Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

PubMed

Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

2018-06-11

Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures

PubMed Central

Kague, Erika; Roy, Paula; Asselin, Garrett; Hu, Gui; Stanley, Alexandra; Albertson, Craig; Simonet, Jacqueline; Fisher, Shannon

2017-01-01

During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures. PMID:26992365

Effects of water temperature on breeding phenology, growth, and metamorphosis of foothill yellow-legged frogs (Rana boylii): a case study of the regulated mainstem and unregulated tributaries of California's Trinity River

Treesearch

Clara Wheeler; James Bettaso; Donald Ashton; Hartwell Welsh

2014-01-01

Many riverine organisms are well adapted to seasonally dynamic environments, but extreme changes in flow and thermal regimes can threaten sustainability of their populations in regulated rivers. Altered thermal regimes may limit recruitment to populations by shifting the timing of breeding activities and affecting the growth and development of early life stages. Stream...

A proposed approach for the assessment of chemicals in indirect potable reuse schemes.

PubMed

Rodriguez, Clemencia; Weinstein, Philip; Cook, Angus; Devine, Brian; Van Buynder, Paul

2007-10-01

The city of Perth in Western Australia is facing a future of compromised water supplies. In recent years, this urban region has been experiencing rapid population growth, coupled with drying climate, which has exacerbated water shortages. As part of the government strategy to secure water sustainability and to address an agenda focused on all elements of the water cycle, a target of 20% reuse of treated wastewater by 2012 was established. This includes a feasibility review of managed aquifer recharge for indirect potable reuse. A characterization of contaminants in wastewater after treatment and an assessment of the health implications are necessary to reassure both regulators and the public. To date, the commonly used approach involves a comparison of measured contaminant concentrations with the established drinking-water standards or other toxicological guidelines for the protection of human health. However, guidelines and standards have not been established for many contaminants in recycled water (unregulated chemicals). This article presents a three-tiered approach for the preliminary health risk assessment of chemicals in order to determine key contaminants that need to be monitored and managed. The proposed benchmark values for the calculation of risk quotients are health based, systematically defined, scientifically defensible, easy to apply, and clear to interpret. The proposed methodology is based on the derivation of health-based levels for unregulated contaminants with toxicity information and a "threshold of toxicological concern" for unregulated contaminants without toxicity data. The application of this approach will help policymakers set guidelines regarding unregulated chemicals in recycled water.

The role of unregulated care providers in home care: A scoping review.

PubMed

Saari, Margaret; Xiao, Sarah; Rowe, Alissa; Patterson, Erin; Killackey, Tieghan; Raffaghello, Julia; Tourangeau, Ann E

2018-04-30

Health care needs of individuals living in the community are increasing. To meet the rising need, unregulated care providers are providing more complex patient care. The aim of this review is to articulate the unregulated care provider role by identifying patient care activities offered by unregulated care providers in home care. A scoping review was conducted. One thousand and eleven published manuscripts were identified in CINAHL, Ageline and MEDLINE. Eleven additional manuscripts were identified through hand searching. Manuscripts were screened for relevancy and data were abstracted to address the research question. Twenty-eight studies originating from Canada, Sweden, Belgium, UK, USA and New Zealand were included. Three categories of patient care activities provided by unregulated care providers were found: (1) personal care and core skills; (2) delegated tasks and added skills; and (3) specialty roles. Unregulated care providers predominantly provide assistance with personal care and activities of daily living. However, unregulated care providers also provide care outside their training, including care once provided by nurses. Guidelines clearly articulating responsibilities of nurses transferring care activities to unregulated care providers should be developed. Processes and policies regarding evaluation and supervision of unregulated care providers providing added skills should be developed to ensure appropriate monitoring and support. © 2018 John Wiley & Sons Ltd.

Tangeretin, a citrus pentamethoxyflavone, exerts cytostatic effect via p53/p21 up-regulation and suppresses metastasis in 7,12-dimethylbenz(α)anthracene-induced rat mammary carcinoma.

PubMed

Arivazhagan, Lakshmi; Sorimuthu Pillai, Subramanian

2014-11-01

Breast cancer is the most commonly diagnosed cancer among women worldwide, which is characterized by unregulated cell growth and metastasis. Many bioactive compounds of plant origin such as tangeretin have been shown to possess potent antioxidant and anticancerous properties. In the present study we have investigated the chemotherapeutic effect of tangeretin against 7,12-dimethylbenz(α)anthracene (DMBA)-induced rat mammary carcinogenesis and studied its underlying mechanism of action. Breast cancer was induced by "air pouch technique" with a single dose of 25mg/kg of DMBA. Tangeretin (50 mg/kg) was administered orally for four weeks. Remarkably, tangeretin treatment controlled the growth of cancer cells which was clearly evidenced by morphological and histological analysis. Also, serum levels of estradiol, progesterone and prolactin; lipid bound sialic acid and total sialic acid and the tissue levels of nitric oxide and protein carbonyls of cancer induced animals were decreased upon tangeretin treatment. Staining of breast tissues for nucleolar organizer regions, mast cells, glycoproteins, lipids and collagen showed that tangeretin treatment to breast cancer induced rats significantly reduced tumorigenesis. Oral tangeretin treatment also effectively reduced the tumor cell proliferation markers such as PCNA, COX-2 and Ki-67. Further, tangeretin treatment arrested the cancer cell division at the G1/S phase via p53/p21 up-regulation and inhibited metastasis by suppressing matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor. Taken together, the data provides new evidence on the mechanism of action of tangeretin in breast cancer and hence extends the hypothesis supporting its potential use in chemotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

MFG-E8 Reprogramming of Macrophages Promotes Wound Healing by Increased bFGF Production and Fibroblast Functions.

PubMed

Laplante, Patrick; Brillant-Marquis, Frédéric; Brissette, Marie-Joëlle; Joannette-Pilon, Benjamin; Cayrol, Romain; Kokta, Victor; Cailhier, Jean-François

2017-09-01

Macrophages are essential for tissue repair. They have a crucial role in cutaneous wound healing, participating actively in the inflammation phase of the process. Unregulated macrophage activation may, however, represent a source of excessive inflammation, leading to abnormal wound healing and hypertrophic scars. Our research group has shown that apoptotic endothelial and epithelial cells secrete MFG-E8, which has the ability to reprogram macrophages from an M1 (proinflammatory) to an M2 (anti-inflammatory, pro-repair) phenotype. Hence, we tested whether modulation of macrophage reprogramming would promote tissue repair. Using a mouse model of wound healing, we showed that the presence and/or addition of MFG-E8 favors wound closure associated with an increase in CD206-positive cells and basic fibroblast growth factor production in healing tissues. More importantly, adoptive transfer of ex vivo MFG-E8-treated macrophages promoted wound closure. We also observed that MFG-E8-treated macrophages produced basic fibroblast growth factor that is responsible for fibroblast migration and proliferation. Taken together, our results strongly suggest that MFG-E8 plays a key role in macrophage reprogramming in tissue healing through induction of an anti-inflammatory M2 phenotype and basic fibroblast growth factor production, leading to fibroblast migration and wound closure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

RON kinase isoforms demonstrate variable cell motility in normal cells.

PubMed

Greenbaum, Alissa; Rajput, Ashwani; Wan, Guanghua

2016-09-01

Aberrant RON (Recepteur d'Origine Nantais) tyrosine kinase activation causes the epithelial cell to evade normal growth pathways, resulting in unregulated cell proliferation, increased cell motility and decreased apoptosis. Wildtype (wt) RON has been shown to play a role in metastasis of epithelial malignancies. It presents an important potential therapeutic target for colorectal, breast, gastric and pancreatic cancer. Little is known about functional differences amongst RON isoforms RON155, RON160 and RON165. The purpose of this study was to determine the effect of various RON kinase isoforms on cell motility. Cell lines with stable expression of wtRON were generated by inserting the coding region of RON in pTagRFP (tagged red fluorescence protein plasmid). The expression constructs of RON variants (RON155, RON160 and RON165) were generated by creating a mutagenesis-based wtRON-pTag RFP plasmid and stably transfected into HEK 293 cells. The wound closure scratch assay was used to investigate the effect on cell migratory capacity of wild type RON and its variants. RON transfected cells demonstrated increased cell motility compared to HEK293 control cells. RON165 cell motility was significantly increased compared to RON160 (mean percentage of wound covered 37.37% vs. 32.40%; p = 0.03). RON tyrosine kinase isoforms have variable cell motility. This may reflect a difference in the behavior of malignant epithelial cells and their capacity for metastasis.

Signaling by Fibroblast Growth Factors (Fgf) and Fibroblast Growth Factor Receptor 2 (Fgfr2)–Activating Mutations Blocks Mineralization and Induces Apoptosis in Osteoblasts

PubMed Central

Mansukhani, Alka; Bellosta, Paola; Sahni, Malika; Basilico, Claudio

2000-01-01

Fibroblast growth factors (FGF) play a critical role in bone growth and development affecting both chondrogenesis and osteogenesis. During the process of intramembranous ossification, which leads to the formation of the flat bones of the skull, unregulated FGF signaling can produce premature suture closure or craniosynostosis and other craniofacial deformities. Indeed, many human craniosynostosis disorders have been linked to activating mutations in FGF receptors (FGFR) 1 and 2, but the precise effects of FGF on the proliferation, maturation and differentiation of the target osteoblastic cells are still unclear. In this report, we studied the effects of FGF treatment on primary murine calvarial osteoblast, and on OB1, a newly established osteoblastic cell line. We show that FGF signaling has a dual effect on osteoblast proliferation and differentiation. FGFs activate the endogenous FGFRs leading to the formation of a Grb2/FRS2/Shp2 complex and activation of MAP kinase. However, immature osteoblasts respond to FGF treatment with increased proliferation, whereas in differentiating cells FGF does not induce DNA synthesis but causes apoptosis. When either primary or OB1 osteoblasts are induced to differentiate, FGF signaling inhibits expression of alkaline phosphatase, and blocks mineralization. To study the effect of craniosynostosis-linked mutations in osteoblasts, we introduced FGFR2 carrying either the C342Y (Crouzon syndrome) or the S252W (Apert syndrome) mutation in OB1 cells. Both mutations inhibited differentiation, while dramatically inducing apoptosis. Furthermore, we could also show that overexpression of FGF2 in transgenic mice leads to increased apoptosis in their calvaria. These data provide the first biochemical analysis of FGF signaling in osteoblasts, and show that FGF can act as a cell death inducer with distinct effects in proliferating and differentiating osteoblasts. PMID:10851026

O-GlcNAc in cancer: An Oncometabolism-fueled vicious cycle.

PubMed

Hanover, John A; Chen, Weiping; Bond, Michelle R

2018-06-01

Cancer cells exhibit unregulated growth, altered metabolism, enhanced metastatic potential and altered cell surface glycans. Fueled by oncometabolism and elevated uptake of glucose and glutamine, the hexosamine biosynthetic pathway (HBP) sustains glycosylation in the endomembrane system. In addition, the elevated pools of UDP-GlcNAc drives the O-GlcNAc modification of key targets in the cytoplasm, nucleus and mitochondrion. These targets include transcription factors, kinases, key cytoplasmic enzymes of intermediary metabolism, and electron transport chain complexes. O-GlcNAcylation can thereby alter epigenetics, transcription, signaling, proteostasis, and bioenergetics, key 'hallmarks of cancer'. In this review, we summarize accumulating evidence that many cancer hallmarks are linked to dysregulation of O-GlcNAc cycling on cancer-relevant targets. We argue that onconutrient and oncometabolite-fueled elevation increases HBP flux and triggers O-GlcNAcylation of key regulatory enzymes in glycolysis, Kreb's cycle, pentose-phosphate pathway, and the HBP itself. The resulting rerouting of glucose metabolites leads to elevated O-GlcNAcylation of oncogenes and tumor suppressors further escalating elevation in HBP flux creating a 'vicious cycle'. Downstream, elevated O-GlcNAcylation alters DNA repair and cellular stress pathways which influence oncogenesis. The elevated steady-state levels of O-GlcNAcylated targets found in many cancers may also provide these cells with a selective advantage for sustained growth, enhanced metastatic potential, and immune evasion in the tumor microenvironment.

Pervasive hydrologic effects on freshwater mussels and riparian trees in southeastern floodplain ecosystems

Treesearch

Andrew L. Rypel; Wendell R. Haag; Robert H. Findlay

2009-01-01

We present long-term growth trends for 13 freshwater mussel species from two unregulated rivers and one regulated river in the southeastern U.S. Coastal Plain. We also collected baldcypress (Taxodium distichum (L.) Rich.) tree cores adjacent to mussel collection sites in one river and directly compared tree and mussel chronologies in this river. To extend our analysis...

The role, practice and training of unregulated birth workers in Australia: A mixed methods study.

PubMed

Rigg, Elizabeth C; Schmied, Virginia; Peters, Kath; Dahlen, Hannah G

2018-05-23

In Australia, the provision of homebirth services by unregulated birthworkers (doulas, ex-registered midwives, traditional midwives and lay workers) has increased. Accessing a homebirth with a registered midwife via mainstream services is limited. Concern is growing that new legislation aimed at prohibiting unregulated birthworkers practice may result in homebirth going underground. To explore the role, practice and training of unregulated birthworkers in Australian and establish what they would do if legislation prohibited their practice. This study used a mixed methods sequential exploratory design to explore the practice, training and role of unregulated birthworkers in Australia. In phase one, four unregulated birthworkers were interviewed in-depth and the findings informed the development of a survey in phase two. This was distributed nationally through two consumer websites, social media, Facebook and email. Data from both phases were integrated. Unregulated birthworkers in Australia provide homebirth services to women with high and low-risk pregnancies when this choice is unavailable or unacceptable within mainstream services. They operate covertly to protect their practice and avoid the scrutiny of authorities. Unregulated birthworkers can be experienced and trained in childbirth care and practice, much like a midwife working within a holistic paradigm of care. Unregulated birthworkers believe they provide women with the homebirth service they want but cannot access. Mainstream service providers need to listen to consumer criticisms, as women seek answers outside the system. Change is needed to improve and align services with women's expectations of homebirth. Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Disruption of the A-Kinase Anchoring Domain in Flagellar Radial Spoke Protein 3 Results in Unregulated Axonemal cAMP-dependent Protein Kinase Activity and Abnormal Flagellar Motility

PubMed Central

Gaillard, Anne R.; Fox, Laura A.; Rhea, Jeanne M.; Craige, Branch

2006-01-01

Biochemical studies of Chlamydomonas flagellar axonemes revealed that radial spoke protein (RSP) 3 is an A-kinase anchoring protein (AKAP). To determine the physiological role of PKA anchoring in the axoneme, an RSP3 mutant, pf14, was transformed with an RSP3 gene containing a mutation in the PKA-binding domain. Analysis of several independent transformants revealed that the transformed cells exhibit an unusual phenotype: a fraction of the cells swim normally; the remainder of the cells twitch feebly or are paralyzed. The abnormal/paralyzed motility is not due to an obvious deficiency of radial spoke assembly, and the phenotype cosegregates with the mutant RSP3. We postulated that paralysis was due to failure in targeting and regulation of axonemal cAMP-dependent protein kinase (PKA). To test this, reactivation experiments of demembranated cells were performed in the absence or presence of PKA inhibitors. Importantly, motility in reactivated cell models mimicked the live cell phenotype with nearly equal fractions of motile and paralyzed cells. PKA inhibitors resulted in a twofold increase in the number of motile cells, rescuing paralysis. These results confirm that flagellar RSP3 is an AKAP and reveal that a mutation in the PKA binding domain results in unregulated axonemal PKA activity and inhibition of normal motility. PMID:16571668

Presentations from the Fourth Unregulated Contaminant Monitoring Rule (UCMR 4) Methods Stakeholder Meeting on May 15, 2013

EPA Pesticide Factsheets

This document contains the presentations from the Unregulated Contaminant Monitoring Rule 4 Methods Stakeholder Meeting held on May 15, 2013 about the Contaminant Candidate List (CCL) and the Unregulated Contaminant Monitoring Rule.

Temporal and spatial scales of geomorphic adjustments to reduced competency following flow regulation in bedload-dominated systems

NASA Astrophysics Data System (ADS)

Curtis, Katherine E.; Renshaw, Carl E.; Magilligan, Francis J.; Dade, William B.

2010-05-01

Because of the combined effects of reduced sediment transport capacity and competency following flow regulation, morphological changes are expected to occur in channels downstream from dams and, specifically, at tributary junctions where local inputs of water and sediment occur. Using a combination of historical aerial photographs, mainstem- and tributary-channel pebble counts, and HEC-RAS flow modeling for two watersheds in south-central VT, one unregulated and the other regulated since 1961, we document the time series of post-regulation channel narrowing and associated bar growth due to the influx of tributary sediment. Channel adjustments at regulated tributary junctions have been significant in ca. 50 years following impoundment, with channels downstream of the confluences narrowing over 15% after an initial ca. 20-year lag before the onset of accelerated narrowing. Moreover, flow modeling suggests that downstream of regulated confluences, the modern median grain size ( d50) along the channel bed is immobile. No significant channel narrowing has occurred either above or below unregulated tributary junctions or on the mainstem upstream of regulated confluences. However, greater channel sediment fining is observed upstream of regulated confluences than above unregulated confluences. Thus, the primary mode of mainstem channel adjustment differs up- and downstream of regulated tributaries. These confluence effects have occurred where the tributary drainage area is only 0.2 times that of the mainstem, well below the threshold ratio of 0.6 required for significant geomorphic effects at unregulated confluences, highlighting the geomorphic scale shift of dams. Lastly, we evaluate the downstream length required for a river to recover from the impacts of impoundment and demonstrate that even distal locations are impacted by flow regulation. Unlike the impacts of flow regulation in the western US where channel incision and bar erosion predominate following impoundment, we find that in situations where bed incision is minimal and where sediment loads are low but bed caliber high, bar growth and channel narrowing are significant adjustments at tributary junctions following impoundment. Therefore, at our sites the effects of dams on reduced competency may be more profound than on reduced sediment transport capacity, highlighting the importance of geologic and geomorphic settings in understanding fluvial responses to impoundment.

High-Throughput Cancer Cell Sphere Formation for 3D Cell Culture.

PubMed

Chen, Yu-Chih; Yoon, Euisik

2017-01-01

Three-dimensional (3D) cell culture is critical in studying cancer pathology and drug response. Though 3D cancer sphere culture can be performed in low-adherent dishes or well plates, the unregulated cell aggregation may skew the results. On contrary, microfluidic 3D culture can allow precise control of cell microenvironments, and provide higher throughput by orders of magnitude. In this chapter, we will look into engineering innovations in a microfluidic platform for high-throughput cancer cell sphere formation and review the implementation methods in detail.

Hands on Stem Cells: How to Make the Elusive Science of Stem Cells Tangible for the Classroom

ERIC Educational Resources Information Center

Sanderson, Aimee

2010-01-01

With new technologies developing so fast, it is difficult for students and teachers alike to keep up to date. Add into the mix skewed media reporting, some creative science fiction films and the unregulated world of the internet, and it becomes increasingly hard to separate fact from fiction. As Australia's largest funding body for stem cell…

School Choice in a Post-Desegregation World

ERIC Educational Resources Information Center

Cobb, Casey D.; Glass, Gene V.

2009-01-01

In contrast to unregulated school choice, regulated choice programs oversee the assignment of students to schools with equity in mind. This article puts forth evidence for three claims with respect to unregulated and regulated school choice: (c) Unregulated choice plans tend to exacerbate the stratification of students along race, class, and…

Activation pathway of Src kinase reveals intermediate states as novel targets for drug design

PubMed Central

Shukla, Diwakar; Meng, Yilin; Roux, Benoît; Pande, Vijay S.

2014-01-01

Unregulated activation of Src kinases leads to aberrant signaling, uncontrolled growth, and differentiation of cancerous cells. Reaching a complete mechanistic understanding of large scale conformational transformations underlying the activation of kinases could greatly help in the development of therapeutic drugs for the treatment of these pathologies. In principle, the nature of conformational transition could be modeled in silico via atomistic molecular dynamics simulations, although this is very challenging due to the long activation timescales. Here, we employ a computational paradigm that couples transition pathway techniques and Markov state model-based massively distributed simulations for mapping the conformational landscape of c-src tyrosine kinase. The computations provide the thermodynamics and kinetics of kinase activation for the first time, and help identify key structural intermediates. Furthermore, the presence of a novel allosteric site in an intermediate state of c-src that could be potentially utilized for drug design is predicted. PMID:24584478

Techniques for estimating peak-streamflow frequency for unregulated streams and streams regulated by small floodwater retarding structures in Oklahoma

USGS Publications Warehouse

Tortorelli, Robert L.

1997-01-01

Statewide regression equations for Oklahoma were determined for estimating peak discharge and flood frequency for selected recurrence intervals from 2 to 500 years for ungaged sites on natural unregulated streams. The most significant independent variables required to estimate peak-streamflow frequency for natural unregulated streams in Oklahoma are contributing drainage area, main-channel slope, and mean-annual precipitation. The regression equations are applicable for watersheds with drainage areas less than 2,510 square miles that are not affected by regulation from manmade works. Limitations on the use of the regression relations and the reliability of regression estimates for natural unregulated streams are discussed. Log-Pearson Type III analysis information, basin and climatic characteristics, and the peak-stream-flow frequency estimates for 251 gaging stations in Oklahoma and adjacent states are listed. Techniques are presented to make a peak-streamflow frequency estimate for gaged sites on natural unregulated streams and to use this result to estimate a nearby ungaged site on the same stream. For ungaged sites on urban streams, an adjustment of the statewide regression equations for natural unregulated streams can be used to estimate peak-streamflow frequency. For ungaged sites on streams regulated by small floodwater retarding structures, an adjustment of the statewide regression equations for natural unregulated streams can be used to estimate peak-streamflow frequency. The statewide regression equations are adjusted by substituting the drainage area below the floodwater retarding structures, or drainage area that represents the percentage of the unregulated basin, in the contributing drainage area parameter to obtain peak-streamflow frequency estimates.

Use of Normal Human Colon Cells to Assess Toxicities of Unregulated Disinfection By-products and Mixtures

EPA Science Inventory

The discovery of chlorination and chloramination by-products other than the regulated trihalomethanes and haloacetic acids has created a need for short-term in vitro assays to address toxicities that might be associated with human exposure. Approximately 600 disinfection by-produ...

Stabilizing in vitro ultrasound-mediated gene transfection by regulating cavitation.

PubMed

Lo, Chia-Wen; Desjouy, Cyril; Chen, Shing-Ru; Lee, Jyun-Lin; Inserra, Claude; Béra, Jean-Christophe; Chen, Wen-Shiang

2014-03-01

It is well known that acoustic cavitation can facilitate the inward transport of genetic materials across cell membranes (sonoporation). However, partially due to the unstationary behavior of the initiation and leveling of cavitation, the sonoporation effect is usually unstable, especially in low intensity conditions. A system which is able to regulate the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop is implemented and its effect on in vitro gene transfection is tested. The regulated system provided better time stability and reproducibility of the cavitation levels than the unregulated conditions. Cultured hepatoma cells (BNL) mixed with 10 μg luciferase plasmids are exposed to 1-MHz pulsed ultrasound with or without cavitation regulation, and the gene transfection efficiency and cell viability are subsequently assessed. Experimental results show that for all exposure intensities (low, medium, and high), stable and intensity dependent, although not higher, gene expression could be achieved in the regulated cavitation system than the unregulated conditions. The cavitation regulation system provides a better control of cavitation and its bioeffect which are crucial important for clinical applications of ultrasound-mediated gene transfection. Copyright © 2013 Elsevier B.V. All rights reserved.

Unregulated provider perceptions of audit and feedback reports in long-term care: cross-sectional survey findings from a quality improvement intervention.

PubMed

Fraser, Kimberly D; O'Rourke, Hannah M; Baylon, Melba Andrea B; Boström, Anne-Marie; Sales, Anne E

2013-02-13

Audit with feedback is a moderately effective approach for improving professional practice in other health care settings. Although unregulated caregivers give the majority of direct care in long-term care settings, little is known about how they understand and perceive feedback reports because unregulated providers have not been directly targeted to receive audit with feedback in quality improvement interventions in long-term care. The purpose of this paper is to describe unregulated care providers' perceptions of usefulness of a feedback report in four Canadian long-term care facilities. We delivered monthly feedback reports to unregulated care providers for 13 months in 2009-2010. The feedback reports described a unit's performance in relation to falls, depression, and pain as compared to eight other units in the study. Follow-up surveys captured participant perceptions of the feedback report. We conducted descriptive analyses of the variables related to participant perceptions and multivariable logistic regression to assess the association between perceived usefulness of the feedback report and a set of independent variables. The vast majority (80%) of unregulated care providers (n = 171) who responded said they understood the reports. Those who discussed the report with others and were interested in other forms of data were more likely to find the feedback report useful for making changes in resident care. This work suggests that unregulated care providers can understand and feel positively about using audit with feedback reports to make changes to resident care. Further research should explore ways to promote fuller engagement of unregulated care providers in decision-making to improve quality of care in long-term care settings.

Unregulated provider perceptions of audit and feedback reports in long-term care: cross-sectional survey findings from a quality improvement intervention

PubMed Central

2013-01-01

Background Audit with feedback is a moderately effective approach for improving professional practice in other health care settings. Although unregulated caregivers give the majority of direct care in long-term care settings, little is known about how they understand and perceive feedback reports because unregulated providers have not been directly targeted to receive audit with feedback in quality improvement interventions in long-term care. The purpose of this paper is to describe unregulated care providers’ perceptions of usefulness of a feedback report in four Canadian long-term care facilities. Methods We delivered monthly feedback reports to unregulated care providers for 13 months in 2009–2010. The feedback reports described a unit’s performance in relation to falls, depression, and pain as compared to eight other units in the study. Follow-up surveys captured participant perceptions of the feedback report. We conducted descriptive analyses of the variables related to participant perceptions and multivariable logistic regression to assess the association between perceived usefulness of the feedback report and a set of independent variables. Results The vast majority (80%) of unregulated care providers (n = 171) who responded said they understood the reports. Those who discussed the report with others and were interested in other forms of data were more likely to find the feedback report useful for making changes in resident care. Conclusions This work suggests that unregulated care providers can understand and feel positively about using audit with feedback reports to make changes to resident care. Further research should explore ways to promote fuller engagement of unregulated care providers in decision-making to improve quality of care in long-term care settings. PMID:23402382

Human Health Risk Assessment Applied to Rural Populations Dependent on Unregulated Drinking Water Sources: A Scoping Review.

PubMed

Ford, Lorelei; Bharadwaj, Lalita; McLeod, Lianne; Waldner, Cheryl

2017-07-28

Safe drinking water is a global challenge for rural populations dependent on unregulated water. A scoping review of research on human health risk assessments (HHRA) applied to this vulnerable population may be used to improve assessments applied by government and researchers. This review aims to summarize and describe the characteristics of HHRA methods, publications, and current literature gaps of HHRA studies on rural populations dependent on unregulated or unspecified drinking water. Peer-reviewed literature was systematically searched (January 2000 to May 2014) and identified at least one drinking water source as unregulated (21%) or unspecified (79%) in 100 studies. Only 7% of reviewed studies identified a rural community dependent on unregulated drinking water. Source water and hazards most frequently cited included groundwater (67%) and chemical water hazards (82%). Most HHRAs (86%) applied deterministic methods with 14% reporting probabilistic and stochastic methods. Publications increased over time with 57% set in Asia, and 47% of studies identified at least one literature gap in the areas of research, risk management, and community exposure. HHRAs applied to rural populations dependent on unregulated water are poorly represented in the literature even though almost half of the global population is rural.

Human Health Risk Assessment Applied to Rural Populations Dependent on Unregulated Drinking Water Sources: A Scoping Review

PubMed Central

Ford, Lorelei; Bharadwaj, Lalita; McLeod, Lianne; Waldner, Cheryl

2017-01-01

Safe drinking water is a global challenge for rural populations dependent on unregulated water. A scoping review of research on human health risk assessments (HHRA) applied to this vulnerable population may be used to improve assessments applied by government and researchers. This review aims to summarize and describe the characteristics of HHRA methods, publications, and current literature gaps of HHRA studies on rural populations dependent on unregulated or unspecified drinking water. Peer-reviewed literature was systematically searched (January 2000 to May 2014) and identified at least one drinking water source as unregulated (21%) or unspecified (79%) in 100 studies. Only 7% of reviewed studies identified a rural community dependent on unregulated drinking water. Source water and hazards most frequently cited included groundwater (67%) and chemical water hazards (82%). Most HHRAs (86%) applied deterministic methods with 14% reporting probabilistic and stochastic methods. Publications increased over time with 57% set in Asia, and 47% of studies identified at least one literature gap in the areas of research, risk management, and community exposure. HHRAs applied to rural populations dependent on unregulated water are poorly represented in the literature even though almost half of the global population is rural. PMID:28788087

Exhaust and evaporative emissions from motorcycles fueled with ethanol gasoline blends.

PubMed

Li, Lan; Ge, Yunshan; Wang, Mingda; Peng, Zihang; Song, Yanan; Zhang, Liwei; Yuan, Wanli

2015-01-01

The emission characteristics of motorcycles using gasoline and E10 (90% gasoline and 10% ethanol by volume) were investigated in this article. Exhaust and evaporative emissions of three motorcycles were investigated on the chassis dynamometer over the Urban Driving Cycle (UDC) and in the Sealed Housing for Evaporative Determination (SHED) including regulated and unregulated emissions. The regulated emissions were detected by an exhaust gas analyzer directly. The unregulated emissions including carbonyls and volatile organic compounds (VOCs) were sampled through battery-operated air pumps using tubes coated with 2,4-dinitrophenylhydrazine (DNPH) and Tenax TA, respectively. The experimental results showed that the emission factors of total hydrocarbons (THC) and carbon monoxide (CO) from E10 fueling motorcycles decreased by 26%-45% and 63%-73%, while the emission factor of NOx increased by 36%-54% compared with those from gasoline fueling motorcycles. For unregulated emissions, the emission amount of VOCs from motorcycles fueled with E10 decreased by 18%-31% while total carbonyls were 2.6-4.5 times higher than those for gasoline. For evaporative emissions of THC and VOCs, for gasoline or E10, the diurnal breathing loss (DBL) was higher than hot soak loss (HSL). Using E10 as a fuel does not make much difference in the amount of evaporative THC, while resulted in a slightly growth of 14%-17% for evaporative BETX (benzene, toluene, ethylbenzene, xylene). Copyright © 2014 Elsevier B.V. All rights reserved.

Assessing the Toxicities of Regulated and Unregulated Disinfection By-products in Normal Human Colon Cells.

EPA Science Inventory

The presence of over six hundred disinfection by-products (DBPs) and less than half of the total organic halides present in finished water has created a need for short-term in vitro assays to address toxicities that might be associated with human exposure. . We are using a normal...

DEVELOPMENT OF NORMAL HUMAN COLON CELL CULTURES TO IDENTIFY UNREGULATED DISINFECTION BY-PRODUCTS (DBPS) WITH CARCINOGENIC POTENTIAL.

