article discusses the collection and processing of data for use in the model, as well as the methods used for building the ISIS pulp and paper database that facilitates the required analyses to support the air quality management of the pulp and paper sector.

Building a Comprehensive Mill-Level Database for the Industrial Sectors Integrated Solutions (ISIS) Model of the U.S. Pulp and Paper Sector

PubMed Central

Modak, Nabanita; Spence, Kelley; Sood, Saloni; Rosati, Jacky Ann

2015-01-01

Air emissions from the U.S. pulp and paper sector have been federally regulated since 1978; however, regulations are periodically reviewed and revised to improve efficiency and effectiveness of existing emission standards. The Industrial Sectors Integrated Solutions (ISIS) model for the pulp and paper sector is currently under development at the U.S. Environmental Protection Agency (EPA), and can be utilized to facilitate multi-pollutant, sector-based analyses that are performed in conjunction with regulatory development. The model utilizes a multi-sector, multi-product dynamic linear modeling framework that evaluates the economic impact of emission reduction strategies for multiple air pollutants. The ISIS model considers facility-level economic, environmental, and technical parameters, as well as sector-level market data, to estimate the impacts of environmental regulations on the pulp and paper industry. Specifically, the model can be used to estimate U.S. and global market impacts of new or more stringent air regulations, such as impacts on product price, exports and imports, market demands, capital investment, and mill closures. One major challenge to developing a representative model is the need for an extensive amount of data. This article discusses the collection and processing of data for use in the model, as well as the methods used for building the ISIS pulp and paper database that facilitates the required analyses to support the air quality management of the pulp and paper sector. PMID:25806516

Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root

PubMed Central

De Ruvo, Micol; Pacifici, Elena; Salvi, Elena; Sozzani, Rosangela; Benfey, Philip N.; Di Paola, Luisa; Marée, Athanasius F. M.; Costantino, Paolo; Grieneisen, Verônica A.; Sabatini, Sabrina

2017-01-01

In multicellular organisms, a stringent control of the transition between cell division and differentiation is crucial for correct tissue and organ development. In the Arabidopsis root, the boundary between dividing and differentiating cells is positioned by the antagonistic interaction of the hormones auxin and cytokinin. Cytokinin affects polar auxin transport, but how this impacts the positional information required to establish this tissue boundary, is still unknown. By combining computational modeling with molecular genetics, we show that boundary formation is dependent on cytokinin’s control on auxin polar transport and degradation. The regulation of both processes shapes the auxin profile in a well-defined auxin minimum. This auxin minimum positions the boundary between dividing and differentiating cells, acting as a trigger for this developmental transition, thus controlling meristem size. PMID:28831001

100-Year flood–it's all about chance

USGS Publications Warehouse

Holmes, Robert R.; Dinicola, Karen

2010-01-01

In the 1960's, the United States government decided to use the 1-percent annual exceedance probability (AEP) flood as the basis for the National Flood Insurance Program. The 1-percent AEP flood was thought to be a fair balance between protecting the public and overly stringent regulation. Because the 1-percent AEP flood has a 1 in 100 chance of being equaled or exceeded in any 1 year, and it has an average recurrence interval of 100 years, it often is referred to as the '100-year flood'. The term '100-year flood' is part of the national lexicon, but is often a source of confusion by those not familiar with flood science and statistics. This poster is an attempt to explain the concept, probabilistic nature, and inherent uncertainties of the '100-year flood' to the layman.

Solving the shrinkage-induced PDMS alignment registration issue in multilayer soft lithography

NASA Astrophysics Data System (ADS)

Moraes, Christopher; Sun, Yu; Simmons, Craig A.

2009-06-01

Shrinkage of polydimethylsiloxane (PDMS) complicates alignment registration between layers during multilayer soft lithography fabrication. This often hinders the development of large-scale microfabricated arrayed devices. Here we report a rapid method to construct large-area, multilayered devices with stringent alignment requirements. This technique, which exploits a previously unrecognized aspect of sandwich mold fabrication, improves device yield, enables highly accurate alignment over large areas of multilayered devices and does not require strict regulation of fabrication conditions or extensive calibration processes. To demonstrate this technique, a microfabricated Braille display was developed and characterized. High device yield and accurate alignment within 15 µm were achieved over three layers for an array of 108 Braille units spread over a 6.5 cm2 area, demonstrating the fabrication of well-aligned devices with greater ease and efficiency than previously possible.

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions

PubMed Central

2014-01-01

Background H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. Results We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Conclusions Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies. Reviewers This article was reviewed by Michael Gromiha, Narayanaswamy Srinivasan and Thomas Dandekar. PMID:24708540

Absence of ppGpp Leads to Increased Mobilization of Intermediately Accumulated Poly(3-Hydroxybutyrate) in Ralstonia eutropha H16

PubMed Central

Juengert, Janina R.; Borisova, Marina; Wolz, Christiane; Brigham, Christopher J.; Sinskey, Anthony J.

2017-01-01

ABSTRACT In this study, we constructed a set of Ralstonia eutropha H16 strains with single, double, or triple deletions of the (p)ppGpp synthase/hydrolase (spoT1), (p)ppGpp synthase (spoT2), and/or polyhydroxybutyrate (PHB) depolymerase (phaZa1 or phaZa3) gene, and we determined the impact on the levels of (p)ppGpp and on accumulated PHB. Mutants with deletions of both the spoT1 and spoT2 genes were unable to synthesize detectable amounts of (p)ppGpp and accumulated only minor amounts of PHB, due to PhaZa1-mediated depolymerization of PHB. In contrast, unusually high levels of PHB were found in strains in which the (p)ppGpp concentration was increased by the overexpression of (p)ppGpp synthase (SpoT2) and the absence of (p)ppGpp hydrolase. Determination of (p)ppGpp levels in wild-type R. eutropha under different growth conditions and induction of the stringent response by amino acid analogs showed that the concentrations of (p)ppGpp during the growth phase determine the amount of PHB remaining in later growth phases by influencing the efficiency of the PHB mobilization system in stationary growth. The data reported for a previously constructed ΔspoT2 strain (C. J. Brigham, D. R. Speth, C. Rha, and A. J. Sinskey, Appl Environ Microbiol 78:8033–8044, 2012, https://doi.org/10.1128/AEM.01693-12) were identified as due to an experimental error in strain construction, and our results are in contrast to the previous indication that the spoT2 gene product is essential for PHB accumulation in R. eutropha. IMPORTANCE Polyhydroxybutyrate (PHB) is an important intracellular carbon and energy storage compound in many prokaryotes and helps cells survive periods of starvation and other stress conditions. Research activities in several laboratories over the past 3 decades have shown that both PHB synthase and PHB depolymerase are constitutively expressed in most PHB-accumulating bacteria, such as Ralstonia eutropha. This implies that PHB synthase and depolymerase activities must be well regulated in order to avoid a futile cycle of simultaneous PHB synthesis and PHB degradation (mobilization). Previous reports suggested that the stringent response in Rhizobium etli and R. eutropha is involved in the regulation of PHB metabolism. However, the levels of (p)ppGpp and the influence of those levels on PHB accumulation and PHB mobilization have not yet been determined for any PHB-accumulating species. In this study, we optimized a (p)ppGpp extraction procedure and a high-performance liquid chromatography–mass spectrometry (HPLC-MS)-based detection method for the quantification of (p)ppGpp in R. eutropha. This enabled us to study the relationship between the concentrations of (p)ppGpp and the accumulated levels of PHB in the wild type and in several constructed mutant strains. We show that overproduction of the alarmone (p)ppGpp correlated with reduced growth and massive overproduction of PHB. In contrast, in the absence of (p)ppGpp, mobilization of PHB was dramatically enhanced. PMID:28455332

Mask etcher data strategy for 45nm and beyond

NASA Astrophysics Data System (ADS)

Lewington, Richard; Ibrahim, Ibrahim M.; Panayil, Sheeba; Kumar, Ajay; Yamartino, John

2006-05-01

Mask Etching for the 45nm technology node and beyond requires a system-level data and diagnostics strategy. This necessity stems from the need to control the performance of the mask etcher to increasingly stringent and diverse requirements of the mask production environment. Increasing mask costs and the capability to acquire and consolidate a wealth of data within the mask etch platform are primary motivators towards harnessing data mines for feedback into the mask etching optimization. There are offline and real-time possibilities and scenarios. Here, we discuss the data architecture, acquisition, and strategies of the Applied Materials Tetra II TM Mask Etch System.

Bipolar mood state reflected in cortico-amygdala resting state connectivity: A cohort and longitudinal study.

PubMed

Brady, Roscoe O; Margolis, Allison; Masters, Grace A; Keshavan, Matcheri; Öngür, Dost

2017-08-01

Using resting-state functional magnetic resonance imaging (rsfMRI), we previously compared cohorts of bipolar I subjects in a manic state to those in a euthymic state to identify mood state-specific patterns of cortico-amygdala connectivity. Our results suggested that mania is reflected in the disruption of emotion regulation circuits. We sought to replicate this finding in a group of subjects with bipolar disorder imaged longitudinally across states of mania and euthymia METHODS: We divided our subjects into three groups: 26 subjects imaged in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged longitudinally across both mood states. We measured differences in amygdala connectivity between the mania and euthymia cohorts. We then used these regions of altered connectivity to examine connectivity in the longitudinal bipolar group using a within-subjects design. Our findings in the mania vs euthymia cohort comparison were replicated in the longitudinal analysis. Bipolar mania was differentiated from euthymia by decreased connectivity between the amygdala and pre-genual anterior cingulate cortex. Mania was also characterized by increased connectivity between amygdala and the supplemental motor area, a region normally anti-correlated to the amygdala in emotion regulation tasks. Stringent controls for movement effects limited the number of subjects in the longitudinal sample. In this first report of rsfMRI conducted longitudinally across mood states, we find that previously observed between-group differences in amygdala connectivity are also found longitudinally within subjects. These results suggest resting state cortico-amygdala connectivity is a biomarker of mood state in bipolar disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells.

PubMed

Safina, Alfiya; Garcia, Henry; Commane, Mairead; Guryanova, Olga; Degan, Seamus; Kolesnikova, Kateryna; Gurova, Katerina V

2013-08-01

Facilitates chromatin transcription (FACT) is a chromatin remodeling complex with two subunits: SSRP1 and SPT16. Mechanisms controlling FACT levels are of interest, since the complex is not expressed in most differentiated cells, but is frequently upregulated in cancer, particularly in poorly differentiated, aggressive tumors. Moreover, inhibition of FACT expression or function in tumor cells interferes with their survival. Here we demonstrate that SSRP1 and SPT16 protein levels decline upon induction of cellular differentiation or senescence in vitro and that similar declines in protein levels for both SSRP1 and SPT16 occur upon RNAi-mediated knockdown of either SSRP1 or SPT16. The interdependence of SSRP1 and SPT16 protein levels was found to be due to their association with SSRP1 and SPT16 mRNAs, which stabilizes the proteins. In particular, presence of SSRP1 mRNA is critical for SPT16 protein stability. In addition, binding of SSRP1 and SPT16 mRNAs to the FACT complex increases the stability and efficiency of translation of the mRNAs. These data support a model in which the FACT complex is stable when SSRP1 mRNA is present, but quickly degrades when SSRP1 mRNA levels drop. In the absence of FACT complex, SSRP1 and SPT16 mRNAs are unstable and inefficiently translated, making reactivation of FACT function unlikely in normal cells. Thus, we have described a complex and unusual mode of regulation controlling cellular FACT levels that results in amplified and stringent control of FACT activity. The FACT dependence of tumor cells suggests that mechanisms controlling FACT levels could be targeted for anticancer therapy.