EPA Science Inventory

Epidemiological studies have linked the consumption of chlorinated surface waters to an increased risk of colorectal cancer. Approximately 600 DBPs, less than half of the total organic carbon in drinking water have been identified. We are developing an in vitro system to i...

The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus.

PubMed

Luebke, Justin L; Shen, Jiangchuan; Bruce, Kevin E; Kehl-Fie, Thomas E; Peng, Hui; Skaar, Eric P; Giedroc, David P

2014-12-01

How cells regulate the bioavailability of utilizable sulfur while mitigating the effects of hydrogen sulfide toxicity is poorly understood. CstR [Copper-sensing operon repressor (CsoR)-like sulfurtransferase repressor] represses the expression of the cst operon encoding a putative sulfide oxidation system in Staphylococcus aureus. Here, we show that the cst operon is strongly and transiently induced by cellular sulfide stress in an acute phase and specific response and that cst-encoded genes are necessary to mitigate the effects of sulfide toxicity. Growth defects are most pronounced when S. aureus is cultured in chemically defined media with thiosulfate (TS) as a sole sulfur source, but are also apparent when cystine is used or in rich media. Under TS growth conditions, cells fail to grow as a result of either unregulated expression of the cst operon in a ΔcstR strain or transformation with a non-inducible C31A/C60A CstR that blocks cst induction. This suggests that the cst operon contributes to cellular sulfide homeostasis. Tandem high-resolution mass spectrometry reveals derivatization of CstR by both inorganic tetrasulfide and an organic persulfide, glutathione persulfide, to yield a mixture of Cys31-Cys60' interprotomer cross-links, including di-, tri- and tetrasulfide bonds, which allosterically inhibit cst operator DNA binding by CstR. © 2014 John Wiley & Sons Ltd.

The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus

PubMed Central

Luebke, Justin L.; Shen, Jiangchuan; Bruce, Kevin E.; Kehl-Fie, Thomas E.; Peng, Hui; Skaar, Eric P.; Giedroc, David P.

2014-01-01

How cells regulate the bioavailability of utilizable sulfur while mitigating the effects of hydrogen sulfide toxicity is poorly understood. CstR (Copper-sensing operon repressor (CsoR)-like sulfurtransferase repressor) represses the expression of the cst operon encoding a putative sulfide oxidation system in Staphylococcus aureus. Here, we show that the cst operon is strongly and transiently induced by cellular sulfide stress in an acute phase and specific response and that cst-encoded genes are necessary to mitigate the effects of sulfide toxicity. Growth defects are most pronounced when S. aureus is cultured in chemically defined media with thiosulfate (TS) as a sole sulfur source, but are also apparent when cystine is used or in rich media. Under TS growth conditions, cells fail to grow as a result of either unregulated expression of the cst operon in a ΔcstR strain or transformation with a non-inducible C31A/C60A CstR that blocks cst induction. This suggests that the cst operon contributes to cellular sulfide homeostasis. Tandem high resolution mass spectrometry reveals derivatization of CstR by both inorganic tetrasulfide and an organic persulfide, glutathione persulfide, to yield a mixture of Cys31-Cys60’ interprotomer crosslinks, including di-, tri- and tetrasulfide bonds, which allosterically inhibit cst operator DNA binding by CstR. PMID:25318663

Drinking water disinfection byproduct iodoacetic acid induces tumorigenic transformation of NIH3T3 cells.

PubMed

Wei, Xiao; Wang, Shu; Zheng, Weiwei; Wang, Xia; Liu, Xiaolin; Jiang, Songhui; Pi, Jingbo; Zheng, Yuxin; He, Gengsheng; Qu, Weidong

2013-06-04

Iodoacetic acid (IAA) and iodoform (IF) are unregulated iodinated disinfection byproducts (DBPs) found in drinking water. Their presence in the drinking water of China has not been documented. Recently, the carcinogenic potential of IAA and IF has been a concern because of their mutagenicity in bacteria and genotoxicity in mammalian cells. Therefore, we measured their concentrations in Shanghai drinking water and assessed their cytotoxicity, genotoxicity, and ability to transform NIH3T3 cells to tumorigenic lines. The concentrations of IAA and IF in Shanghai drinking water varied between summer and winter with maximum winter levels of 2.18 μg/L IAA and 0.86 μg/L IF. IAA with a lethal concentration 50 (LC50) of 2.77 μM exhibited more potent cytotoxicity in NIH3T3 cells than IF (LC50 = 83.37 μM). IAA, but not IF, induced a concentration-dependent DNA damage measured by γ-H2AX staining and increased tail moment in single-cell gel electrophoresis. Neither IAA nor IF increased micronucleus frequency. Prolonged exposure of NIH3T3 cells to IAA increased the frequencies of transformed cells with anchorage-independent growth and agglutination with concanavalin A. IAA-transformed cells formed aggressive fibrosarcomas after inoculation into Balb/c nude mice. This study demonstrated that IAA has a biological activity that is consistent with a carcinogen and human exposure should be of concern.

Using Age-Based Life History Data to Investigate the Life Cycle and Vulnerability of Octopus cyanea

PubMed Central

Herwig, Jade N.; Depczynski, Martial; Roberts, John D.; Semmens, Jayson M.; Gagliano, Monica; Heyward, Andrew J.

2012-01-01

Octopus cyanea is taken as an unregulated, recreationally fished species from the intertidal reefs of Ningaloo, Western Australia. Yet despite its exploitation and importance in many artisanal fisheries throughout the world, little is known about its life history, ecology and vulnerability. We used stylet increment analysis to age a wild O. cyanea population for the first time and gonad histology to examine their reproductive characteristics. O. cyanea conforms to many cephalopod life history generalisations having rapid, non-asymptotic growth, a short life-span and high levels of mortality. Males were found to mature at much younger ages and sizes than females with reproductive activity concentrated in the spring and summer months. The female dominated sex-ratios in association with female brooding behaviours also suggest that larger conspicuous females may be more prone to capture and suggests that this intertidal octopus population has the potential to be negatively impacted in an unregulated fishery. Size at age and maturity comparisons between our temperate bordering population and lower latitude Tanzanian and Hawaiian populations indicated stark differences in growth rates that correlate with water temperatures. The variability in life history traits between global populations suggests that management of O. cyanea populations should be tailored to each unique set of life history characteristics and that stylet increment analysis may provide the integrity needed to accurately assess this. PMID:22912898

Streamflow statistics for unregulated and regulated conditions for selected locations on the Yellowstone, Tongue, and Powder Rivers, Montana, 1928-2002

USGS Publications Warehouse

Chase, Katherine J.

2013-01-01

Major floods in 1996 and 1997 on the Yellowstone River in Montana intensified public debate over the effects of human activities on the Yellowstone River. In 1999, the Yellowstone River Conservation District Council was formed to address conservation issues on the river. The Yellowstone River Conservation District Council partnered with the U.S. Army Corps of Engineers to conduct a cumulative-effects study on the main stem of the Yellowstone River. The cumulative-effects study is intended to provide a basis for future management decisions in the watershed. Streamflow statistics, such as flow-frequency and flow-duration data calculated for unregulated and regulated streamflow conditions, are a necessary component of the cumulative effects study. The U.S. Geological Survey, in cooperation with the Yellowstone River Conservation District Council and the U.S. Army Corps of Engineers, calculated streamflow statistics for unregulated and regulated conditions for the Yellowstone, Tongue, and Powder Rivers for the 1928–2002 study period. Unregulated streamflow represents flow conditions that might have occurred during the 1928–2002 study period if there had been no water-resources development in the Yellowstone River Basin. Regulated streamflow represents estimates of flow conditions during the 1928–2002 study period if the level of water-resources development existing in 2002 was in place during the entire study period. Peak-flow frequency estimates for regulated and unregulated streamflow were developed using methods described in Bulletin 17B. High-flow frequency and low-flow frequency data were developed for regulated and unregulated streamflows from the annual series of highest and lowest (respectively) mean flows for specified n-day consecutive periods within the calendar year. Flow-duration data, and monthly and annual streamflow characteristics, also were calculated for the unregulated and regulated streamflows.

Fibroblast growth factor (FGF) signaling in development and skeletal diseases.

PubMed

Teven, Chad M; Farina, Evan M; Rivas, Jane; Reid, Russell R

2014-12-01

Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.

Fibroblast growth factor (FGF) signaling in development and skeletal diseases

PubMed Central

Teven, Chad M.; Farina, Evan M.; Rivas, Jane; Reid, Russell R.

2014-01-01

Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development. PMID:25679016

Distinct Molecular Events during Secretory Granule Biogenesis Revealed by Sensitivities to Brefeldin A

PubMed Central

Fernandez, Carlos J.; Haugwitz, Michael; Eaton, Benjamin; Moore, Hsiao-Ping H.

1997-01-01

The biogenesis of peptide hormone secretory granules involves a series of sorting, modification, and trafficking steps that initiate in the trans-Golgi and trans-Golgi network (TGN). To investigate their temporal order and interrelationships, we have developed a pulse–chase protocol that follows the synthesis and packaging of a sulfated hormone, pro-opiomelanocortin (POMC). In AtT-20 cells, sulfate is incorporated into POMC predominantly on N-linked endoglycosidase H-resistant oligosaccharides. Subcellular fractionation and pharmacological studies confirm that this sulfation occurs at the trans-Golgi/TGN. Subsequent to sulfation, POMC undergoes a number of molecular events before final storage in dense-core granules. The first step involves the transfer of POMC from the sulfation compartment to a processing compartment (immature secretory granules, ISGs): Inhibiting export of pulse-labeled POMC by brefeldin A (BFA) or a 20°C block prevents its proteolytic conversion to mature adrenocorticotropic hormone. Proteolytic cleavage products were found in vesicular fractions corresponding to ISGs, suggesting that the processing machinery is not appreciably activated until POMC exits the sulfation compartment. A large portion of the labeled hormone is secreted from ISGs as incompletely processed intermediates. This unregulated secretory process occurs only during a limited time window: Granules that have matured for 2 to 3 h exhibit very little unregulated release, as evidenced by the efficient storage of the 15-kDa N-terminal fragment that is generated by a relatively late cleavage event within the maturing granule. The second step of granule biogenesis thus involves two maturation events: proteolytic activation of POMC in ISGs and a transition of the organelle from a state of high unregulated release to one that favors intracellular storage. By using BFA, we show that the two processes occurring in ISGs may be uncoupled: although the unregulated secretion from ISGs is impaired by BFA, proteolytic processing of POMC within this organelle proceeds unaffected. The finding that BFA impairs constitutive secretion from both the TGN and ISGs also suggests that these secretory processes may be related in mechanism. Finally, our data indicate that the unusually high levels of unregulated secretion often associated with endocrine tumors may result, at least in part, from inefficient storage of secretory products at the level of ISGs. PMID:9362061

Distinct molecular events during secretory granule biogenesis revealed by sensitivities to brefeldin A.

PubMed

Fernandez, C J; Haugwitz, M; Eaton, B; Moore, H P

1997-11-01

The biogenesis of peptide hormone secretory granules involves a series of sorting, modification, and trafficking steps that initiate in the trans-Golgi and trans-Golgi network (TGN). To investigate their temporal order and interrelationships, we have developed a pulse-chase protocol that follows the synthesis and packaging of a sulfated hormone, pro-opiomelanocortin (POMC). In AtT-20 cells, sulfate is incorporated into POMC predominantly on N-linked endoglycosidase H-resistant oligosaccharides. Subcellular fractionation and pharmacological studies confirm that this sulfation occurs at the trans-Golgi/TGN. Subsequent to sulfation, POMC undergoes a number of molecular events before final storage in dense-core granules. The first step involves the transfer of POMC from the sulfation compartment to a processing compartment (immature secretory granules, ISGs): Inhibiting export of pulse-labeled POMC by brefeldin A (BFA) or a 20 degrees C block prevents its proteolytic conversion to mature adrenocorticotropic hormone. Proteolytic cleavage products were found in vesicular fractions corresponding to ISGs, suggesting that the processing machinery is not appreciably activated until POMC exits the sulfation compartment. A large portion of the labeled hormone is secreted from ISGs as incompletely processed intermediates. This unregulated secretory process occurs only during a limited time window: Granules that have matured for 2 to 3 h exhibit very little unregulated release, as evidenced by the efficient storage of the 15-kDa N-terminal fragment that is generated by a relatively late cleavage event within the maturing granule. The second step of granule biogenesis thus involves two maturation events: proteolytic activation of POMC in ISGs and a transition of the organelle from a state of high unregulated release to one that favors intracellular storage. By using BFA, we show that the two processes occurring in ISGs may be uncoupled: although the unregulated secretion from ISGs is impaired by BFA, proteolytic processing of POMC within this organelle proceeds unaffected. The finding that BFA impairs constitutive secretion from both the TGN and ISGs also suggests that these secretory processes may be related in mechanism. Finally, our data indicate that the unusually high levels of unregulated secretion often associated with endocrine tumors may result, at least in part, from inefficient storage of secretory products at the level of ISGs.

Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response.

PubMed

Delledonne, M; Zeier, J; Marocco, A; Lamb, C

2001-11-06

Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles in the activation of disease resistance mechanisms both in animals and plants. In animals NO cooperates with ROIs to kill tumor cells and for macrophage killing of bacteria. Such cytotoxic events occur because unregulated NO levels drive a diffusion-limited reaction with O(2)(-) to generate peroxynitrite (ONOO(-)), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after interaction of NO not with O(2)- but with H(2)O(2) generated from O(2)(-) by superoxide dismutase. Increasing the level of O(2)(-) reduces NO-mediated toxicity, and ONOO(-) is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O(2)(-) dismutation to H(2)O(2) to minimize the loss of NO by reaction with O(2)(-) and to trigger hypersensitive cell death through NO/H(2)O(2) cooperation. However, O(2)(-) rather than H(2)O(2) is the primary ROI signal for pathogen induction of glutathione S-transferase, and the rates of production and dismutation of O(2)(-) generated during the oxidative burst play a crucial role in the modulation and integration of NO/H(2)O(2) signaling in the HR. Thus although plants and animals use a similar repertoire of signals in disease resistance, ROIs and NO are deployed in strikingly different ways to trigger host cell death.

Proposed Fourth Unregulated Contaminant Monitoring Rule (UCMR 4) Meeting Presentations

EPA Pesticide Factsheets

This document contains the proposed Unregulated Contaminant Monitoring Rule (UCMR 4) Meeting Presentations from a public webinar held by EPA's Office of Ground Water and Drinking Water on January 13, 2016.

Combining Anti-ERBB3 Antibodies Specific for Domain I and Domain III Enhances the Anti-Tumor Activity over the Individual Monoclonal Antibodies

PubMed Central

D’Souza, Jimson W.; Shchaveleva, Irina; Marks, James D.; Litwin, Samuel; Robinson, Matthew K.

2014-01-01

Background Inappropriate signaling through the epidermal growth factor receptor family (EGFR1/ERBB1, ERBB2/HER2, ERBB3/HER3, and ERBB4/HER4) of receptor tyrosine kinases leads to unregulated activation of multiple downstream signaling pathways that are linked to cancer formation and progression. In particular, ERBB3 plays a critical role in linking ERBB signaling to the phosphoinositide 3-kinase and Akt signaling pathway and increased levels of ERBB3-dependent signaling is also increasingly recognized as a mechanism for acquired resistance to ERBB-targeted therapies. Methods We had previously reported the isolation of a panel of anti-ERBB3 single-chain Fv antibodies through use of phage-display technology. In the current study scFv specific for domain I (F4) and domain III (A5) were converted into human IgG1 formats and analyzed for efficacy. Results Treatment of cells with an oligoclonal mixture of the A5/F4 IgGs appeared more effective at blocking both ligand-induced and ligand-independent signaling through ERBB3 than either single IgG alone. This correlated with improved ability to inhibit the cell growth both as a single agent and in combination with other ERBB-targeted therapies. Treatment of NCI-N87 tumor xenografts with the A5/F4 oligoclonal led to a statistically significant decrease in tumor growth rate that was further enhanced in combination with trastuzumab. Conclusion These results suggest that an oligoclonal antibody mixture may be a more effective approach to downregulate ERBB3-dependent signaling. PMID:25386657

Elevated Arsenic and Uranium Concentrations in Unregulated Water Sources on the Navajo Nation, USA.

PubMed

Hoover, Joseph; Gonzales, Melissa; Shuey, Chris; Barney, Yolanda; Lewis, Johnnye

2017-01-01

Regional water pollution and use of unregulated water sources can be an important mixed metals exposure pathway for rural populations located in areas with limited water infrastructure and an extensive mining history. Using censored data analysis and mapping techniques we analyzed the joint geospatial distribution of arsenic and uranium in unregulated water sources throughout the Navajo Nation, where over 500 abandoned uranium mine sites are located in the rural southwestern United States. Results indicated that arsenic and uranium concentrations exceeded national drinking water standards in 15.1 % (arsenic) and 12.8 % (uranium) of tested water sources. Unregulated sources in close proximity (i.e., within 6 km) to abandoned uranium mines yielded significantly higher concentrations of arsenic or uranium than more distant sources. The demonstrated regional trends for potential co-exposure to these chemicals have implications for public policy and future research. Specifically, to generate solutions that reduce human exposure to water pollution from unregulated sources in rural areas, the potential for co-exposure to arsenic and uranium requires expanded documentation and examination. Recommendations for prioritizing policy and research decisions related to the documentation of existing health exposures and risk reduction strategies are also provided.

Learn About the Unregulated Contaminant Monitoring Rule

EPA Pesticide Factsheets

EPA uses the Unregulated Contaminant Monitoring program to collect data for contaminants suspected to be present in drinking water, but that do not have health-based standards set under the Safe Drinking Water Act (SDWA)

Occurrence Data for the Unregulated Contaminant Monitoring Rule

EPA Pesticide Factsheets

EPA uses the Unregulated Contaminant Monitoring Rule (UCMR) to collect data for contaminants suspected to be present in drinking water, but that do not have health-based standards set under the Safe Drinking Water Act (SDWA)

List of Laboratories Approved by EPA for the Fourth Unregulated Contaminant Monitoring Rule (UCMR 4)

EPA Pesticide Factsheets

This document provides a list of laboratories that met the Unregulated Contaminant Monitoring Rule 4 (UCMR 4) Laboratory Approval Program application and Proficiency Testing (PT) criteria for the methods indicated.

List of Laboratories Approved by EPA for the Third Unregulated Contaminant Monitoring Rule (UCMR 3)

EPA Pesticide Factsheets

This document provides a list of laboratories that met the Unregulated Contaminant Monitoring Rule 3 (UCMR 3) Laboratory Approval Program application and Proficiency Testing (PT) criteria for the methods indicated.

A historical overview of the electrical power systems in the US manned and some US unmanned spacecraft

NASA Technical Reports Server (NTRS)

Maisel, J. E.

1984-01-01

A historical overview of electrical power systems used in the U.S. manned spacecraft and some of the U.S. unmanned spacecraft is presented in this investigation. A time frame of approximately 25 years, the period for 1959 to 1984, is covered in this report. Results indicate that the nominal bus voltage was 28 volts dc in most spacecraft and all other voltage levels were derived from this voltage through such techniques as voltage inversion or rectification, or a combination. Most spacecraft used solar arrays for the main source of power except for those spacecraft that had a relatively short flight duration, or deep spaceprobes that were designed for very long flight duration. Fuel cells were used on Gemini, Apollo, and Space Shuttle (short duration flights) while radioisotope thermoelectric generators were employed on the Pioneer, Jupiter/Saturn, Viking Lander, and Voyager spacecraft (long duration flights). The main dc bus voltage was unregulated on the manned spacecraft with voltage regulation provided at the user loads. A combination of regulated, semiregulated, and unregulated buses were used on the unmanned spacecraft depending on the type of load. For example, scientific instruments were usually connected to regulated buses while fans, relays, etc. were energized from an unregulated bus. Different forms of voltage regulation, such as shunt, buck/boot, and pulse-width modulated regulators, were used. This report includes a comprehensive bibliography on spacecraft electrical power systems for the space programs investigated.

Revisions to the Fourth Unregulated Contaminant Monitoring Rule (UCMR 4) Meeting Presentations

EPA Pesticide Factsheets

This document contains the Revisions to the Unregulated Contaminant Monitoring Rule (UCMR 4) Meeting Presentations from a public meeting and webinar held by EPA's Office of Ground Water and Drinking Water on June 25, 2014.

Comparison of Special Group Experiences in Establishing Independent Motor Carrier Businesses : Volume 2. Main Text.

DOT National Transportation Integrated Search

1979-08-01

The report examines the experiences and special problems of minority trucking firms. The firms are classified as unregulated local truckers, unregulated owner-operators, and regulated interstate common carriers. Random samples are developed for minor...

Comparison of Special Group Experiences in Establishing Independent Motor Carrier Businesses : Volume 1. Executive Summary.

DOT National Transportation Integrated Search

1979-08-01

The report summarizes the experiences and special problems of minority trucking firms. The firms are classified as unregulated local truckers, unregulated owner-operators, and regulated interstate common carriers. Although the general findings reflec...

Development of EPA Method 525.3 for the Analysis of Semivolatiles in Drinking Water

EPA Science Inventory

The United States Environmental Protection Agency (EPA) Office of Ground Water and Drinking Water (OGWDW) collects nationwide occurrence data on contaminants in drinking water using the Unregulated Contaminant Monitoring Regulations (UCMRs). The unregulated contaminants, which ar...

Oxytocin--its role in male reproduction and new potential therapeutic uses.

PubMed

Thackare, Hemlata; Nicholson, Helen D; Whittington, Kate

2006-01-01

Oxytocin (OT) is traditionally thought of as a "female" neurohypophysis hormone due to its role in parturition and milk ejection. However, OT is recognized as having endocrine and paracrine roles in male reproduction. At ejaculation, a burst of OT is released from the neurohypophysis into the systemic circulation and stimulates contractions of the reproductive tract aiding sperm release. There is conclusive evidence that OT is synthesized within the mammalian testis, epididymis and prostate and the presence of OT receptors (OTRs) through the reproductive tract supports a local action for this peptide. OT has a paracrine role in stimulating contractility of the seminiferous tubules, epididymis and the prostate gland. Interestingly, OT has also been shown to modulate androgen levels in these tissues via stimulation of the conversion of testosterone to dihydrotestostone (DHT) by 5alpha-reductase. The elucidation of OT's role in male reproduction has suggested a number of potential therapeutic uses for this hormone. Exogenous administration of OT has, in some cases, been shown to increase the numbers of ejaculated sperm, possibly by stimulating contractions of the reproductive tract and thus aiding sperm passage. Within the prostate, OT has been shown to affect gland growth both directly and via its interaction with androgen metabolism. Prostate pathologies due to unregulated cell proliferation/growth, such as benign prostatic hyperplasia and cancer, are unfortunately very common and few effective treatments are available. Greater understanding of paracrine growth mediators, such as OT, is likely to provide new mechanisms for treating such pathologies.

Minireview: roles of the forkhead transcription factor FOXL2 in granulosa cell biology and pathology.

PubMed

Pisarska, Margareta D; Barlow, Gillian; Kuo, Fang-Ting

2011-04-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells.

Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology

PubMed Central

Barlow, Gillian; Kuo, Fang-Ting

2011-01-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells. PMID:21248146

The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression

PubMed Central

Mesplède, Thibault; Island, Marie-Laure; Christeff, Nicolas; Petek, Fahrettin; Doly, Janine; Navarro, Sébastien

2005-01-01

Alpha interferon (IFN-α) and IFN-β are able to interfere with viral infection. They exert a vast array of biologic functions, including growth arrest, cell differentiation, and immune system regulation. This regulation extends from innate immunity to cellular and humoral adaptive immune responses. A strict control of expression is needed to prevent detrimental effects of unregulated IFN. Multiple IFN-A subtypes are coordinately induced in human and mouse cells infected by virus and exhibit differences in expression of their individual mRNAs. We demonstrated that the weakly expressed IFN-A11 gene is negatively regulated after viral infection, due to a distal negative regulatory element, binding homeoprotein pituitary homeobox 1 (Pitx1). Here we show that the POU protein Oct-1 binds in vitro and in vivo to the IFN-A11 promoter and represses IFN-A expression upon interferon regulatory factor overexpression. Furthermore, we show that Oct-1-deficient MEFs exhibit increased in vivo IFN-A gene expression and increased antiviral activity. Finally, the IFN-A expression pattern is modified in Oct-1-deficient MEFs. The broad representation of effective and potent octamer-like sequences within IFN-A promoters suggests an important role for Oct-1 in IFN-A regulation. PMID:16166650

Apoptosis and microvessel density in gastric cancer: correlation with tumor stage and prognosis.

PubMed

Aurello, Paolo; Bellagamba, Riccardo; Rossi Del Monte, Simone; D'Angelo, Francesco; Nigri, Giuseppe; Cicchini, Claudia; Ravaioli, Matteo; Ramacciato, Giovanni

2009-12-01

Gastric cancer remains one of the most common human malignancies with a poor prognosis. Apoptosis is known to be a programmed cell death and its inhibition is involved in the unregulated cellular growth that leads to neoplasms. Microvessel density (MVD) has been investigated as a promoting factor for angiogenesis with conflicting results about its relation to survival. The aim of our study was to search a correlation between these factors and some clinicopathological features and prognosis. Identification of apoptotic cells was performed applying the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and recorded as apoptotic index (A.I.), whereas monoclonal antibodies were used for the study of MVD. A significant correlation was found between low and high A.I. and the subgroup of patients in Stages I and II (P < 0.02); 20 per cent of patients with a low A.I. showed an overall survival longer than 5 years versus 44 per cent of patients with an high A.I. (P = 0.041). High MVD was significantly related to the T stage (P = 0.036) and to a poorer 5-year overall survival (P < 0.05). Further studies are required to confirm the role of apoptosis and MVD in the development and progression of gastric cancer.

A Phytophthora sojae cytoplasmic effector mediates disease resistance and abiotic stress tolerance in Nicotiana benthamiana.

PubMed

Zhang, Meixiang; Ahmed Rajput, Nasir; Shen, Danyu; Sun, Peng; Zeng, Wentao; Liu, Tingli; Juma Mafurah, Joseph; Dou, Daolong

2015-06-03

Each oomycete pathogen encodes a large number of effectors. Some effectors can be used in crop disease resistance breeding, such as to accelerate R gene cloning and utilisation. Since cytoplasmic effectors may cause acute physiological changes in host cells at very low concentrations, we assume that some of these effectors can serve as functional genes for transgenic plants. Here, we generated transgenic Nicotiana benthamiana plants that express a Phytophthora sojae CRN (crinkling and necrosis) effector, PsCRN115. We showed that its expression did not significantly affect the growth and development of N. benthamiana, but significantly improved disease resistance and tolerance to salt and drought stresses. Furthermore, we found that expression of heat-shock-protein and cytochrome-P450 encoding genes were unregulated in PsCRN115-transgenic N. benthamiana based on digital gene expression profiling analyses, suggesting the increased plant defence may be achieved by upregulation of these stress-related genes in transgenic plants. Thus, PsCRN115 may be used to improve plant tolerance to biotic and abiotic stresses.

40 CFR 141.207 - Special notice of the availability of unregulated contaminant monitoring results.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Special notice of the availability of unregulated contaminant monitoring results. 141.207 Section 141.207 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public...

75 FR 17379 - Identification of Nations Whose Fishing Vessels Are Engaged in Illegal, Unreported, or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... Identification of Nations Whose Fishing Vessels Are Engaged in Illegal, Unreported, or Unregulated Fishing and/or... illegal, unregulated, or unreported (IUU) fishing or bycatch of protected living marine resources (PLMRs... High Seas Driftnet Fishing Moratorium Protection Act (Moratorium Protection Act). On March 5, 2010...

40 CFR 141.35 - Reporting for unregulated contaminant monitoring results.

Code of Federal Regulations, 2010 CFR

2010-07-01

... addition, you must notify the public of the availability of unregulated contaminant monitoring data as... single monitoring event at the same sampling location), EPA will use the highest of the reported values... value up to 30 characters assigned by the laboratory to uniquely identify containers, or groups of...

40 CFR 141.207 - Special notice of the availability of unregulated contaminant monitoring results.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.207 Special notice of the availability of unregulated... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Special notice of the availability of...

Development of LC/MS/MS Methods for Implementation in US EPA’s Drinking Water Unregulated Contaminant Monitoring Regulations

EPA Science Inventory

Well-characterized and standardized methods are the foundation upon which monitoring of regulated and unregulated contaminants in drinking water are based. To obtain reliable, high quality data for trace analysis of contaminants, these methods must be rugged, selective and sensit...

Famine versus feast: understanding the metabolism of tumors in vivo.

PubMed

Mayers, Jared R; Vander Heiden, Matthew G

2015-03-01

To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Responsibilities of Health Care Professionals in Counseling and Educating Patients With Incurable Neurological Diseases Regarding "Stem Cell Tourism": Caveat Emptor.

PubMed

Bowman, Michelle; Racke, Michael; Kissel, John; Imitola, Jaime

2015-11-01

"Stem cell tourism" is a rising Internet-based industry that aims to offer unproven procedures to patients with incurable diseases. This unregulated activity is reaching the neurologist's office as well as across the world, as patients request information or clearance for such procedures. Herein, we posit the need for medical societies and licensing boards to bring this issue to the forefront of neurology because it has the potential to affect patient care with risk of morbidity and mortality, as well as to undermine public confidence in legitimate stem cell research for incurable neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis.

77 FR 26071 - Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

... 142 Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems... (UCMR 3) for Public Water Systems AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule... action are public water systems (PWSs). All large community and non-transient non-community water systems...

Movements of Diadromous Fish in Large Unregulated Tropical Rivers Inferred from Geochemical Tracers

PubMed Central

Walther, Benjamin D.; Dempster, Tim; Letnic, Mike; McCulloch, Malcolm T.

2011-01-01

Patterns of migration and habitat use in diadromous fishes can be highly variable among individuals. Most investigations into diadromous movement patterns have been restricted to populations in regulated rivers, and little information exists for those in unregulated catchments. We quantified movements of migratory barramundi Lates calcarifer (Bloch) in two large unregulated rivers in northern Australia using both elemental (Sr/Ba) and isotope (87Sr/86Sr) ratios in aragonitic ear stones, or otoliths. Chemical life history profiles indicated significant individual variation in habitat use, particularly among chemically distinct freshwater habitats within a catchment. A global zoning algorithm was used to quantify distinct changes in chemical signatures across profiles. This algorithm identified between 2 and 6 distinct chemical habitats in individual profiles, indicating variable movement among habitats. Profiles of 87Sr/86Sr ratios were notably distinct among individuals, with highly radiogenic values recorded in some otoliths. This variation suggested that fish made full use of habitats across the entire catchment basin. Our results show that unrestricted movement among freshwater habitats is an important component of diadromous life histories for populations in unregulated systems. PMID:21494693

Delayed effects of flood control on a flood-dependent riparian forest

USGS Publications Warehouse

Katz, Gabrielle L.; Friedman, Jonathan M.; Beatty, Susan W.

2005-01-01

The downstream effects of dams on riparian forests are strongly mediated by the character and magnitude of adjustment of the fluvial–geomorphic system. To examine the effects of flow regulation on sand-bed streams in eastern Colorado, we studied the riparian forest on three river segments, the dam-regulated South Fork Republican River downstream of Bonny Dam, the unregulated South Fork Republican River upstream of Bonny Dam, and the unregulated Arikaree River. Although Bonny Dam significantly reduced peak and mean discharge downstream since 1951, there was little difference in forest structure between the regulated and unregulated segments. On all river segments, the riparian forest was dominated by the native pioneer tree, Populus deltoides, which became established during a period of channel narrowing beginning after the 1935 flood of record and ending by 1965. The nonnative Elaeagnus angustifolia was present on all river segments, with recruitment ongoing. The lack of contrast in forest structure between regulated and unregulated reaches resulted primarily from the fact that no large floods occurred on any of the study segments since dam construction. Most of the riparian forest in the study area was located on the broad narrowing terrace, which was rarely inundated on the unregulated segments, resulting in little contrast with the regulated segment. A minor dam effect occurred on the small modern floodplain, which was actively disturbed on the unregulated segments, but not on the regulated segments. Although Bonny Dam had the potential to significantly influence downstream riparian ecosystems, this influence had not been expressed, and may never be if a large flood does not occur within the lifetime of the dam. Minor dam effects to riparian systems can be expected downstream of large dams in some settings, including the present example in which there was insufficient time for the dam effects to by fully expressed.

A regional classification of unregulated stream flows: spatial resolution and hierarchical frameworks.

Treesearch

Ryan A. McManamay; Donald J. Orth; Charles A. Dolloff; Emmaneul A. Firmpong

2012-01-01

River regulation has resulted in substantial losses in habitat connectivity, biodiversity and ecosystem services. River managers are faced with a growing need to protect the key aspects of the natural flow regime. A practical approach to providing environmental flow standards is to create a regional framework by classifying unregulated streams into groups of similar...

77 FR 39182 - Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 141 and 142 [Docket No. EPA-HQ-OW-2009-0090; FRL-9660-4] RIN 2040-AF10 Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems Correction In rule document 2012-9978 appearing on pages 26072-26101 in the issue of...

77 FR 43523 - Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 141 and 142 [Docket No. EPA-HQ-OW-2009-0090; FRL-9660-4] RIN 2040-AF10 Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems Correction In rule document 2012-9978 appearing on pages 26072-26101 in the issue of...

Corrective Action Plan for Corrective Action Unit 453: Area 9 UXO Landfill, Tonopah Test Range, Nevada

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

Bechtel Nevada

1998-09-30

This corrective action plan proposes the closure method for the area 9 unexploded Ordnance landfill, corrective action unit 453 located at the Tonopah Test Range. The area 9 UXO landfill consists of corrective action site no. 09-55-001-0952 and is comprised of three individual landfill cells designated as A9-1, A9-2, and A9-3. The three landfill cells received wastes from daily operations at area 9 and from range cleanups which were performed after weapons testing. Cell locations and contents were not well documented due to the unregulated disposal practices commonly associated with early landfill operations. However, site process knowledge indicates that themore » landfill cells were used for solid waste disposal, including disposal of UXO.« less

Learning to Label: An Investigation into Ways of Conceptualizing Curriculum Diversity in a Korean Unregulated School Choice Area

ERIC Educational Resources Information Center

Sung, Youl-Kwan

2009-01-01

This study seeks to explore whether unregulated school choice has the potential to diversify the high school curriculum, as elitist conservatives and neoliberals in Korean argue. Making use of qualitative research methods, this paper examines how national curriculum policies are implemented at two selected high schools (high-achievement 1,…

Effects of Fear Appeals on Communicating Potential Health Risks of Unregulated Dietary Supplements to College Students

ERIC Educational Resources Information Center

Kim, Hyang-Sook; Sheffield, Donna; Almutairi, Talal

2014-01-01

Background: Fear appeals are commonly used in health communication to reduce risk. It is not clear, however, whether familiarity with a health topic can lessen the threat intended. The use of unregulated dietary supplements among young adults is one such area that needs study. Purpose: The study examined the effect of fear appeals on…

Plant diversity in riparian forests in northwest Colorado: Effects of time and river regulation

Treesearch

Amanda L. Uowolo; Dan Binkley; E. Carol Adair

2005-01-01

During the 20th Century the flow of most rivers in the United States was regulated by diversions and dams, with major impacts on riparian forests. Few unregulated rivers remain to provide baseline information for assessing these impacts. We characterized patterns in riparian plant communities along chronosequences on the unregulated Yampa River and the regulated Green...

An empirical analysis of the multimarket contact theory in pharmaceutical markets.

PubMed

Coronado, Javier; Jiménez-Martín, Sergi; Marín, Pedro L

2014-07-01

Multimarket contact theory predicts that firms will optimally reduce prices in markets where collusive prices are sustainable and allocate the slack of the corresponding incentive compatibility to increase prices in markets where collusion is not sustainable. Binding price caps in collusive markets will have different effects over the multimarket contact mechanism depending on the severity of the cap. Setting a price cap close to the unregulated case will increase the size of the redistribution of market power whereas stronger regulation will even reduce prices in unregulated markets. Therefore, price regulations aiming at capping prices in a specific market will also affect markets that are not subject to specific mandatory price regulations. We find evidence of the theory predictions using information for nine OECD countries for pharmaceutical markets. Unregulated US markets are shown to respond to the redistribution effect; Canadian markets, known to be subject to soft price regulations, with respect to the former, are shown to be consistent with a stronger redistribution effect. EU markets and Japan are either consistent with the effect of a medium regulation or strong regulation. In this last case multimarket contact cannot explain prices, and these are expected to be lower compared to the unregulated benchmark.

Fish abundance and population stability in a reservoir tailwater and an unregulated headwater stream

USGS Publications Warehouse

Jacobs, K.E.; Swink, W.D.

1983-01-01

Fish abundance and population stability were compared in the tailwater and in an unregulated tributary of Barren River Lake, a flood control reservoir in south central Kentucky. Fish abundance was greater in the tailwater near the dam and was dominated by three species common in the reservoir: gizzard shad (Dorosoma cepedianum), bluegills (Lepomis macrochirus), and white crappies (Pomoxis annularis). Three riverine suckers were less abundant in the tailwater than in the unregulated stream: northern hog suckers (Hypentelium nigricans), black redhorse (Moxostoma duquesnei), and golden redhorse (Moxostoma erythrurum). The fish populations in the tailwater, particularly common carp (Cyprinus carpio), northern hog suckers, black redhorse, and golden redhorse, were less stable than those in the unregulated stream. Population stability is defined as the extent to which fish remain in a stream section. This study suggests that the occurrence of reservoir species in the tailwater was the result of fish passage from the reservoir during high discharges in fall and winter. Reservoir operations (altered flow, low summer water temperature, and poor summer water quality) probably were responsible for the unstable populations of common carp and riverine suckers in the tailwater.

Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

PubMed Central

Maselli, Andrew; Furukawa, Ruth; Thomson, Susanne A. M.; Davis, Richard C.; Fechheimer, Marcus

2003-01-01

Hirano bodies are paracrystalline actin filament-containing structures reported to be associated with a variety of neurodegenerative diseases. However, the biological function of Hirano bodies remains poorly understood, since nearly all prior studies of these structures were done with postmortem samples of tissue. In the present study, we generated a full-length form of a Dictyostelium 34-kDa actin cross-linking protein with point mutations in the first putative EF hand, termed 34-kDa ΔEF1. The 34-kDa ΔEF1 protein binds calcium normally but has activated actin binding that is unregulated by calcium. The expression of the 34-kDa ΔEF1 protein in Dictyostelium induces the formation of Hirano bodies, as assessed by both fluorescence microscopy and transmission electron microscopy. Dictyostelium cells bearing Hirano bodies grow normally, indicating that Hirano bodies are not associated with cell death and are not deleterious to cell growth. Moreover, the expression of the 34-kDa ΔEF1 protein rescues the phenotypes of cells lacking the 34-kDa protein and cells lacking both the 34-kDa protein and α-actinin. Finally, the expression of the 34-kDa ΔEF1 protein also initiates the formation of Hirano bodies in cultured mouse fibroblasts. These results show that the failure to regulate the activity and/or affinity of an actin cross-linking protein can provide a signal for the formation of Hirano bodies. More generally, the formation of Hirano bodies is a cellular response to or a consequence of aberrant function of the actin cytoskeleton. PMID:12912897

Unregulated drinking water initiative for environmental surveillance and public health.

PubMed

Backer, Lorraine C; Tosta, Nancy

2011-03-01

The critical public health need to assess and protect the drinking water used by 37 million Americans requires attention and resources. NCEH, in partnership with states, has begun the process to identify information available on unregulated drinking water sources to improve the availability of data to support decisive public health actions and resource allocation. Far more attention and resources are needed to complete this process.

Methods for estimating the magnitude and frequency of peak streamflows for unregulated streams in Oklahoma

USGS Publications Warehouse

Lewis, Jason M.

2010-01-01

Peak-streamflow regression equations were determined for estimating flows with exceedance probabilities from 50 to 0.2 percent for the state of Oklahoma. These regression equations incorporate basin characteristics to estimate peak-streamflow magnitude and frequency throughout the state by use of a generalized least squares regression analysis. The most statistically significant independent variables required to estimate peak-streamflow magnitude and frequency for unregulated streams in Oklahoma are contributing drainage area, mean-annual precipitation, and main-channel slope. The regression equations are applicable for watershed basins with drainage areas less than 2,510 square miles that are not affected by regulation. The resulting regression equations had a standard model error ranging from 31 to 46 percent. Annual-maximum peak flows observed at 231 streamflow-gaging stations through water year 2008 were used for the regression analysis. Gage peak-streamflow estimates were used from previous work unless 2008 gaging-station data were available, in which new peak-streamflow estimates were calculated. The U.S. Geological Survey StreamStats web application was used to obtain the independent variables required for the peak-streamflow regression equations. Limitations on the use of the regression equations and the reliability of regression estimates for natural unregulated streams are described. Log-Pearson Type III analysis information, basin and climate characteristics, and the peak-streamflow frequency estimates for the 231 gaging stations in and near Oklahoma are listed. Methodologies are presented to estimate peak streamflows at ungaged sites by using estimates from gaging stations on unregulated streams. For ungaged sites on urban streams and streams regulated by small floodwater retarding structures, an adjustment of the statewide regression equations for natural unregulated streams can be used to estimate peak-streamflow magnitude and frequency.

Cations as Switches of Amyloid-Mediated Membrane Disruption Mechanisms: Calcium and IAPP

PubMed Central

Sciacca, Michele F.M.; Milardi, Danilo; Messina, Grazia M.L.; Marletta, Giovanni; Brender, Jeffrey R.; Ramamoorthy, Ayyalusamy; La Rosa, Carmelo

2013-01-01

Disruption of the integrity of the plasma membrane by amyloidogenic proteins is linked to the pathogenesis of a number of common age-related diseases. Although accumulating evidence suggests that adverse environmental stressors such as unbalanced levels of metal ions may trigger amyloid-mediated membrane damage, many features of the molecular mechanisms underlying these events are unknown. Using human islet amyloid polypeptide (hIAPP, aka amylin), an amyloidogenic peptide associated with β-cell death in type 2 diabetes, we demonstrate that the presence of Ca2+ ions inhibits membrane damage occurring immediately after the interaction of freshly dissolved hIAPP with the membrane, but significantly enhances fiber-dependent membrane disruption. In particular, dye leakage, quartz crystal microbalance, atomic force microscopy, and NMR experiments show that Ca2+ ions promote a shallow membrane insertion of hIAPP, which leads to the removal of lipids from the bilayer through a detergent-like mechanism triggered by fiber growth. Because both types of membrane-damage mechanisms are common to amyloid toxicity by most amyloidogenic proteins, it is likely that unregulated ion homeostasis, amyloid aggregation, and membrane disruption are all parts of a self-perpetuating cycle that fuels amyloid cytotoxicity. PMID:23332070

The lateral In2O3 nanowires and pyramid networks manipulation by controlled substrate surface energy in annealing evolution

NASA Astrophysics Data System (ADS)

Shariati, Mohsen; Darjani, Mojtaba

2016-02-01

The continuous laterally aligned growth of In2O3 nanocrystal networks extended with nanowire and pyramid connections under annealing influence has been reported. These nanostructures have been grown on Si substrate by using oxygen-assisted annealing process through PVD growth technique. The formation of In2O3 nanocrystals has been achieved by the successive growth of critical self-nucleated condensation in three orientations. The preferred direction was the route between two pyramids especially in the smallest surface energy. The effects of substrate temperature in annealing process on the morphological properties of the as-grown nanostructures were investigated. The annealing technique showed that by controlling the surface energy, the morphology of structures was changed from unregulated array to defined nanostructures; especially nanowires 50 nm in width. The obtained nanostructures also were investigated by the (transmission electron microscopy) TEM, Raman spectrum and the (X-ray diffraction) XRD patterns. They indicated that the self-assembled In2O3 nanocrystal networks have been fabricated by the vapor-solid (VS) growth mechanism. The growth mechanism process was prompted to attribute the relationship among the kinetics parameters, surface diffusion and morphology of nanostructures.

The oncolytic peptide LTX-315 triggers necrotic cell death

PubMed Central

Forveille, Sabrina; Zhou, Heng; Sauvat, Allan; Bezu, Lucillia; Müller, Kevin; Liu, Peng; Zitvogel, Laurence; Pierron, Gérard; Rekdal, Øystein; Kepp, Oliver; Kroemer, Guido

2015-01-01

The oncolytic peptide LTX-315 has been designed for killing human cancer cells and turned out to stimulate anti-cancer immune responses when locally injected into tumors established in immunocompetent mice. Here, we investigated the question whether LTX-315 induces apoptosis or necrosis. Transmission electron microscopy or morphometric analysis of chromatin-stained tumor cells revealed that LTX-315 failed to induce apoptotic nuclear condensation and rather induced a necrotic phenotype. Accordingly, LTX-315 failed to stimulate the activation of caspase-3, and inhibition of caspases by means of Z-VAD-fmk was unable to reduce cell killing by LTX-315. In addition, 2 prominent inhibitors of regulated necrosis (necroptosis), namely, necrostatin-1 and cycosporin A, failed to reduce LTX-315-induced cell death. In conclusion, it appears that LTX-315 triggers unregulated necrosis, which may contribute to its pro-inflammatory and pro-immune effects. PMID:26566869

Ambient temperature effects on broadband UV-B measurements using fluorescent phosphor (MgWO4)-based detectors

NASA Technical Reports Server (NTRS)

Dichter, Bronislaw K.; Beaubien, David J.; Beaubien, Arthur F.

1994-01-01

Results of field tests on a group of broadband UV-B pyranometers are presented. A brief description of the instrument is given. The effects of ambient temperature on thermally unregulated fluorescent phosphor (Robertson type) meters are presented and compared with the performance of thermally stabilized instruments. Means for correcting data from thermally unregulated instruments, where the prevailing ambient temperatures are known, are outlined.

Euro 6 Unregulated Pollutant Characterization and Statistical Analysis of After-Treatment Device and Driving-Condition Impact on Recent Passenger-Car Emissions.

PubMed

Martinet, Simon; Liu, Yao; Louis, Cédric; Tassel, Patrick; Perret, Pascal; Chaumond, Agnès; André, Michel

2017-05-16

This study aims to measure and analyze unregulated compound emissions for two Euro 6 diesel and gasoline vehicles. The vehicles were tested on a chassis dynamometer under various driving cycles: Artemis driving cycles (urban, road, and motorway), the New European Driving Cycle (NEDC) and the World Harmonized Light-Duty Test Cycle (WLTC) for Europe, and world approval cycles. The emissions of unregulated compounds (such as total particle number (PN) (over 5.6 nm); black carbon (BC); NO 2 ; benzene, toluene, ethylbenzene, and xylene (BTEX); carbonyl compounds; and polycyclic aromatic hydrocarbons (PAHs)) were measured with several online devices, and different samples were collected using cartridges and quartz filters. Furthermore, a preliminary statistical analysis was performed on eight Euro 4-6 diesel and gasoline vehicles to study the impacts of driving conditions and after-treatment and engine technologies on emissions of regulated and unregulated pollutants. The results indicate that urban conditions with cold starts induce high emissions of BTEX and carbonyl compounds. Motorway conditions are characterized by high emissions of particle numbers and CO, which mainly induced by gasoline vehicles. Compared with gasoline vehicles, diesel vehicles equipped with catalyzed or additive DPF emit fewer particles but more NO x and carbonyl compounds.

Concentrations and characteristics of organic carbon in surface water in Arizona: Influence of urbanization

USGS Publications Warehouse

Westerhoff, P.; Anning, D.

2000-01-01

Dissolved (DOC) and total (TOC) organic carbon concentrations and compositions were studied for several river systems in Arizona, USA. DOC composition was characterized by ultraviolet and visible absorption and fluorescence emission (excitation wavelength of 370 nm) spectra characteristics. Ephemeral sites had the highest DOC concentrations, and unregulated perennial sites had lower concentrations than unregulated intermittent sites, regulated sites, and sites downstream from wastewater-treatment plants (p < 0.05). Reservoir outflows and wastewater-treatment plant effluent were higher in DOC concentration (p < 0.05) and exhibited less variability in concentration than inflows to the reservoirs. Specific ultraviolet absorbance values at 254 nm were typically less than 2 m-1(milligram DOC per liter)-1 and lower than values found in most temperate-region rivers, but specific ultraviolet absorbance values increased during runoff events. Fluorescence measurements indicated that DOC in desert streams typically exhibit characteristics of autochthonous sources; however, DOC in unregulated upland rivers and desert streams experienced sudden shifts from autochthonous to allochthonous sources during runoff events. The urban water system (reservoir systems and wastewater-treatment plants) was found to affect temporal variability in DOC concentration and composition. (C) 2000 Elsevier Science B.V.Dissolved (DOC) and total (TOC) organic carbon concentrations and compositions were studied for several river systems in Arizona, USA. DOC composition was characterized by ultraviolet and visible absorption and fluorescence emission (excitation wavelength of 370 nm) spectra characteristics. Ephemeral sites had the highest DOC concentrations, and unregulated perennial sites had lower concentrations than unregulated intermittent sites, regulated sites, and sites downstream from wastewater-treatment plants (p<0.05). Reservoir outflows and wastewater-treatment plant effluent were higher in DOC concentration (p<0.05) and exhibited less variability in concentration than inflows to the reservoirs. Specific ultraviolet absorbance values at 254 nm were typically less than 2 m-1(milligram DOC per liter)-1 and lower than values found in most temperate-region rivers, but specific ultraviolet absorbance values increased during runoff events. Fluorescence measurements indicated that DOC in desert streams typically exhibit characteristics of autochthonous sources; however, DOC in unregulated upland rivers and desert streams experienced sudden shifts from autochthonous to allochthonous sources during runoff events. The urban water system (reservoir systems and wastewater-treatment plants) was found to affect temporal variability in DOC concentration and composition.The influence of urbanization, becoming increasingly common in arid regions, on dissolved organic carbon (DOC) concentrations in surface water resources was studied. DOC concentration and composition, seasonal watershed runoff events, streamflow variations, water management practices, and urban infrastructure in several Arizona watersheds were monitored. Ephemeral sites had the highest DOC levels, and unregulated perennial sites and lower concentrations than unregulated intermittent sites, regulated sites, and sites downstream from wastewater treatment plants. Reservoir outflows and wastewater treatment plant effluent had higher and less variable DOC concentrations than inflows to reservoirs. UV absorbance values, fluorescence measurements, and other indicators suggest that urban water systems (reservoirs and wastewater treatment plants) affect temporal variability in DOC concentration and composition.

SIALIC ACIDS AND AUTOIMMUNE DISEASE

PubMed Central

Mahajan, Vinay S.; Pillai, Shiv

2016-01-01

summary An important underlying mechanism that contributes to autoimmunity is the loss of inhibitory signaling in the immune system. Sialic acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely expressed in hematopoietic cells. The majority of Siglecs are inhibitory receptors expressed in immune cells that bind to sialic acid containing ligands and recruit SH2-domain containing tyrosine phosphatases to their cytoplasmic tails. They deliver inhibitory signals that can contribute to the constraining of immune cells and thus protect the host from autoimmunity. The inhibitory functions of CD22/Siglec-2 and Siglec-G and their contributions to tolerance and autoimmunity, primarily in the B lymphocyte context, are considered in some detail in this review. The relevance to autoimmunity and unregulated inflammation of modified sialic acids, enzymes that modify sialic acid, and other sialic acid binding proteins are also reviewed. PMID:26683151

Mercury levels in largemouth bass (Micropterus salmoides) from regulated and unregulated rivers.

PubMed

Dharampal, Prarthana S; Findlay, Robert H

2017-03-01

Within areas of comparable atmospheric mercury deposition rates methylmercury burden in largemouth bass populations vary significantly between regulated and unregulated rivers. To investigate if trophic dynamics strongly influenced pollutant body load, we sampled largemouth bass from two adjacent rivers, one regulated and one unregulated, and applied a suite of biochemical and stable isotope assays to compare their trophic dynamics. Total mercury burden in the bass from the unregulated Sipsey River (Elrod, AL, USA) and the regulated Black Warrior River (Demopolis, AL, USA) averaged 0.87 mg kg -1 and 0.19 mg kg -1 wet weight, respectively. For both populations, age, weight, and length were positively correlated with muscle mercury concentration. Compound specific stable isotope analysis of amino acids showed the trophic position of both populations was just under four. Quantitative and isotopic analysis of neutral lipid fatty acid of Sipsey River bass indicated a greater reliance upon the detrital component of the food web compared to Demopolis Reservoir bass which fed within the autochthonous, pelagic component of the food web. Since the close proximity of the rivers makes differences in atmospheric deposition unlikely and both populations had similar trophic position, our findings indicate that food web dynamics should be included among the factors that can strongly influence mercury concentration in fish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Streamflow statistics for unregulated and regulated conditions for selected locations on the Upper Yellowstone and Bighorn Rivers, Montana and Wyoming, 1928-2002

USGS Publications Warehouse

Chase, Katherine J.

2014-01-01

Major floods in 1996 and 1997 intensified public debate about the effects of human activities on the Yellowstone River. In 1999, the Yellowstone River Conservation District Council was formed to address conservation issues on the river. The Yellowstone River Conservation District Council partnered with the U.S. Army Corps of Engineers to carry out a cumulative effects study on the main stem of the Yellowstone River. The cumulative effects study is intended to provide a basis for future management decisions within the watershed. Streamflow statistics, such as flow-frequency data calculated for unregulated and regulated streamflow conditions, are a necessary component of the cumulative effects study. The U.S. Geological Survey, in cooperation with the Yellowstone River Conservation District Council and the U.S. Army Corps of Engineers, calculated low-flow frequency data and general monthly and annual statistics for unregulated and regulated streamflow conditions for the Upper Yellowstone and Bighorn Rivers for the 1928–2002 study period; these data are presented in this report. Unregulated streamflow represents flow conditions during the 1928–2002 study period if there had been no water-resources development in the Yellowstone River Basin. Regulated streamflow represents estimates of flow conditions during the 1928–2002 study period if the level of water-resources development existing in 2002 was in place during the entire study period.

Dark proteins: effect of inclusion body formation on quantification of protein expression.

PubMed

Iafolla, Marco A J; Mazumder, Mostafizur; Sardana, Vandit; Velauthapillai, Tharsan; Pannu, Karanbir; McMillen, David R

2008-09-01

Plasmid-borne gene expression systems have found wide application in the emerging fields of systems biology and synthetic biology, where plasmids are used to implement simple network architectures, either to test systems biology hypotheses about issues such as gene expression noise or as a means of exerting artificial control over a cell's dynamics. In both these cases, fluorescent proteins are commonly applied as a means of monitoring the expression of genes in the living cell, and efforts have been made to quantify protein expression levels through fluorescence intensity calibration and by monitoring the partitioning of proteins among the two daughter cells after division; such quantification is important in formulating the predictive models desired in systems and synthetic biology research. A potential pitfall of using plasmid-based gene expression systems is that the high protein levels associated with expression from plasmids can lead to the formation of inclusion bodies, insoluble aggregates of misfolded, nonfunctional proteins that will not generate fluorescence output; proteins caught in these inclusion bodies are thus "dark" to fluorescence-based detection methods. If significant numbers of proteins are incorporated into inclusion bodies rather than becoming biologically active, quantitative results obtained by fluorescent measurements will be skewed; we investigate this phenomenon here. We have created two plasmid constructs with differing average copy numbers, both incorporating an unregulated promoter (P(LtetO-1) in the absence of TetR) expressing the GFP derivative enhanced green fluorescent protein (EGFP), and inserted them into Escherichia coli bacterial cells (a common model organism for work on the dynamics of prokaryotic gene expression). We extracted the inclusion bodies, denatured them, and refolded them to render them active, obtaining a measurement of the average number of EGFP per cell locked into these aggregates; at the same time, we used calibrated fluorescent intensity measurements to determine the average number of active EGFP present per cell. Both measurements were carried out as a function of cellular doubling time, over a range of 45-75 min. We found that the ratio of inclusion body EGFP to active EGFP varied strongly as a function of the cellular growth rate, and that the number of "dark" proteins in the aggregates could in fact be substantial, reaching ratios as high as approximately five proteins locked into inclusion bodies for every active protein (at the fastest growth rate), and dropping to ratios well below 1 (for the slowest growth rate). Our results suggest that efforts to compare computational models to protein numbers derived from fluorescence measurements should take inclusion body loss into account, especially when working with rapidly growing cells. 2008 Wiley-Liss, Inc.

Assessing Ecological Flow Needs and Risks for Springs and Baseflow Streams With Growth and Climate Change

NASA Astrophysics Data System (ADS)

Springer, A. E.; Stevens, L. E.

2008-12-01

Ecological flow needs assessments are beginning to become an important part of regulated river management, but are more challenging for unregulated rivers. Water needs for ecosystems are greater than just consumptive use by riparian and aquatic vegetation and include the magnitude, frequency, duration and timing of flows and the depth and annual fluctuations of groundwater levels of baseflow supported streams. An ecological flow needs assessment was adapted and applied to an unregulated, baseflow dependent river in the arid to semi-arid Southwestern U.S. A separate process was developed to determine groundwater sources potentially at risk from climate, land management, or groundwater use changes in a large regional groundwater basin in the same semi-arid region. In 2007 and 2008, workshops with ecological, cultural, and physical experts from agencies, universities, tribes, and other organizations were convened. Flow-ecology response functions were developed with either conceptual or actual information for a baseflow dependent river, and scoring systems were developed to assign values to categories of risks to groundwater sources in a large groundwater basin. A reduction of baseflow to the river was predicted to lead to a decline in cottonwood and willow tree abundance, decreases in riparian forest diversity, and increases in non-native tree species, such as tamarisk. These types of forest vegetation changes would likely cause reductions or loss of some bird species. Loss of riffle habitat through declines in groundwater discharge and the associated river levels would likely lead to declines in native fish and amphibian species. A research agenda was developed to develop techniques to monitor, assess and hopefully better manage the aquifers supporting the baseflow dependent river to prevent potential threshold responses of the ecosystems. The scoring system for categories of risk was applied to four systems (aquifers, springs, standing water bodies, and streams) in the groundwater basin. The process was developed to allow water managers to assess and prioritize potential impacts to the biological, historical, or cultural aspects of the four types of systems from groundwater abstraction. These approaches can be adapted to other baseflow dependent, unregulated rivers or to assess risks to natural features associated with water sources in other regions.

Estimation of unregulated monthly, annual, and peak streamflows in Forest City Stream and lake levels in East Grand Lake, United States-Canada border between Maine and New Brunswick

USGS Publications Warehouse

Lombard, Pamela J.

2018-04-30

The U.S. Geological Survey, in cooperation with the International Joint Commission, compiled historical data on regulated streamflows and lake levels and estimated unregulated streamflows and lake levels on Forest City Stream at Forest City, Maine, and East Grand Lake on the United States-Canada border between Maine and New Brunswick to study the effects on streamflows and lake levels if two or all three dam gates are left open. Historical regulated monthly mean streamflows in Forest City Stream at the outlet of East Grand Lake (referred to as Grand Lake by Environment Canada) fluctuated between 114 cubic feet per second (ft3 /s) (3.23 cubic meters per second [m3 /s]) in November and 318 ft3 /s (9.01 m3 /s) in September from 1975 to 2015 according to Environment Canada streamgaging data. Unregulated monthly mean streamflows at this location estimated from regression equations for unregulated sites range from 59.2 ft3 /s (1.68 m3 /s) in September to 653 ft3 /s (18.5 m3 /s) in April. Historical lake levels in East Grand Lake fluctuated between 431.3 feet (ft) (131.5 meters [m]) in October and 434.0 ft (132.3 m) in May from 1969 to 2016 according to Environment Canada lake level data for East Grand Lake. Average monthly lake levels modeled by using the estimated hydrology for unregulated flows, and an outflow rating built from a hydraulic model with all gates at the dam open, range from 427.7 ft (130.4 m) in September to 431.1 ft (131.4 m) in April. Average monthly lake levels would likely be from 1.8 to 5.4 ft (0.55 to 1.6 m) lower with the gates at the dam opened than they have been historically. The greatest lake level changes would be from June through September.

Flood-frequency prediction methods for unregulated streams of Tennessee, 2000

USGS Publications Warehouse

Law, George S.; Tasker, Gary D.

2003-01-01

Up-to-date flood-frequency prediction methods for unregulated, ungaged rivers and streams of Tennessee have been developed. Prediction methods include the regional-regression method and the newer region-of-influence method. The prediction methods were developed using stream-gage records from unregulated streams draining basins having from 1 percent to about 30 percent total impervious area. These methods, however, should not be used in heavily developed or storm-sewered basins with impervious areas greater than 10 percent. The methods can be used to estimate 2-, 5-, 10-, 25-, 50-, 100-, and 500-year recurrence-interval floods of most unregulated rural streams in Tennessee. A computer application was developed that automates the calculation of flood frequency for unregulated, ungaged rivers and streams of Tennessee. Regional-regression equations were derived by using both single-variable and multivariable regional-regression analysis. Contributing drainage area is the explanatory variable used in the single-variable equations. Contributing drainage area, main-channel slope, and a climate factor are the explanatory variables used in the multivariable equations. Deleted-residual standard error for the single-variable equations ranged from 32 to 65 percent. Deleted-residual standard error for the multivariable equations ranged from 31 to 63 percent. These equations are included in the computer application to allow easy comparison of results produced by the different methods. The region-of-influence method calculates multivariable regression equations for each ungaged site and recurrence interval using basin characteristics from 60 similar sites selected from the study area. Explanatory variables that may be used in regression equations computed by the region-of-influence method include contributing drainage area, main-channel slope, a climate factor, and a physiographic-region factor. Deleted-residual standard error for the region-of-influence method tended to be only slightly smaller than those for the regional-regression method and ranged from 27 to 62 percent.