A Specialized Aspartokinase Enhances the Biosynthesis of the Osmoprotectants Ectoine and Hydroxyectoine in Pseudomonas stutzeriA1501▿ †

PubMed Central

Stöveken, Nadine; Pittelkow, Marco; Sinner, Tatjana; Jensen, Roy A.; Heider, Johann; Bremer, Erhard

2011-01-01

The compatible solutes ectoine and hydroxyectoine are widely produced by bacteria as protectants against osmotic and temperature stress. l-Aspartate-beta-semialdehyde is used as the precursor molecule for ectoine/hydroxyectoine biosynthesis that is catalyzed by the EctABCD enzymes. l-Aspartate-beta-semialdehyde is a central intermediate in different biosynthetic pathways and is produced from l-aspartate by aspartokinase (Ask) and aspartate-semialdehyde-dehydrogenase (Asd). Ask activity is typically stringently regulated by allosteric control to avoid gratuitous synthesis of aspartylphosphate. Many organisms have evolved multiple forms of aspartokinase, and feedback regulation of these specialized Ask enzymes is often adapted to the cognate biochemical pathways. The ectoine/hydroxyectoine biosynthetic genes (ectABCD) are followed in a considerable number of microorganisms by an askgene (ask_ect), suggesting that Ask_Ect is a specialized enzyme for this osmoadaptive biosynthetic pathway. However, none of these Ask_Ect enzymes have been functionally characterized. Pseudomonas stutzeriA1501 synthesizes both ectoine and hydroxyectoine in response to increased salinity, and it possesses two Ask enzymes: Ask_Lys and Ask_Ect. We purified both Ask enzymes and found significant differences with regard to their allosteric control: Ask_LysC was inhibited by threonine and in a concerted fashion by threonine and lysine, whereas Ask_Ect showed inhibition only by threonine. The ectABCD_askgenes from P. stutzeriA1501 were cloned and functionally expressed in Escherichia coli, and this led to osmostress protection. An E. colistrain carrying the plasmid-based ectABCD_askgene cluster produced significantly more ectoine/hydroxyectoine than a strain expressing the ectABCDgene cluster alone. This finding suggests a specialized role for Ask_Ect in ectoine/hydroxyectoine biosynthesis. PMID:21725014

Periodontal diseases and risk of oral cancer in Southern India: Results from the HeNCe Life study.

PubMed

Laprise, Claudie; Shahul, Hameed Puthiyannal; Madathil, Sreenath Arekunnath; Thekkepurakkal, Akhil Soman; Castonguay, Geneviève; Varghese, Ipe; Shiraz, Shameena; Allison, Paul; Schlecht, Nicolas F; Rousseau, Marie-Claude; Franco, Eduardo L; Nicolau, Belinda

2016-10-01

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital-based case-control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change-in-estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10-3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer. © 2016 UICC.

On the development of a methodology for extensive in-situ and continuous atmospheric CO2 monitoring

NASA Astrophysics Data System (ADS)

Wang, K.; Chang, S.; Jhang, T.

2010-12-01

Carbon dioxide is recognized as the dominating greenhouse gas contributing to anthropogenic global warming. Stringent controls on carbon dioxide emissions are viewed as necessary steps in controlling atmospheric carbon dioxide concentrations. From the view point of policy making, regulation of carbon dioxide emissions and its monitoring are keys to the success of stringent controls on carbon dioxide emissions. Especially, extensive atmospheric CO2 monitoring is a crucial step to ensure that CO2 emission control strategies are closely followed. In this work we develop a methodology that enables reliable and accurate in-situ and continuous atmospheric CO2 monitoring for policy making. The methodology comprises the use of gas filter correlation (GFC) instrument for in-situ CO2 monitoring, the use of CO2 working standards accompanying the continuous measurements, and the use of NOAA WMO CO2 standard gases for calibrating the working standards. The use of GFC instruments enables 1-second data sampling frequency with the interference of water vapor removed from added dryer. The CO2 measurements are conducted in the following timed and cycled manner: zero CO2 measurement, two standard CO2 gases measurements, and ambient air measurements. The standard CO2 gases are calibrated again NOAA WMO CO2 standards. The methodology is used in indoor CO2 measurements in a commercial office (about 120 people working inside), ambient CO2 measurements, and installed in a fleet of in-service commercial cargo ships for monitoring CO2 over global marine boundary layer. These measurements demonstrate our method is reliable, accurate, and traceable to NOAA WMO CO2 standards. The portability of the instrument and the working standards make the method readily applied for large-scale and extensive CO2 measurements.

Different Levels of Catabolite Repression Optimize Growth in Stable and Variable Environments

PubMed Central

New, Aaron M.; Cerulus, Bram; Govers, Sander K.; Perez-Samper, Gemma; Zhu, Bo; Boogmans, Sarah; Xavier, Joao B.; Verstrepen, Kevin J.

2014-01-01

Organisms respond to environmental changes by adapting the expression of key genes. However, such transcriptional reprogramming requires time and energy, and may also leave the organism ill-adapted when the original environment returns. Here, we study the dynamics of transcriptional reprogramming and fitness in the model eukaryote Saccharomyces cerevisiae in response to changing carbon environments. Population and single-cell analyses reveal that some wild yeast strains rapidly and uniformly adapt gene expression and growth to changing carbon sources, whereas other strains respond more slowly, resulting in long periods of slow growth (the so-called “lag phase”) and large differences between individual cells within the population. We exploit this natural heterogeneity to evolve a set of mutants that demonstrate how the frequency and duration of changes in carbon source can favor different carbon catabolite repression strategies. At one end of this spectrum are “specialist” strategies that display high rates of growth in stable environments, with more stringent catabolite repression and slower transcriptional reprogramming. The other mutants display less stringent catabolite repression, resulting in leaky expression of genes that are not required for growth in glucose. This “generalist” strategy reduces fitness in glucose, but allows faster transcriptional reprogramming and shorter lag phases when the cells need to shift to alternative carbon sources. Whole-genome sequencing of these mutants reveals that mutations in key regulatory genes such as HXK2 and STD1 adjust the regulation and transcriptional noise of metabolic genes, with some mutations leading to alternative gene regulatory strategies that allow “stochastic sensing” of the environment. Together, our study unmasks how variable and stable environments favor distinct strategies of transcriptional reprogramming and growth. PMID:24453942

Effect of sociocultural cleavage on genetic differentiation: a study from North India.

PubMed

Khan, Faisal; Pandey, Atul Kumar; Borkar, Meenal; Tripathi, Manorma; Talwar, Sudha; Bisen, P S; Agrawal, Suraksha

2008-06-01

Indian populations possess an exclusive genetic profile primarily due to the many migratory events, which caused an extensive range of genetic diversity, and also due to stringent and austere sociocultural barriers that structure these populations into different endogamous groups. In the present study we attempt to explore the genetic relationships between various endogamous North Indian populations and to determine the effect of stringent social regulations on their gene pool. Twenty STR markers were genotyped in 1,800 random North Indians from 9 endogamous populations belonging to upper-caste and middle-caste Hindus and Muslims. All nine populations had high allelic diversity (176 alleles) and average observed heterozygosity (0.742 +/- 0.06), suggesting strong intrapopulation diversity. The average F(ST) value over all loci was as low as 0.0084. However, within-group F(ST) and genetic distance analysis showed that populations of the same group were genetically closer to each other. The genetic distance of Muslims from middle castes (F(ST) = 0.0090; DA = 0.0266) was significantly higher than that of Muslims from upper castes (F(ST) = 0.0050; DA = 0.0148). Phylogenetic trees (neighbor-joining and maximum-likelihood) show the basal cluster pattern of three clusters corresponding to Muslims, upper-caste, and middle-caste populations, with Muslims clustered with upper-caste populations. Based on the results, we conclude that the extensive gene flow through a series of migrations and invasions has created an enormous amount of genetic diversity. The interpopulation differences are minimal but have a definite pattern, in which populations of different socioreligious groups have more genetic similarity within the same group and are genetically more distant from populations of other groups. Finally, North Indian Muslims show a differential genetic relationship with upper- and middle-caste populations.

Evaluating Environmental Governance along Cross-Border Electricity Supply Chains with Policy-Informed Life Cycle Assessment: The California-Mexico Energy Exchange.

PubMed

Bolorinos, Jose; Ajami, Newsha K; Muñoz Meléndez, Gabriela; Jackson, Robert B

2018-05-01

This paper presents a "policy-informed" life cycle assessment of a cross-border electricity supply chain that links the impact of each unit process to its governing policy framework. An assessment method is developed and applied to the California-Mexico energy exchange as a unique case study. CO 2 -equivalent emissions impacts, water withdrawals, and air quality impacts associated with California's imports of electricity from Mexican combined-cycle facilities fueled by natural gas from the U.S. Southwest are estimated, and U.S. and Mexican state and federal environmental regulations are examined to assess well-to-wire consistency of energy policies. Results indicate most of the water withdrawn per kWh exported to California occurs in Baja California, most of the air quality impacts accrue in the U.S. Southwest, and emissions of CO 2 -equivalents are more evenly divided between the two regions. California energy policy design addresses generation-phase CO 2 emissions, but not upstream CO 2 -eq emissions of methane during the fuel cycle. Water and air quality impacts are not regulated consistently due to varying U.S. state policies and a lack of stringent federal regulation of unconventional gas development. Considering local impacts and the regulatory context where they occur provides essential qualitative information for functional-unit-based measures of life cycle impact and is necessary for a more complete environmental impact assessment.

Continuous reduction of cyclic adsorbed and desorbed NO(x) in diesel emission using nonthermal plasma.

PubMed

Kuwahara, Takuya; Nakaguchi, Harunobu; Kuroki, Tomoyuki; Okubo, Masaaki

2016-05-05

Considering the recent stringent regulations governing diesel NO(x) emission, an aftertreatment system for the reduction of NO(x) in the exhaust gas has been proposed and studied. The proposed system is a hybrid method combining nonthermal plasma and NOx adsorbent. The system does not require precious metal catalysts or harmful chemicals such as urea and ammonia. In the present system, NO(x) in diesel emission is treated by adsorption and desorption by adsorbent as well as nonthermal plasma reduction. In addition, the remaining NO(x) in the adsorbent is desorbed again in the supplied air by residual heat. The desorbed NO(x) in air recirculates into the intake of the engine, and this process, i.e., exhaust gas components' recirculation (EGCR) achieves NO(x) reduction. Alternate utilization of two adsorption chambers in the system can achieve high-efficiency NO(x) removal continuously. An experiment with a stationary diesel engine for electric power generation demonstrates an energy efficiency of 154 g(NO2)/kWh for NO(x) removal and continuous NO(x) reduction of 70.3%. Considering the regulation against diesel emission in Japan, i.e., the new regulation to be imposed on vehicles of 3.5-7.5 ton since 2016, the present aftertreatment system fulfills the requirement with only 1.0% of engine power. Copyright © 2016. Published by Elsevier B.V.

Historic and future trends of vehicle emissions in Beijing, 1998-2020: A policy assessment for the most stringent vehicle emission control program in China

NASA Astrophysics Data System (ADS)

Zhang, Shaojun; Wu, Ye; Wu, Xiaomeng; Li, Mengliang; Ge, Yunshan; Liang, Bin; Xu, Yueyun; Zhou, Yu; Liu, Huan; Fu, Lixin; Hao, Jiming

2014-06-01

As a pioneer in controlling vehicle emissions within China, Beijing released the Clean Air Action Plan 2013-2017 document in August 2013 to improve its urban air quality. It has put forward this plan containing the most stringent emission control policies and strategies to be adopted for on-road vehicles of Beijing. This paper estimates the historic and future trends and uncertainties in vehicle emissions of Beijing from 1998 to 2020 by applying a new emission factor model for the Beijing vehicle fleet (EMBEV). Our updated results show that total emissions of CO, THC, NOx and PM2.5 from the Beijing vehicle fleet are 507 (395-819) kt, 59.1 (41.2-90.5) kt, 74.7 (54.9-103.9) kt and 2.69 (1.91-4.17) kt, respectively, at a 95% confidence level. This represents significant reductions of 58%, 59%, 31% and 62%, respectively, relative to the total vehicle emissions in 1998. The past trends clearly posed a challenge to NOx emission mitigation for the Beijing vehicle fleet, especially in light of those increasing NOx emissions from heavy-duty diesel vehicles (HDDVs) which have partly offset the reduction benefit from light-duty gasoline vehicles (LDGVs). Because of recently announced vehicle emission controls to be adopted in Beijing, including tighter emissions standards, limitations on vehicle growth by more stringent license control, promotion of alternative fuel technologies (e.g., natural gas) and the scrappage of older vehicles, estimated vehicle emissions in Beijing will continue to be mitigated by 74% of CO, 68% of THC, 56% of NOx and 72% of PM2.5 in 2020 compared to 2010 levels. Considering that many of the megacities in China are facing tremendous pressures to mitigate emissions from on-road vehicles, our assessment will provide a timely case study of significance for policy-makers in China.

Abatement of tropospheric ozone: effects of strategies to improve air quality on public health and other sectors.

PubMed

Guest, C S; Morgan, P; Moss, J R; Woodward, A J; McMichael, A J

1996-06-01

The National Health and Medical Research Council's air quality goal for ozone in the troposphere (near the earth's surface) is 0.12 parts per million (ppm), averaged over one hour, similar to the United States standard, but less stringent than the guideline for Europe. We aimed to identify the environmental, economic and social changes that would be associated with changing the goal. Methods included literature review, economic assessments and group interviews. The group to benefit from lower exposures may include outdoor workers, school children and people not in regular day-time work indoors, because ozone is most prevalent during the daylight hours of the warmer months. A lower level could improve the yield of some crops. The causes and effects of tropospheric ozone are not appreciated except among groups with relevant commercial, industrial or scientific experience. However, the consultations identified frustration about the social problems caused by dependence on private motor vehicles. Short-term costs of compliance with a more stringent goal would fall principally on the users of transport. The value of the benefits was enough for many to support making the ozone goal more stringent, but those who required a demonstration of financial benefit (even including savings of health care costs) did not support any change to the goal. Based primarily on averted detriment to health, we recommend the more stringent level of 0.08 ppm (one-hour average) as the goal for the year 2005 in Australia and elsewhere. The addition of a goal with longer averaging time is also proposed.

Reassessing policy paradigms: A comparison of the global tobacco and alcohol industries.

PubMed

Hawkins, Benjamin; Holden, Chris; Eckhardt, Jappe; Lee, Kelley

2018-01-01

Tobacco is widely considered to be a uniquely harmful product for human health. Since the mid-1990s, the strategies of transnational tobacco corporations to undermine effective tobacco control policy has been extensively documented through internal industry documents. Consequently, the sale, use and marketing of tobacco products are subject to extensive regulation and formal measures to exclude the industry from policy-making have been adopted in the Framework Convention on Tobacco Control. In contrast to tobacco, alcohol is subject to less stringent forms of regulation, and the alcohol industry continues to play a central role in policy-making in many countries and at the global level. This article examines whether there is a sufficient rationale for such different regulatory approaches, through a comparative analysis of the political economy of the tobacco and alcohol industries including the structure of the industries, and the market and political strategies they pursue. Despite some important differences, the extensive similarities which exist between the tobacco and alcohol industries in terms of market structure and strategy, and political strategy, call into question the rationale for both the relatively weak regulatory approach taken towards alcohol, and the continued participation of alcohol corporations in policy-making processes.

A common-sense approach to asbestos in roofing

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

Steinmetz, W.R. Jr.

The word asbestos carries an ominous connotation to many plant engineers and building owners. Many are caught up in the hype surrounding asbestos abatement. Others are confused about how to face the questions surrounding this mysterious, dangerous, and often misunderstood substance. Asbestos issues cast a particularly perplexing spell over decisions about how to deal with the material in the removal of roofing systems. The product is an excellent roofing choice because it is fire-resistant, durable, and nonrotting. And most significantly on the other hand, asbestos causes three deadly diseases: lung cancer, asbestosis, and mesothelioma (cancer of the lung lining andmore » always fatal). This danger prompted enactment of the Asbestos Hazard Emergency Response Act (AHERA) in the early 1980s. The regulation required every K-12 school in the US to develop a management plant for dealing with asbestos. Since then, much has been done to raise awareness of the issues surrounding this material. The standard`s earliest form based removal requirements primarily on exposure levels. A 1994 revision, however, extended stringent removal requirements to all roof removal work involving asbestos, regardless of exposure level. This paper looks at the regulations, concerns, considerations, and procedures for dealing with the problem.« less

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

Fritz, Brad G.; Lamb, Brian K.; Westberg, Halvor

Volatile organic compounds (VOCs) are precursors to ground level ozone. Ground level ozone is the major component of photochemical smog, and has been linked to a variety of adverse health effects. These health effects include cancer, heart disease, pneumonia and death. In order to reduce ground level ozone, VOC emissions are being more stringently regulated. One VOC source that may come under regulation is lumber drying. Drying lumber is known to emit VOC into the atmosphere. This research evaluates the validity of VOC emission measurements from a small-scale kiln to approximate VOC emissions from kilns at commercial mills. We alsomore » report emission factors for three lumber species commonly harvested in the northwest United States (Douglas-fir, ponderosa pine, & grand fir). This work was done with a novel tracer ratio technique at a small laboratory kiln and a large commercial lumber drying facility. The measured emission factors were 0.51 g/kgOD for Douglas-fir, 0.7 g/kgOD for ponderosa pine, and 0.15 g/kgOD for grand fir. Aldehyde emission rates from lumber drying were also measured in some experiments. Results indicate that aldehyde emissions can constitute a significant percentage of the total VOC emissions.« less

Cholesterol Regulates Multiple Forms of Vesicle Endocytosis at a Mammalian Central Synapse

PubMed Central

Yue, Hai-Yuan; Xu, Jianhua

2015-01-01

Endocytosis in synapses sustains neurotransmission by recycling vesicle membrane and maintaining the homeostasis of synaptic membrane. A role of membrane cholesterol in synaptic endocytosis remains controversial because of conflicting observations, technical limitations in previous studies, and potential interference from nonspecific effects after cholesterol manipulation. Furthermore, it is unclear whether cholesterol participates in distinct forms of endocytosis that function under different activity levels. In this study, applying the whole-cell membrane capacitance measurement to monitor endocytosis in real time at the rat calyx of Held terminals, we found that disrupting cholesterol with dialysis of cholesterol oxidase (COase) or methyl-β-cyclodextrin (MCD) impaired three different forms of endocytosis, i.e., slow endocytosis, rapid endocytosis, and endocytosis of the retrievable membrane that exists at the surface before stimulation. The effects were observed when disruption of cholesterol was mild enough not to change Ca2+ channel current or vesicle exocytosis, indicative of stringent cholesterol requirement in synaptic endocytosis. Extracting cholesterol with high concentrations of MCD reduced exocytosis, mainly by decreasing the readily releasable pool (RRP) and the vesicle replenishment after RRP depletion. Our study suggests that cholesterol is an important, universal regulator in multiple forms of vesicle endocytosis at mammalian central synapses. PMID:25893258

Tissue Engineering Stem Cells – An e-Governance Strategy

PubMed Central

Grange, Simon

2011-01-01

The rules of governance are changing. They are necessarily becoming more stringent as interventions offered to treat conditions carry unpredictable side effects, often associated with novel therapeutic vectors. The clinical relevance of this relates to the obligations of those involved in research, to ensure the best protection for subjects whilst encouraging the development of the field. Existing evidence supports the concept of e-Governance both in operational health research and more broadly in the strategic domain of policy formation. Building on the impact of the UK Comprehensive Research Network and recent EU Directives, it is now possible to focus on the issues of regulation for cell therapies in musculoskeletal science through the development of the Advanced Therapeutic Medicinal Products (ATMP) category of research products. This article reviews the framework that has borne this and the need for more detailed Virtual Research Integration and Collaboration (VRIC) systems to ensure regulatory compliance. Technology research and development plans must develop in close association between tissue engineering and treating clinicians. The scope of this strategy relates to the handling of human tissues the transport and storage of specimens in accordance with current EU directives and the Human Tissue Authority (HTA) regulations. PMID:21886693

Augmenting the Genetic Toolbox for Sulfolobus islandicus with a Stringent Positive Selectable Marker for Agmatine Prototrophy

PubMed Central

Cooper, Tara E.; Krause, David J.

2013-01-01

Sulfolobus species have become the model organisms for studying the unique biology of the crenarchaeal division of the archaeal domain. In particular, Sulfolobus islandicus provides a powerful opportunity to explore natural variation via experimental functional genomics. To support these efforts, we further expanded genetic tools for S. islandicus by developing a stringent positive selection for agmatine prototrophs in strains in which the argD gene, encoding arginine decarboxylase, has been deleted. Strains with deletions in argD were shown to be auxotrophic for agmatine even in nutrient-rich medium, but growth could be restored by either supplementation of exogenous agmatine or reintroduction of a functional copy of the argD gene from S. solfataricus P2 into the ΔargD host. Using this stringent selection, a robust targeted gene knockout system was established via an improved next generation of the MID (marker insertion and unmarked target gene deletion) method. Application of this novel system was validated by targeted knockout of the upsEF genes involved in UV-inducible cell aggregation formation. PMID:23835176

Bay breeze climatology at two sites along the Chesapeake bay from 1986-2010: Implications for surface ozone.

PubMed

Stauffer, Ryan M; Thompson, Anne M

Hourly surface meteorological measurements were coupled with surface ozone (O 3 ) mixing ratio measurements at Hampton, Virginia and Baltimore, Maryland, two sites along the Chesapeake Bay in the Mid-Atlantic United States, to examine the behavior of surface O 3 during bay breeze events and quantify the impact of the bay breeze on local O 3 pollution. Analyses were performed for the months of May through September for the years 1986 to 2010. The years were split into three groups to account for increasingly stringent environmental regulations that reduced regional emissions of nitrogen oxides (NO x ): 1986-1994, 1995-2002, and 2003-2010. Each day in the 25-year record was marked either as a bay breeze day, a non-bay breeze day, or a rainy/cloudy day based on the meteorological data. Mean eight hour (8-h) averaged surface O 3 values during bay breeze events were 3 to 5 parts per billion by volume (ppbv) higher at Hampton and Baltimore than on non-bay breeze days in all year periods. Anomalies from mean surface O 3 were highest in the afternoon at both sites during bay breeze days in the 2003-2010 study period. In conjunction with an overall lowering of baseline O 3 after the 1995-2002 period, the percentage of total exceedances of the Environmental Protection Agency (EPA) 75 ppbv 8-h O 3 standard that occurred on bay breeze days increased at Hampton for 2003-2010, while remaining steady at Baltimore. These results suggest that bay breeze circulations are becoming more important to causing exceedance events at particular sites in the region, and support the hypothesis of Martins et al. (2012) that highly localized meteorology increasingly drives air quality events at Hampton.

A Genome-Wide siRNA Screen in Mammalian Cells for Regulators of S6 Phosphorylation

PubMed Central

Papageorgiou, Angela; Rapley, Joseph; Mesirov, Jill P.; Tamayo, Pablo; Avruch, Joseph

2015-01-01

mTOR complex1, the major regulator of mRNA translation in all eukaryotic cells, is strongly activated in most cancers. We performed a genome-wide RNAi screen in a human cancer cell line, seeking genes that regulate S6 phosphorylation, readout of mTORC1 activity. Applying a stringent selection, we retrieved nearly 600 genes wherein at least two RNAis gave significant reduction in S6-P. This cohort contains known regulators of mTOR complex 1 and is significantly enriched in genes whose depletion affects the proliferation/viability of the large set of cancer cell lines in the Achilles database in a manner paralleling that caused by mTOR depletion. We next examined the effect of RNAi pools directed at 534 of these gene products on S6-P in TSC1 null mouse embryo fibroblasts. 76 RNAis reduced S6 phosphorylation significantly in 2 or 3 replicates. Surprisingly, among this cohort of genes the only elements previously associated with the maintenance of mTORC1 activity are two subunits of the vacuolar ATPase and the CUL4 subunit DDB1. RNAi against a second set of 84 targets reduced S6-P in only one of three replicates. However, an indication that this group also bears attention is the presence of rpS6KB1 itself, Rac1 and MAP4K3, a protein kinase that supports amino acid signaling to rpS6KB1. The finding that S6 phosphorylation requires a previously unidentified, functionally diverse cohort of genes that participate in fundamental cellular processes such as mRNA translation, RNA processing, DNA repair and metabolism suggests the operation of feedback pathways in the regulation of mTORC1 operating through novel mechanisms. PMID:25790369

The importance of product definitions in US e-cigarette laws and regulations

PubMed Central

Lempert, Lauren K; Grana, Rachel; Glantz, Stanton A

2014-01-01

Background How electronic cigarettes and similar products (e-cigarettes) are defined affects how they are regulated, particularly whether existing laws for cigarettes apply, including sales and marketing, youth access, smoke-free and taxation laws. Methods We examined the text of 46 bills that define e-cigarettes enacted in 40 states and characterised how e-cigarettes and similar products were defined. Results States enact laws creating new product categories for e-cigarettes separate from the ‘tobacco product’ category (eg, ‘alternative nicotine product,’ ‘vapour product,’ ‘electronic nicotine device’), with four states explicitly excluding e-cigarettes from ‘tobacco products.’ Twenty-eight states do not include e-cigarettes in their definitions of ‘tobacco products’ or ‘smoking,’ eight include e-cigarettes as ‘tobacco products,’ three include e-cigarettes in ‘smoking.’ Sixteen states’ definitions of e-cigarettes require nicotine, and five states pre-empt more stringent local laws. Tobacco and e-cigarette industry representatives tried to shape laws that benefit their interests. Conclusions Definitions separating e-cigarettes from other tobacco products are common. Similar to past ‘Trojan horse’ policies, e-cigarette policies that initially appear to restrict sales (eg, limit youth access) may actually undermine regulation if they establish local pre-emption or create definitions that divide e-cigarettes from other tobacco products. Comparable issues are raised by the European Union Tobacco Products Directive and e-cigarette regulations in other countries. Policymakers should carefully draft legislation with definitions of e-cigarettes that broadly define the products, do not require nicotine or tobacco, do not pre-empt stronger regulations and explicitly include e-cigarettes in smoke-free and taxation laws. PMID:25512432

The importance of product definitions in US e-cigarette laws and regulations.