Meeting report of the International Consortium of Stem Cell Networks' Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis/Motor Neuron Disease.

PubMed

Chaddah, Maya R; Dickie, Brian G; Lyall, Drew; Marshall, Caroline J; Sykes, J Ben; Bruijn, Lucie I

2011-09-01

The International Consortium of Stem Cell Networks' (ICSCN) Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disease (MND) was held on 24-25 January 2011. Twenty scientific talks addressed aspects of cell derivation and characterization; preclinical research and phased clinical trials involving stem cells; latest developments in induced pluripotent (iPS) cell technology; industry involvement and investment. Three moderated panel discussions focused on unregulated ALS/MND treatments, and the state of the art and barriers to future progress in using stem cells for ALS/MND. This review highlights the major insights that emanated from the workshop around the lessons learned and barriers to progress for using stem cells for understanding disease mechanism, drug discovery, and as therapy for ALS/MND. The full meeting report is only available in the online version of the journal. Please find this material with the following direct link to the article: http://www.informahealthcare.com/als/doi/10.3109/17482968.2011.590992 .

Performance evaluation of a biodiesel fuelled transportation engine retrofitted with a non-noble metal catalysed diesel oxidation catalyst for controlling unregulated emissions.

PubMed

Shukla, Pravesh Chandra; Gupta, Tarun; Agarwal, Avinash Kumar

2018-02-15

In present study, engine exhaust was sampled for measurement and analysis of unregulated emissions from a four cylinder transportation diesel engine using a state-of-the-art FTIR (Fourier transform infrared spectroscopy) emission analyzer. Test fuels used were Karanja biodiesel blend (B20) and baseline mineral diesel. Real-time emission measurements were performed for raw exhaust as well as exhaust sampled downstream of the two in-house prepared non-noble metal based diesel oxidation catalysts (DOCs) and a baseline commercial DOC based on noble metals. Two prepared non-noble metal based DOCs were based on Co-Ce mixed oxide and Lanthanum based perovskite catalysts. Perovskite based DOC performed superior compared to Co-Ce mixed oxide catalyst based DOC. Commercial noble metal based DOC was found to be the most effective in reducing unregulated hydrocarbon emissions in the engine exhaust, followed by the two in-house prepared non-noble metal based DOCs. Copyright © 2017 Elsevier B.V. All rights reserved.

The unregulated commercialization of stem cell treatments: a global perspective.

PubMed

Sipp, Douglas

2011-12-01

Research into the biological properties and clinical potential of stem cells has spurred strong public investment, industry development, media coverage, and patient interest in recent years. To date, however, few clinical applications of demonstrated safety and efficacy have been developed with the exception of uses of hematopoietic stem cells in the treatment of diseases of the blood and immune systems. This lack of an evidence basis notwithstanding, hundreds of companies and private clinics around the world now sell putative stem cell treatments for an enormously broad range of medical and quality-of-life conditions. This represents a major challenge for legitimate scientists working in the field, for authorities seeking to protect their constituencies, and for patients and consumers targeted by such companies' marketing strategies. In this review, I provide an overview of the global industry in pseudomedical stem cell treatments, with an investigation of claims in a single disease area (amyotrophic lateral sclerosis), and make recommendations for the introduction and enforcement of appropriate regulatory responses to this problem.

Cations as switches of amyloid-mediated membrane disruption mechanisms: calcium and IAPP.

PubMed

Sciacca, Michele F M; Milardi, Danilo; Messina, Grazia M L; Marletta, Giovanni; Brender, Jeffrey R; Ramamoorthy, Ayyalusamy; La Rosa, Carmelo

2013-01-08

Disruption of the integrity of the plasma membrane by amyloidogenic proteins is linked to the pathogenesis of a number of common age-related diseases. Although accumulating evidence suggests that adverse environmental stressors such as unbalanced levels of metal ions may trigger amyloid-mediated membrane damage, many features of the molecular mechanisms underlying these events are unknown. Using human islet amyloid polypeptide (hIAPP, aka amylin), an amyloidogenic peptide associated with β-cell death in type 2 diabetes, we demonstrate that the presence of Ca(2+) ions inhibits membrane damage occurring immediately after the interaction of freshly dissolved hIAPP with the membrane, but significantly enhances fiber-dependent membrane disruption. In particular, dye leakage, quartz crystal microbalance, atomic force microscopy, and NMR experiments show that Ca(2+) ions promote a shallow membrane insertion of hIAPP, which leads to the removal of lipids from the bilayer through a detergent-like mechanism triggered by fiber growth. Because both types of membrane-damage mechanisms are common to amyloid toxicity by most amyloidogenic proteins, it is likely that unregulated ion homeostasis, amyloid aggregation, and membrane disruption are all parts of a self-perpetuating cycle that fuels amyloid cytotoxicity. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Governing stem cell therapy in India: regulatory vacuum or jurisdictional ambiguity?

PubMed Central

Tiwari, Shashank S.; Raman, Sujatha

2014-01-01

Stem cell treatments are being offered in Indian clinics although preclinical evidence of their efficacy and safety is lacking. This is attributed to a governance vacuum created by the lack of legally binding research guidelines. By contrast, this paper highlights jurisdictional ambiguities arising from trying to regulate stem cell therapy under the auspices of research guidelines when treatments are offered in a private market disconnected from clinical trials. While statutory laws have been strengthened in 2014, prospects for their implementation remain weak, given embedded challenges of putting healthcare laws and professional codes into practice. Finally, attending to the capacities of consumer law and civil society activism to remedy the problem of unregulated treatments, the paper finds that the very definition of a governance vacuum needs to be reframed to clarify whose rights to health care are threatened by the proliferation of commercial treatments and individualized negligence-based remedies for grievances. PMID:25431534

The European Court of Human Rights’ Ruling on Unproven Stem Cell Therapies: A Missed Opportunity?

PubMed Central

Rial-Sebbag, Emmanuelle; Blasimme, Alessandro

2014-01-01

Abstract On May 6th 2014, the European Court of Human Rights added yet a new element to the judicial history of stem cells as it ruled in Durisotto v. Italy [appeal n. 62804/13]. The ruling rejected a patient claim to access an unproven cell therapy—an outcome that is certainly to be welcomed. However, this ruling is a missed occasion to clarify and reaffirm some important legal distinctions that could have greatly benefited the whole field of regenerative medicine. We claim that the ethical and political assumptions that sustain the regulation of expanded access programs to new therapies should be carefully scrutinized, with particular attention to the justifications for the risks connected to unconventional therapies. A clear legal definition of what counts as compassionate cure as distinct from unregulated and untested therapies cannot be provided unless those points are previously addressed. PMID:25457960

Boron transport in plants: co-ordinated regulation of transporters

PubMed Central

Miwa, Kyoko; Fujiwara, Toru

2010-01-01

Background The essentiality of boron (B) for plant growth was established >85 years ago. In the last decade, it has been revealed that one of the physiological roles of B is cross-linking the pectic polysaccharide rhamnogalacturonan II in primary cell walls. Borate cross-linking of pectic networks serves both for physical strength of cell walls and for cell adhesion. On the other hand, high concentrations of B are toxic to plant growth. To avoid deficiency and toxicity problems, it is important for plants to maintain their tissue B concentrations within an optimum range by regulating transport processes. Boron transport was long believed to be a passive, unregulated process, but the identification of B transporters has suggested that plants sense and respond to the B conditions and regulate transporters to maintain B homeostasis. Scope Transporters responsible for efficient B uptake by roots, xylem loading and B distribution among leaves have been described. These transporters are required under B limitation for efficient acquisition and utilization of B. Transporters important for tolerating high B levels in the environment have also been identified, and these transporters export B from roots back to the soil. Two types of transporters are involved in these processes: NIPs (nodulin-26-like intrinsic proteins), boric acid channels, and BORs, B exporters. It is demonstrated that the expression of genes encoding these transporters is finely regulated in response to B availability in the environment to ensure tissue B homeostasis. Furthermore, plants tolerant to stress produced by low B or high B in the environment can be generated through altered expression of these transporters. Conclusions The identification of the first B transporter led to the discovery that B transport was a process mediated not only by passive diffusion but also by transporters whose activity was regulated in response to B conditions. Now it is evident that plants sense internal and external B conditions and regulate B transport by modulating the expression and/or accumulation of these transporters. Results obtained in model plants are applicable to other plant species, and such knowledge may be useful in designing plants or crops tolerant to soils containing low or high B. PMID:20228086

Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

NASA Astrophysics Data System (ADS)

He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi

2016-07-01

Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.

Surgical trauma induces overgrowth in lower limb gigantism: regulation with use of rapamycin is promising.

PubMed

Pinto, Rohan Sebastian; Harrison, William David; Graham, Kenneth; Nayagam, Durai

2018-01-04

We describe an unclassified overgrowth syndrome characterised by unregulated growth of dermal fibroblasts in the lower limbs of a 35-year-old woman. A PIK3CA gene mutation resulted in lower limb gigantism. Below the waist, she weighed 117 kg with each leg measuring over 100 cm in circumference. Her total adiposity was 50% accounted for by her legs mainly. Liposuction and surgical debulking were performed to reduce the size of the limbs but had exacerbated the overgrowth in her lower limbs. Systemic sepsis from an infected foot ulcer necessitated treatment by an above-knee amputation. Postoperatively, the stump increased in size by 19 kg. A trial of rapamycin to reverse the growth of the stump has shown promise. We discuss the clinical and genetic features of this previously unclassified disorder and the orthopaedic considerations involved. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Bioethical challenges of stem cell tourism].

PubMed

Ventura-Juncá, Patricio; Erices, Alejandro; Santos, Manuel J

2013-08-01

Stem cells have drawn extraordinary attention from scientists and the general public due to their potential to generate effective therapies for incurable diseases. At the same time, the production of embryonic stem cells involves a serious ethical issue concerning the destruction of human embryos. Although adult stem cells and induced pluripotential cells do not pose this ethical objection, there are other bioethical challenges common to all types of stem cells related particularly to the clinical use of stem cells. Their clinical use should be based on clinical trials, and in special situations, medical innovation, both of which have particular ethical dimensions. The media has raised unfounded expectations in patients and the public about the real clinical benefits of stem cells. At the same time, the number of unregulated clinics is increasing around the world, making direct offers through Internet of unproven stem cell therapies that attract desperate patients that have not found solutions in standard medicine. This is what is called stem cells tourism. This article reviews this situation, its consequences and the need for international cooperation to establish effective regulations to prevent the exploitation of patients and to endanger the prestige of legitimate stem cell research.

Development of a Precipitation-Runoff Model to Simulate Unregulated Streamflow in the Salmon Creek Basin, Okanogan County, Washington

USGS Publications Warehouse

van Heeswijk, Marijke

2006-01-01

Surface water has been diverted from the Salmon Creek Basin for irrigation purposes since the early 1900s, when the Bureau of Reclamation built the Okanogan Project. Spring snowmelt runoff is stored in two reservoirs, Conconully Reservoir and Salmon Lake Reservoir, and gradually released during the growing season. As a result of the out-of-basin streamflow diversions, the lower 4.3 miles of Salmon Creek typically has been a dry creek bed for almost 100 years, except during the spring snowmelt season during years of high runoff. To continue meeting the water needs of irrigators but also leave water in lower Salmon Creek for fish passage and to help restore the natural ecosystem, changes are being considered in how the Okanogan Project is operated. This report documents development of a precipitation-runoff model for the Salmon Creek Basin that can be used to simulate daily unregulated streamflows. The precipitation-runoff model is a component of a Decision Support System (DSS) that includes a water-operations model the Bureau of Reclamation plans to develop to study the water resources of the Salmon Creek Basin. The DSS will be similar to the DSS that the Bureau of Reclamation and the U.S. Geological Survey developed previously for the Yakima River Basin in central southern Washington. The precipitation-runoff model was calibrated for water years 1950-89 and tested for water years 1990-96. The model was used to simulate daily streamflows that were aggregated on a monthly basis and calibrated against historical monthly streamflows for Salmon Creek at Conconully Dam. Additional calibration data were provided by the snowpack water-equivalent record for a SNOTEL station in the basin. Model input time series of daily precipitation and minimum and maximum air temperatures were based on data from climate stations in the study area. Historical records of unregulated streamflow for Salmon Creek at Conconully Dam do not exist for water years 1950-96. Instead, estimates of historical monthly mean unregulated streamflow based on reservoir outflows and storage changes were used as a surrogate for the missing data and to calibrate and test the model. The estimated unregulated streamflows were corrected for evaporative losses from Conconully Reservoir (about 1 ft3/s) and ground-water losses from the basin (about 2 ft3/s). The total of the corrections was about 9 percent of the mean uncorrected streamflow of 32.2 ft3/s (23,300 acre-ft/yr) for water years 1949-96. For the calibration period, the basinwide mean annual evapotranspiration was simulated to be 19.1 inches, or about 83 percent of the mean annual precipitation of 23.1 inches. Model calibration and testing indicated that the daily streamflows simulated using the precipitation-runoff model should be used only to analyze historical and forecasted annual mean and April-July mean streamflows for Salmon Creek at Conconully Dam. Because of the paucity of model input data and uncertainty in the estimated unregulated streamflows, the model is not adequately calibrated and tested to estimate monthly mean streamflows for individual months, such as during low-flow periods, or for shorter periods such as during peak flows. No data were available to test the accuracy of simulated streamflows for lower Salmon Creek. As a result, simulated streamflows for lower Salmon Creek should be used with caution. For the calibration period (water years 1950-89), both the simulated mean annual streamflow and the simulated mean April-July streamflow compared well with the estimated uncorrected unregulated streamflow (UUS) and corrected unregulated streamflow (CUS). The simulated mean annual streamflow exceeded UUS by 5.9 percent and was less than CUS by 2.7 percent. Similarly, the simulated mean April-July streamflow exceeded UUS by 1.8 percent and was less than CUS by 3.1 percent. However, streamflow was significantly undersimulated during the low-flow, baseflow-dominated months of November through F

The dynamics of acute inflammation

NASA Astrophysics Data System (ADS)

Kumar, Rukmini

The acute inflammatory response is the non-specific and immediate reaction of the body to pathogenic organisms, tissue trauma and unregulated cell growth. An imbalance in this response could lead to a condition commonly known as "shock" or "sepsis". This thesis is an attempt to elucidate the dynamics of acute inflammatory response to infection and contribute to its systemic understanding through mathematical modeling and analysis. The models of immunity discussed use Ordinary Differential Equations (ODEs) to model the variation of concentration in time of the various interacting species. Chapter 2 discusses three such models of increasing complexity. Sections 2.1 and 2.2 discuss smaller models that capture the core features of inflammation and offer general predictions concerning the design of the system. Phase-space and bifurcation analyses have been used to examine the behavior at various parameter regimes. Section 2.3 discusses a global physiological model that includes several equations modeling the concentration (or numbers) of cells, cytokines and other mediators. The conclusions drawn from the reduced and detailed models about the qualitative effects of the parameters are very similar and these similarities have also been discussed. In Chapter 3, the specific applications of the biologically detailed model are discussed in greater detail. These include a simulation of anthrax infection and an in silico simulation of a clinical trial. Such simulations are very useful to biologists and could prove to be invaluable tools in drug design. Finally, Chapter 4 discusses the general problem of extinction of populations modeled as continuous variables in ODES is discussed. The average time to extinction and threshold are estimated based on analyzing the equivalent stochastic processes.

Graves' disease: diagnostic and therapeutic challenges (multimedia activity).

PubMed

Kahaly, George J; Grebe, Stefan K G; Lupo, Mark A; McDonald, Nicole; Sipos, Jennifer A

2011-06-01

Graves' disease is the most common cause of hyperthyroidism in the United States. Graves' disease occurs more often in women with a female:male ratio of 5:1 and a population prevalence of 1% to 2%. A genetic determinant to the susceptibility to Graves' disease is suspected because of familial clustering of the disease, a high sibling recurrence risk, the familial occurrence of thyroid autoantibodies, and the 30% concordance in disease status between identical twins. Graves' disease is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid antigen-specific T cells into the thyroid and thyroid-stimulating hormone receptor expressing tissues, with the production of autoantibodies to well-defined thyroidal antigens, such as thyroid peroxidase, thyroglobulin, and the thyroid-stimulating hormone receptor. The thyroid-stimulating hormone receptor is central to the regulation of thyroid growth and function. Stimulatory autoantibodies in Graves' disease activate the thyroid-stimulating hormone receptor leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Below-normal levels of baseline serum thyroid-stimulating hormone receptor, normal to elevated serum levels of T4, elevated serum levels of T3 and thyroid-stimulating hormone receptor autoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis of Graves' disease (available at: http://supplements.amjmed.com/2010/hyperthyroid/faculty.php). This Resource Center is also available through the website of The American Journal of Medicine (www.amjmed.com). Click on the “Thyroid/Graves' Disease” link in the “Resource Centers” section, found on the right side of the Journal homepage. Copyright © 2011 Elsevier Inc. All rights reserved.

Wilderness campsite conditions under an unregulated camping policy: an eastern example

USGS Publications Warehouse

Leung, Y.-F.; Marion, J.L.

2000-01-01

This study identified and assessed 110 campsites in seven designated wilderness areas in the Jefferson National Forest of Virginia. The campsites were unevenly distributed within each wilderness, concentrating along trail corridors and near popular destination areas. With a few exceptions, most campsites surveyed were in good condition. The findings indicate that management actions should be directed at reducing both the number of campsites and the problems associated with campsite expansion. The Forest?s unregulated camping policy could be focused through educational programs to encourage dispersed camping or camping containment to further reduce social and resource impacts.

Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities

PubMed Central

Rather, Rafiq A.; Bhagat, Madhulika

2018-01-01

Cancer is a genetic disease characterized by unregulated growth and dissemination of malignantly transformed neoplastic cells. The process of cancer development goes through several stages of biochemical and genetic alterations in a target cell. Several dietary alkaloids have been found to inhibit the molecular events and signaling pathways associated with various stages of cancer development and therefore are useful in cancer chemoprevention. Cancer chemoprevention has long been recognized as an important prophylactic strategy to reduce the burden of cancer on health care system. Cancer chemoprevention assumes the use of one or more pharmacologically active agents to block, suppress, prevent, or reverse the development of invasive cancer. Piperine is an active alkaloid with an excellent spectrum of therapeutic activities such as anti-oxidant, anti-inflammatory, immunomodulatory, anti-asthmatic, anti-convulsant, anti-mutagenic, antimycobacterial, anti-amoebic, and anti-cancer activities. In this article, we made an attempt to sum up the current knowledge on piperine that supports the chemopreventive potential of this dietary phytochemical. Many mechanisms have been purported to understand the chemopreventive action of piperine. Piperine has been reported to inhibit the proliferation and survival of many types of cancer cells through its influence on activation of apoptotic signaling and inhibition of cell cycle progression. Piperine is known to affect cancer cells in variety of other ways such as influencing the redox homeostasis, inhibiting cancer stem cell (CSC) self-renewal and modulation of ER stress and autophagy. Piperine can modify activity of many enzymes and transcription factors to inhibit invasion, metastasis, and angiogenesis. Piperine is a potent inhibitor of p-glycoprotein (P-gp) and has a significant effect on the drug metabolizing enzyme (DME) system. Because of its inhibitory influence on P-gp activity, piperine can reverse multidrug resistance (MDR) in cancer cells and acts as bioavailability enhancer for many chemotherapeutic agents. In this article, we emphasize the potential of piperine as a promising cancer chemopreventive agent and the knowledge we collected in this review can be applied in the strategic design of future researches particularly human intervention trials with piperine. PMID:29497610

Effect of gasoline/methanol blends on motorcycle emissions: Exhaust and evaporative emissions

NASA Astrophysics Data System (ADS)

Li, Lan; Ge, Yunshan; Wang, Mingda; Li, Jiaqiang; Peng, Zihang; Song, Yanan; Zhang, Liwei

2015-02-01

The emission characteristics of motorcycles using gasoline and M15 (consisting of 85% gasoline and 15% methanol by volume) were investigated in this article. Exhaust and evaporative emissions, including regulated and unregulated emissions, of three motorcycles were investigated on the chassis dynamometer over the Urban Driving Cycle (UDC) and in the Sealed Housing for Evaporative Determination (SHED), respectively. The regulated emissions were detected by an exhaust gas analyzer directly. The unregulated emissions, including carbonyls, volatile organic compounds (VOCs) and methanol, were sampled through battery-operated air pumps using tubes coated with 2,4-dintrophenylhydrazine (DNPH), Tenax TA and silica gel, respectively. The experimental results showed that, for exhaust emission, compared with those from gasoline fueled motorcycles, the concentration of total hydrocarbons (THC) and CO from motorcycles fueled with M15 decreased by 11%-34.5% and 63%-84% respectively, while the concentration of NOx increased by 76.9%-107.7%. Compared with those from gasoline fueled motorcycles, BTEX from motorcycles fueled with M15 decreased by 16%-60% while formaldehyde increased by 16.4%-52.5%. For evaporative emission, diurnal losses were more than hot soak losses and turned out to be dominated in evaporative emissions. In addition, compared with gasoline fueling motorcycles, the evaporative emissions of THC, carbonyls and VOCs from motorcycles fueled with M15 increased by 11.7%-37%, 38%-45% and 16%-42%, respectively. It should be noted that the growth rate of methanol was as high as 297%-1429%. It is important to reduce the evaporative emissions of methanol fueling motorcycles.

Modernization of gas-turbine engines with high-frequency induction motors

NASA Astrophysics Data System (ADS)

Abramovich, B. N.; Sychev, Yu A.; Kuznetsov, P. A.

2018-03-01

Main tendencies of growth of electric energy consumption in general and mining industries were analyzed in the paper. A key role of electric drive in this process was designated. A review about advantages and disadvantages of unregulated gearboxes with mechanical units that are commonly used in domestically produced gas-turbine engines was made. This review allows one to propose different gas-turbine engines modernization schemes with the help of PWM-driven high-frequency induction motors. Induction motors with the double rotor winding were examined. A simulation of high-frequency induction motors with double rotor windings in Matlab-Simulink software was carried out based on equivalent circuit parameters. Obtained characteristics of new motors were compared with serially produced analogues. After the simulation, results were implemented in the real prototype.

Destruction of the recreational, asthetic, agricultural, wildlife conservation and preservation, and residential uses of the land as a result of the abuses of the manufacturing, commercial, extractive, construction, and transportation industries

NASA Technical Reports Server (NTRS)

1975-01-01

Explicit concern over land use and abuse stems from the recognition of the negative impacts of unrestrained and unregulated economic, industrial, and population growth upon finite land resources. Only one quarter of the total surface area of the earth is land, and of that a large portion is uninhabitable. The present stresses upon the land include urbanization, urban sprawl and urban congestion; electrical, nuclear industrial park siting requirements; land degradation through stripping surface minerals; land degradation through disposal of radioactive wastes, sewage sludge, solid waste and other industrial wastes; rising demand for agricultural land; and the erosion and destruction of land through elimination of protective coverings such as forests, grasslands, and wetlands.

The Massachusetts Sustainable-Yield Estimator: A decision-support tool to assess water availability at ungaged stream locations in Massachusetts

USGS Publications Warehouse

Archfield, Stacey A.; Vogel, Richard M.; Steeves, Peter A.; Brandt, Sara L.; Weiskel, Peter K.; Garabedian, Stephen P.

2010-01-01

Federal, State and local water-resource managers require a variety of data and modeling tools to better understand water resources. The U.S. Geological Survey, in cooperation with the Massachusetts Department of Environmental Protection, has developed a statewide, interactive decision-support tool to meet this need. The decision-support tool, referred to as the Massachusetts Sustainable-Yield Estimator (MA SYE) provides screening-level estimates of the sustainable yield of a basin, defined as the difference between the unregulated streamflow and some user-specified quantity of water that must remain in the stream to support such functions as recreational activities or aquatic habitat. The MA SYE tool was designed, in part, because the quantity of surface water available in a basin is a time-varying quantity subject to competing demands for water. To compute sustainable yield, the MA SYE tool estimates a daily time series of unregulated, daily mean streamflow for a 44-year period of record spanning October 1, 1960, through September 30, 2004. Selected streamflow quantiles from an unregulated, daily flow-duration curve are estimated by solving six regression equations that are a function of physical and climate basin characteristics at an ungaged site on a stream of interest. Streamflow is then interpolated between the estimated quantiles to obtain a continuous daily flow-duration curve. A time series of unregulated daily streamflow subsequently is created by transferring the timing of the daily streamflow at a reference streamgage to the ungaged site by equating exceedence probabilities of contemporaneous flow at the two locations. One of 66 reference streamgages is selected by kriging, a geostatistical method, which is used to map the spatial relation among correlations between the time series of the logarithm of daily streamflows at each reference streamgage and the ungaged site. Estimated unregulated, daily mean streamflows show good agreement with observed unregulated, daily mean streamflow at 18 streamgages located across southern New England. Nash-Sutcliffe efficiency goodness-of-fit values are between 0.69 and 0.98, and percent root-mean-square-error values are between 19 and 283 percent. The MA SYE tool provides an estimate of streamflow adjusted for current (2000-04) water withdrawals and discharges using a spatially referenced database of permitted groundwater and surface-water withdrawal and discharge volumes. For a user-selected basin, the database is queried to obtain the locations of water withdrawal or discharge volumes within the basin. Groundwater and surface-water withdrawals and discharges are subtracted and added, respectively, from the unregulated, daily streamflow at an ungaged site to obtain a streamflow time series that includes the effects of these withdrawals and discharges. Users also have the option of applying an analytical solution to the time-varying, groundwater withdrawal and discharge volumes that take into account the effects of the aquifer properties on the timing and magnitude of streamflow alteration. For the MA SYE tool, it is assumed that groundwater and surface-water divides are coincident. For areas of southeastern Massachusetts and Cape Cod where this assumption is known to be violated, groundwater-flow models are used to estimate average monthly streamflows at fixed locations. There are several limitations to the quality and quantity of the spatially referenced database of groundwater and surface-water withdrawals and discharges. The adjusted streamflow values do not account for the effects on streamflow of climate change, septic-system discharge, impervious area, non-public water-supply withdrawals less than 100,000 gallons per day, and impounded surface-water bodies.

Methods for estimating the magnitude and frequency of peak discharges of rural, unregulated streams in Virginia

USGS Publications Warehouse

Bisese, James A.

1995-01-01

Methods are presented for estimating the peak discharges of rural, unregulated streams in Virginia. A Pearson Type III distribution is fitted to the logarithms of the unregulated annual peak-discharge records from 363 stream-gaging stations in Virginia to estimate the peak discharge at these stations for recurrence intervals of 2 to 500 years. Peak-discharge characteristics for 284 unregulated stations are divided into eight regions based on physiographic province, and regressed on basin characteristics, including drainage area, main channel length, main channel slope, mean basin elevation, percentage of forest cover, mean annual precipitation, and maximum rainfall intensity. Regression equations for each region are computed by use of the generalized least-squares method, which accounts for spatial and temporal correlation between nearby gaging stations. This regression technique weights the significance of each station to the regional equation based on the length of records collected at each cation, the correlation between annual peak discharges among the stations, and the standard deviation of the annual peak discharge for each station.Drainage area proved to be the only significant explanatory variable in four regions, while other regions have as many as three significant variables. Standard errors of the regression equations range from 30 to 80 percent. Alternate equations using drainage area only are provided for the five regions with more than one significant explanatory variable.Methods and sample computations are provided to estimate peak discharges at gaged and engaged sites in Virginia for recurrence intervals of 2, 5, 10, 25, 50, 100, 200, and 500 years, and to adjust the regression estimates for sites on gaged streams where nearby gaging-station records are available.

Growth-corruption-health triaca and environmental degradation: empirical evidence from Indonesia, Malaysia, and Thailand.

PubMed

Azam, Muhammad; Khan, Abdul Qayyum

2017-07-01

This study examines the impact of economic growth, corruption, health, and poverty on environmental degradation for three countries from ASEAN, namely Indonesia, Malaysia, and Thailand using annual data over the period of 1994-2014. The relationship between environmental degradation (pollution) by carbon dioxide (CO 2 ) emissions and economic growth is examined along with some other variables, namely health expenditure, poverty, agriculture value added growth, industrial value added growth, and corruption. The ordinary least squares (OLS) method is applied as an analytical technique for parameter estimation. The empirical results reveal that almost all variables are statistically significant at the 5% level of significance, whereby test rejects the null hypotheses of non-cointegration, indicating that all variables play an important role in affecting the environment across countries. Empirical results also indicate that economic growth has significant positive impact, while health expenditures show significantly negative impact on the environment. Corruption has significant positive effect on environment in the case of Malaysia; while in the case of Indonesia and Thailand, it has insignificant results. However, for the individual analysis across countries, the regression estimate suggests that economic growth has a significant positive relationship with environment for Indonesia, while it is found insignificantly negative and positive in the case of Malaysia and Thailand, respectively, during the period under the study. Empirical findings of the study suggest that policy-makers require to make technological-friendly environment sequentially to surmount unregulated pollution, steady population transfers from rural areas to urban areas are also important, and poverty alleviation and better health provision can also help to improve the environment.

The methods of formaldehyde emission testing of engine: A review

NASA Astrophysics Data System (ADS)

Zhang, Chunhui; Geng, Peng; Cao, Erming; Wei, Lijiang

2015-12-01

A number of measurements have been provided to detect formaldehyde in the atmosphere, but there are no clear unified standards in engine exhaust. Nowadays, formaldehyde, an unregulated emission from methanol engine, has been attracting increasing attention by researchers. This paper presents the detection techniques for formaldehyde emitted from the engines applied in recent market, introducing the approaches in terms of unregulated emission tests of formaldehyde, which involved gas chromatography, liquid chromatography, chromatography-mass spectrometry, chromatography-spectrum, Fourier infrared spectroscopy and spectrophotometry. The author also introduces the comparison regarding to the advantages of the existing detection techniques based on the principle, to compare with engine exhaust sampling method, the treatment in advance of detection, obtaining approaches accessing to the qualitative and quantitative analysis of chromatograms or spectra. The accuratest result obtained was chromatography though it cannot be used continuously. It also can be utilized to develop high requirements of emissions and other regulations. Fourier infrared spectroscopy has the advantage of continuous detection for a variety of unregulated emissions and can be applied to the bench in variable condition. However, its accuracy is not as good as chromatography. As the conclusion, a detection technique is chosen based on different requirements.

Outcomes related to effective nurse supervision in long-term care homes: an integrative review.