PubMed

Lempert, Lauren K; Grana, Rachel; Glantz, Stanton A

2016-04-01

How electronic cigarettes and similar products (e-cigarettes) are defined affects how they are regulated, particularly whether existing laws for cigarettes apply, including sales and marketing, youth access, smoke-free and taxation laws. We examined the text of 46 bills that define e-cigarettes enacted in 40 states and characterised how e-cigarettes and similar products were defined. States enact laws creating new product categories for e-cigarettes separate from the 'tobacco product' category (eg, 'alternative nicotine product,' 'vapour product,' 'electronic nicotine device'), with four states explicitly excluding e-cigarettes from 'tobacco products.' Twenty-eight states do not include e-cigarettes in their definitions of 'tobacco products' or 'smoking,' eight include e-cigarettes as 'tobacco products,' three include e-cigarettes in 'smoking.' Sixteen states' definitions of e-cigarettes require nicotine, and five states pre-empt more stringent local laws. Tobacco and e-cigarette industry representatives tried to shape laws that benefit their interests. Definitions separating e-cigarettes from other tobacco products are common. Similar to past 'Trojan horse' policies, e-cigarette policies that initially appear to restrict sales (eg, limit youth access) may actually undermine regulation if they establish local pre-emption or create definitions that divide e-cigarettes from other tobacco products. Comparable issues are raised by the European Union Tobacco Products Directive and e-cigarette regulations in other countries. Policymakers should carefully draft legislation with definitions of e-cigarettes that broadly define the products, do not require nicotine or tobacco, do not pre-empt stronger regulations and explicitly include e-cigarettes in smoke-free and taxation laws. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Detecting Chemical Weapons: Threats, Requirements, Solutions, and Future Challenges

NASA Astrophysics Data System (ADS)

Boso, Brian

2011-03-01

Although chemicals have been reportedly used as weapons for thousands of years, it was not until 1915 at Ypres, France that an industrial chemical, chlorine, was used in World War I as an offensive weapon in significant quantity, causing mass casualties. From that point until today the development, detection, production and protection from chemical weapons has be an organized endeavor of many of the world's armed forces and in more recent times, non-governmental terrorist organizations. The number of Chemical Warfare Agents (CWAs) has steadily increased as research into more toxic substances continued for most of the 20 th century. Today there are over 70 substances including harassing agents like tear gas, incapacitating agents, and lethal agents like blister, blood, chocking, and nerve agents. The requirements for detecting chemical weapons vary depending on the context in which they are encountered and the concept of operation of the organization deploying the detection equipment. The US DoD, for example, has as a requirement, that US forces be able to continue their mission, even in the event of a chemical attack. This places stringent requirements on detection equipment. It must be lightweight (<2 lbs), detect a large array of chemical warfare agents and toxic industrial chemicals, detect and warn at concentration levels and time duration to prevent acute health effects, meet military ruggedness specifications and work over a wide range of temperature and humidity, and have a very high probability of detection with a similarly low probability of false positives. The current technology of choice to meet these stringent requirements is Ion Mobility Spectrometry. Many technologies are capable of detecting chemicals at the trace levels required and have been extensively developed for this application, including, but not limited to: mass spectroscopy, IR spectroscopy, RAMAN spectroscopy, MEMs micro-cantilever sensors, surface acoustic wave sensors, differential mobility spectrometry, and amplifying fluorescence polymers. In the future the requirements for detection equipment will continue to become even more stringent. The continuing increase in the sheer number of threats that will need to be detected, the development of binary agents requiring that even the precursor chemicals be detected, the development of new types of agents unlike any of the current chemistries, and the expansion of the list of toxic industrial chemical will require new techniques with higher specificity and more sensitivity.

Current Scenario of Spurious and Substandard Medicines in India: A Systematic Review

PubMed Central

Khan, A. N.; Khar, R. K.

2015-01-01

Globally, every country is the victim of substandard or spurious drugs, which result in life threatening issues, financial loss of consumer and manufacturer and loss in trust on health system. The aim of this enumerative review was to probe the extent on poor quality drugs with their consequences on public health and the preventive measures taken by the Indian pharmaceutical regulatory system. Government and non-government studies, literature and news were gathered from journals and authentic websites. All data from 2000 to 2013 were compiled and interpreted to reveal the real story of poor quality drugs in India. For minimizing spurious/falsely-labelled/falsified/counterfeit drugs or not of standard quality drugs, there is urgent requirement of more stringent regulation and legal action against the problem. However, India has taken some preventive steps in the country to fight against the poor quality drugs for protecting and promoting the public health. PMID:25767312

Sugar, ethics and legislation.

PubMed

Azize, Joseph

2010-05-01

There are serious ethical and legal issues concerning the sale of sugar products, especially to children, yet one cannot address children's consumption without addressing consumption across society. The ethical principles are not even controversial. However, sugar has been insufficiently scrutinised, probably because sweetness is popular and plays a prominent, but dispensable, cultural role. Sugar is both addictive and toxic, although it is a very mild, very slow-working poison. Yet, over time, its effects can be quite serious. The social and health problems have proved grave and intractable. Given the nature of sugar, it should be regulated like alcohol and tobacco, if not more stringently, given its greater social and cultural penetration across all ages. That is, sales of sugar products at school canteens should be banned, advertising severely limited, full disclosure of sugar content made mandatory, warnings placed on certain products, and sugar itself should be taxed.

Cytosolic ppGpp accumulation induces retarded plant growth and development.

PubMed

Ihara, Yuta; Masuda, Shinji

2016-01-01

In bacteria a second messenger, guanosine 5'-diphosphate 3'-diphosphate (ppGpp), synthesized upon nutrient starvation, controls many gene expressions and enzyme activities, which is necessary for growth under changeable environments. Recent studies have shown that ppGpp synthase and hydrolase are also conserved in eukaryotes, although their functions are not well understood. We recently showed that ppGpp-overaccumulation in Arabidopsis chloroplasts results in robust growth under nutrient-limited conditions, demonstrating that the bacterial-like stringent response at least functions in plastids. To test if ppGpp also functions in the cytosol, we constructed the transgenic Arabidopsis expressing Bacillus subtilis ppGpp synthase gene yjbM. Upon induction of the gene, the mutant synthesizes ∼10-20-fold higher levels of ppGpp, and its fresh weight was reduced to ˜80% that of the wild type. These results indicate that cytosolic ppGpp negatively regulates plant growth and development.

Germline Editing: Editors Cautionary.

PubMed

Krishan, K; Kanchan, T; Singh, B; Baryah, N; Puri, S

2018-01-01

This communication is regarding the recent editing of the genome of the human embryo with CRISPR/Cas9 which generated a debate amongst the biological scientists around the world. Editing human germline genes may act as godsend in some serious genetic and other disorders as the genes related to these disorders can be replaced effectively. The scientists are in dilemma whether the human germline gene modification is a boon or bane for the human society. Though editing human germline genes may be an answer to many serious genetic disorders however; it may have unpredictable effects on future generations. The ethical issues regarding the germline editing need further discussion which may have implications on human race and on-going human evolution. Thus, the researchers need to be doubly cautious and some stringent regulations should be framed regarding the various aspects of germ line gene modifications and any potential conflict with nature for future outcome.

Controllability analysis and decentralized control of a wet limestone flue gas desulfurization plant

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

Perales, A.L.V.; Ortiz, F.J.G.; Ollero, P.

2008-12-15

Presently, decentralized feedback control is the only control strategy used in wet limestone flue gas desulfurization (WLFGD) plants. Proper tuning of this control strategy is becoming an important issue in WLFGD plants because more stringent SO{sub 2} regulations have come into force recently. Controllability analysis is a highly valuable tool for proper design of control systems, but it has not been applied to WLFGD plants so far. In this paper a decentralized control strategy is designed and applied to a WLFGD pilot plant taking into account the conclusions of a controllability analysis. The results reveal that good SO{sub 2} controlmore » in WLFGD plants can be achieved mainly because the main disturbance of the process is well-aligned with the plant and interactions between control loops are beneficial to SO{sub 2} control.« less

Regulating genetically modified food. Policy trajectories, political culture, and risk perceptions in the U.S., Canada, and EU.

PubMed

Wohlers, Anton E

2010-09-01

This paper examines whether national differences in political culture add an explanatory dimension to the formulation of policy in the area of biotechnology, especially with respect to genetically modified food. The analysis links the formulation of protective regulatory policies governing genetically modified food to both country and region-specific differences in uncertainty tolerance levels and risk perceptions in the United States, Canada, and European Union. Based on polling data and document analysis, the findings illustrate that these differences matter. Following a mostly opportunistic risk perception within an environment of high tolerance for uncertainty, policymakers in the United States and Canada modified existing regulatory frameworks that govern genetically modified food in their respective countries. In contrast, the mostly cautious perception of new food technologies and low tolerance for uncertainty among European Union member states has contributed to the creation of elaborate and stringent regulatory policies governing genetically modified food.

[Hazardous materials and work safety in veterinary practice. 1: Hazardous material definition and characterization, practice documentation and general rules for handling].

PubMed

Sliwinski-Korell, A; Lutz, F

1998-04-01

In the last years the standards for professional handling of hazardous material as well as health and safety in the veterinary practice became considerably more stringent. This is expressed in various safety regulations, particularly the decree of hazardous material and the legislative directives concerning health and safety at work. In part 1, a definition based on the law for hazardous material is given and the potential risks are mentioned. The correct documentation regarding the protection of the purchase, storage, working conditions and removal of hazardous material and of the personal is explained. General rules for the handling of hazardous material are described. In part 2, particular emphasis is put on the handling of flammable liquids, disinfectants, cytostatica, pressurised gas, liquid nitrogen, narcotics, mailing of potentially infectious material and safe disposal of hazardous waste. Advice about possible unrecognized hazards and references is also given.

Multimodal Chemosensory Circuits Controlling Male Courtship in Drosophila.

PubMed

Clowney, E Josephine; Iguchi, Shinya; Bussell, Jennifer J; Scheer, Elias; Ruta, Vanessa

2015-09-02

Throughout the animal kingdom, internal states generate long-lasting and self-perpetuating chains of behavior. In Drosophila, males instinctively pursue females with a lengthy and elaborate courtship ritual triggered by activation of sexually dimorphic P1 interneurons. Gustatory pheromones are thought to activate P1 neurons but the circuit mechanisms that dictate their sensory responses to gate entry into courtship remain unknown. Here, we use circuit mapping and in vivo functional imaging techniques to trace gustatory and olfactory pheromone circuits to their point of convergence onto P1 neurons and reveal how their combined input underlies selective tuning to appropriate sexual partners. We identify inhibition, even in response to courtship-promoting pheromones, as a key circuit element that tunes and tempers P1 neuron activity. Our results suggest a circuit mechanism in which balanced excitation and inhibition underlie discrimination of prospective mates and stringently regulate the transition to courtship in Drosophila. Copyright © 2015 Elsevier Inc. All rights reserved.

ISG hybrid powertrain: a rule-based driver model incorporating look-ahead information

NASA Astrophysics Data System (ADS)

Shen, Shuiwen; Zhang, Junzhi; Chen, Xiaojiang; Zhong, Qing-Chang; Thornton, Roger

2010-03-01

According to European regulations, if the amount of regenerative braking is determined by the travel of the brake pedal, more stringent standards must be applied, otherwise it may adversely affect the existing vehicle safety system. The use of engine or vehicle speed to derive regenerative braking is one way to avoid strict design standards, but this introduces discontinuity in powertrain torque when the driver releases the acceleration pedal or applies the brake pedal. This is shown to cause oscillations in the pedal input and powertrain torque when a conventional driver model is adopted. Look-ahead information, together with other predicted vehicle states, are adopted to control the vehicle speed, in particular, during deceleration, and to improve the driver model so that oscillations can be avoided. The improved driver model makes analysis and validation of the control strategy for an integrated starter generator (ISG) hybrid powertrain possible.

Low-Noise Potential of Advanced Fan Stage Stator Vane Designs Verified in NASA Lewis Wind Tunnel Test

NASA Technical Reports Server (NTRS)

Hughes, Christopher E.

1999-01-01

With the advent of new, more stringent noise regulations in the next century, aircraft engine manufacturers are investigating new technologies to make the current generation of aircraft engines as well as the next generation of advanced engines quieter without sacrificing operating performance. A current NASA initiative called the Advanced Subsonic Technology (AST) Program has set as a goal a 6-EPNdB (effective perceived noise) reduction in aircraft engine noise relative to 1992 technology levels by the year 2000. As part of this noise program, and in cooperation with the Allison Engine Company, an advanced, low-noise, high-bypass-ratio fan stage design and several advanced technology stator vane designs were recently tested in NASA Lewis Research Center's 9- by 15-Foot Low-Speed Wind Tunnel (an anechoic facility). The project was called the NASA/Allison Low Noise Fan.

Multimodal chemosensory circuits controlling male courtship in Drosophila

PubMed Central

Clowney, E. Josephine; Iguchi, Shinya; Bussell, Jennifer J.; Scheer, Elias; Ruta, Vanessa

2015-01-01

Summary Throughout the animal kingdom, internal states generate long-lasting and self-perpetuating chains of behavior. In Drosophila, males instinctively pursue females with a lengthy and elaborate courtship ritual triggered by activation of sexually dimorphic P1 interneurons. Gustatory pheromones are thought to activate P1 neurons but the circuit mechanisms that dictate their sensory responses to gate entry into courtship remain unknown. Here, we use circuit mapping and in vivo functional imaging techniques to trace gustatory and olfactory pheromone circuits to their point of convergence onto P1 neurons and reveal how their combined input underlies selective tuning to appropriate sexual partners. We identify inhibition, even in response to courtship-promoting pheromones, as a key circuit element that tunes and tempers P1 neuron activity. Our results suggest a circuit mechanism in which balanced excitation and inhibition underlie discrimination of prospective mates and stringently regulate the transition to courtship in Drosophila. PMID:26279475

Hospital costs and specialization: benefits of limiting the number of product lines.

PubMed

Eastaugh, Steven R

2009-01-01

Trends in hospital specialization are studied using multiple regression analysis for the period 1999-2008. The observed 31.3 percent rise in specialization was associated with a 9.5 percent decline in unit cost per admission. The number of specialized hospitals has grown by 149 percent in the past decade. Other hospitals are getting more specialized by reducing their product lines. Specialization has been highest in competitive West Coast markets and lowest in the rate-regulated states (New York and Massachusetts). Hospitals have less incentive to contain costs by decreasing the array of services offered in stringent rate-setting states. The term "underspecialization" is advanced to capture the inability of some hospitals to selectively prune out product lines in order to specialize. Such hospitals spread resources so thin that many good departments suffer. Unit cost per case (DRG-adjusted) is higher in the less specialized hospitals.

Mapping the local protein interactome of the NuA3 histone acetyltransferase

PubMed Central

Smart, Sherri K; Mackintosh, Samuel G; Edmondson, Ricky D; Taverna, Sean D; Tackett, Alan J

2009-01-01

Protein–protein interactions modulate cellular functions ranging from the activity of enzymes to signal transduction cascades. A technology termed transient isotopic differentiation of interactions as random or targeted (transient I-DIRT) is described for the identification of stable and transient protein–protein interactions in vivo. The procedure combines mild in vivo chemical cross-linking and non-stringent affinity purification to isolate low abundance chromatin-associated protein complexes. Using isotopic labeling and mass spectrometric readout, purified proteins are categorized with respect to the protein ‘bait’ as stable, transient, or contaminant. Here we characterize the local interactome of the chromatin-associated NuA3 histone lysine-acetyltransferase protein complex. We describe transient associations with the yFACT nucleosome assembly complex, RSC chromatin remodeling complex and a nucleosome assembly protein. These novel, physical associations with yFACT, RSC, and Nap1 provide insight into the mechanism of NuA3-associated transcription and chromatin regulation. PMID:19621382

Advanced Turbo-Charging Research and Development

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

None

2008-02-27

The objective of this project is to conduct analysis, design, procurement and test of a high pressure ratio, wide flow range, and high EGR system with two stages of turbocharging. The system needs to meet the stringent 2010MY emissions regulations at 20% + better fuel economy than its nearest gasoline competitor while allowing equivalent vehicle launch characteristics and higher torque capability than its nearest gasoline competitor. The system will also need to meet light truck/ SUV life requirements, which will require validation or development of components traditionally used only in passenger car applications. The conceived system is termed 'seriessequential turbocharger'more » because the turbocharger system operates in series at appropriate times and also sequentially when required. This is accomplished using intelligent design and control of flow passages and valves. Components of the seriessequential system will also be applicable to parallel-sequential systems which are also expected to be in use for future light truck/SUV applications.« less

Power Management Integrated Circuit for Indoor Photovoltaic Energy Harvesting System

NASA Astrophysics Data System (ADS)

Jain, Vipul

In today's world, power dissipation is a main concern for battery operated mobile devices. Key design decisions are being governed by power rather than area/delay because power requirements are growing more stringent every year. Hence, a hybrid power management system is proposed, which uses both a solar panel to harvest energy from indoor lighting and a battery to power the load. The system tracks the maximum power point of the solar panel and regulates the battery and microcontroller output load voltages through the use of an on-chip switched-capacitor DC-DC converter. System performance is verified through simulation at the 180nm technology node and is made to be integrated on-chip with 0.25 second startup time, 79% efficiency, --8/+14% ripple on the load, an average 1micro A of quiescent current (3.7micro W of power) and total on-chip area of 1.8mm2 .

Design of a Selective Substrate and Activity Based Probe for Human Neutrophil Serine Protease 4

PubMed Central

Kasperkiewicz, Paulina; Poreba, Marcin; Snipas, Scott J.; Lin, S. Jack; Kirchhofer, Daniel; Salvesen, Guy S.; Drag, Marcin

2015-01-01

Human neutrophil serine protease 4 (NSP4), also known as PRSS57, is a recently discovered fourth member of the neutrophil serine proteases family. Although its biological function is not precisely defined, it is suggested to regulate neutrophil response and innate immune reactions. To create optimal substrates and visualization probes for NSP4 that distinguish it from other NSPs we have employed a Hybrid Combinatorial Substrate Library approach that utilizes natural and unnatural amino acids to explore protease subsite preferences. Library results were validated by synthesizing individual substrates, leading to the identification of an optimal substrate peptide. This substrate was converted to a covalent diphenyl phosphonate probe with an embedded biotin tag. This probe demonstrated high inhibitory activity and stringent specificity and may be suitable for visualizing NSP4 in the background of other NSPs. PMID:26172376

Generation and Evaluation of Prophylactic mRNA Vaccines Against Allergy.

PubMed

Weiss, Richard; Scheiblhofer, Sandra; Thalhamer, Josef

2017-01-01

Due to the worldwide increase in allergies and a limited efficacy of therapeutic interventions, the need for prophylactic vaccination against allergies has been recognized. mRNA and DNA vaccines have demonstrated their high potential for preventing allergic sensitization by inducing an immunological bias that prevents TH2 sensitization. However, only mRNA vaccines fulfill the stringent safety requirements for vaccination of healthy children. In this chapter, we describe the generation of conventional as well as self-replicating mRNA vaccines and methods to test their prophylactic efficacy in animal models.

Environmental management problems in India

NASA Astrophysics Data System (ADS)

Bowonder, B.

1986-09-01

Environmental problems are becoming serious in India because of the interacting effects of increasing population density, industrialization and urbanization, and poor environmental management practices. Unless stringent regulatory measures are taken, environmental systems will be irreversibly degraded. Lack of political commitment, lack of a comprehensive environmental policy, poor environmental awareness, functional fragmentation of the public administration system, poor mass media concern, and prevalence of poverty are some of the major factors responsible for increasing the severity of the problems. Environmental problems in India are highly complex, and management procedures have to be developed to achieve coordination between various functional departments, and for this, political leaders have to be convinced of the need to initiate environmental protection measures.

Hologram interferometry in automotive component vibration testing

NASA Astrophysics Data System (ADS)

Brown, Gordon M.; Forbes, Jamie W.; Marchi, Mitchell M.; Wales, Raymond R.

1993-02-01

An ever increasing variety of automotive component vibration testing is being pursued at Ford Motor Company, U.S.A. The driving force for use of hologram interferometry in these tests is the continuing need to design component structures to meet more stringent functional performance criteria. Parameters such as noise and vibration, sound quality, and reliability must be optimized for the lightest weight component possible. Continually increasing customer expectations and regulatory pressures on fuel economy and safety mandate that vehicles be built from highly optimized components. This paper includes applications of holographic interferometry for powertrain support structure tuning, body panel noise reduction, wiper system noise and vibration path analysis, and other vehicle component studies.

miR-142-3p is involved in CD25+ CD4 T cell proliferation by targeting the expression of glycoprotein A repetitions predominant.

PubMed

Zhou, Qihui; Haupt, Sonja; Prots, Iryna; Thümmler, Katja; Kremmer, Elisabeth; Lipsky, Peter E; Schulze-Koops, Hendrik; Skapenko, Alla

2013-06-15

Because of the numerous targets of microRNAs (miRNAs), functional dissection of specific miRNA/mRNA interactions is important to understand the complex miRNA regulatory mechanisms. Glycoprotein A repetitions predominant (GARP) is specifically expressed on regulatory CD25(+) CD4 T cells upon their activation. GARP has a long 3' untranslated region containing five highly conserved regions suggesting miRNA regulation of its expression. Although GARP is physiologically expressed on a cell subset characterized by stringent control of proliferation, amplification of the GARP gene has been found in many tumors characterized by uncontrolled proliferation. In this study, we investigated in detail miRNA regulation of GARP expression, in particular by miR-142-3p, and dissected the functional outcome of miR-142-3p/GARP mRNA interaction. We demonstrate that miR-142-3p binds directly to the 3' untranslated region of GARP and represses GARP protein expression by Argonaute 2-associated degradation of GARP mRNA. Functionally, miR-142-3p-mediated regulation of GARP is involved in the expansion of CD25(+) CD4 T cells in response to stimulation. The data indicate that miR-142-3p regulates GARP expression on CD25(+) CD4 T cells and, as a result, their expansion in response to activation. Our data provide novel insight into the molecular mechanisms controlling regulatory T cell expansion. They may also have implications for understanding tumor cell biology.

Stringent Control of NFE2L3 (Nuclear Factor, Erythroid 2-Like 3; NRF3) Protein Degradation by FBW7 (F-box/WD Repeat-containing Protein 7) and Glycogen Synthase Kinase 3 (GSK3)*

PubMed Central

Kannan, Meenakshi B.; Dodard-Friedman, Isadore; Blank, Volker

2015-01-01

The NFE2L3 transcription factor has been implicated in various cellular processes, including carcinogenesis, stress response, differentiation, and inflammation. Previously it has been shown that NFE2L3 has a rapid turnover and is stabilized by proteasomal inhibitors. The mechanisms regulating the degradation of this protein have not been investigated. Here we report ubiquitination of NFE2L3 and demonstrate that F-box/WD repeat-containing protein 7 (FBW7 or FBWX7), a component of Skp1, Cullin 1, F-box containing complex (SCF)-type E3 ligase, is the E3 ligase mediating the degradation of NFE2L3. We showed that FBW7 interacts with NFE2L3 and that dimerization of FBW7 is required for the degradation of the transcription factor. We also demonstrate that the kinase glycogen synthase kinase 3 (GSK3) mediates the FBW7-dependent ubiquitination of NFE2L3. We show phosphorylation of NFE2L3 by GSK3 and its significance in the regulation of NFE2L3 by the tumor suppressor FBW7. FBW7 abrogated NFE2L3-mediated repression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene antioxidant response element (ARE). Our findings reveal FBW7 and GSK3 as novel regulators of the NFE2L3 transcription factor and a potential mechanism by which FBW7 might regulate detoxification and the cellular response to stress. PMID:26306035

Deforestation risk due to commodity crop expansion in sub-Saharan Africa

NASA Astrophysics Data System (ADS)

Ordway, Elsa M.; Asner, Gregory P.; Lambin, Eric F.

2017-04-01

Rapid integration of global agricultural markets and subsequent cropland displacement in recent decades increased large-scale tropical deforestation in South America and Southeast Asia. Growing land scarcity and more stringent land use regulations in these regions could incentivize the offshoring of export-oriented commodity crops to sub-Saharan Africa (SSA). We assess the effects of domestic- and export-oriented agricultural expansion on deforestation in SSA in recent decades. Analyses were conducted at the global, regional and local scales. We found that commodity crops are expanding in SSA, increasing pressure on tropical forests. Four Congo Basin countries, Sierra Leone, Liberia, and Côte d’Ivoire were most at risk in terms of exposure, vulnerability and pressures from agricultural expansion. These countries averaged the highest percent forest cover (58% ± 17.93) and lowest proportions of potentially available cropland outside forest areas (1% ± 0.89). Foreign investment in these countries was concentrated in oil palm production (81%), with a median investment area of 41 582 thousand ha. Cocoa, the fastest expanding export-oriented crop across SSA, accounted for 57% of global expansion in 2000-2013 at a rate of 132 thousand ha yr-1. However, cocoa only amounted to 0.89% of foreign land investment. Commodity crop expansion in SSA appears largely driven by small- and medium-scale farmers rather than industrial plantations. Land-use changes associated with large-scale investments remain to be observed in many countries. Although domestic demand for commodity crops was associated with most agricultural expansion, we provide evidence of a growing influence of distant markets on land-use change in SSA.