PubMed

McGilton, Katherine S; Chu, Charlene H; Shaw, Alexander C; Wong, Rosalind; Ploeg, Jenny

2016-11-01

The aim of this integrative review was to describe the organisational, unregulated nurse, and resident outcomes associated with effective supervisory performance of regulated nurses (registered nurses or registered practical nurses) in long-term care homes. While there are data on the influence of regulated nurse staffing levels on resident outcomes, the influence of effective supervisory performance of regulated nurses on resident and organisational outcomes, nursing assistant outcomes have yet to be comprehensively explored. A search of six databases was made for articles dating from 2000 to 2015. Twenty-four articles were selected and an integrative review was performed. Effective nurse supervision had statistically significant positive associations (P < 0.05, P < 0.000) with six different organisational, unregulated nurse and resident outcomes: nurse assistant job satisfaction, turnover/intention to leave, effectiveness, decision making, job stress and consumer satisfaction. Qualitative analyses corroborate these findings. There appear to be some associations between effective supervisory performance of regulated nurses with positive organisational, unregulated nursing and resident outcomes. Nursing managers and leaders in long-term care may promote improvements in effective nurse supervision performance as a way of reducing turnover and improving resident outcomes. © 2016 John Wiley & Sons Ltd.

Regulated and unregulated emissions from a diesel engine fueled with diesel fuel blended with diethyl adipate

NASA Astrophysics Data System (ADS)

Zhu, Ruijun; Cheung, C. S.; Huang, Zuohua; Wang, Xibin

2011-04-01

Experiments were carried out on a four-cylinder direct-injection diesel engine operating on Euro V diesel fuel blended with diethyl adipate (DEA). The blended fuels contain 8.1%, 16.4%, 25% and 33.8% by volume fraction of DEA, corresponding to 3%, 6%, 9% and 12% by mass of oxygen in the blends. The engine performance and exhaust gas emissions of the different fuels were investigated at five engine loads at a steady speed of 1800 rev/min. The results indicated an increase of brake specific fuel consumption and brake thermal efficiency when the engine was fueled with the blended fuels. In comparison with diesel fuel, the blended fuels resulted in an increase in hydrocarbon (HC) and carbon monoxide (CO), but a decrease in particulate mass concentrations. The nitrogen oxides (NO x) emission experienced a slight variation among the test fuels. In regard to the unregulated gaseous emissions, formaldehyde and acetaldehyde increased, while 1,3-butadiene, ethene, ethyne, propylene and BTX (benzene, toluene and xylene) in general decreased. A diesel oxidation catalyst (DOC) was found to reduce significantly most of the investigated unregulated pollutants when the exhaust gas temperature was sufficiently high.

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression.

PubMed

Trinh, Alice T; Ball, Bret G; Weber, Erin; Gallaher, Timothy K; Gluzman-Poltorak, Zoya; Anderson, French; Basile, Lena A

2009-12-30

Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements in T-cell specific gene expression were observed with the incorporation of additional cis-regulatory elements, such as a human polyadenylation signal and intron 7 from the human ADA gene. These studies suggest that the combination of an authentically regulated ADA gene in a murine retroviral vector, together with additional locus-specific regulatory refinements, will yield a vector with a safer profile and greater efficacy in terms of high-level, therapeutic, regulated gene expression for the treatment of ADA-deficient severe combined immunodeficiency.

Representations of stem cell clinics on Twitter.

PubMed

Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

2014-12-01

The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients.

Estimating design-flood discharges for streams in Iowa using drainage-basin and channel-geometry characteristics

USGS Publications Warehouse

Eash, D.A.

1993-01-01

Procedures provided for applying the drainage-basin and channel-geometry regression equations depend on whether the design-flood discharge estimate is for a site on an ungaged stream, an ungaged site on a gaged stream, or a gaged site. When both a drainage-basin and a channel-geometry regression-equation estimate are available for a stream site, a procedure is presented for determining a weighted average of the two flood estimates. The drainage-basin regression equations are applicable to unregulated rural drainage areas less than 1,060 square miles, and the channel-geometry regression equations are applicable to unregulated rural streams in Iowa with stabilized channels.

Techniques for estimating selected streamflow characteristics of rural unregulated streams in Ohio

USGS Publications Warehouse

Koltun, G.F.; Whitehead, Matthew T.

2002-01-01

This report provides equations for estimating mean annual streamflow, mean monthly streamflows, harmonic mean streamflow, and streamflow quartiles (the 25th-, 50th-, and 75th-percentile streamflows) as a function of selected basin characteristics for rural, unregulated streams in Ohio. The equations were developed from streamflow statistics and basin-characteristics data for as many as 219 active or discontinued streamflow-gaging stations on rural, unregulated streams in Ohio with 10 or more years of homogenous daily streamflow record. Streamflow statistics and basin-characteristics data for the 219 stations are presented in this report. Simple equations (based on drainage area only) and best-fit equations (based on drainage area and at least two other basin characteristics) were developed by means of ordinary least-squares regression techniques. Application of the best-fit equations generally involves quantification of basin characteristics that require or are facilitated by use of a geographic information system. In contrast, the simple equations can be used with information that can be obtained without use of a geographic information system; however, the simple equations have larger prediction errors than the best-fit equations and exhibit geographic biases for most streamflow statistics. The best-fit equations should be used instead of the simple equations whenever possible.

Experimental investigation of regulated and unregulated emissions from a diesel engine fueled with Euro V diesel fuel and fumigation methanol

NASA Astrophysics Data System (ADS)

Zhang, Z. H.; Cheung, C. S.; Chan, T. L.; Yao, C. D.

2010-03-01

Experiments were conducted on a four-cylinder direct-injection diesel engine with part of the engine load taken up by fumigation methanol injected into the air intake of each cylinder to investigate the regulated and unregulated gaseous emissions and particulate emission of the engine under five engine loads at an engine speed of 1920 rev min -1. The fumigation methanol was injected to top up 10%, 20% and 30% of the engine load under different engine operating conditions. The experimental results show that at low engine loads, the brake thermal efficiency (BTE) decreases with increase in fumigation methanol; but at high engine loads, the BTE is not significantly affected by fumigation methanol. The fumigation methanol results in significant increase in hydrocarbon (HC), carbon monoxide (CO) and nitrogen dioxide (NO 2) emissions, but decrease in nitrogen oxides (NO x). For the unregulated gaseous emissions, unburned methanol, formaldehyde and BTX (benzene, toluene and xylene) emissions increase but ethyne, ethene and 1,3-butadiene emissions decrease. Particulate mass and number concentrations also decrease with increase in fumigation methanol. A diesel oxidation catalyst (DOC) is found to reduce significantly most of the pollutants, including the air toxics, when the exhaust gas temperature is sufficiently high.

Experimental investigation of regulated and unregulated emissions from a diesel engine fueled with ultralow-sulfur diesel fuel blended with ethanol and dodecanol

NASA Astrophysics Data System (ADS)

Cheung, C. S.; Di, Yage; Huang, Zuohua

Experiments were conducted on a four-cylinder direct-injection diesel engine using ultralow-sulfur diesel as the main fuel, ethanol as the oxygenate additive and dodecanol as the solvent, to investigate the regulated and unregulated emissions of the engine under five engine loads at an engine speed of 1800 rev min -1. Blended fuels containing 6.1%, 12.2%, 18.2% and 24.2% by volume of ethanol, corresponding to 2%, 4%, 6% and 8% by mass of oxygen in the blended fuel, were used. The results indicate that with an increase in ethanol in the fuel, the brake specific fuel consumption becomes higher while there is little change in the brake thermal efficiency. Regarding the regulated emissions, HC and CO increase significantly at low engine load but might decrease at high engine load, NO x emission slightly decreases at low engine load but slightly increases at high engine load, while particulate mass decreases significantly at high engine load. For the unregulated gaseous emissions, unburned ethanol and acetaldehyde increase but formaldehyde, ethene, ethyne, 1,3-butadiene and BTX (benzene, toluene and xylene) in general decrease, especially at high engine load. A diesel oxidation catalyst (DOC) is found to reduce significantly most of the pollutants, including the air toxics.

The dynamics of adapting, unregulated populations and a modified fundamental theorem.

PubMed

O'Dwyer, James P

2013-01-06

A population in a novel environment will accumulate adaptive mutations over time, and the dynamics of this process depend on the underlying fitness landscape: the fitness of and mutational distance between possible genotypes in the population. Despite its fundamental importance for understanding the evolution of a population, inferring this landscape from empirical data has been problematic. We develop a theoretical framework to describe the adaptation of a stochastic, asexual, unregulated, polymorphic population undergoing beneficial, neutral and deleterious mutations on a correlated fitness landscape. We generate quantitative predictions for the change in the mean fitness and within-population variance in fitness over time, and find a simple, analytical relationship between the distribution of fitness effects arising from a single mutation, and the change in mean population fitness over time: a variant of Fisher's 'fundamental theorem' which explicitly depends on the form of the landscape. Our framework can therefore be thought of in three ways: (i) as a set of theoretical predictions for adaptation in an exponentially growing phase, with applications in pathogen populations, tumours or other unregulated populations; (ii) as an analytically tractable problem to potentially guide theoretical analysis of regulated populations; and (iii) as a basis for developing empirical methods to infer general features of a fitness landscape.

Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

PubMed

Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

2017-12-01

The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

Regulation of Mct1 by cAMP-dependent internalization in rat brain endothelial cells.

PubMed

Smith, Jeffrey P; Uhernik, Amy L; Li, Lun; Liu, Zejian; Drewes, Lester R

2012-10-22

In the cerebrovascular endothelium, monocarboxylic acid transporter 1 (Mct1) controls blood-brain transport of short chain monocarboxylic and keto acids, including pyruvate and lactate, to support brain energy metabolism. Mct1 function is acutely decreased in rat brain cerebrovascular endothelial cells by β-adrenergic signaling through cyclic adenosine monophosphate (cAMP); however, the mechanism for this acute reduction in transport capacity is unknown. In this report, we demonstrate that cAMP induces the dephosphorylation and internalization of Mct1 from the plasma membrane into caveolae and early endosomes in the RBE4 rat brain cerebrovascular endothelial cell line. Additionally, we provide evidence that Mct1 constitutively cycles through clathrin vesicles and recycling endosomes in a pathway that is not dependent upon cAMP signaling in these cells. Our results are important because they show for the first time the regulated and unregulated vesicular trafficking of Mct1 in cerebrovascular endothelial cells; processes which have significance for better understanding normal brain energy metabolism, and the etiology and potential therapeutic approaches to treating brain diseases, such as stroke, in which lactic acidosis is a key component. Copyright © 2012 Elsevier B.V. All rights reserved.

Regulation of Mct1 by cAMP-dependent internalization in rat brain endothelial cells

PubMed Central

Smith, Jeffrey P.; Uhernik, Amy L.; Li, Lun; Liu, Zejian; Drewes, Lester R.

2012-01-01

In the cerebrovascular endothelium, monocarboxylic acid transporter 1 (Mct1) controls blood-brain transport of short chain monocarboxylic and keto acids, including pyruvate and lactate, to support brain energy metabolism. Mct1 function is acutely decreased in rat brain cerebrovascular endothelial cells by β-adrenergic signaling through cyclic adenosine monophosphate (cAMP); however, the mechanism for this acute reduction in transport capacity is unknown. In this report, we demonstrate that cAMP induces the dephosphorylation and internalization of Mct1 from the plasma membrane into caveolae and early endosomes in the RBE4 rat brain cerebrovascular endothelial cell line. Additionally, we provide evidence that Mct1 constitutively cycles through clathrin vesicles and recycling endosomes in a pathway that is not dependent upon cAMP signaling in these cells. Our results are important because they show for the first time the regulated and unregulated vesicular trafficking of Mct1 in cerebrovascular endothelial cells; processes which have significance for better understanding normal brain energy metabolism, and the etiology and potential therapeutic approaches to treating brain diseases, such as stroke, in which lactic acidosis is a key component PMID:22925948

Necroptosis: a potential, promising target and switch in acute pancreatitis.

PubMed

Wang, Gang; Qu, Feng-Zhi; Li, Le; Lv, Jia-Chen; Sun, Bei

2016-02-01

Pancreatic acinar cell death is the major pathophysiological change in early acute pancreatitis (AP), and the death modalities are important factors determining its progression and prognosis. During AP, acinar cells undergo two major modes of death, including necrosis and apoptosis. Acinar necrosis can lead to intensely local and systemic inflammatory responses, which both induce and aggravate the lesion. Necrosis has long been considered an unregulated, and passive cell death process. Since the effective interventions of necrosis are difficult to perform, its relevant studies have not received adequate attention. Necroptosis is a newly discovered cell death modality characterized by both necrosis and apoptosis, i.e., it is actively regulated by special genes, while has the typical morphological features of necrosis. Currently, necroptosis is gradually becoming an important topic in the fields of inflammatory diseases. The preliminary results from necroptosis in AP have confirmed the existence of acinar cell necroptosis, which may be a potential target for effectively regulating inflammatory injuries and improving its outcomes; however, the functional changes and mechanisms of necroptosis still require further investigation. This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets.

Molecular biological characteristics of the recruitment of hematopoietic stem cells from bone marrow niche in chronic myeloid leukemia

PubMed Central

Zhu, Biao; Zhang, Jianbo; Chen, Jiao; Li, Chenglong; Wang, Xiaodong

2015-01-01

Chronic myeloid leukemia (CML) can be contextualized as a disease of unregulated self-renewal of stem cells which exist in a quiescent state and are instructed to differentiate and mobilize to circulation under pathologic circumstances leading to tumor invasion and metastasis. Here we found that matrix metalloproteinase-9 (MMP-9), induced by TGF-β1, upregulated s-KitL and s-ICAM-1, permitting the transfer of c-kit+ hematopoietic stem cells (HSCs) from the quiescent to proliferative niche in CML. Further study showed that this MMP-9 production was raised by CML specific BCR/ABL+ oncogene mediated TGF-β1. Besides, phosphatidylinositol-3 kinase (PI3K)/Akt/nuclear factor (NF)-κB signaling pathway was evidenced to govern this stem cell recruitment in CML pathogenesis. Overall, our observations defined a novel critical role for TGF-β1 induced PI3K/Akt/NF-κB signaling pathway in the recruitment of the malignant cells in CML by releasing s-KitL and s-ICAM-1 and this was through a distinct PI3K/Akt/NF-κB signaling pathway. PMID:26722450

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

Granderson, G.D.

The purpose of the dissertation is to examine the impact of rate-of-return regulation on the cost of transporting natural gas in interstate commerce. Of particular interest is the effect of the regulation on the input choice of a firm. Does regulation induce a regulated firm to produce its selected level of output at greater than minimum cost The theoretical model is based on the work of Rolf Faere and James Logan who investigate the duality relationship between the cost and production functions of a rate-of-return regulated firm. Faere and Logan derive the cost function for a regulated firm as themore » minimum cost of producing the firm's selected level of output, subject to the regulatory constraint. The regulated cost function is used to recover the unregulated cost function. A firm's unregulated cost function is the minimum cost of producing its selected level of output. Characteristics of the production technology are obtained from duality between the production and unregulated cost functions. Using data on 20 pipeline companies from 1977 to 1987, the author estimates a random effects model that consists of a regulated cost function and its associated input share equations. The model is estimated as a set of seemingly unrelated regressions. The empirical results are used to test the Faere and Logan theory and the traditional Averch-Johnson hypothesis of overcapitalization. Parameter estimates are used to recover the unregulated cost function and to calculate the amount by which transportation costs are increased by the regulation of the industry. Empirical results show that a firm's transportation cost decreases as the allowed rate of return increases and the regulatory constraint becomes less tight. Elimination of the regulatory constraint would lead to a reduction in costs on average of 5.278%. There is evidence that firms overcapitalize on pipeline capital. There is inconclusive evidence on whether firms overcapitalized on compressor station capital.« less

Effects of flow regime on benthic algae and macroinvertebrates - A comparison between regulated and unregulated rivers.

PubMed

Schneider, Susanne C; Petrin, Zlatko

2017-02-01

Natural fluctuations in flow are important for maintaining the ecological integrity of riverine ecosystems. However, the flow regime of many rivers has been modified. We assessed the impact of water chemistry, habitat and streamflow characteristics on macroinvertebrates and benthic algae, comparing 20 regulated with 20 unregulated sites. Flow regime, calculated from daily averaged discharge over the five years preceding sampling, was generally more stable at regulated sites, with higher relative discharges in winter, lower relative discharges in spring and smaller differences between upper and lower percentiles. However, no consistent differences in benthic algal or macroinvertebrate structural and functional traits occurred between regulated and unregulated sites. When regulated and unregulated sites were pooled, overall flow regime, calculated as principal components of discharge characteristics over the five years preceding sampling, affected macroinvertebrate species assemblages, but not indices used for ecosystem status assessment or functional feeding groups. This indicates that, while species identity shifted with changing flow regime, the exchanged taxa had similar feeding habits. In contrast to macroinvertebrates, overall flow regime did not affect benthic algae. Our results indicate that overall flow regime affected the species pool of macroinvertebrates from which recolonization after extreme events may occur, but not of benthic algae. When individual components of flow regime were analyzed separately, high June (i.e. three months before sampling) flow maxima were associated with low benthic algal taxon richness, presumably due to scouring. Macroinvertebrate taxon richness decreased with lower relative minimum discharges, presumably due to temporary drying of parts of the riverbed. However, recolonization after such extreme events presumably is fast. Generally, macroinvertebrate and benthic algal assemblages were more closely related to water physico-chemical than to hydrological variables. Our results suggest that macroinvertebrate and benthic algal indices commonly used for ecological status assessment are applicable also in regulated rivers. Copyright © 2016 Elsevier B.V. All rights reserved.

Flow and habitat effects on juvenile fish abundance in natural and altered flow regimes

USGS Publications Warehouse

Freeman, Mary C.; Bowen, Z.H.; Bovee, K.D.; Irwin, E.R.

2001-01-01

Conserving biological resources native to large river systems increasingly depends on how flow-regulated segments of these rivers are managed. Improving management will require a better understanding of linkages between river biota and temporal variability of flow and instream habitat. However, few studies have quantified responses of native fish populations to multiyear (>2 yr) patterns of hydrologic or habitat variability in flow-regulated systems. To provide these data, we quantified young-of-year (YOY) fish abundance during four years in relation to hydrologic and habitat variability in two segments of the Tallapoosa River in the southeastern United States. One segment had an unregulated flow regime, whereas the other was flow-regulated by a peak-load generating hydropower dam. We sampled fishes annually and explored how continuously recorded flow data and physical habitat simulation models (PHABSIM) for spring (April-June) and summer (July-August) preceding each sample explained fish abundances. Patterns of YOY abundance in relation to habitat availability (median area) and habitat persistence (longest period with habitat area continuously above the long-term median area) differed between unregulated and flow-regulated sites. At the unregulated site, YOY abundances were most frequently correlated with availability of shallow-slow habitat in summer (10 species) and persistence of shallow-slow and shallow-fast habitat in spring (nine species). Additionally, abundances were negatively correlated with 1-h maximum flow in summer (five species). At the flow-regulated site, YOY abundances were more frequently correlated with persistence of shallow-water habitats (four species in spring; six species in summer) than with habitat availability or magnitude of flow extremes. The associations of YOY with habitat persistence at the flow-regulated site corresponded to the effects of flow regulation on habitat patterns. Flow regulation reduced median flows during spring and summer, which resulted in median availability of shallow-water habitats comparable to the unregulated site. However, habitat persistence was severely reduced by flow fluctuations resulting from pulsed water releases for peak-load power generation. Habitat persistence, comparable to levels in the unregulated site, only occurred during summer when low rainfall or other factors occasionally curtailed power generation. As a consequence, summer-spawning species numerically dominated the fish assemblage at the flow-regulated site; five of six spring-spawning species occurring at both study sites were significantly less abundant at the flow-regulated site. Persistence of native fishes in flow-regulated systems depends, in part, on the seasonal occurrence of stable habitat conditions that facilitate reproduction and YOY survival.

Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

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

Ge, Yuqing; Zhou, Fengbiao; Chen, Hong

2010-07-09

Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was amore » positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.« less

Eye growth and myopia development: Unifying theory and Matlab model.

PubMed

Hung, George K; Mahadas, Kausalendra; Mohammad, Faisal

2016-03-01

The aim of this article is to present an updated unifying theory of the mechanisms underlying eye growth and myopia development. A series of model simulation programs were developed to illustrate the mechanism of eye growth regulation and myopia development. Two fundamental processes are presumed to govern the relationship between physiological optics and eye growth: genetically pre-programmed signaling and blur feedback. Cornea/lens is considered to have only a genetically pre-programmed component, whereas eye growth is considered to have both a genetically pre-programmed and a blur feedback component. Moreover, based on the Incremental Retinal-Defocus Theory (IRDT), the rate of change of blur size provides the direction for blur-driven regulation. The various factors affecting eye growth are shown in 5 simulations: (1 - unregulated eye growth): blur feedback is rendered ineffective, as in the case of form deprivation, so there is only genetically pre-programmed eye growth, generally resulting in myopia; (2 - regulated eye growth): blur feedback regulation demonstrates the emmetropization process, with abnormally excessive or reduced eye growth leading to myopia and hyperopia, respectively; (3 - repeated near-far viewing): simulation of large-to-small change in blur size as seen in the accommodative stimulus/response function, and via IRDT as well as nearwork-induced transient myopia (NITM), leading to the development of myopia; (4 - neurochemical bulk flow and diffusion): release of dopamine from the inner plexiform layer of the retina, and the subsequent diffusion and relay of neurochemical cascade show that a decrease in dopamine results in a reduction of proteoglycan synthesis rate, which leads to myopia; (5 - Simulink model): model of genetically pre-programmed signaling and blur feedback components that allows for different input functions to simulate experimental manipulations that result in hyperopia, emmetropia, and myopia. These model simulation programs (available upon request) can provide a useful tutorial for the general scientist and serve as a quantitative tool for researchers in eye growth and myopia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Private health insurance and access to healthcare.

PubMed

Duggal, Ravi

2011-01-01

The health insurance business in India has seen a growth of over 25% per annum in the last few years with the expansion of the private health insurance sector. The premium incomes of health insurance have crossed the Rs 8,000 crore mark with the share of private companies increasing to over 41%. This is despite the fact that from the perspective of patients, health insurance is not a good deal, especially when they need it most. This raises a number of ethical issues regarding how the health insurance business runs and how medical practice adjusts to it for profiteering. This article uses the personal experience of the author to argue that health insurance in an unregulated environment can only lead to unethical practices, further victimising the patient. Further, publicly financed healthcare which operates in an environment regulating both public and private healthcare provisioning is the only way to assure access to ethical and equitable healthcare to people.

Medical education in India: current challenges and the way forward.

PubMed

Solanki, Anjali; Kashyap, Surender

2014-12-01

Medical education in India is suffering from various shortcomings at conceptual as well as implementation level. With the expansion in medical education, the doctor to patient ratio has increased but these numbers do not align well with the overall quality of medical care in the country. To address this issue, a comprehensive analysis of various associated factors is essential. Indian medical education is suffering from a maldistribution of resources, unregulated growth in the private sector, lack of uniform admission procedures and traditional curricula lacking innovative approaches. To achieve higher standards of medical education, our goal should be to re-evaluate each and every aspect; create an efficient accreditation system; promote an equal distribution of resources, redesign curricula with stricter implementation and improved assessment methodologies; all of which will generate efficient medical graduates and consequently better health care delivery, and resulting in desired change within the system.

Fish assemblage, density, and growth in lateral habitats within natural and regulated sections of Washington's Elwha River prior to dam removal

USGS Publications Warehouse

Connolly, P.J.; Brenkman, S.J.

2008-01-01

We characterized seasonal fish assemblage, relative density, and growth in river margins above and between two Elwha River dams scheduled for removal. Fish assemblage and relative density differed in the lateral habitats of the middle-regulated and upper-unregulated sections of the Elwha River. Rainbow trout was the numerically dominant salmonid in both sections, with bull trout present in low numbers. Sculpin were common in the middle section, but not detected in the upper section. In 2004, mean length and biomass of age-0 rainbow trout were significantly smaller in the middle section than in the upper section by the end of the growing season (September). In 2005, an earlier emergence of rainbow trout in the middle section (July) compared to the upper section (August) corresponded with warmer water temperatures in the middle section. Despite lower growth, the margins of mainstem units in the middle section supported higher mean areal densities and biomass of age-0 rainbow trout than the up-per section. These results suggest that growth performance of age-0 rainbow trout was lower in the middle section than in the upper section, which could have been a density-dependent response, or a result of poor food production in the sediment-starved regulated section, or both. Based on our findings, we believe that seasonal sampling of river margins within reference reaches is a cost effective and repeatable method for detection of biologically important short- and long-term changes in emergence timing, density, and growth of rainbow trout before and after dam removals in the Elwha River.

All-d-Enantiomer of β-Amyloid Peptide Forms Ion Channels in Lipid Bilayers

PubMed Central

2012-01-01

Alzheimer’s disease (AD) is the most common type of senile dementia in aging populations. Amyloid β (Aβ)-mediated dysregulation of ionic homeostasis is the prevailing underlying mechanism leading to synaptic degeneration and neuronal death. Aβ-dependent ionic dysregulation most likely occurs either directly via unregulated ionic transport through the membrane or indirectly via Aβ binding to cell membrane receptors and subsequent opening of existing ion channels or transporters. Receptor binding is expected to involve a high degree of stereospecificity. Here, we investigated whether an Aβ peptide enantiomer, whose entire sequence consists of d-amino acids, can form ion-conducting channels; these channels can directly mediate Aβ effects even in the absence of receptor–peptide interactions. Using complementary approaches of planar lipid bilayer (PLB) electrophysiological recordings and molecular dynamics (MD) simulations, we show that the d-Aβ isomer exhibits ion conductance behavior in the bilayer indistinguishable from that described earlier for the l-Aβ isomer. The d isomer forms channel-like pores with heterogeneous ionic conductance similar to the l-Aβ isomer channels, and the d-isomer channel conductance is blocked by Zn2+, a known blocker of l-Aβ isomer channels. MD simulations further verify formation of β-barrel-like Aβ channels with d- and l-isomers, illustrating that both d- and l-Aβ barrels can conduct cations. The calculated values of the single-channel conductance are approximately in the range of the experimental values. These findings are in agreement with amyloids forming Ca2+ leaking, unregulated channels in AD, and suggest that Aβ toxicity is mediated through a receptor-independent, nonstereoselective mechanism. PMID:22423218

Hand-Ground Nanoscale ZnII -Based Coordination Polymers Derived from NSAIDs: Cell Migration Inhibition of Human Breast Cancer Cells.

PubMed

Paul, Mithun; Sarkar, Koushik; Deb, Jolly; Dastidar, Parthasarathi

2017-04-27

Increased levels of intracellular prostaglandin E 2 (PGE 2 ) have been linked with the unregulated cancer cell migration that often leads to metastasis. Non-steroidal anti-inflammatory drugs (NSAIDs) are known inhibitors of cyclooxygenase (COX) enzymes, which are responsible for the increased PGE 2 concentration in inflamed as well as cancer cells. Here, we demonstrate that NSAID-derived Zn II -based coordination polymers are able to inhibit cell migration of human breast cancer cells. Various NSAIDs were anchored to a series of 1D Zn II coordination polymers through carboxylate-Zn coordination, and these structures were fully characterized by single-crystal X-ray diffraction. Hand grinding in a pestle and mortar resulted in the first reported example of nanoscale coordination polymers that were suitable for biological studies. Two such hand-ground nanoscale coordination polymers NCP1 a and NCP2 a, which contained naproxen (a well-studied NSAID), were successfully internalized by the human breast cancer cells MDA-MB-231, as was evident from cellular imaging by using a fluorescence microscope. They were able to kill the cancer cells (MTT assay) more efficiently than the corresponding mother drug naproxen, and most importantly, they significantly inhibited cancer cell migration thereby displaying anticancer activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regulation of Tumor Progression by Programmed Necrosis

PubMed Central

Jeon, Hyun Min; Jeong, Eui Kyong; Lee, Yig Ji; Kim, Cho Hee; Park, Hye Gyeong

2018-01-01

Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness. PMID:29636841

Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes

PubMed Central

Ostolaza, Helena; Martín, César; González-Bullón, David; Uribe, Kepa B.; Etxaniz, Asier

2017-01-01

Adenylate cyclase toxin (ACT) is one of the principal virulence factors secreted by the whooping cough causative bacterium Bordetella pertussis, and it has a critical role in colonization of the respiratory tract and establishment of the disease. ACT targets phagocytes via binding to the CD11b/CD18 integrin and delivers its N-terminal adenylate cyclase (AC) domain directly to the cell cytosol, where it catalyzes unregulated conversion of cytosolic ATP into cAMP upon activation by binding to cellular calmodulin. High cAMP levels disrupt bactericidal functions of the immune cells, ultimately leading to cell death. In spite of its relevance in the ACT biology, the mechanism by which its ≈400 amino acid-long AC domain is transported through the target plasma membrane, and is released into the target cytosol, remains enigmatic. This article is devoted to refresh our knowledge on the mechanism of AC translocation across biological membranes. Two models, the so-called “two-step model” and the recently-proposed “toroidal pore model”, will be considered. PMID:28934133

Experimental investigation on regulated and unregulated emissions of a diesel engine fueled with ultra-low sulfur diesel fuel blended with biodiesel from waste cooking oil.

PubMed

Di, Yage; Cheung, C S; Huang, Zuohua

2009-01-01

Experiments were conducted on a 4-cylinder direct-injection diesel engine using ultra-low sulfur diesel, bi oesel and their blends, to investigate the regulated and unregulated emissions of the engine under five engine loads at an engine speed of 1800 rev/min. Blended fuels containing 19.6%, 39.4%, 59.4% and 79.6% by volume of biodiesel, corresponding to 2%, 4%, 6% and 8% by mass of oxygen in the blended fuel, were used. Biodiesel used in this study was converted from waste cooking oil. The following results are obtained with an increase of biodiesel in the fuel. The brake specific fuel consumption and the brake thermal efficiency increase. The HC and CO emissions decrease while NO(x) and NO(2) emissions increase. The smoke opacity and particulate mass concentrations reduce significantly at high engine load. In addition, for submicron particles, the geometry mean diameter of the particles becomes smaller while the total number concentration increases. For the unregulated gaseous emissions, generally, the emissions of formaldehyde, 1,3-butadiene, toluene, xylene decrease, however, acetaldehyde and benzene emissions increase. The results indicate that the combination of ultra-low sulfur diesel and biodiesel from waste cooking oil gives similar results to those in the literature using higher sulfur diesel fuels and biodiesel from other sources.

Effects of diesel/biodiesel blends on regulated and unregulated pollutants from a passenger vehicle operated over the European and the Athens driving cycles

NASA Astrophysics Data System (ADS)

Karavalakis, George; Stournas, Stamoulis; Bakeas, Evangelos

This paper presents the regulated and unregulated exhaust emissions of a diesel passenger vehicle, operated with low sulphur automotive diesel and soy methyl ester blends. Emission and fuel consumption measurements were conducted under real driving conditions (Athens Driving Cycle, ADC) and compared with those of a modified New European Driving Cycle (NEDC) using a chassis dynamometer. A Euro II compliant diesel vehicle was used in this study, equipped with an indirect injection diesel engine, fuelled with diesel fuel and biodiesel blends at proportions of 5, 10, and 20% respectively. Unregulated emissions of 11 polycyclic aromatic hydrocarbons (PAHs), 5 nitro-PAHs, 13 carbonyl compounds (CBCs) and the soluble organic fraction (SOF) of the particulate matter were measured. Qualitative hydrocarbon analysis was also performed on the SOF. Regulated emissions of NO x, CO, HC, CO 2, and PM were also measured over the two test cycles. It was established that some of the emissions measured over the (hot-start) NEDC differed from the real-world cycle. Significant differences were also observed in the vehicle's fuel consumption between the two test cycles. The addition of biodiesel reduced the regulated emissions of CO, HC and PM, while an increase in NO x was observed over the ADC. Carbonyl emissions, PAHs and nitro-PAHs were reduced with the addition of biodiesel over both driving cycles.