Microbial removal of alkanes from dilute gaseous waste streams: kinetics and mass transfer considerations.

PubMed

Barton, J W; Klasson, K T; Koran, L J; Davison, B H

1997-01-01

Treatment of dilute gaseous hydrocarbon waste streams remains a current need for many industries, particularly as increasingly stringent environmental regulations and oversight force emission reduction. Biofiltration systems hold promise for providing low-cost alternatives to more traditional, energy-intensive treatment methods such as incineration and adsorption. Elucidation of engineering principles governing the behavior of such systems, including mass transfer limitations, will broaden their applicability. Our processes exploit a microbial consortium to treat a mixture of 0.5% n-pentane and 0.5% isobutane in air. Since hydrocarbon gases are sparingly soluble in water, good mixing and high surface area between the gas and liquid phases are essential for biodegradation to be effective. One liquid-continuous columnar bioreactor was operated for more than 30 months with continued degradation of n-pentane and isobutane as sole carbon and energy sources. The maximum degradation rate observed in this gas-recycle system was 2 g of volatile organic compounds (VOC)/(m3.h). A trickle-bed bioreactor was operated continuously for over 24 months to provide a higher surface area (using a structured packing) with increased rates. Degradation rates consistently achieved were approximately 50 g of VOC/(m3.h) via single pass in this gas-continuous columnar system. Effective mass transfer coefficients comparable to literature values were also measured for this reactor; these values were substantially higher than those found in the gas-recycle reactor. Control of biomass levels was implemented by limiting the level of available nitrogen in the recirculating aqueous media, enabling long-term stability of reactor performance.

Moderate forest disturbance as a stringent test for gap and big-leaf models

NASA Astrophysics Data System (ADS)

Bond-Lamberty, B. P.; Fisk, J.; Holm, J. A.; Bailey, V. L.; Gough, C. M.

2014-12-01

Disturbance-induced tree mortality is a key factor regulating the carbon balance of a forest, but tree mortality and its subsequent effects are poorly represented processes in terrestrial ecosystem models. In particular, it is unclear whether models can robustly simulate moderate (non-catastrophic) disturbances, which tend to increase biological and structural complexity and are increasingly common in aging U.S. forests. We tested whether three forest ecosystem models—Biome-BGC, a classic big-leaf model, and the ED and ZELIG gap-oriented models—could reproduce the resilience to moderate disturbance observed in an experimentally manipulated forest (the Forest Accelerated Succession Experiment in northern Michigan, USA, in which 38% of canopy dominants were stem girdled and compared to control plots). Each model was parameterized, spun up, and disturbed following similar protocols, and run for 5 years post-disturbance. The models replicated observed declines in aboveground biomass well. Biome-BGC captured the timing and rebound of observed leaf area index (LAI), while ED and ZELIG correctly estimated the magnitude of LAI decline. None of the models fully captured the observed post-disturbance C fluxes. Biome-BGC net primary production (NPP) was correctly resilient, but for the wrong reasons, while ED and ZELIG exhibited large, unobserved drops in NPP and net ecosystem production. The biological mechanisms proposed to explain the observed rapid resilience of the C cycle are typically not incorporated by these or other models. As a result we expect that most ecosystem models, developed to simulate processes following stand-replacing disturbances, will not simulate well the gradual and less extensive tree mortality characteristic of moderate disturbances.

Moderate forest disturbance as a stringent test for gap and big-leaf models

NASA Astrophysics Data System (ADS)

Bond-Lamberty, B.; Fisk, J.; Holm, J. A.; Bailey, V.; Gough, C. M.

2014-07-01

Disturbance-induced tree mortality is a key factor regulating the carbon balance of a forest, but tree mortality and its subsequent effects are poorly represented processes in terrestrial ecosystem models. In particular, it is unclear whether models can robustly simulate moderate (non-catastrophic) disturbances, which tend to increase biological and structural complexity and are increasingly common in aging US forests. We tested whether three forest ecosystem models - Biome-BGC, a classic big-leaf model, and the ED and ZELIG gap-oriented models - could reproduce the resilience to moderate disturbance observed in an experimentally manipulated forest (the Forest Accelerated Succession Experiment in northern Michigan, USA, in which 38% of canopy dominants were stem girdled and compared to control plots). Each model was parameterized, spun up, and disturbed following similar protocols, and run for 5 years post-disturbance. The models replicated observed declines in aboveground biomass well. Biome-BGC captured the timing and rebound of observed leaf area index (LAI), while ED and ZELIG correctly estimated the magnitude of LAI decline. None of the models fully captured the observed post-disturbance C fluxes. Biome-BGC net primary production (NPP) was correctly resilient, but for the wrong reasons, while ED and ZELIG exhibited large, unobserved drops in NPP and net ecosystem production. The biological mechanisms proposed to explain the observed rapid resilience of the C cycle are typically not incorporated by these or other models. As a result we expect that most ecosystem models, developed to simulate processes following stand-replacing disturbances, will not simulate well the gradual and less extensive tree mortality characteristic of moderate disturbances.

An overview of a 5-year research program on acid deposition in China

NASA Astrophysics Data System (ADS)

Wang, T.; He, K.; Xu, X.; Zhang, P.; Bai, Y.; Wang, Z.; Zhang, X.; Duan, L.; Li, W.; Chai, F.

2011-12-01

Despite concerted research and regulative control of sulfur dioxide in China, acid rain remained a serious environmental issue, due to a sharp increase in the combustion of fossil fuel in the 2000s. In 2005, the Ministry of Science and Technology of China funded a five-year comprehensive research program on acid deposition. This talk will give an overview of the activities and the key findings from this study, covering emission, atmospheric processes, and deposition, effects on soil and stream waters, and impact on typical trees/plants in China. The main results include (1) China still experiences acidic rainfalls in southern and eastern regions, although the situation has stabilized after 2006 due to stringent control of SO2 by the Chinese Government; (2) Sulfate is the dominant acidic compound, but the contribution of nitrate has increased; (3) cloud-water composition in eastern China is strongly influenced by anthropogenic emissions; (4) the persistent fall of acid rain in the 30 years has lead to acidification of some streams/rivers and soils in southern China; (5) the studied plants have shown varying response to acid rain; (6) some new insights have been obtained on atmospheric chemistry, atmospheric transport, soil chemistry, and ecological impacts, some of which will be discussed in this talk. Compared to the situation in North America and Europe, China's acid deposition is still serious, and continued control of sulfur and nitrogen emission is required. There is an urgent need to establish a long-term observation network/program to monitor the impact of acid deposition on soil, streams/rivers/lakes, and forests.

Impact of oxygenation on the performance of three non-Saccharomyces yeasts in co-fermentation with Saccharomyces cerevisiae.

PubMed

Shekhawat, Kirti; Bauer, Florian F; Setati, Mathabatha E

2017-03-01

The sequential or co-inoculation of grape must with non-Saccharomyces yeast species and Saccharomyces cerevisiae wine yeast strains has recently become a common practice in winemaking. The procedure intends to enhance unique aroma and flavor profiles of wine. The extent of the impact of non-Saccharomyces strains depends on their ability to produce biomass and to remain metabolically active for a sufficiently long period. However, mixed-culture wine fermentations tend to become rapidly dominated by S. cerevisiae, reducing or eliminating the non-Saccharomyces yeast contribution. For an efficient application of these yeasts, it is therefore essential to understand the environmental factors that modulate the population dynamics of such ecosystems. Several environmental parameters have been shown to influence population dynamics, but their specific effect remains largely uncharacterized. In this study, the population dynamics in co-fermentations of S. cerevisiae and three non-Saccharomyces yeast species: Torulaspora delbrueckii, Lachancea thermotolerans, and Metschnikowia pulcherrima, was investigated as a function of oxygen availability. In all cases, oxygen availability strongly influenced population dynamics, but clear species-dependent differences were observed. Our data show that L. thermotolerans required the least oxygen, followed by T. delbrueckii and M. pulcherrima. Distinct species-specific chemical volatile profiles correlated in all cases with increased persistence of non-Saccharomyces yeasts, in particular increases in some higher alcohols and medium chain fatty acids. The results highlight the role of oxygen in regulating the succession of yeasts during wine fermentations and suggests that more stringent aeration strategies would be necessary to support the persistence of non-Saccharomyces yeasts in real must fermentations.

Hematopoietic Colony Formation from Human Growth Factor-Dependent TF1 Cells and Human Cord Blood Myeloid Progenitor Cells Depends on SHP2 Phosphatase Function

PubMed Central

Etienne-Julan, Maryse; Gotoh, Akihiko; Braun, Stephen E.; Lu, Li; Cooper, Scott; Feng, Gen-Sheng; Li, Xing Jun

2013-01-01

The protein tyrosine phosphatase, SHP2, is widely expressed; however, previous studies demonstrated that hematopoietic cell development more stringently requires Shp2 expression compared to other tissues. Furthermore, somatic gain-of-function SHP2 mutants are commonly found in human myeloid leukemias. Given that pharmacologic inhibitors to SHP2 phosphatase activity are currently in development as putative antileukemic agents, we conducted a series of experiments examining the necessity of SHP2 phosphatase activity for human hematopoiesis. Anti-sense oligonucleotides to human SHP2 coding sequences reduced human cord blood- and human cell line, TF1-derived colony formation. Expression of truncated SHP2 bearing its Src homology 2 (SH2) domains, but lacking the phosphatase domain similarly reduced human cord blood- and TF1-derived colony formation. Mechanistically, expression of truncated SHP2 reduced the interaction between endogenous, full-length SHP2 with the adapter protein, Grb2. To verify the role of SHP2 phosphatase function in human hematopoietic cell development, human cord blood CD34+ cells were transduced with a leukemia-associated phosphatase gain-of-function SHP2 mutant or with a phosphatase dead SHP2 mutant, which indicated that increased phosphatase function enhanced, while decreased SHP2 phosphatase function reduced, human cord blood-derived colonies. Collectively, these findings indicate that SHP2 phosphatase function regulates human hematopoietic cell development and imply that the phosphatase component of SHP2 may serve as a pharmacologic target in human leukemias bearing increased SHP2 phosphatase activity. PMID:23082805

Hematopoietic colony formation from human growth factor-dependent TF1 cells and human cord blood myeloid progenitor cells depends on SHP2 phosphatase function.

PubMed

Broxmeyer, Hal E; Etienne-Julan, Maryse; Gotoh, Akihiko; Braun, Stephen E; Lu, Li; Cooper, Scott; Feng, Gen-Sheng; Li, Xing Jun; Chan, Rebecca J

2013-03-15

The protein tyrosine phosphatase, SHP2, is widely expressed; however, previous studies demonstrated that hematopoietic cell development more stringently requires Shp2 expression compared to other tissues. Furthermore, somatic gain-of-function SHP2 mutants are commonly found in human myeloid leukemias. Given that pharmacologic inhibitors to SHP2 phosphatase activity are currently in development as putative antileukemic agents, we conducted a series of experiments examining the necessity of SHP2 phosphatase activity for human hematopoiesis. Anti-sense oligonucleotides to human SHP2 coding sequences reduced human cord blood- and human cell line, TF1-derived colony formation. Expression of truncated SHP2 bearing its Src homology 2 (SH2) domains, but lacking the phosphatase domain similarly reduced human cord blood- and TF1-derived colony formation. Mechanistically, expression of truncated SHP2 reduced the interaction between endogenous, full-length SHP2 with the adapter protein, Grb2. To verify the role of SHP2 phosphatase function in human hematopoietic cell development, human cord blood CD34+ cells were transduced with a leukemia-associated phosphatase gain-of-function SHP2 mutant or with a phosphatase dead SHP2 mutant, which indicated that increased phosphatase function enhanced, while decreased SHP2 phosphatase function reduced, human cord blood-derived colonies. Collectively, these findings indicate that SHP2 phosphatase function regulates human hematopoietic cell development and imply that the phosphatase component of SHP2 may serve as a pharmacologic target in human leukemias bearing increased SHP2 phosphatase activity.

Abuse Liability and Reinforcing Efficacy of Oral Tramadol in Humans

PubMed Central

Babalonis, Shanna; Lofwall, Michelle R.; Nuzzo, Paul A.; Siegel, Anthony J.; Walsh, Sharon L.