Global budgets in Maryland: early evidence on revenues, expenses, and margins in regulated and unregulated services.

PubMed

Malmmose, Margit; Mortensen, Karoline; Holm, Claus

2018-04-02

Maryland implemented one of the most aggressive payment innovations the nation has seen in several decades when it introduced global budgets in all its acute care hospitals in 2014. Prior to this, a pilot program, total patient revenue (TPR), was established for 8 rural hospitals in 2010. Using financial hospital report data from the Health Services Cost Review Commission from 2007 to 2013, we examined the hospitals' financial results including revenue, costs, and profit/loss margins to explore the impact of the adoption of the TPR pilot global budget program relative to the remaining hospitals in the state. We analyze financial results for both regulated (included in the global budget and subject to rate-setting) and unregulated services in order to capture a holistic image of the hospitals' actual revenue, cost and margin structures. Common size and difference-in-differences analyses of the data suggest that regulated profit ratios for treatment hospitals increased (from 5% in 2007 to 8% in 2013) and regulated expense-to-gross patient revenue ratios decreased (75% in 2007 and 68% in 2013) relative to the controls. Simultaneously, the profit margins for treatment hospitals' unregulated services decreased (- 12% in 2007 and - 17% in 2013), which reduced the overall margin significantly. This analysis therefore indicates cost shifting and less profit gain from the program than identified by solely focusing on the regulated margins.

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression

PubMed Central

2009-01-01

Background Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. Methods A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Results Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements in T-cell specific gene expression were observed with the incorporation of additional cis-regulatory elements, such as a human polyadenylation signal and intron 7 from the human ADA gene. Conclusion These studies suggest that the combination of an authentically regulated ADA gene in a murine retroviral vector, together with additional locus-specific regulatory refinements, will yield a vector with a safer profile and greater efficacy in terms of high-level, therapeutic, regulated gene expression for the treatment of ADA-deficient severe combined immunodeficiency. PMID:20042112

Vinpocetine regulates cation channel permeability of inner retinal neurons in the ischaemic retina.

PubMed

Nivison-Smith, Lisa; Acosta, Monica L; Misra, Stuti; O'Brien, Brendan J; Kalloniatis, Michael

2014-01-01

Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetine's regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Smooth muscle tension induces invasive remodeling of the zebrafish intestine.

PubMed

Seiler, Christoph; Davuluri, Gangarao; Abrams, Joshua; Byfield, Fitzroy J; Janmey, Paul A; Pack, Michael

2012-01-01

The signals that initiate cell invasion are not well understood, but there is increasing evidence that extracellular physical signals play an important role. Here we show that epithelial cell invasion in the intestine of zebrafish meltdown (mlt) mutants arises in response to unregulated contractile tone in the surrounding smooth muscle cell layer. Physical signaling in mlt drives formation of membrane protrusions within the epithelium that resemble invadopodia, matrix-degrading protrusions present in invasive cancer cells. Knockdown of Tks5, a Src substrate that is required for invadopodia formation in mammalian cells blocked formation of the protrusions and rescued invasion in mlt. Activation of Src-signaling induced invadopodia-like protrusions in wild type epithelial cells, however the cells did not migrate into the tissue stroma, thus indicating that the protrusions were required but not sufficient for invasion in this in vivo model. Transcriptional profiling experiments showed that genes responsive to reactive oxygen species (ROS) were upregulated in mlt larvae. ROS generators induced invadopodia-like protrusions and invasion in heterozygous mlt larvae but had no effect in wild type larvae. Co-activation of oncogenic Ras and Wnt signaling enhanced the responsiveness of mlt heterozygotes to the ROS generators. These findings present the first direct evidence that invadopodia play a role in tissue cell invasion in vivo. In addition, they identify an inducible physical signaling pathway sensitive to redox and oncogenic signaling that can drive this process.

Smooth Muscle Tension Induces Invasive Remodeling of the Zebrafish Intestine

PubMed Central

Seiler, Christoph; Davuluri, Gangarao; Abrams, Joshua; Byfield, Fitzroy J.; Janmey, Paul A.; Pack, Michael

2012-01-01

The signals that initiate cell invasion are not well understood, but there is increasing evidence that extracellular physical signals play an important role. Here we show that epithelial cell invasion in the intestine of zebrafish meltdown (mlt) mutants arises in response to unregulated contractile tone in the surrounding smooth muscle cell layer. Physical signaling in mlt drives formation of membrane protrusions within the epithelium that resemble invadopodia, matrix-degrading protrusions present in invasive cancer cells. Knockdown of Tks5, a Src substrate that is required for invadopodia formation in mammalian cells blocked formation of the protrusions and rescued invasion in mlt. Activation of Src-signaling induced invadopodia-like protrusions in wild type epithelial cells, however the cells did not migrate into the tissue stroma, thus indicating that the protrusions were required but not sufficient for invasion in this in vivo model. Transcriptional profiling experiments showed that genes responsive to reactive oxygen species (ROS) were upregulated in mlt larvae. ROS generators induced invadopodia-like protrusions and invasion in heterozygous mlt larvae but had no effect in wild type larvae. Co-activation of oncogenic Ras and Wnt signaling enhanced the responsiveness of mlt heterozygotes to the ROS generators. These findings present the first direct evidence that invadopodia play a role in tissue cell invasion in vivo. In addition, they identify an inducible physical signaling pathway sensitive to redox and oncogenic signaling that can drive this process. PMID:22973180

Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy

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

Thomas, P.M.; Wohllk, N.; Huang, E.

1996-09-01

Familial persistent hyperinsulinemic hypoglycemia of infancy is a disorder of glucose homeostasis and is characterized by unregulated insulin secretion and profound hypoglycemia. Loss-of-function mutations in the second nucleotide-binding fold of the sulfonylurea receptor, a subunit of the pancreatic-islet {beta}-cell ATP-dependent potassium channel, has been demonstrated to be causative for persistent hyperinsulinemic hypoglycemia of infancy. We now describe three additional mutations in the first nucleotide-binding fold of the sulfonylurea-receptor gene. One point mutation disrupts the highly conserved Walker A motif of the first nucleotide-binding-fold region. The other two mutations occur in noncoding sequences required for RNA processing and are predicted tomore » disrupt the normal splicing pathway of the sulfonylurea-receptor mRNA precursor. These data suggest that both nucleotide-binding-fold regions of the sulfortylurea receptor are required for normal regulation of {beta}-cell ATP-dependent potassium channel activity and insulin secretion. 32 refs., 4 figs., 1 tab.« less

Lymphatic dysregulation in intestinal inflammation: new insights into inflammatory bowel disease pathomechanisms.

PubMed

Becker, F; Yi, P; Al-Kofahi, M; Ganta, V C; Morris, J; Alexander, J S

2014-03-01

Alterations in the intestinal lymphatic network are well-established features of human and experimental inflammatory bowel disease (IBD). Such lymphangiogenic expansion might enhance classic intestinal lymphatic transport, eliminating excess accumulations of fluid, inflammatory cells and mediators, and could therefore be interpreted as an 'adaptive' response to acute and chronic inflammatory processes. However, whether these new lymphatic vessels are functional, unregulated or immature (and what factors may promote 'maturation' of these vessels) is currently an area under intense investigation. It is still controversial whether impaired lymphatic function in IBD is a direct consequence of the intestinal inflammation, or a preceding lymphangitis-like event. Current research has uncovered novel regulatory factors as well as new roles for familiar signaling pathways, which appear to be linked to inflammation-induced lymphatic alterations. The current review summarizes mechanisms amplifying lymphatic dysregulation and remodeling in intestinal inflammation at the organ, cell and molecular levels and discusses the influence of lymphangiogenesis and intestinal lymphatic transport function as they relate to IBD pathophysiology.

50 CFR 300.200 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-10-01

... sharks where the nation has not adopted a regulatory program for the conservation of sharks, comparable..., unreported, or unregulated fishing, reduce bycatch of protected living marine resources, and achieve shark...

50 CFR 300.200 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-10-01

... sharks where the nation has not adopted a regulatory program for the conservation of sharks, comparable..., unreported, or unregulated fishing, reduce bycatch of protected living marine resources, and achieve shark...

Environmental Auditing Policy Statement

EPA Pesticide Factsheets

EPA's policy on the use of environmental auditing by regulated entities to help achieve and maintain compliance with environmental laws and regulations, as well as to help identify and correct unregulated environmental hazards.

Ethical clinical translation of stem cell interventions for neurologic disease.

PubMed

Cote, David J; Bredenoord, Annelien L; Smith, Timothy R; Ammirati, Mario; Brennum, Jannick; Mendez, Ivar; Ammar, Ahmed S; Balak, Naci; Bolles, Gene; Esene, Ignatius Ngene; Mathiesen, Tiit; Broekman, Marike L

2017-01-17

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease. © 2016 American Academy of Neurology.

Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53.

PubMed

Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

2015-11-02

Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway.

Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53

PubMed Central

Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

2015-01-01

Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway. PMID:26522181

Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma

PubMed Central

Monje, Michelle; Mitra, Siddhartha S.; Freret, Morgan E.; Raveh, Tal B.; Kim, James; Masek, Marilyn; Attema, Joanne L.; Haddix, Terri; Edwards, Michael S. B.; Fisher, Paul G.; Weissman, Irving L.; Rowitch, David H.; Vogel, Hannes; Wong, Albert J.; Beachy, Philip A.

2011-01-01

Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor. PMID:21368213

50 CFR 300.200 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-10-01

... to satisfy the requirement in section 403 of the Magnuson-Stevens Fishery Conservation and Management Reauthorization Act of 2006 (“Act”) to publish a definition of the term “Illegal, unreported, or unregulated...

2006 public transportation fact book

DOT National Transportation Integrated Search

2006-04-01

This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, : military, and non-public service (e.g., governmental and corporate shuttles), and special application systems (e.g...

2004 public transportation fact book

DOT National Transportation Integrated Search

2004-03-01

This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, : military, and non-public service (e.g., governmental and corporate shuttles), and special application systems (e.g...

2005 public transportation fact book

DOT National Transportation Integrated Search

2005-04-01

This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, military, and non-public service (e.g., governmental and corporate shuttles), and special application systems (e.g.,...

Development of health-based screening levels for use in state- or local-scale water-quality assessments

USGS Publications Warehouse

Toccalino, Patricia L.; Nowell, Lisa; Wilber, William; Zogorski, John S.; Donohue, Joyce; Eiden, Catherine; Krietzman, Sandra; Post, Gloria

2003-01-01

The U.S. Geological Survey (USGS) has a need to communicate the significance of the water-quality findings of its National Water-Quality Assessment (NAWQA) Program in a human-health context. Historically, the USGS has assessed water-quality conditions by comparing water concentration data against established drinking-water standards and guidelines. However, because drinking- water standards and guidelines do not exist for many of the contaminants analyzed by the NAWQA Program and other USGS studies, this approach has proven to be insufficient for placing USGS data in a human-health context. To help meet this need, health-based screening level (HBSL) concentrations or ranges are being determined for unregulated compounds (that is, those for which Federal or State drinking-water standards have not been established), using a consensus approach that was developed collaboratively by the USGS, U.S. Environmental Protection Agency(USEPA), New Jersey Department of Environmental Protection, and Oregon Health & Science University. USEPA Office of Water methodologies for calculating Lifetime Health Advisory and Risk-Specific Dose values for drinking water are being used to develop HBSL concentrations (for unregulated noncarcinogens) and HBSL concentration ranges (for most unregulated carcinogens). This report describes the methodologies used to develop HBSL concentrations and ranges for unregulated compounds in State- and local-scale analyses, and discusses how HBSL values can be used as tools in water-quality assessments. Comparisons of measured water concentrations with Maximum Contaminant Level values and HBSL values require that water-quality data be placed in the proper context, with regard to both hydrology and human health. The use of these HBSL concentrations and ranges by USGS will increase by 27 percent the number of NAWQA contaminants for which health-based benchmarks are available for comparison with USGS water-quality data. USGS can use HBSL values to assist the USEPA and State and local agencies by providing them with comparisons of measured water concentrations to scientifically defensible human health-based benchmarks, and by alerting them when measured concentrations approach or exceed these benchmarks.

EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT

NASA Astrophysics Data System (ADS)

Xiaokaiti, Yilixiati; Wu, Haoming; Chen, Ya; Yang, Haopeng; Duan, Jianhui; Li, Xin; Pan, Yan; Tie, Lu; Zhang, Liangren; Li, Xuejun

2015-07-01

Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.

EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT.

PubMed

Xiaokaiti, Yilixiati; Wu, Haoming; Chen, Ya; Yang, Haopeng; Duan, Jianhui; Li, Xin; Pan, Yan; Tie, Lu; Zhang, Liangren; Li, Xuejun

2015-07-16

Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.

Generation of small molecules to interfere with regulated necrosis.

PubMed

Degterev, Alexei; Linkermann, Andreas

2016-06-01

Interference with regulated necrosis for clinical purposes carries broad therapeutic relevance and, if successfully achieved, has a potential to revolutionize everyday clinical routine. Necrosis was interpreted as something that no clinician might ever be able to prevent due to the unregulated nature of this form of cell death. However, given our growing understanding of the existence of regulated forms of necrosis and the roles of key enzymes of these pathways, e.g., kinases, peroxidases, etc., the possibility emerges to identify efficient and selective small molecule inhibitors of pathologic necrosis. Here, we review the published literature on small molecule inhibition of regulated necrosis and provide an outlook on how combination therapy may be most effective in treatment of necrosis-associated clinical situations like stroke, myocardial infarction, sepsis, cancer and solid organ transplantation.

2007 public transportation fact book

DOT National Transportation Integrated Search

2007-05-01

This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, : military, and services not available to the general public, or segments of the general public (e.g., governmental ...

Development-related expression patterns of protein-coding and miRNA genes involved in porcine muscle growth.

PubMed

Wang, F J; Jin, L; Guo, Y Q; Liu, R; He, M N; Li, M Z; Li, X W

2014-11-27

Muscle growth and development is associated with remarkable changes in protein-coding and microRNA (miRNA) gene expression. To determine the expression patterns of genes and miRNAs related to muscle growth and development, we measured the expression levels of 25 protein-coding and 16 miRNA genes in skeletal and cardiac muscles throughout 5 developmental stages by quantitative reverse transcription-polymerase chain reaction. The Short Time-Series Expression Miner (STEM) software clustering results showed that growth-related genes were downregulated at all developmental stages in both the psoas major and longissimus dorsi muscles, indicating their involvement in early developmental stages. Furthermore, genes related to muscle atrophy, such as forkhead box 1 and muscle ring finger, showed unregulated expression with increasing age, suggesting a decrease in protein synthesis during the later stages of skeletal muscle development. We found that development of the cardiac muscle was a complex process in which growth-related genes were highly expressed during embryonic development, but they did not show uniform postnatal expression patterns. Moreover, the expression level of miR-499, which enhances the expression of the β-myosin heavy chain, was significantly different in the psoas major and longissimus dorsi muscles, suggesting the involvement of miR-499 in the determination of skeletal muscle fiber types. We also performed correlation analyses of messenger RNA and miRNA expression. We found negative relationships between miR-486 and forkhead box 1, and miR-133a and serum response factor at all developmental stages, suggesting that forkhead box 1 and serum response factor are potential targets of miR-486 and miR-133a, respectively.

SBAR Panel: NPDES Comprehensive Storm Water Phase II Regulations

EPA Pesticide Factsheets

SBAR panel on proposed regulations to address currently unregulated discharges of storm water and provide regulatory relief to industrial facilities where industrial materials and activities are not exposed to storm water

Charge regulation circuit

DOEpatents

Ball, Don G.

1992-01-01

A charge regulation circuit provides regulation of an unregulated voltage supply in the range of 0.01%. The charge regulation circuit is utilized in a preferred embodiment in providing regulated voltage for controlling the operation of a laser.

75 FR 72778 - Pipeline Safety: Technical Pipeline Safety Advisory Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... pipeline safety regulations to the remaining unregulated rural onshore hazardous liquid low-stress... Low-Stress Lines'' on June 22, 2010 (75 FR 35366). The meeting agenda will include the committee's...

75 FR 52535 - Availability of Draft Toxicological Profile

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

... toxicological profile on unregulated hazardous substances that was prepared for the Department of Defense (DOD... DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency for Toxic Substances and Disease Registry [ATSDR... Registry (ATSDR), [[Page 52536

Fact Sheets about the Fourth Unregulated Contaminant Monitoring Rule (UCMR 4)

EPA Pesticide Factsheets

Fact Sheets explaining the program, contaminants for monitoring, water systems applicable, timeframe & monitoring frequency, monitoring locations, critical requirements, data elements and where to find additional information on monitoring data.

Extensive feeding on sockeye salmon Oncorhynchus nerka smolts by bull trout Salvelinus confluentus during initial outmigration into a small, unregulated and inland British Columbia river

USGS Publications Warehouse

Furey, Nathan B.; Hinch, Scott G.; Lotto, A.G.; Beauchamp, David A.

2015-01-01

Stomach contents were collected and analysed from 22 bull trout Salvelinus confluentus at the edge of the Chilko Lake and Chilko River in British Columbia, Canada, during spring outmigration of sockeye salmon Oncorhynchus nerka smolts. Twenty of the 22 (>90%) stomachs contained prey items, virtually all identifiable prey items were outmigrant O. nerka smolts and stomach contents represented a large portion (0·0–12·6%) of estimated S. confluentus mass. The results demonstrate nearly exclusive and intense feeding by S. confluentus on outmigrant smolts, and support recent telemetry observations of high disappearance rates of O. nerka smolts leaving large natural lake systems prior to entering high-order unregulated river systems.

Extensive feeding on sockeye salmon Oncorhynchus nerka smolts by bull trout Salvelinus confluentus during initial outmigration into a small, unregulated and inland British Columbia river.

PubMed

Furey, N B; Hinch, S G; Lotto, A G; Beauchamp, D A

2015-01-01

Stomach contents were collected and analysed from 22 bull trout Salvelinus confluentus at the edge of the Chilko Lake and Chilko River in British Columbia, Canada, during spring outmigration of sockeye salmon Oncorhynchus nerka smolts. Twenty of the 22 (>90%) stomachs contained prey items, virtually all identifiable prey items were outmigrant O. nerka smolts and stomach contents represented a large portion (0·0-12·6%) of estimated S. confluentus mass. The results demonstrate nearly exclusive and intense feeding by S. confluentus on outmigrant smolts, and support recent telemetry observations of high disappearance rates of O. nerka smolts leaving large natural lake systems prior to entering high-order unregulated river systems. © 2014 The Fisheries Society of the British Isles.

A comparison of campfire impacts and policies in seven protected areas

USGS Publications Warehouse

Reid, S.E.; Marion, J.L.

2005-01-01

Using resource-monitoring data from seven protected areas, the effectiveness of three campfire policies-campfire ban, designated campfires, and unregulated campfires-were assessed based on the number of fire sites and the amount of tree damage. Results indicate that unregulated campfire policies permitted substantial numbers of fire sites and tree damage in campsites, although fire bans did not eliminate or even substantially decrease these problems. A designated campfire policy was effective in decreasing number of fire sites, but little difference was found among policies regarding tree damage. Given the importance of campfires to visitor experiences, campfire prohibitions could be viewed as unnecessarily restrictive based on their limited success in preventing resource damage. Conclusions encourage protected-area managers to consider designated campfire policies and prohibitions on axes, hatchets, and saws to better meet resource protection and visitor experience mandates.

Emission reduction potential of using gas-to-liquid and dimethyl ether fuels on a turbocharged diesel engine.

PubMed

Xinling, Li; Zhen, Huang

2009-03-15

A study of engine performance characteristics and both of regulated (CO, HC, NO(x), and smoke) and unregulated (ultrafine particle number, mass concentrations and size distribution) emissions for a turbocharged diesel engine fueled with conventional diesel, gas-to-liquid (GTL) and dimethyl ether (DME) fuels respectively at different engine loads and speeds have been carried out. The results indicated that fuel components significantly affected the engine performance and regulated/unregulated emissions. GTL exhibited almost the same power and torque output as diesel, while improved fuel economy. GTL significantly reduced regulated emissions with average reductions of 21.2% in CO, 15.7% in HC, 15.6% in NO(x) and 22.1% in smoke in comparison to diesel, as well as average reductions in unregulated emissions of total ultrafine particle number (N(tot)) and mass (M(tot)) emissions by 85.3% and 43.9%. DME can significantly increase torque and power, compared with the original diesel engine, as well as significantly reduced regulated emissions of 40.1% in HC, 48.2% in NO(x) and smoke free throughout all the engine conditions. However, N(tot) for DME is close to that for diesel. The reason is that the accumulation mode particle number emissions for DME are very low due to the characteristics of oxygen content and no C-C bond, which promotes the processes of nucleation and condensation of the semi-volatile compounds in the exhaust gas, as a result, a lot of nucleation mode particles produce.

ATPase activity and light scattering of acto-heavy meromyosin: dependence on ATP concentration and on ionic strength.

PubMed

Dancker, P

1975-01-01

1. The dependence on ATP concentration of ATPase activity and light scattering decrease of acto-HMM could be described at very low ionic strength by one hyperbolic adsorption isotherm with a dissociation constant of 3 X 10(-6)M. Hence the increase of ATP ase activity was paralleled by a decrease in light scattering. At higher values of ionic strength ATPase activity stopped rising before HMM was completely saturated with ATP. Higher ionic strength prevented ATPase activity from further increasing when the rigor links (links between actin and nucleotide-free myosin), which have formerly protected the ATPase against the suppressing action of higher ionic strength have fallen below a certain amount. This protecting influence of rigor links did not require tropomyosin-troponin. 2. For complete activation of ATPase activity by actin less actin was needed when HMM was incompletely saturated with ATP than when it was completely saturated with ATP. 3. The apparent affinity of ATP to regulated acto-HMM (which contained tropomyosin-troponin) was lower than to unregulated acto-HMM (which was devoid of tropomyosin-troponin). In the presence of rigor complexes (indicated by an incomplete decrease of light scattering) the ATPase activity of regulated acto-HMM was higher than that of unregulated acto-HMM. At increasing ATP concentrations the ATPase activity of regulated acto-HMM stopped rising at a similar degree of saturation with ATP as the ATPase activity of unregulated acto-HMM at the same ionic strength.

Experimental investigation on regulated and unregulated emissions of a diesel/methanol compound combustion engine with and without diesel oxidation catalyst.

PubMed

Zhang, Z H; Cheung, C S; Chan, T L; Yao, C D

2010-01-15

The use of methanol in combination with diesel fuel is an effective measure to reduce particulate matter (PM) and nitrogen oxides (NOx) emissions from in-use diesel vehicles. In this study, a diesel/methanol compound combustion (DMCC) scheme was proposed and a 4-cylinder naturally-aspirated direct-injection diesel engine modified to operate on the proposed combustion scheme. The effect of DMCC and diesel oxidation catalyst (DOC) on the regulated emissions of total hydrocarbons (THC), carbon monoxide (CO), NOx and PM was investigated based on the Japanese 13 Mode test cycle. Certain unregulated emissions, including methane, ethyne, ethene, 1,3-butadiene, BTX (benzene, toluene, xylene), unburned methanol and formaldehyde were also evaluated based on the same test cycle. In addition, the soluble organic fraction (SOF) in the particulate and the particulate number concentration and size distribution were investigated at certain selected modes of operation. The results show that the DMCC scheme can effectively reduce NOx, particulate mass and number concentrations, ethyne, ethene and 1,3-butadiene emissions but significantly increase the emissions of THC, CO, NO(2), BTX, unburned methanol, formaldehyde, and the proportion of SOF in the particles. After the DOC, the emission of THC, CO, NO(2), as well as the unregulated gaseous emissions, can be significantly reduced when the exhaust gas temperature is sufficiently high while the particulate mass concentration is further reduced due to oxidation of the SOF. Copyright 2009 Elsevier B.V. All rights reserved.

International trade and air pollution: estimating the economic costs of air emissions from waterborne commerce vessels in the United States.

PubMed

Gallagher, Kevin P

2005-10-01

Although there is a burgeoning literature on the effects of international trade on the environment, relatively little work has been done on where trade most directly effects the environment: the transportation sector. This article shows how international trade is affecting air pollution emissions in the United States' shipping sector. Recent work has shown that cargo ships have been long overlooked regarding their contribution to air pollution. Indeed, ship emissions have recently been deemed "the last unregulated source of traditional air pollutants". Air pollution from ships has a number of significant local, national, and global environmental effects. Building on past studies, we examine the economic costs of this increasing and unregulated form of environmental damage. We find that total emissions from ships are largely increasing due to the increase in foreign commerce (or international trade). The economic costs of SO2 pollution range from dollars 697 million to dollars 3.9 billion during the period examined, or dollars 77 to dollars 435 million on an annual basis. The bulk of the cost is from foreign commerce, where the annual costs average to dollars 42 to dollars 241 million. For NOx emissions the costs are dollars 3.7 billion over the entire period or dollars 412 million per year. Because foreign trade is driving the growth in US shipping, we also estimate the effect of the Uruguay Round on emissions. Separating out the effects of global trade agreements reveals that the trade agreement-led emissions amounted to dollars 96 to dollars 542 million for SO2 between 1993 and 2001, or dollars 10 to dollars 60 million per year. For NOx they were dollars 745 million for the whole period or dollars 82 million per year. Without adequate policy responses, we predict that these trends and costs will continue into the future.

Documents for SBAR Panel: NPDES Comprehensive Storm Water Phase II Regulations

EPA Pesticide Factsheets

SBAR panel on proposed regulations to address currently unregulated discharges of storm water and provide regulatory relief to industrial facilities where industrial materials and activities are not exposed to storm water

Targeting of regulated necrosis in kidney disease.

PubMed

Martin-Sanchez, Diego; Poveda, Jonay; Fontecha-Barriuso, Miguel; Ruiz-Andres, Olga; Sanchez-Niño, María Dolores; Ruiz-Ortega, Marta; Ortiz, Alberto; Sanz, Ana Belén

The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors) may trigger necrosis and, thus, inflammation-mediated kidney injury. Second, and most revolutionary, the concept of regulated necrosis emerged. Several modalities of regulated necrosis were described, such as necroptosis, ferroptosis, pyroptosis and mitochondria permeability transition regulated necrosis. Similar to apoptosis, regulated necrosis is modulated by specific molecules that behave as therapeutic targets. Contrary to apoptosis, regulated necrosis may be extremely pro-inflammatory and, importantly for kidney transplantation, immunogenic. Furthermore, regulated necrosis may trigger synchronized necrosis, in which all cells within a given tubule die in a synchronized manner. We now review the different modalities of regulated necrosis, the evidence for a role in diverse forms of kidney injury and the new opportunities for therapeutic intervention. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Functional Toll-like Receptor 4 Overexpression in Papillary Thyroid Cancer by MAPK/ERK-Induced ETS1 Transcriptional Activity.

PubMed

Peyret, Victoria; Nazar, Magalí; Martín, Mariano; Quintar, Amado A; Fernandez, Elmer A; Geysels, Romina C; Fuziwara, Cesar S; Montesinos, María M; Maldonado, Cristina A; Santisteban, Pilar; Kimura, Edna T; Pellizas, Claudia G; Nicola, Juan P; Masini-Repiso, Ana M

2018-05-01

Emerging evidence suggests that unregulated Toll-like receptor (TLR) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTC) mainly harboring the BRAF V600E mutation was studied. TLR4 was overexpressed in PTC compared with nonneoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues. In agreement, conditional BRAF V600E expression in normal rat thyroid cells and mouse thyroid tissue upregulated TLR4 expression levels. Furthermore, functional TLR4 expression was demonstrated in PTC cells by increased NF-κB transcriptional activity in response to the exogenous TLR4-agonist lipopolysaccharide. Of note, The Cancer Genome Atlas data analysis revealed that BRAF V600E -positive tumors with high TLR4 expression were associated with shorter disease-free survival. Transcriptomic data analysis indicated a positive correlation between TLR4 expression levels and MAPK/ERK signaling activation. Consistently, chemical blockade of MAPK/ERK signaling abrogated BRAF V600E -induced TLR4 expression. A detailed study of the TLR4 promoter revealed a critical MAPK/ERK-sensitive Ets-binding site involved in BRAF V600E responsiveness. Subsequent investigation revealed that the Ets-binding factor ETS1 is critical for BRAF V600E -induced MAPK/ERK signaling-dependent TLR4 gene expression. Together, these data indicate that functional TLR4 overexpression in PTCs is a consequence of thyroid tumor-oncogenic driver dysregulation of MAPK/ERK/ETS1 signaling. Implications: Considering the participation of aberrant NF-κB signaling activation in the promotion of thyroid tumor growth and the association of high TLR4 expression with more aggressive tumors, this study suggests a prooncogenic potential of TLR4 downstream signaling in thyroid tumorigenesis. Mol Cancer Res; 16(5); 833-45. ©2018 AACR . ©2018 American Association for Cancer Research.

Blue Darts: Award-Winning OP-EDS

DTIC Science & Technology

2008-08-01

representative government in Iraq that assumes responsibility for gover - 9 nance in toto, including the guarantee of individual civil rights, internal...industrial expansion, population pressures, pollution and other environmental changes, and unregulated tourism . These threatened sites must be immediately

Estimating flow-duration and low-flow frequency statistics for unregulated streams in Oregon.

DOT National Transportation Integrated Search

2008-08-01

Flow statistical datasets, basin-characteristic datasets, and regression equations were developed to provide decision makers with surface-water information needed for activities such as water-quality regulation, water-rights adjudication, biological ...

PFOA and PFOS: Analytics

EPA Science Inventory

EPA Method 537 was developed for the analysis of perfluoroalkyl acids (PFAAs) in drinking water to address the occurrence monitoring needs under EPA’s Unregulated Contaminant Monitoring Regulation (UCMR). The method employs solid-phase extraction with analysis by liquid chr...

Unregulated Autonomy: Uncredentialed Educational Interpreters in Rural Schools.

PubMed

Fitzmaurice, Stephen

2017-01-01

Although many rural Deaf and Hard of Hearing students attend public schools most of the day and use the services of educational interpreters to gain access to the school environment, little information exists on what interpreters are doing in rural school systems in the absence of credentialing requirements. The researcher used ethnographic interviews and field observations of three educational interpreters with no certification or professional assessment to explore how uncredentialed interpreters were enacting their role in a rural high school. The findings indicate that uncredentialed interpreters in rural settings perform four major functions during their school day: preparing the environment, staff, and materials; interpreting a variety of content; interacting with numerous stakeholders; and directly instructing Deaf and Hard of Hearing students. Generally, educational interpreters in rural districts operate with unregulated autonomy, a situation that warrants further research and a national standard for all educational interpreters.