2012-01-01

BACKGROUND Tramadol, a monoaminergic reuptake inhibitor, is hepatically metabolized to an opioid agonist (M1). This atypical analgesic is generally considered to have limited abuse liability. Recent reports of its abuse have increased in the U.S., leading to more stringent regulation in some states, but not nationally. The purpose of this study was to examine the relative abuse liability and reinforcing efficacy of tramadol in comparison to a high (oxycodone) and low efficacy (codeine) opioid agonist. METHODS Nine healthy, non-dependent prescription opioid abusers (6 male, 3 female) participated in this within-subject, randomized, double blind, placebo-controlled study. Participants completed 14 paired sessions (7 sample, 7 self-administration). During each sample session, an oral dose of tramadol (200, 400 mg), oxycodone (20, 40 mg), codeine (100, 200 mg) or placebo was administered, and a full array of abuse liability measures was collected. During self-administration sessions, volunteers were given the opportunity to work (via progressive ratio) for the sample dose or money. RESULTS All active doses were self-administered; placebo engendered no responding. The high doses of tramadol and oxycodone were readily self-administered (70%, 59% of available drug, respectively); lower doses and both codeine doses maintained intermediate levels of drug taking. All three drugs dose-dependently increased measures indicative of abuse liability, relative to placebo; however, the magnitude and time course of these and other pharmacodynamic effects varied qualitatively across drugs. CONCLUSIONS This study demonstrates that, like other mu opioids, higher doses of tramadol function as reinforcers in opioid abusers, providing new empirical data for regulatory evaluation. PMID:23098678

Addressing continuous data measured with different instruments for participants excluded from trial analysis: a guide for systematic reviewers.

PubMed

Ebrahim, Shanil; Johnston, Bradley C; Akl, Elie A; Mustafa, Reem A; Sun, Xin; Walter, Stephen D; Heels-Ansdell, Diane; Alonso-Coello, Pablo; Guyatt, Gordon H

2014-05-01

We previously developed an approach to address the impact of missing participant data in meta-analyses of continuous variables in trials that used the same measurement instrument. We extend this approach to meta-analyses including trials that use different instruments to measure the same construct. We reviewed the available literature, conducted an iterative consultative process, and developed an approach involving a complete-case analysis complemented by sensitivity analyses that apply a series of increasingly stringent assumptions about results in patients with missing continuous outcome data. Our approach involves choosing the reference measurement instrument; converting scores from different instruments to the units of the reference instrument; developing four successively more stringent imputation strategies for addressing missing participant data; calculating a pooled mean difference for the complete-case analysis and imputation strategies; calculating the proportion of patients who experienced an important treatment effect; and judging the impact of the imputation strategies on the confidence in the estimate of effect. We applied our approach to an example systematic review of respiratory rehabilitation for chronic obstructive pulmonary disease. Our extended approach provides quantitative guidance for addressing missing participant data in systematic reviews of trials using different instruments to measure the same construct. Copyright © 2014 Elsevier Inc. All rights reserved.

Antibodies Biotinylated Using a Synthetic Z-domain from Protein A Provide Stringent In Situ Protein Detection

PubMed Central

Konrad, Anna; Ashok, Nikhil; Pontén, Fredrik; Hober, Sophia; Asplund, Anna

2013-01-01

Antibody-based protein profiling on a global scale using immunohistochemistry constitutes an emerging strategy for mapping of the human proteome, which is crucial for an increased understanding of biological processes in the cell. Immunohistochemistry is often performed indirectly using secondary antibodies for detection, with the benefit of signal amplification. Direct immunohistochemistry instead brings the advantage of multiplexing; however, it requires labeling of the primary antibody. Many antibody-labeling kits do not specifically target IgG and may therefore cause labeling of stabilizing proteins present in the antibody solution. A new conjugation method has been developed that utilizes a modified Z-domain of protein A (ZBPA) to specifically target the Fc part of antibodies. The aim of the present study was to compare the ZBPA conjugation method and a commercially available labeling kit, Lightning-Link, for in situ protein detection. Fourteen antibodies were biotinylated with each method and stained using immunohistochemistry. For all antibodies tested, ZBPA biotinylation resulted in distinct immunoreactivity without off-target staining, regardless of the presence of stabilizing proteins in the buffer, whereas the majority of the Lightning-Link biotinylated antibodies displayed a characteristic pattern of nonspecific staining. We conclude that biotinylated ZBPA domain provides a stringent method for antibody biotinylation, advantageous for in situ protein detection in tissues. PMID:23920108

Reducing secondary organic aerosol formation from gasoline vehicle exhaust

PubMed Central

Zhao, Yunliang; Saleh, Rawad; Presto, Albert A.; Gordon, Timothy D.; Drozd, Greg T.; Goldstein, Allen H.; Robinson, Allen L.

2017-01-01

On-road gasoline vehicles are a major source of secondary organic aerosol (SOA) in urban areas. We investigated SOA formation by oxidizing dilute, ambient-level exhaust concentrations from a fleet of on-road gasoline vehicles in a smog chamber. We measured less SOA formation from newer vehicles meeting more stringent emissions standards. This suggests that the natural replacement of older vehicles with newer ones that meet more stringent emissions standards should reduce SOA levels in urban environments. However, SOA production depends on both precursor concentrations (emissions) and atmospheric chemistry (SOA yields). We found a strongly nonlinear relationship between SOA formation and the ratio of nonmethane organic gas to oxides of nitrogen (NOx) (NMOG:NOx), which affects the fate of peroxy radicals. For example, changing the NMOG:NOx from 4 to 10 ppbC/ppbNOx increased the SOA yield from dilute gasoline vehicle exhaust by a factor of 8. We investigated the implications of this relationship for the Los Angeles area. Although organic gas emissions from gasoline vehicles in Los Angeles are expected to fall by almost 80% over the next two decades, we predict no reduction in SOA production from these emissions due to the effects of rising NMOG:NOx on SOA yields. This highlights the importance of integrated emission control policies for NOx and organic gases. PMID:28630318

Acid rain recovery may help to mitigate the impacts of climate change on thermally sensitive fish in lakes across eastern North America.

PubMed

Warren, Dana R; Kraft, Clifford E; Josephson, Daniel C; Driscoll, Charles T

2017-06-01

From the 1970s to 1990s, more stringent air quality regulations were implemented across North America and Europe to reduce chemical emissions that contribute to acid rain. Surface water pH slowly increased during the following decades, but biological recovery lagged behind chemical recovery. Fortunately, this situation is changing. In the past few years, northeastern US fish populations have begun to recover in lakes that were historically incapable of sustaining wild fish due to acidic conditions. As lake ecosystems across the eastern United States recover from acid deposition, the stress to the most susceptible populations of native coldwater fish appears to be shifting from acidification effects to thermal impacts associated with changing climate. Extreme summer temperature events - which are expected to occur with increasing frequency in the coming century - can stress and ultimately kill native coldwater fish in lakes where thermal stratification is absent or highly limited. Based on data from northeastern North America, we argue that recovery from acid deposition has the potential to improve the resilience of coldwater fish populations in some lakes to impacts of climate change. This will occur as the amount of dissolved organic carbon (DOC) in the water increases with increasing lake pH. Increased DOC will reduce water clarity and lead to shallower and more persistent lake thermoclines that can provide larger areas of coldwater thermal refuge habitat. Recovery from acidification will not eliminate the threat of climate change to coldwater fish, but secondary effects of acid recovery may improve the resistance of coldwater fish populations in lakes to the effects of elevated summer temperatures in historically acidified ecosystems. This analysis highlights the importance of considering the legacy of past ecosystem impacts and how recovery or persistence of those effects may interact with climate change impacts on biota in the coming decades. © 2016 John Wiley & Sons Ltd.

Safety of community drinking-water and outbreaks of waterborne enteric disease: Israel, 1976-97.

PubMed Central

Tulchinsky, T. H.; Burla, E.; Clayman, M.; Sadik, C.; Brown, A.; Goldberger, S.

2000-01-01

Waterborne disease remains a major public health problem in many countries. We report findings on nearly three decades of waterborne disease in Israel and the part these diseases play in the total national burden of enteric disease. During the 1970s and 1980s, Israel's community water supplies were frequently of poor quality according to the microbiological standards at that time, and the country experienced many outbreaks of waterborne enteric disease. New regulations raised water quality standards and made chlorination of community water supplies mandatory, as well as imposing more stringent guidelines on maintaining water sources and distribution systems for both surface water and groundwater. This was followed by improved compliance and water quality, and a marked decline in the number of outbreaks of waterborne disease; no outbreaks were detected between 1992 and 1997. The incidence of waterborne salmonellosis, shigellosis, and typhoid declined markedly as proportions of the total burden of these diseases, but peaked during the time in which there were frequent outbreaks of waterborne disease (1980-85). Long-term trends in the total incidence of reported infectious enteric diseases from all sources, including typhoid, shigellosis, and viral hepatitis (all types) declined, while the total incidence of salmonellosis increased. Mandatory chlorination has had an important impact on improving water quality, in reducing outbreaks of waterborne disease in Israel, and reducing the total burden of enteric disease in the country. PMID:11196499

Reduction in (pro-)inflammatory responses of lung cells exposed in vitro to diesel exhaust treated with a non-catalyzed diesel particle filter

NASA Astrophysics Data System (ADS)

Steiner, Sandro; Czerwinski, Jan; Comte, Pierre; Müller, Loretta L.; Heeb, Norbert V.; Mayer, Andreas; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

2013-12-01

Increasingly stringent regulation of particulate matter emissions from diesel vehicles has led to the widespread use of diesel particle filters (DPFs), the effect of which on exhaust toxicity is so far poorly understood. We exposed a cellular model of the human respiratory epithelium at the air-liquid interface to non-catalyzed wall-flow DPF-filtered diesel exhaust and compared the resulting biological responses to the ones observed upon exposure to unfiltered exhaust. Filtered diesel exhaust acted highly oxidative, even though to a lesser extent than unfiltered exhaust (quantification of total reduced glutathione), and both exhaust types triggered comparable responses to oxidative stress (measurement of heme-oxygenase 1 (HMOX1) and superoxide-dismutase (SOD1) gene expression). Further, diesel exhaust filtration significantly reduced pro-inflammatory responses (measurement of tumor necrosis factor (TNF) and interleukin-8 (IL-8) gene expression and quantification of the secretion of their gene products TNF-α and IL-8). Because inflammatory processes are central to the onset of adverse respiratory health effects caused by diesel exhaust inhalation, our results imply that DPFs may make a valuable contribution to the detoxification of diesel vehicle emissions. The induction of significant oxidative stress by filtered diesel exhaust however, also implies that the non-particulate exhaust components also need to be considered for lung cell risk assessment.

Landfill leachate management in Istanbul: applications and alternatives.

PubMed

Calli, Baris; Mertoglu, Bulent; Inanc, Bulent

2005-05-01

Treatment alternatives for Istanbul, Komurcuoda Landfill (KL) leachate that is currently transported to the nearest central wastewater treatment plant were comprehensively investigated with laboratory scale experiments. As flow rate of leachate increases parallel to increment in landfilled solid waste, an individual treatment will be needed to reduce the transportation cost and pollution load on central treatment. However, if the leachate is separately treated and discharged to a brook, in that case more stringent discharge standards will be valid and therefore advanced processes in addition to conventional ones should be included. In laboratory scale experiments, the young landfill leachate having BOD5/COD ratio above 0.6 was successfully treated with efficiencies above 90% in upflow anaerobic reactors if pH is kept below free ammonia inhibition level. Subsequently, nitrification of anaerobically treated leachate was performed with rates of about 8.5 mg NH4+-Ng-1 VSS h-1 and efficiencies above 99% were provided with automated pH regulation by using sodium bicarbonate. Furthermore, denitrification rates as high as 8.1 mg NOx-N g-1VSS h-1 was obtained when carbon source was externally supplied. In addition to nitrification and denitrification, air stripping and struvite precipitation were also applied to remove ammonia in leachate and in average 94% and 98% efficiencies were achieved, respectively. Finally, in average 85% of biologically inert COD was successfully removed by using either ozone or Fenton's oxidation.

Removal of phenol from aqueous solution using polymer inclusion membrane based on mixture of CTA and CA

NASA Astrophysics Data System (ADS)

Benosmane, Nadjib; Boutemeur, Baya; Hamdi, Safouane M.; Hamdi, Maamar

2018-03-01

Nowadays, there are increasingly stringent regulations requiring more and more treatment of industrial effluents to generate product waters which could be easily reused or disposed of to the environment without any harmful effects. In the present work, the removal of phenol from aqueous solution across polymer inclusion membrane (PIM), based on mixture of cellulose triacetate and cellulose acetate as support (75/25%), calix[4]resorcinarene derivative as a carrier and 2-nitrophenyl octyl ether (2-NPOE) as plasticizer was investigated. The experimental part of this investigation involved the influence of carrier nature, plasticizer concentration, pH phases, and phenol initial concentration on the removal efficiency of phenol from synthetic wastewater. A PIM containing 0.1 g (of mixture polymer), (0.15 g/g mixture of polymer) of carrier and (0.03 ml/g mixture of polymer) of 2-NPOE provided the highest percentage of phenol removal efficiency over a 6-day transport; the removal was found to be about 95%, indeed the removal was found to be highly dependent of pH phases. The feed solution in these transport experiments was at pH 2, while the stripping solution contained 0.20 M NaOH. This study claims that the PIM with a mixture of cellulose derivatives can be used effectively to remove phenols from wastewaters.