Body piercing medical concerns with cutting-edge fashion.

PubMed

Koenig, L M; Carnes, M

1999-06-01

To review the current information on medical complications, psychological implications, and legislative issues related to body piercing, a largely unregulated industry in the United States. We conducted a MEDLINE search of English language articles from 1966 until May 1998 using the search terms "body piercing" and "ear piercing." Bibliographies of these references were reviewed for additional citations. We also conducted an Internet search for "body piercing" on the World Wide Web. In this manuscript, we review the available body piercing literature. We conclude that body piercing is an increasingly common practice in the United States, that this practice carries substantial risk of morbidity, and that most body piercing in the United States is being performed by unlicensed, unregulated individuals. Primary care physicians are seeing growing numbers of patients with body pierces. Practitioners must be able to recognize, treat, and counsel patients on body piercing complications and be alert to associated psychological conditions in patients who undergo body piercing.

Development and Application of Health-Based Screening Levels for Use in Water-Quality Assessments

USGS Publications Warehouse

Toccalino, Patricia L.

2007-01-01

Health-Based Screening Levels (HBSLs) are non-enforceable water-quality benchmarks that were developed by the U.S. Geological Survey in collaboration with the U.S. Environmental Protection Agency (USEPA) and others. HBSLs supplement existing Federal drinking-water standards and guidelines, thereby providing a basis for a more comprehensive evaluation of contaminant-occurrence data in the context of human health. Since the original methodology used to calculate HBSLs for unregulated contaminants was published in 2003, revisions have been made to the HBSL methodology in order to reflect updates to relevant USEPA policies. These revisions allow for the use of the most recent, USEPA peer-reviewed, publicly available human-health toxicity information in the development of HBSLs. This report summarizes the revisions to the HBSL methodology for unregulated contaminants, and updates the guidance on the use of HBSLs for interpreting water-quality data in the context of human health.

Impact of mycotoxins on human health in developing countries.

PubMed

Shephard, G S

2008-02-01

Adverse human health effects from the consumption of mycotoxins have occurred for many centuries. Although mycotoxin contamination of agricultural products still occurs in the developed world, the application of modern agricultural practices and the presence of a legislatively regulated food processing and marketing system have greatly reduced mycotoxin exposure in these populations. At the mycotoxin contamination levels generally found in food products traded in these market economies, adverse human health effects have largely been overcome. However, in the developing world, where climatic and crop storage conditions are frequently conducive to fungal growth and mycotoxin production, much of the population relies on subsistence farming or on unregulated local markets. The extent to which mycotoxins affect human health is difficult to investigate in countries whose health systems lack capacity and in which resources are limited. Aflatoxin B(1), the toxin on which major resources have been expended, has long been linked to liver cancer, yet its other effects, such as immune suppression and growth faltering previously observed in veterinary studies, are only now being investigated and characterized in human populations. The extent to which factors such as immune suppression contribute to the overall burden of infectious disease is difficult to quantify, but is undoubtedly significant. Thus, food safety remains an important opportunity for addressing current health problems in developing countries.

ROS-activated calcium signaling mechanisms regulating endothelial barrier function.

PubMed

Di, Anke; Mehta, Dolly; Malik, Asrar B

2016-09-01

Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential of glyburide to reduce intracerebral edema in brain metastases.

PubMed

Boggs, Drexell Hunter; Simard, J Marc; Steven, Andrew; Mehta, Minesh P

2014-04-01

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.

Structural Basis for Antagonism by Suramin of Heparin Binding to Vaccinia Complement Protein

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

Ganesh, Vannakambadi K.; Muthuvel, Suresh Kumar; Smith, Scott A.

2010-07-19

Suramin is a competitive inhibitor of heparin binding to many proteins, including viral envelope proteins, protein tyrosine phosphatases, and fibroblast growth factors (FGFs). It has been clinically evaluated as a potential therapeutic in treatment of cancers caused by unregulated angiogenesis, triggered by FGFs. Although it has shown clinical promise in treatment of several cancers, suramin has many undesirable side effects. There is currently no experimental structure that reveals the molecular interactions responsible for suramin inhibition of heparin binding, which could be of potential use in structure-assisted design of improved analogues of suramin. We report the structure of suramin, in complexmore » with the heparin-binding site of vaccinia virus complement control protein (VCP), which interacts with heparin in a geometrically similar manner to many FGFs. The larger than anticipated flexibility of suramin manifested in this structure, and other details of VCP-suramin interactions, might provide useful structural information for interpreting interactions of suramin with many proteins.« less

Pakistan and the Millennium Development Goals for Maternal and Child Health: progress and the way forward.

PubMed

Rizvi, Arjumand; Bhatti, Zaid; Das, Jai K; Bhutta, Zulfiqar A

2015-01-01

The world has made substantial progress in reducing maternal and child mortality, but many countries are projected to fall short of achieving their Millennium Development Goals (MDGs) 4 and 5 targets. The major objective of this paper is to examine progress in Pakistan in reducing maternal and child mortality and malnutrition over the last two decades. Data from recent national and international surveys suggest that Pakistan lags behind on all of its MDGs related to maternal and child health and, for some indicators especially related to nutrition, the situation has worsened from the baseline of 1990. Progress in addressing key social determinants such as poverty, female education and empowerment has also been slow and unregulated population growth has further compromised progress. There is a need to integrate the various different sectors and programmes to achieve the desired results effectively and efficiently as many of the determinants and influencing factors are outside the health sector.

EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT

PubMed Central

Xiaokaiti, Yilixiati; Wu, Haoming; Chen, Ya; Yang, Haopeng; Duan, Jianhui; Li, Xin; Pan, Yan; Tie, Lu; Zhang, Liangren; Li, Xuejun

2015-01-01

Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway. PMID:26177797

Apoptosis and Necrosis in the Liver

PubMed Central

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

2013-01-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

Apoptosis and necrosis in the liver.

PubMed

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L; Gores, Gregory J

2013-04-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of "programmed" necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article.

Benthic invertebrates and periphyton in the Elwha river basin: Current conditions and predicted response to dam removal

USGS Publications Warehouse

Morley, S.A.; Duda, J.J.; Coe, H.J.; Kloehn, K.K.; McHenry, M.L.

2008-01-01

The impending removal of two dams on the Elwha River in Washington State offers a unique opportunity to study ecosystem restoration at a watershed scale. We examine how periphyton and benthic invertebrate assemblages vary across regulated and unregulated sections of the Elwha River and across different habitat types, and establish baseline data for tracking future changes following dam removal. We collected multiple years of data on physical habitat, water chemistry, periphyton, and benthic invertebrates from 52 sites on the Elwha River and a reference section on the Quinault River, a neighboring basin. We found that substrate in regulated river sections was coarser and less heterogeneous in size than in unregulated sections, and summer water temperature and specific conductivity higher. Periphyton biomass was also consistently higher in regulated than unregulated sections. Benthic invertebrate assemblage structure at sites above both dams was distinct from sites between and below the dams, due in large part to dominance of mayfly taxa compared to higher relative abundance of midges and non-insect taxa at downstream sites. Following dam removal, we anticipate that both periphyton and benthic invertebrate abundance and diversity will temporarily decrease between and below dams as a result of sediment released from behind the reservoirs. Over the long-term, increased floodplain heterogeneity and recolonization by anadromous fish will alter benthic invertebrate and periphyton assemblages via increases in niche diversity and inputs of marine-derived nutrients. The extended timeline predicted for Elwha River recovery and the complexities of forecasting ecological response highlights the need for more long-term assessments of dam removal and river restoration practices.

[FTIR detection of unregulated emissions from a diesel engine with biodiesel fuel].

PubMed

Tan, Pi-qiang; Hu, Zhi-yuan; Lou, Di-ming

2012-02-01

Biodiesel, as one of the most promising alternative fuels, has received more attention because of limited fossil fuels. A comparison of biodiesel and petroleum diesel fuel is discussed as regards engine unregulated exhaust emissions. A diesel fuel, a pure biodiesel fuel, and fuel with 20% V/V biodiesel blend ratio were tested without engine modification The present study examines six typical unregulated emissions by Fourier transform infrared spectroscopy (FTIR) method: formaldehyde (HCHO), acetaldehyde (C2 H4 O), acetone (C3 H6 O), toluene (C7 H8), sulfur dioxide (SO2), and carbon dioxide (CO2). The results show addition of biodiesel fuel increases the formaldehyde emission, and B20 fuel has little change, but the formaldehyde emission of pure biodiesel shows a clear trend of addition. Compared with the pure diesel fuel, the acetaldehyde of B20 fuel has a distinct decrease, and the acetaldehyde emission of pure biodiesel is lower than that of the pure diesel fuel at low and middle engine loads, but higher at high engine load. The acetone emission is very low, and increases for B20 and pure biodiesel fuels as compared to diesel fuel. Compared with the diesel fuel, the toluene and sulfur dioxide values of the engine show a distinct decrease with biodiesel blend ratio increasing. It is clear that the biodiesel could reduce aromatic compounds and emissions of diesel engines. The carbon dioxide emission of pure biodiesel has a little lower value than diesel, showing that the biodiesel benefits control of greenhouse gas.

Influence of oxidized biodiesel blends on regulated and unregulated emissions from a diesel passenger car.

PubMed

Karavalakis, Georgios; Bakeas, Evangelos; Stournas, Stamos

2010-07-01

This paper investigates the effects of biodiesel blends on regulated and unregulated emissions from a Euro 4 diesel passenger car, fitted with a diesel oxidation catalyst and a diesel particle filter (DPF). Emission and fuel consumption measurements were conducted for the New European Driving Cycle (NEDC) and the Artemis driving cycles. Criteria pollutants, along with carbonyl, polycyclic aromatic hydrocarbon (PAH) and nitrate PAH and oxygenate PAH emissions, were measured and recorded. A soy-based biodiesel and an oxidized biodiesel, obtained from used frying oils, were blended with an ultra low sulfur diesel at proportions of 20, 30, and 50% by volume. The results showed that the DPF had the ability to significantly reduce particulate matter (PM) emissions over all driving conditions. Carbon monoxide (CO) and hydrocarbon (HC) emissions were also reduced with biodiesel; however, a notable increase in nitrogen oxide (NO(x)) emissions was observed with biodiesel blends. Carbon dioxide (CO(2)) emissions and fuel consumption followed similar patterns and increased with biodiesel. The influence of fuel type and properties was particularly noticeable on the unregulated pollutants. The use of the oxidized biodiesel blends led to significant increases in carbonyl emissions, especially in compounds which are associated with potential health risks such as formaldehyde, acetaldehyde, and acrolein. Sharp increases in most PAH compounds and especially those which are known for their toxic and carcinogenic potency were observed with the oxidized blends. The presence of polymerization products and cyclic acids were the main factors that influenced the PAH emissions profile.

Flood-frequency characteristics of Wisconsin streams

USGS Publications Warehouse

Walker, John F.; Peppler, Marie C.; Danz, Mari E.; Hubbard, Laura E.

2017-05-22

Flood-frequency characteristics for 360 gaged sites on unregulated rural streams in Wisconsin are presented for percent annual exceedance probabilities ranging from 0.2 to 50 using a statewide skewness map developed for this report. Equations of the relations between flood-frequency and drainage-basin characteristics were developed by multiple-regression analyses. Flood-frequency characteristics for ungaged sites on unregulated, rural streams can be estimated by use of the equations presented in this report. The State was divided into eight areas of similar physiographic characteristics. The most significant basin characteristics are drainage area, soil saturated hydraulic conductivity, main-channel slope, and several land-use variables. The standard error of prediction for the equation for the 1-percent annual exceedance probability flood ranges from 56 to 70 percent for Wisconsin Streams; these values are larger than results presented in previous reports. The increase in the standard error of prediction is likely due to increased variability of the annual-peak discharges, resulting in increased variability in the magnitude of flood peaks at higher frequencies. For each of the unregulated rural streamflow-gaging stations, a weighted estimate based on the at-site log Pearson type III analysis and the multiple regression results was determined. The weighted estimate generally has a lower uncertainty than either the Log Pearson type III or multiple regression estimates. For regulated streams, a graphical method for estimating flood-frequency characteristics was developed from the relations of discharge and drainage area for selected annual exceedance probabilities. Graphs for the major regulated streams in Wisconsin are presented in the report.

Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

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

B McCray; E Skordalakes; J Taylor

2011-12-31

Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Throughmore » extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.« less

Lung Cancer Risk Associated with Regulated and Unregulated Chrysotile Asbestos Fibers.

PubMed

Hamra, Ghassan B; Richardson, David B; Dement, John; Loomis, Dana

2017-03-01

Regulation of asbestos fibers in the workplace is partly determined by which fibers can be visually counted. However, a majority of fibers are too short and thin to count this way and are, consequently, not subject to regulation. We estimate lung cancer risk associated with asbestos fibers of varying length and width. We apply an order-constrained prior both to leverage external information from toxicological studies of asbestos health effects. This prior assumes that risk from asbestos fibers increases with increasing length and decreases with increasing width. When we apply a shared mean for the effect of all asbestos fiber exposure groups, the rate ratios for each fiber group per unit exposure appear mostly equal. Rate ratio estimates for fibers of diameter <0.25 μm and length <1.5 and 1.5-5.0 μm are the most precise. When applying an order-constrained prior, we find that estimates of lung cancer rate ratio per unit of exposure to unregulated fibers 20-40 and >40 μm in the thinnest fiber group are similar in magnitude to estimates of risk associated with long fibers in the regulated fraction of airborne asbestos fibers. Rate ratio estimates for longer fibers are larger than those for shorter fibers, but thicker and thinner fibers do not differ as the toxicologically derived prior had expected. Credible intervals for fiber size-specific risk estimates overlap; thus, we cannot conclude that there are substantial differences in effect by fiber size. Nonetheless, our results suggest that some unregulated asbestos fibers may be associated with increased incidence of lung cancer.

Endothelial cell expression of haemoglobin α regulates nitric oxide signalling.

PubMed

Straub, Adam C; Lohman, Alexander W; Billaud, Marie; Johnstone, Scott R; Dwyer, Scott T; Lee, Monica Y; Bortz, Pamela Schoppee; Best, Angela K; Columbus, Linda; Gaston, Benjamin; Isakson, Brant E

2012-11-15

Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems. For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone, but the regulation of these processes is not adequately explained by simple NO diffusion from endothelium to smooth muscle. Here we report a new model for the regulation of NO signalling by demonstrating that haemoglobin (Hb) α (encoded by the HBA1 and HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells and enriched at the myoendothelial junction, where it regulates the effects of NO on vascular reactivity. Notably, this function is unique to Hb α and is abrogated by its genetic depletion. Mechanistically, endothelial Hb α haem iron in the Fe(3+) state permits NO signalling, and this signalling is shut off when Hb α is reduced to the Fe(2+) state by endothelial cytochrome b5 reductase 3 (CYB5R3, also known as diaphorase 1). Genetic and pharmacological inhibition of CYB5R3 increases NO bioactivity in small arteries. These data reveal a new mechanism by which the regulation of the intracellular Hb α oxidation state controls NOS signalling in non-erythroid cells. This model may be relevant to haem-containing globins in a broad range of NOS-containing somatic cells.

OVERVIEW OF USEPA'S WATER SUPPLY & WATER RESOURCES DIVISION PROGRAM

EPA Science Inventory

The United States Environmental Protection Agency's (USEPA) Water Supply and Water Resources Division (WSWRD) conducts a wide range of research on regulated and unregulated contaminants in drinking water, water distribution systems, homeland security, source water protection, and...

Contaminants of Emerging Concerns

EPA Science Inventory

In the past decade, the scientific community and general public have become increasingly aware of the potential for the presence of unregulated, and generally unmonitored contaminants, found at low concentrations (sub-ug/L) in surface, ground and drinking water. The most common...

Multiple organ failure - death of consumer protection?

PubMed

Steinman, H A; Jobson, M R

2010-07-15

The enormously profitable complementary medicines, dietary supplements and traditional medicines markets are largely unregulated internationally and South Africa. Attempts to ensure that consumers are not exposed to harmful or ineffective products have met with varying success around the world.

Enterovirus and Norovirus Monitoring under UCMR3

EPA Science Inventory

This presentation describes the Unregulated Contaminant Monitoring Rule round 3 (UCMR3) monitoring program for enterovirus and norovirus in groundwater. It provides the data on microbial indicators and virus occurrence during the monitoring period. Enteric virus occurrence was ab...

40 CFR 761.64 - Disposal of wastes generated as a result of research and development activities authorized under...

Code of Federal Regulations, 2010 CFR

2010-07-01

... includes: sample preparation, sample extraction, extract cleanup, extract concentration, addition of PCB... concentration of PCBs are unregulated for PCB disposal under this part. (b) All other wastes generated during...

Post regulation circuit with energy storage

DOEpatents

Ball, Don G.; Birx, Daniel L.; Cook, Edward G.

1992-01-01

A charge regulation circuit provides regulation of an unregulated voltage supply and provides energy storage. The charge regulation circuit according to the present invention provides energy storage without unnecessary dissipation of energy through a resistor as in prior art approaches.

77 FR 41334 - Request for Comments: Customer Due Diligence Requirements for Financial Institutions; Public Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... domestic or foreign entity, (2) regulated or unregulated for anti-money laundering purposes, etc.), (ii... little to no independent economic value. See FinCEN Guidance, FIN-2006-G014, ``Potential Money Laundering...

A Best Practices Guide to Talking to your Customers about Chronic Contaminants in Drinking Water

EPA Pesticide Factsheets

This fact sheet will help you understand the importance of communicating with the public about chronic contaminants - both regulated and unregulated. It also describes effective strategies for getting your message out.

A Best Practices Guide for Talking to your Customers about Chronic Contaminants in Drinking Water

EPA Pesticide Factsheets

This fact sheet helps one to understand the importance of communicating with the public about chronic contaminants – both regulated and unregulated. It also describes effective strategies for getting your message out.

Brassica carinata as an alternative oil crop for the production of biodiesel in Italy: engine performance and regulated and unregulated exhaust emissions.

PubMed

Cardone, Massimo; Prati, Maria Vittoria; Rocco, Vittorio; Seggiani, Maurizia; Senatore, Adolfo; Vitoloi, Sandra

2002-11-01

A comparison of the performance of Brassica carinata oil-derived biodiesel with a commercial rapeseed oil-derived biodiesel and petroleum diesel fuel is discussed as regards engine performance and regulated and unregulated exhaust emissions. B. carinata is an oil crop that can be cultivated in coastal areas of central-southern Italy, where it is more difficult to achieve the productivity potentials of Brassica napus (by far the most common rapeseed cultivated in continental Europe). Experimental tests were carried out on a turbocharged direct injection passenger car diesel engine fueled with 100% biodiesel. The unregulated exhaust emissions were characterized by determining the SOOT and soluble organic fraction content in the particulate matter, together with analysis of the content and speciation of polycyclic aromatic hydrocarbons, some of which are potentially carcinogenic, and of carbonyl compounds (aldehydes, ketones) that act as ozone precursors. B. carinata and commercial biodiesel behaved similarly as far as engine performance and regulated and unregulated emissions were concerned. When compared with petroleum diesel fuel, the engine test bench analysis did not show any appreciable variation of output engine torque values, while there was a significant difference in specific fuel consumption data at the lowest loads for the biofuels and petroleum diesel fuel. The biofuels were observed to produce higher levels of NOx concentrations and lower levels of PM with respect to the diesel fuel. The engine heat release analysis conducted shows that there is a potential for increased thermal NOx generation when firing biodiesel with no prior modification to the injection timing. It seems that, for both the biofuels, this behavior is caused by an advanced combustion evolution, which is particularly apparent at the higher loads. When compared with petroleum diesel fuel, biodiesel emissions contain less SOOT, and a greater fraction of the particulate was soluble. The analysis and speciation of the soluble organic fraction of biodiesel particulate suggest that the carcinogenic potential of the biodiesel emissions is probably lower than that of petroleum diesel. Its better adaptivity and productivity in clay and sandy-type soils and in semiarid temperate climate and the fact that the performance of its derived biodiesel is quite similar to commercial biodiesel make B. carinata a promising oil crop that could offer the possibility of exploiting the Mediterranean marginal areas for energetic purposes.

Regulated and unregulated emissions from highway heavy-duty diesel engines complying with U.S. Environmental Protection Agency 2007 emissions standards.

PubMed

Khalek, Imad A; Bougher, Thomas L; Merritt, Patrick M; Zielinska, Barbara

2011-04-01

As part of the Advanced Collaborative Emissions Study (ACES), regulated and unregulated exhaust emissions from four different 2007 model year U.S. Environmental Protection Agency (EPA)-compliant heavy-duty highway diesel engines were measured on an engine dynamometer. The engines were equipped with exhaust high-efficiency catalyzed diesel particle filters (C-DPFs) that are actively regenerated or cleaned using the engine control module. Regulated emissions of carbon monoxide, nonmethane hydrocarbons, and particulate matter (PM) were on average 97, 89, and 86% lower than the 2007 EPA standard, respectively, and oxides of nitrogen (NOx) were on average 9% lower. Unregulated exhaust emissions of nitrogen dioxide (NO2) emissions were on, average 1.3 and 2.8 times higher than the NO, emissions reported in previous work using 1998- and 2004-technology engines, respectively. However, compared with other work performed on 1994- to 2004-technology engines, average emission reductions in the range of 71-99% were observed for a very comprehensive list of unregulated engine exhaust pollutants and air toxic contaminants that included metals and other elements, elemental carbon (EC), inorganic ions, and gas- and particle-phase volatile and semi-volatile organic carbon (OC) compounds. The low PM mass emitted from the 2007 technology ACES engines was composed mainly of sulfate (53%) and OC (30%), with a small fraction of EC (13%) and metals and other elements (4%). The fraction of EC is expected to remain small, regardless of engine operation, because of the presence of the high-efficiency C-DPF in the exhaust. This is different from typical PM composition of pre-2007 engines with EC in the range of 10-90%, depending on engine operation. Most of the particles emitted from the 2007 engines were mainly volatile nuclei mode in the sub-30-nm size range. An increase in volatile nanoparticles was observed during C-DPF active regeneration, during which the observed particle number was similar to that observed in emissions of pre-2007 engines. However, on average, when combining engine operation with and without active regeneration events, particle number emissions with the 2007 engines were 90% lower than the particle number emitted from a 2004-technology engine tested in an earlier program.

Pre-treatment with vinpocetine protects against retinal ischemia.

PubMed

Nivison-Smith, Lisa; Khoo, Pauline; Acosta, Monica L; Kalloniatis, Michael

2017-01-01

Vinpocetine has been shown to have beneficial effects for tissues of the central nervous system subjected to ischemia and other related metabolic insults. We recently showed vinpocetine promotes glucose availability, prevents unregulated cation channel permeability and regulates glial reactivity when present during retinal ischemia. Less is known however about the ability of vinpocetine to protect against future ischemic insults. This study explores the effect of vinpocetine when used as a pre-treatment in an ex vivo model for retinal ischemia using cation channel permeability of agmatine (AGB) combined with immunohistochemistry as a measure for cell functionality. We found that vinpocetine pre-treatment reduced cation channel permeability and apoptotic marker immunoreactivity in the GCL and increased parvalbumin immunoreactivity of inner retinal neurons in the inner nuclear layer following ischemic insult. Vinpocetine pre-treatment also reduced Müller cell reactivity following ischemic insults of up to 120 min compared to untreated controls. Many of vinpocetine's effects however were transient in nature suggesting the drug can protect retinal neurons against future ischemic damage but may have limited long-term applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autoimmune thyrotoxicosis: diagnostic challenges.

PubMed

Ponto, Katharina A; Kahaly, George J

2012-09-01

Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. Published by Elsevier Inc.

INTRODUCTION TO THE VFARS WORKSHOP

EPA Science Inventory

A 1996 amendment to the Safe Drinking Water Act requires the EPA to periodically develop a list of currently unregulated contaminants and select five contaminants for regulatory decisions every five years. The National Research Council (NRC) was enlisted to assist the Agency in ...

Fatigue risk management in aviation maintenance : current best practices and potential future countermeasures.

DOT National Transportation Integrated Search

2011-06-01

The unregulated hours and frequent night work characteristic of maintenance can produce significant levels of : employee fatigue, with a resultant risk of maintenance error. Fatigue Risk Management Systems (FRMS) are : widely used to manage fatigue a...

Emerging Contaminants in the Drinking Water Cycle

EPA Science Inventory

In the past decade, the scientific community and general public have become increasingly aware of the potential for the presence of unregulated, and generally unmonitored contaminants, found at low concentrations (sub-µg/L) in surface, ground and drinking water. The most common...

Illegal, Unreported, and Unregulated Fishing Enforcement Act of 2009

THOMAS, 111th Congress

Rep. Bordallo, Madeleine Z. [D-GU-At Large

2009-02-13

Senate - 09/23/2009 Received in the Senate and Read twice and referred to the Committee on Commerce, Science, and Transportation. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

A Realistic International Economics.

ERIC Educational Resources Information Center

Culbertson, John M.

1987-01-01

Criticizes college textbooks for adopting a "party line" of laissez-faire economic doctrine which asserts the benefits of free trade. Offers an alternative interpretation of international trade, covering such topics as the effect of unregulated international trade on wage levels, and international lending. (JDH)

75 FR 8063 - Stakeholder Meeting Regarding Revisions to the Unregulated Contaminant Monitoring Regulation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

... meeting will be held at the Crystal City Marriott at Reagan National Airport, in the Salon D Room, at 1999 Jefferson Davis Highway, Arlington, VA 22202. The hotel is located near the Ronald Reagan Washington...

Toxicological Review of Cyanobacterial Toxins: Anatoxin-a (External Review Draft)

EPA Science Inventory

The National Center for Environmental Assessment has prepared the Toxicological Reviews of Cyanobacterial Toxins: Anatoxin-a, Cylindrospermopsin and Microcystins (LR, RR, YR and LA) as a series of dose-response assessments to support the health assessment of unregulated contamina...

Toxicological Review of Cyanobacterial Toxins: Cylindrospermopsin (External Review Draft)

EPA Science Inventory

The National Center for Environmental Assessment has prepared the Toxicological Reviews of Cyanobacterial Toxins: Anatoxin-a, Cylindrospermopsin and Microcystins (LR, RR, YR and LA) as a series of dose-response assessments to support the health assessment of unregulated contamina...

Wild turkey

Treesearch

William F. Moore; John C. Kilgo; William D. Carlisle; Michael B. Caudell

2005-01-01

Wild turkeys (Meleagris gallopavo) were once abundant throughout the southeast, but unregulated hunting and habitat destruction greatly reduced populations to a few thousand birds by 1930 (Hust and Dickson 1992). Though intensive restocking efforts beginning in the 1950s, protection from hunting, and reforestation, southeastern turkey populations...

Real-time Raman and SRS imaging of living human macrophages reveals cell-to-cell heterogeneity and dynamics of lipid uptake.

PubMed

Stiebing, Clara; Meyer, Tobias; Rimke, Ingo; Matthäus, Christian; Schmitt, Michael; Lorkowski, Stefan; Popp, Jürgen

2017-09-01

Monitoring living cells in real-time is important in order to unravel complex dynamic processes in life sciences. In particular the dynamics of initiation and progression of degenerative diseases is intensely studied. In atherosclerosis the thickening of arterial walls is related to high lipid levels in the blood stream, which trigger the lipid uptake and formation of droplets as neutral lipid reservoirs in macrophages in the arterial wall. Unregulated lipid uptake finally results in foam cell formation, which is a hallmark of atherosclerosis. In previous studies, the uptake and storage of different fatty acids was monitored by measuring fixed cells. Commonly employed fluorescence staining protocols are often error prone because of cytotoxicity and unspecific fluorescence backgrounds. By following living cells with Raman spectroscopic imaging, lipid uptake of macrophages was studied with real-time data acquisition. Isotopic labeling using deuterated palmitic acid has been combined with spontaneous and stimulated Raman imaging to investigate the dynamic process of fatty acid storage in human macrophages for incubation times from 45 min to 37 h. Striking heterogeneity in the uptake rate and the total concentration of deuterated palmitic acid covering two orders of magnitude is detected in single as well as ensembles of cultured human macrophages. SRS signal of deuterated palmitic acid measured at the CD vibration band after incorporation into living macrophages. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation

PubMed Central

2010-01-01

Background Appropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death. Results We present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1. Conclusions We propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast. PMID:21108829

Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review.

PubMed

Benoit, Eric; O'Donnell, Thomas F; Patel, Amit N

2013-01-01

Researchers have accumulated a decade of experience with autologous cell therapy in the treatment of critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of cell therapy in CLI. We searched the literature for clinical trials of autologous cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Safety analysis included evaluation of death, cancer, unregulated angiogenesis, and procedural adverse events such as bleeding. Efficacy analysis included the clinical endpoints amputation and death as well as functional and surrogate endpoints. We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received cell therapy. The overall adverse event rate was low (4.2%). Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in cancer incidence when analyzed against population rates. With regard to efficacy, cell therapy patients had a significantly lower amputation rate than control patients (OR 0.36, p = 0.0004). Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of amputation and death. Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and cancer and treatment with cell therapy decreases the risk of amputation. Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.

Emerging Contaminants in the Drinking Water Cycle.

EPA Science Inventory

In the past decade, the scientific community and general public have become increasingly aware of the potential for the presence of unregulated, and generally unmonitored contaminants, found at low concentrations (sub-g/L) in surface, ground and drinking water. The most common...

Relative Mesothelioma Potencies for Unregulated Respirable Elongated Mineral and Synthetic Particles

EPA Science Inventory

For decades uncertainties and contradictions have surrounded the issue of whether exposures to respirable elongated mineral and synthetic particles (REMPs and RESPs) present health risks such as those recognized for exposures to elongated asbestiform mineral particles from the fi...

Safety concerns of herbal products and traditional Chinese herbal medicines: Dehydropyrrolizidine alkaloids and aristolochic acid

USDA-ARS?s Scientific Manuscript database

In many countries, including the United States, herbal supplements, tisanes and vegetable products, including traditional Chinese medicines, are largely unregulated and their content is not registered, monitored or verified. Consequently, potent plant toxins including dehydropyrrolizidine alkaloids ...

Bilogical Treatment for Ammonia Oxidation in Drinking Water Facilities

EPA Science Inventory

Ammonia is an unregulated compound, but is naturally occurring in many drinking water sources. It is also used by some treatment facilities to produce chloramines for disinfection purposes. Because ammonia is non-toxic, its presence in drinking water is often disregarded. Thro...

NEW DISINFECTION BY-PRODUCT ISSUES: EMERGING DBP'S AND ALTERNATIVE ROUTES OF EXPOSURE

EPA Science Inventory

This paper discusses current issues with drinking water disinfection by-products (DBPs), which include emerging (unregulated) DBPs that can be formed at greater levels with alternative disinfectants (as compared to chlorine) and routes of human exposure (which include inhalation ...