Air-pollution emission control in China: impacts on soil acidification recovery and constraints due to drought.

PubMed

Duan, Lei; Liu, Jing; Xin, Yan; Larssen, Thorjørn

2013-10-01

The Chinese government has established compulsory targets to reduce sulfur dioxide (SO2) and nitrogen oxide (NOx) emissions by 8% and 10%, respectively, during 2010-2015. In this study, the effect of the policy was evaluated by predicting the recovery of acidified forest soil in Chongqing, an area severely impacted by acid rain in southwest China. Since precipitation has decreased significantly in this area in recent years, the impact of drought on soil acidification was also considered. A dynamic acidification model, MAGIC, was used to predict future trends in soil chemistry under different scenarios for deposition reduction as well as drought. We found that the current regulation of SO2 emission abatement did not significantly increase soil water pH values, the Ca2+ to Al3+ molar ratio (Ca/Al), or soil base saturation to the level of 2000 before 2050. NOx emission control would have less of an effect on acidification recovery, while emission reduction of particulate matter could offset the benefits of SO2 reduction by greatly decreasing the deposition of base cations, particularly Ca(2+). Continuous droughts in the future might also delay acidification recovery. Therefore, more stringent SO2 emission control should be implemented to facilitate the recovery of seriously acidified areas in China. © 2013 Elsevier B.V. All rights reserved.

Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.

PubMed

Goldberg, Alexander A; Richard, Vincent R; Kyryakov, Pavlo; Bourque, Simon D; Beach, Adam; Burstein, Michelle T; Glebov, Anastasia; Koupaki, Olivia; Boukh-Viner, Tatiana; Gregg, Christopher; Juneau, Mylène; English, Ann M; Thomas, David Y; Titorenko, Vladimir I

2010-07-01

In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA.

Antimicrobial food packaging: potential and pitfalls

PubMed Central

Malhotra, Bhanu; Keshwani, Anu; Kharkwal, Harsha

2015-01-01

Nowadays food preservation, quality maintenance, and safety are major growing concerns of the food industry. It is evident that over time consumers’ demand for natural and safe food products with stringent regulations to prevent food-borne infectious diseases. Antimicrobial packaging which is thought to be a subset of active packaging and controlled release packaging is one such promising technology which effectively impregnates the antimicrobial into the food packaging film material and subsequently delivers it over the stipulated period of time to kill the pathogenic microorganisms affecting food products thereby increasing the shelf life to severe folds. This paper presents a picture of the recent research on antimicrobial agents that are aimed at enhancing and improving food quality and safety by reduction of pathogen growth and extension of shelf life, in a form of a comprehensive review. Examination of the available antimicrobial packaging technologies is also presented along with their significant impact on food safety. This article entails various antimicrobial agents for commercial applications, as well as the difference between the use of antimicrobials under laboratory scale and real time applications. Development of resistance amongst microorganisms is considered as a future implication of antimicrobials with an aim to come up with actual efficacies in extension of shelf life as well as reduction in bacterial growth through the upcoming and promising use of antimicrobials in food packaging for the forthcoming research down the line. PMID:26136740

Flexible Distributed Energy & Water from Waste for Food and Beverage Industry

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

Shi, Ruijie

Food and beverage plants inherently consume a large quantity of water and generate a high volume of wastewater rich in organic content. On one hand, water discharge regulations are getting more stringent over the time, necessitating the use of different technologies to reduce the amount of wastewater and improve the effluent water quality. On the other hand, growing energy and water costs are driving the plants to extract and reuse valuable energy and water from the wastewater stream. An integrated waste-tovalue system uses a combination of anaerobic digester (AD), reciprocating gas engine/boiler, membrane bioreactor (MBR), and reverse osmosis (RO) tomore » recover valuable energy as heat and/or electricity as well as purify the water for reuse. While individual anaerobic digestion and membrane bioreactors are being used in increasing numbers, there is a growing need to integrate them together in a waste-to-value system for enhanced energy and water recovery. However, currently operation of these systems relies heavily on the plant operator to perform periodic sampling and off-line lab analysis to monitor the system performance, detect any abnormal condition due to variations in the wastewater and decide on appropriate remedial action needed. This leads to a conservative design and operation of these systems to avoid any potential upsets that can destabilize the system.« less

Impact of donor age in liver transplantation from donation after circulatory death donors: A decade of experience at Cleveland Clinic.

PubMed

Firl, Daniel J; Hashimoto, Koji; O'Rourke, Colin; Diago-Uso, Teresa; Fujiki, Masato; Aucejo, Federico N; Quintini, Cristiano; Kelly, Dympna M; Miller, Charles M; Fung, John J; Eghtesad, Bijan

2015-12-01

The use of liver grafts from donation after circulatory death (DCD) donors remains controversial, particularly with donors of advanced age. This retrospective study investigated the impact of donor age in DCD liver transplantation. We examined 92 recipients who received DCD grafts and 92 matched recipients who received donation after brain death (DBD) grafts at Cleveland Clinic from January 2005 to June 2014. DCD grafts met stringent criteria to minimize risk factors in both donors and recipients. The 1-, 3-, and 5-year graft survival in DCD recipients was significantly inferior to that in DBD recipients (82%, 71%, 66% versus 92%, 87%, 85%, respectively; P = 0.03). Six DCD recipients (7%), but no DBD recipients, experienced ischemic-type biliary stricture (P = 0.01). However, the incidence of biliary stricture was not associated with donor age (P = 0.57). Interestingly, recipients receiving DCD grafts from donors who were <45 years of age (n = 55) showed similar graft survival rates compared to those receiving DCD grafts from donors who were ≥45 years of age (n = 37; 80%, 69%, 66% versus 83%, 72%, 66%, respectively; P = 0.67). Cox proportional hazards modeling in all study populations (n = 184) revealed advanced donor age (P = 0.05) and the use of a DCD graft (P = 0.03) as unfavorable factors for graft survival. Logistic regression analysis showed that the risk of DBD graft failure increased with increasing age, but the risk of DCD graft failure did not increase with increasing age (P = 0.13). In conclusion, these data suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation. DCD grafts should not be discarded because of donor age, per se, and could help expand the donor pool for liver transplantation. © 2015 American Association for the Study of Liver Diseases.

The Further Development of Heat-Resistant Materials for Aircraft Engines

NASA Technical Reports Server (NTRS)

Bollenrath, Franz

1946-01-01

The present report deals with the problems involved in the greater utilization and development of aircraft engine materials, and specifically; piston materials, cylinder heads, exhaust valves, and exhaust gas turbine blading. The blades of the exhaust gas turbine are likely to be the highest stressed components of modern power plants from a thermal-mechanical and chemical standpoint, even though the requirements on exhaust valves of engines with gasoline injection are in general no less stringent. For the fire plate in Diesel engines the specifications for mechanical strength and design are not so stringent, and the question of heat resistance, which under these circumstances is easier obtainable, predominates.

76 FR 57515 - Energy Conservation Program: Energy Conservation Standards for Residential Refrigerators...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

...The Energy Policy and Conservation Act (EPCA) prescribes energy conservation standards for various consumer products and commercial and industrial equipment, including refrigerators, refrigerator-freezers, and freezers. EPCA also requires the U.S. Department of Energy (DOE) to determine if more stringent, amended standards for these products are technologically feasible and economically justified, and would save a significant amount of energy. In this final rule, DOE is adopting more stringent energy conservation standards for refrigerators, refrigerator-freezers, and freezers. It has determined that the amended energy conservation standards for these products would result in the significant conservation of energy and are technologically feasible and economically justified.

Why European and United States drug regulators are not speaking with one voice on anti-influenza drugs: regulatory review methodologies and the importance of 'deep' product reviews.

PubMed

Mulinari, Shai; Davis, Courtney

2017-11-09

Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza. In Europe, Relenza was evaluated via the so-called national procedure with Sweden as the reference country. We show that FDA reviewers, unlike their European (i.e. Swedish) counterpart, (1) rejected the manufacturer's insistence on pooling efficacy data, (2) remained wary of subgroup analyses, and (3) insisted on stringent statistical analyses. These differences meant that the FDA was less likely to depart from prevailing regulatory and scientific standards in interpreting trial results. We argue that the differences are explained largely by divergent institutionalised review methodologies, i.e. the European regulator's reliance on manufacturer-compiled summaries compared to the FDA's examination of original data and documentation from trials. The FDA's more probing and meticulous evaluative methodology allowed its reviewers to develop 'deep' knowledge concerning the clinical and statistical facets of trials, and more informed opinions regarding suitable methods for analysing trial results. These findings challenge the current emphasis on evaluating regulatory performance mainly in terms of speed of review. We propose that persistent uncertainty and knowledge deficits regarding NIs could have been ameliorated had regulators engaged in the public debates over the drugs' efficacy and explained their contrasting methodologies and judgments. Regulators use major resources to evaluate drugs, but if regulators' assessments are not effectively disseminated and used, resources are used inefficiently.

Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue

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

Tilton, Susan C.; Markillie, Lye Meng; Hays, Spencer

Our goal here was to identify dose and temporal dependent radiation responses in a complex tissue, reconstituted human skin. Direct sequencing of RNA (RNA-seq) was used to quantify altered transcripts following exposure to 0.1, 2 and 10 Gy of ionizing radiation at 3 and 8 hours. These doses include a low dose in the range of some medical diagnostic procedures (0.1 Gy), a dose typically received during radiotherapy (2.0 Gy) and a lethal dose (10 Gy). These doses could be received after an intentional or accidental radiation exposure and biomarkers are needed to rapidly and accurately triage exposed individuals. Amore » total of 1701 genes were deemed to be significantly affected by high dose radiation exposure with the majority of genes affected at 10 Gy. A group of 29 genes including GDF15, BBC3, PPM1D, FDXR, GADD45A, MDM2, CDKN1A, TP53INP1, CYCSP27, SESN1, SESN2, PCNA, and AEN were similarly altered at both 2 and 10 Gy, but not 0.1 Gy, at multiple time points. A much larger group of up regulated genes, including those involved in inflammatory responses, was significantly altered only after a 10 Gy exposure. At high doses, down regulated genes were associated with cell cycle regulation and exhibited an apparent linear response between 2 and 10 Gy. While only a handful of genes were significantly affected by 0.1 Gy exposure using stringent statistical filters, groups of related genes regulating cell cycle progression and inflammatory responses consistently exhibited opposite trends in their regulation compared to the high dose exposures. Differential regulation of PLK1 signaling at low and high doses was confirmed using qRT-PCR. These results indicate that some alterations in gene expression are qualitatively different at low and high doses of radiation in this model system.« less

The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system

PubMed Central

Sahr, Tobias; Rusniok, Christophe; Impens, Francis; Oliva, Giulia; Sismeiro, Odile; Coppée, Jean-Yves

2017-01-01

The carbon storage regulator protein CsrA regulates cellular processes post-transcriptionally by binding to target-RNAs altering translation efficiency and/or their stability. Here we identified and analyzed the direct targets of CsrA in the human pathogen Legionella pneumophila. Genome wide transcriptome, proteome and RNA co-immunoprecipitation followed by deep sequencing of a wild type and a csrA mutant strain identified 479 RNAs with potential CsrA interaction sites located in the untranslated and/or coding regions of mRNAs or of known non-coding sRNAs. Further analyses revealed that CsrA exhibits a dual regulatory role in virulence as it affects the expression of the regulators FleQ, LqsR, LetE and RpoS but it also directly regulates the timely expression of over 40 Dot/Icm substrates. CsrA controls its own expression and the stringent response through a regulatory feedback loop as evidenced by its binding to RelA-mRNA and links it to quorum sensing and motility. CsrA is a central player in the carbon, amino acid, fatty acid metabolism and energy transfer and directly affects the biosynthesis of cofactors, vitamins and secondary metabolites. We describe the first L. pneumophila riboswitch, a thiamine pyrophosphate riboswitch whose regulatory impact is fine-tuned by CsrA, and identified a unique regulatory mode of CsrA, the active stabilization of RNA anti-terminator conformations inside a coding sequence preventing Rho-dependent termination of the gap operon through transcriptional polarity effects. This allows L. pneumophila to regulate the pentose phosphate pathway and the glycolysis combined or individually although they share genes in a single operon. Thus the L. pneumophila genome has evolved to acclimate at least five different modes of regulation by CsrA giving it a truly unique position in its life cycle. PMID:28212376