U.S. Environmental Protection Agency and Emerging Contaminants

EPA Science Inventory

In the past decade, the scientific community and general public have become increasingly aware of the potential for the presence of unregulated, and generally unmonitored contaminants, found at low concentrations (sub-ug/L) in surface, ground and drinking water. The most common...

PHARMACEUTICALS IN THE ENVIRONMENT: OVERVIEW OF SIGNIFICANCE, CONCERNS, AND SOLUTIONS

EPA Science Inventory

Pharmaceuticals and personal care products (PPCPs) comprise large, diverse arrays of chemicals that can occur in the environment as unregulated pollutants. They originate largely from the combined activities and actions of multitudes of individuals as well as from veterinary and ...

EMERGING CONTAMINANTS IN THE WATER CYCLE: FATE AND TRANSPORT

EPA Science Inventory

In the past decade, the scientific community and general public have become increasingly aware of the potential for the presence of unregulated, and generally unmonitored contaminants, found at low concentrations in surface, ground and drinking water. The most common pathway for...

Emerging Contaminants in the Drinking Water Cycle - MCEARD

EPA Science Inventory

In the past decade, the scientific community and general public have become increasingly aware of the potential for the presence of unregulated, and generally unmonitored contaminants, found at low concentrations (sub-g/L) in surface, ground and drinking water. The most common...

Iatrogenic greenhouse gases: the role of anaesthetic agents.

PubMed

Uzoigwe, Chika E; Sanchez Franco, Luis C; Forrest, Michael D

2016-01-01

The contribution of health-care activity to climate change is not negligible and is increasing. Anaesthetic greenhouse gases, in particular the fluranes, have a much more potent global warming capacity, volume for volume, than carbon dioxide, but their emissions remain completely unregulated.

Techniques for estimating flood peak discharges for unregulated streams and streams regulated by small floodwater retarding structures in Oklahoma

USGS Publications Warehouse

Tortorelli, R.L.; Bergman, D.L.

1985-01-01

Statewide regression relations for Oklahoma were determined for estimating peak discharge of floods for selected recurrence intervals from 2 to 500 years. The independent variables required for estimating flood discharge for rural streams are contributing drainage area and mean annual precipitation. Main-channel slope, a variable used in previous reports, was found to contribute very little to the accuracy of the relations and was not used. The regression equations are applicable for watersheds with drainage areas less than 2,500 square miles that are not significantly affected by regulation from manmade works. These relations are presented in graphical form for easy application. Limitations on the use of the regression relations and the reliability of regression estimates for rural unregulated streams are discussed. Basin and climatic characteristics, log-Pearson Type III statistics and the flood-frequency relations for 226 gaging stations in Oklahoma and adjacent states are presented. Regression relations are investigated for estimating flood magnitude and frequency for watersheds affected by regulation from small FRS (floodwater retarding structures) built by the U.S. Soil Conservation Service in their watershed protection and flood prevention program. Gaging-station data from nine FRS regulated sites in Oklahoma and one FRS regulated site in Kansas are used. For sites regulated by FRS, an adjustment of the statewide rural regression relations can be used to estimate flood magnitude and frequency. The statewide regression equations are used by substituting the drainage area below the FRS, or drainage area that represents the percent of the basin unregulated, in the contributing drainage area parameter to obtain flood-frequency estimates. Flood-frequency curves and flow-duration curves are presented for five gaged sites to illustrate the effects of FRS regulation on peak discharge.

Formation of regulated and unregulated disinfection byproducts during chlorination of algal organic matter extracted from freshwater and marine algae.

PubMed

Liu, Chao; Ersan, Mahmut S; Plewa, Michael J; Amy, Gary; Karanfil, Tanju

2018-05-29

Seasonal algal blooms in freshwater and marine water can increase the input of algal organic matter (AOM) to the pool of dissolved organic matter. The impact of bromide (Br - ) and iodide (I - ) on the formation of regulated and unregulated disinfection byproducts (DBPs) was studied from chlorination of AOM solutions extracted from three species of cultured isolates of freshwater and marine algae (Microcystis aeruginosa (MA), Synechococcus (SYN), and Alexandrium tamarense (AT)). Comparable concentrations of DBPs were formed from three types of AOM. In the absence of Br - , trihalomethanes (THMs), haloacetic acids (HAAs), and haloacetaldehydes (HALs) were the main groups of DBP formed, and haloacetonitriles (HANs) were formed at lower concentrations. In contrast, the formation of iodinated THMs was <8 nM (1.7 μg/L) since most of initial I - was oxidized to iodate. Increasing initial Br - concentrations increased the formation of THMs and HANs, while concentrations of total organic halogen and HAA remained stable. On the contrary, total HAL concentrations decreased due to the instability of bromated HALs. Decreasing the specific UV absorbance (SUVA) value of AOM favours bromine substitution since bromine more preferentially reacts with low reactivity organic matter than chlorine. Increasing the pH enhanced the formation of THMs but decreased the formation of HANs. Concentrations of HANs and HALs decreased at high pH (e.g., 9.0), high initial chlorine concentration and long reaction time due to the decomposition. Based on the cytotoxicity calculations, unregulated HANs and HALs were the main contributors for the total toxicity of DBPs measured, even though based on the weight regulated THMs and HAAs predominated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determining the effects of dams on subdaily variation in river flows at a whole-basin scale

USGS Publications Warehouse

Zimmerman, J.K.H.; Letcher, B.H.; Nislow, K.H.; Lutz, K.A.; Magilligan, F.J.

2010-01-01

River regulation can alter the frequency and magnitude of subdaily flow variations causing major impacts on ecological structure and function. We developed an approach to quantify subdaily flow variation for multiple sites across a large watershed to assess the potential impacts of different dam operations (flood control, run-of-river hydropower and peaking hydropower) on natural communities. We used hourly flow data over a 9-year period from 30 stream gages throughout the Connecticut River basin to calculate four metrics of subdaily flow variation and to compare sites downstream of dams with unregulated sites. Our objectives were to (1) determine the temporal scale of data needed to characterize subdaily variability; (2) compare the frequency of days with high subdaily flow variation downstream of dams and unregulated sites; (3) analyse the magnitude of subdaily variation at all sites and (4) identify individual sites that had subdaily variation significantly higher than unregulated locations. We found that estimates of flow variability based on daily mean flow data were not sufficient to characterize subdaily flow patterns. Alteration of subdaily flows was evident in the number of days natural ranges of variability were exceeded, rather than in the magnitude of subdaily variation, suggesting that all rivers may exhibit highly variable subdaily flows, but altered rivers exhibit this variability more frequently. Peaking hydropower facilities had the most highly altered subdaily flows; however, we observed significantly altered ranges of subdaily variability downstream of some flood-control and run-of-river hydropower dams. Our analysis can be used to identify situations where dam operating procedures could be modified to reduce the level of hydrologic alteration. ?? 2009 John Wiley & Sons, Ltd.

Grid-connected wind and photovoltaic system

NASA Astrophysics Data System (ADS)

Devabakthuni, Sindhuja

The objective of this thesis is to design a grid connected wind and photovoltaic system. A new model of converter control was designed which maintains the voltage of the bus to grid as constant when combined system of solar and wind is connected to AC bus. The model is designed to track maximum power at each point irrespective of changes in irradiance, temperature and wind speed which affects the power supplied to grid. Solar power from the sun is not constant as it is affected by changes in irradiances and temperature. Even the wind power is affected by wind speed. A MPPT controller was designed for both systems. A boost converter is designed which uses the pulses from MPPT controller to boost the output. Wind system consists of wind turbine block from the MATLAB with a pitch angle controller to maintain optimum pitch angle. The output from wind turbine is connected to a permanent magnet synchronous generator. The unregulated DC output from the photovoltaic system is directly given to boost converter. The AC output from the wind system is given to an uncontrolled rectifier to get a unregulated DC output. The unregulated DC output goes to the boost converter. A voltage source inverter was designed which converts the rectified DC output from the boost converter to AC power. The inverter is designed to maintain constant AC bus voltage irrespective of the disturbances in the power supply. Photovoltaic and wind systems are individually designed for 5KW each in MATLAB-Simulink environment. In this thesis, the models were subjected to changes in irradiance, temperature and wind speed and the results were interpreted. The model was successful in tracking maximum at every instant and the AC bus voltage was maintained constant throughout the simulation.

Project Catch: A space based solution to combat illegal, unreported and unregulated fishing. Part I: Vessel monitoring system

NASA Astrophysics Data System (ADS)

Detsis, Emmanouil; Brodsky, Yuval; Knudtson, Peter; Cuba, Manuel; Fuqua, Heidi; Szalai, Bianca

2012-11-01

Space assets have a unique opportunity to play a more active role in global resource management. There is a clear need to develop resource management tools in a global framework. Illegal, Unregulated and Unreported (IUU) fishing is placing pressure on the health and size of fishing stocks around the world. Earth observation systems can provide fishery management organizations with cost effective monitoring of large swaths of ocean. Project Catch is a fisheries management project based upon the complimentary, but independent Catch-VMS and Catch-GIS systems. Catch-VMS is a Vessel Monitoring System with increased fidelity over existing offerings. Catch-GIS is a Geographical Information System that combines VMS information with existing Earth Observation data and other data sources to identify Illegal, Unregulated and Unreported (IUU) fishing. Project Catch was undertaken by 19 Masters students from the 2010 class of the International Space University. In this paper, the space-based system architecture of Project Catch is presented and analyzed. The rationale for the creation of the system, as well as the engineering trade-off studies in its creation, are discussed. The Catch-VMS proposal was envisaged in order to address two specific problems: (1) the expansion of illegal fishing to high-latitude regions where existing satellite systems coverage is an issue and (2) the lack of coverage in remote oceanic regions due to reliance on coastal-based monitoring. Catch-VMS utilizes ship-borne transponders and hosted-payload receivers on a Global Navigation Satellite System in order to monitor the position and activity of compliant fishing vessels. Coverage is global and continuous with multiple satellites in view providing positional verification through multilateration techniques. The second part of the paper briefly describes the Catch-GIS system and investigates its cost of implementation.

COMPARISON OF CLEAN DIESEL BUSES TO CNG BUSES

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

Lowell, D.; Parsley, W.; Bush,C

2003-08-24

Using previously published data on regulated and unregulated emissions, this paper will compare the environmental performance of current generation transit buses operated on compressed natural gas (CNG) to current generation transit buses operated on ultra low sulfur diesel fuel (ULSD) and incorporating diesel particulate filters (DPF). Unregulated emissions evaluated include toxic compounds associated with adverse health effects (carbonyl, PAH, NPAH, benzene) as well as PM particle count and size distribution. For all regulated and unregulated emissions, both technologies are shown to be comparable. DPF equipped diesel buses and CNG buses have virtually identical levels of PM mass emissions and particlemore » number emissions. DPF-equipped diesel buses have lower HC and CO emissions and lower emissions of toxic substances such as benzene, carbonyls and PAHs than CNG buses. CNG buses have lower NOx emissions than DPF-equipped buses, though CNG bus NOx emissions are shown to be much more variable. In addition, this paper will compare the capital and operating costs of CNG and DPF-equipped buses. The cost comparison is primarily based on the experience of MTA New York City Transit in operating CNG buses since 1995 and DPF-equipped buses fueled with ULSD since 2001. Published data on the experience of other large transit agencies in operating CNG buses is used to validate the NYCT experience. The incremental cost (compared to ''baseline'' diesel) of operating a typical 200-bus depot is shown to be six times higher for CNG buses than for ''clean diesel'' buses. The contributors to this increased cost for CNG buses are almost equally split between increased capital costs for purchase of buses and installation of fueling infrastructure, and increased operating costs for purchase of fuel, bus maintenance, and fuel station maintenance.« less

Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

NASA Astrophysics Data System (ADS)

Senavirathne, Gayan; Bertram, Jeffrey G.; Jaszczur, Malgorzata; Chaurasiya, Kathy R.; Pham, Phuong; Mak, Chi H.; Goodman, Myron F.; Rueda, David

2015-12-01

Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ~5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer.

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Airway Fibrinogenolysis and the Initiation of Allergic Inflammation

PubMed Central

Millien, Valentine Ongeri; Lu, Wen; Mak, Garbo; Yuan, Xiaoyi; Knight, J. Morgan; Porter, Paul; Kheradmand, Farrah

2014-01-01

The past 15 years of allergic disease research have produced extraordinary improvements in our understanding of the pathogenesis of airway allergic diseases such as asthma. Whereas it was previously viewed as largely an immunoglobulin E-mediated process, the gradual recognition that T cells, especially Type 2 T helper (Th2) cells and Th17 cells, play a major role in asthma and related afflictions has inspired clinical trials targeting cytokine-based inflammatory pathways that show great promise. What has yet to be clarified about the pathogenesis of allergic inflammatory disorders, however, are the fundamental initiating factors, both exogenous and endogenous, that drive and sustain B- and T-cell responses that underlie the expression of chronic disease. Here we review how proteinases derived from diverse sources drive allergic responses. A central discovery supporting the proteinase hypothesis of allergic disease pathophysiology is the role played by airway fibrinogen, which in part appears to serve as a sensor of unregulated proteinase activity and which, when cleaved, both participates in a novel allergic signaling pathway through Toll-like receptor 4 and forms fibrin clots that contribute to airway obstruction. Unresolved at present is the ultimate source of airway allergenic proteinases. From among many potential candidates, perhaps the most intriguing is the possibility such enzymes derive from airway fungi. Together, these new findings expand both our knowledge of allergic disease pathophysiology and options for therapeutic intervention. PMID:25525732

Cancer and necroptosis: friend or foe?

PubMed

Philipp, Stephan; Sosna, Justyna; Adam, Dieter

2016-06-01

Regulated cell death is one major factor to ensure homoeostasis in multicellular organisms. For decades, apoptosis was considered as the sole form of regulated cell death, whereas necrosis was believed to be accidental and unregulated. Due to this view, research on necrosis was somewhat neglected, especially in the field of anti-cancer treatment. However, new interest in necrosis has been sparked by the recent discovery of different forms of necrosis that show indeed regulated pathways. More and more studies now address the molecular pathways of regulated necrosis and its connections within the cellular signaling networks. Necroptosis, a subform of regulated necrosis, has so far hardly been focused on with regard to a future treatment of cancer patients and may emerge as a novel and effective approach to eliminate tumor cells. However, and similar to apoptosis, tumor cells can develop resistances against necroptosis to ensure their own survival. In this context, new molecules that enhance necroptosis are currently being identified to overcome such resistances. This review discusses cancer and necroptosis as friends or foes, i.e. the options to exploit necroptosis in anti-cancer therapies ("foes"), but also potential limitations that may block or actually cause necroptosis to act in a protumoral manner ("friends"). The balance between these two possible roles will determine whether necroptosis can indeed be used as a promising tool for early diagnosis of tumors, prevention of metastasis and anti-cancer treatment.

Safety concerns of herbal products and traditional Chinese herbal medicines: Dehydopyrrolizidine alkaloids and aristolochic acid

USDA-ARS?s Scientific Manuscript database

In many countries, including the United States, herbal supplements, tisanes and vegetable products including traditional Chinese medicines are largely unregulated and their content is not registered, monitored or verified. Consequently potent plant toxins including dehydopyrrolizidine alkaloids and...

DISTRIBUTION SYSTEM EVALUATIONS OF THE CONTAMINANT CANDIDATE LIST

EPA Science Inventory

The Safe Drinking Water Act (SDWA), as amended in 1996, requires EPA to establish a list of unregulated microbiological and chemical contaminants to aid in priority setting for the Agency's drinking water program. The list is referred to as the Contaminant Candidate List (CCL). A...

BACTERIAL PATHOGENIC RESEARCH IN RESPONSE TO CONTAMINANT CANDIDATE LIST NEEDS

EPA Science Inventory

The Safe Drinking Water Act, as amended in 1996, requires EPA to establish a Contaminant Candidate List (CCL) of unregulated microbiological and chemical contaminants to aid in priority setting for the Agency's drinking water program. At predetermined intervals the Agency must s...

Health Risk Estimation for Unregulated DBPs in Chloraminated Drinking Water

EPA Science Inventory

Disinfection by-products (DBPs) are formed when natural organic matter (NOM) reacts with chemical oxidants in the water disinfection process. Halogenated DBPs are both cytotoxic and genotoxic, which have the potential to cause adverse health effects (1). Currently, 4 species of t...

An historical perspective on eutrophication in the Pensacola Bay Estuary, FL, USA

EPA Science Inventory

In this chapter, we provide a brief description of the Pensacola Bay estuary, examining the available historical data for evidence of trends in eutrophication within the estuary. Common to many industrialized estuaries, Pensacola Bay has been subjected to unregulated point source...

Chloride Released from Three Permeable Pavement Surfaces after Winter Salt Application

EPA Science Inventory

EPA does not classify chloride as a priority pollutant. It is often unregulated in stormwater runoff but has been a target stressor for Total Maximum Daily Load (TMDL) allotments developed for multiple waterbodies. Previous research has shown that road salt applications increas...

STUDIES ON THE USE OF AMPICILLIN-DEXTRIN AGAR ASAS AEROMONAS RECOVERY MEDIUM

EPA Science Inventory

The Contaminant Candidate List (CCL) includes the unregulated chemical and microbiological contaminants the EPA has identified as possibly posing a significant public risk to consumers if present in drinking water (1). There are three bacterial species listed in the CCL (Aeromon...

PHARMACEUTICALS IN THE ENVIRONMENT: OVERVIEW OF SIGNIFICANCE, CONCERNS AND SOLUTIONS

EPA Science Inventory

Pharmaceuticals and personal care products (PPCPs) comprise a large and diverse array of unregulated pollutants that can occur in the environment from the combined activities and actions of multitudes of individuals as well as from veterinary and agricultural use
(http://epa....

Toxicological Review of Cyanobacterial Toxins: Microcystins Lr, Rr, Yr and La (External Review Draft)

EPA Science Inventory

The National Center for Environmental Assessment has prepared the Toxicological Reviews of Cyanobacterial Toxins: Anatoxin-a, Cylindrospermopsin and Microcystins (LR, RR, YR and LA) as a series of dose-response assessments to support the health assessment of unregulated contamina...

Unregulated Drinking Water Systems.

PubMed

Farquhar, Doug

2018-02-01

(1)One in 9 Americans gets his or her drinking water from a private well. (2) An estimated 20 percent of private wells have contaminants above Environmental Protection Agency drinking water standards.(3) Disease outbreaks from private wells are increasing, according to the Centers for Disease Control and Prevention.

Standardization of exhaled breath condensate (EBC) collection using a feedback regulated breathing pattern

EPA Science Inventory

Collection of exhaled breath condensate (EBC) fluid by cooling of expired breath is a potentially valuable approach for the detection of biomarkers associated with disease or exposure to xenobiotics. EBC is generally collected using unregulated breathing patterns, perceived to el...

Characterization of exhaust emissions from diesel-powered passenger cars with particular reference to unregulated components

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

Lies, K.H.; Postulka, A.; Gring, H.

Besides regulated components VW's research program in the field of characterization of diesel emissions comprises a detailed analysis of the particulates and a comprehensive study of a number of unregulated gaseous compounds. The following chemical compounds and classes of compounds are measured: particulates, traces of metals, major elements, sulfates, sulfur dioxide, hydrogen sulfide, hydrogen cyanide, aldehydes, ammonia, phenols, individual hydrocarbons, and odor (DOAS). The test fleet of this investigation included a number of VW and Audi cars equipped with 4-, and 5-cylinder diesel engines (naturally aspirated and turbocharged). All measurements were performed on a chassis dynamometer in accordance with themore » specification of the known US-test-procedures: Federal Test Procedure, Sulfate Emission Test, Fuel Economy Test. For sampling , in principle, the dilution tunnel technique was used combined with an automatically working collection system. This micro-processor controlled system involves 13 individual sample lines, 8 for gaseous and 5 for particulate components.« less

Influenza vaccination and decisional conflict among regulated and unregulated direct nursing care providers in long-term-care homes.

PubMed

Sullivan, Shannon M; Pierrynowski-Gallant, Donna; Chambers, Larry; O'Connor, Annette; Bowman, Sherry; McNeil, Shelly; Strang, Robert; Knoefel, Frank

2008-02-01

The purpose of this study was to determine whether direct nursing care providers have decisional conflict about receiving influenza vaccinations and characteristics associated with decisional conflict. The researchers used a self-administered questionnaire mailed to direct nursing care providers in two long-term-care organizations. Most direct nursing care providers in both organizations (80% and 93%, respectively) intended to get the influenza vaccine. Unregulated direct nursing care providers had more decisional conflict than regulated providers, especially related to feeling uninformed about the pros and cons of influenza vaccination. Unclear valuing of the pros and cons of influenza vaccination was related to the age of the direct care providers in both organizations. Decisional conflict and influenza vaccination practices may be determined, in part, by age and by the culture of a health care organization. A decision aid to improve knowledge and clarify values may improve decision quality and increase influenza vaccination rates.

Estimating magnitude and frequency of peak discharges for rural, unregulated, streams in West Virginia

USGS Publications Warehouse

Wiley, J.B.; Atkins, John T.; Tasker, Gary D.

2000-01-01

Multiple and simple least-squares regression models for the log10-transformed 100-year discharge with independent variables describing the basin characteristics (log10-transformed and untransformed) for 267 streamflow-gaging stations were evaluated, and the regression residuals were plotted as areal distributions that defined three regions of the State, designated East, North, and South. Exploratory data analysis procedures identified 31 gaging stations at which discharges are different than would be expected for West Virginia. Regional equations for the 2-, 5-, 10-, 25-, 50-, 100-, 200-, and 500-year peak discharges were determined by generalized least-squares regression using data from 236 gaging stations. Log10-transformed drainage area was the most significant independent variable for all regions.Equations developed in this study are applicable only to rural, unregulated, streams within the boundaries of West Virginia. The accuracy of estimating equations is quantified by measuring the average prediction error (from 27.7 to 44.7 percent) and equivalent years of record (from 1.6 to 20.0 years).

Techniques for estimating flood-depth frequency relations for streams in West Virginia

USGS Publications Warehouse

Wiley, J.B.

1987-01-01

Multiple regression analyses are applied to data from 119 U.S. Geological Survey streamflow stations to develop equations that estimate baseline depth (depth of 50% flow duration) and 100-yr flood depth on unregulated streams in West Virginia. Drainage basin characteristics determined from the 100-yr flood depth analysis were used to develop 2-, 10-, 25-, 50-, and 500-yr regional flood depth equations. Two regions with distinct baseline depth equations and three regions with distinct flood depth equations are delineated. Drainage area is the most significant independent variable found in the central and northern areas of the state where mean basin elevation also is significant. The equations are applicable to any unregulated site in West Virginia where values of independent variables are within the range evaluated for the region. Examples of inapplicable sites include those in reaches below dams, within and directly upstream from bridge or culvert constrictions, within encroached reaches, in karst areas, and where streams flow through lakes or swamps. (Author 's abstract)

Exhaust emissions from light- and heavy-duty vehicles: chemical composition, impact of exhaust after treatment, and fuel parameters.

PubMed Central

Westerholm, R; Egebäck, K E

1994-01-01

This paper presents results from the characterization of vehicle exhaust that were obtained primarily within the Swedish Urban Air Project, "Tätortsprojektet." Exhaust emissions from both gasoline- and diesel-fueled vehicles have been investigated with respect to regulated pollutants (carbon monoxide [CO], hydrocarbon [HC], nitrogen oxides [NOx], and particulate), unregulated pollutants, and in bioassay tests (Ames test, TCDD receptor affinity tests). Unregulated pollutants present in both the particle- and the semi-volatile phases were characterized. Special interest was focused on the impact of fuel composition on heavy-duty diesel vehicle emissions. It was confirmed that there exists a quantifiable relationship between diesel-fuel variables of the fuel blends, the chemical composition of the emissions, and their biological effects. According to the results from the multivariate analysis, the most important fuel parameters are: polycyclic aromatic hydrocarbons (PAH) content, 90% distillation point, final boiling point, specific heat, aromatic content, density, and sulfur content. PMID:7529699

The Wiley Protocol: an analysis of ethical issues.

PubMed

Rosenthal, M Sara

2008-01-01

: This review explores the ethical issues surrounding an unregulated protocol that is advertised to women through consumer books, the popular press, and the Internet, known as the Wiley Protocol. : A content analysis of relevant documents was conducted, followed by telephone interviews with investigators and former participants to verify facts. : The Wiley Protocol is an example of unregulated research involving potentially unsafe doses of bioidentical hormones applied to an unselected population of women. This protocol fails to use research ethics guidelines such as informed consent, investigator expertise, sound methodology, standardized data collection, and data safety monitoring. : Clinical ethics breaches include lack of full disclosure of risks, coercive influences, as well as misinformation about the study goals and safety. Breaches of professional ethics include conflicts of interest with respect to financial incentives, patient accrual, and inadequate standards of awareness and proficiency among participating investigators. It appears evident that the failure to regulate nutriceuticals and products of compounding pharmacy has provided the opportunity for these ethical violations.

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

NASA Astrophysics Data System (ADS)

Raju, G. J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G. A. V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P. V. B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-06-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors.

Radiology Resident Supply and Demand: A Regional Perspective.

PubMed

Pfeifer, Cory M

2017-09-01

Radiology was subject to crippling deficits in the number of jobs available to graduates of training programs from 2012 through 2015. As the specialty transitions to the assimilation of osteopathic training programs and the welcoming of direct competition from new integrated interventional radiology programs, the assessment of growth in radiology training positions over the 10 years preceding this pivotal time will serve to characterize the genesis of the crisis while inspiring stakeholders to avoid similar negative fluctuations in the future. The number of per capita radiology trainees in each region was derived from data published by the National Resident Matching Program, as were annual match statistics over the years 2012 through 2016. Data regarding new interventional radiology and diagnostic radiology enrollees were also obtained from the National Resident Matching Program. The seven states with the most per capita radiology residents were in the Mid-Atlantic and Northeastern United States in both 2006 and 2016, and three of these seven also showed the greatest per capita growth over the course of the 10 years studied. New radiology programs were accredited during the peak of the job shortage. Integrated interventional radiology training created 24 de novo radiology residents in the 2017 match. Fill rates are weakly positively correlated with program size. Unregulated radiology program growth persisted during the decade leading up to 2016. The region with the fewest jobs available since 2012 is also home to the greatest number of per capita radiology residents. Numerous published opinions during the crisis did not result in enforced policy change. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Necroptosis, necrostatins and tissue injury

PubMed Central

Smith, Christopher CT; Yellon, Derek M

2011-01-01

Abstract Cell death is an integral part of the life of an organism being necessary for the maintenance of organs and tissues. If, however, cell death is allowed to proceed unrestricted, tissue damage and degenerative disease may ensue. Until recently, three morphologically distinct types of cell death were recognized, apoptosis (type I), autophagy (type II) and necrosis (type III). Apoptosis is a highly regulated, genetically determined mechanism designed to dismantle cells systematically (e.g. cells that are no longer functionally viable), via protease (caspase) action, and maintain homeostasis. Autophagy is responsible for the degradation of cytoplasmic material, e.g. proteins and organelles, through autophagosome formation and subsequent proteolytic degradation by lysosomes, and is normally considered in the context of survival although it is sometimes associated with cell death. Necrosis was formerly considered to be an accidental, unregulated form of cell death resulting from excessive stress, although it has been suggested that this is an over-simplistic view as necrosis may under certain circumstances involve the mobilization of specific transduction mechanisms. Indeed, recently, an alternative death pathway, termed necroptosis, was delineated and proposed as a form of ‘programmed necrosis’. Identified with the aid of specific inhibitors called necrostatins, necroptosis shares characteristics with both necrosis and apoptosis. Necroptosis involves Fas/tumour necrosis factor-α death domain receptor activation and inhibition of receptor-interacting protein I kinase, and it has been suggested that it may contribute to the development of neurological and myocardial diseases. Significantly, necrostatin-like drugs have been mooted as possible future therapeutic agents for the treatment of degenerative conditions. PMID:21564515

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

PubMed

Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Nucleocytoplasmic protein translocation during mitosis in the social amoebozoan Dictyostelium discoideum.

PubMed

O'Day, Danton H; Budniak, Aldona

2015-02-01

Mitosis is a fundamental and essential life process. It underlies the duplication and survival of all cells and, as a result, all eukaryotic organisms. Since uncontrolled mitosis is a dreaded component of many cancers, a full understanding of the process is critical. Evolution has led to the existence of three types of mitosis: closed, open, and semi-open. The significance of these different mitotic species, how they can lead to a full understanding of the critical events that underlie the asexual duplication of all cells, and how they may generate new insights into controlling unregulated cell division remains to be determined. The eukaryotic microbe Dictyostelium discoideum has proved to be a valuable biomedical model organism. While it appears to utilize closed mitosis, a review of the literature suggests that it possesses a form of mitosis that lies in the middle between truly open and fully closed mitosis-it utilizes a form of semi-open mitosis. Here, the nucleocytoplasmic translocation patterns of the proteins that have been studied during mitosis in the social amoebozoan D. discoideum are detailed followed by a discussion of how some of them provide support for the hypothesis of semi-open mitosis. © 2014 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

Nitric oxide is required for the auxin-induced activation of NADPH-dependent thioredoxin reductase and protein denitrosylation during root growth responses in arabidopsis.

PubMed

Correa-Aragunde, Natalia; Cejudo, Francisco J; Lamattina, Lorenzo

2015-09-01

Auxin is the main phytohormone controlling root development in plants. This study uses pharmacological and genetic approaches to examine the role of auxin and nitric oxide (NO) in the activation of NADPH-dependent thioredoxin reductase (NTR), and the effect that this activity has on root growth responses in Arabidopsis thaliana. Arabidopsis seedlings were treated with auxin with or without the NTR inhibitors auranofin (ANF) and 1-chloro-2, 4-dinitrobenzene (DNCB). NTR activity, lateral root (LR) formation and S-nitrosothiol content were measured in roots. Protein S-nitrosylation was analysed by the biotin switch method in wild-type arabidopsis and in the double mutant ntra ntrb. The auxin-mediated induction of NTR activity is inhibited by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), suggesting that NO is downstream of auxin in this regulatory pathway. The NTR inhibitors ANF and DNCB prevent auxin-mediated activation of NTR and LR formation. Moreover, ANF and DNCB also inhibit auxin-induced DR5 : : GUS and BA3 : : GUS gene expression, suggesting that the auxin signalling pathway is compromised without full NTR activity. Treatment of roots with ANF and DNCB increases total nitrosothiols (SNO) content and protein S-nitrosylation, suggesting a role of the NTR-thioredoxin (Trx)-redox system in protein denitrosylation. In agreement with these results, the level of S-nitrosylated proteins is increased in the arabidopsis double mutant ntra ntrb as compared with the wild-type. The results support for the idea that NTR is involved in protein denitrosylation during auxin-mediated root development. The fact that a high NO concentration induces NTR activity suggests that a feedback mechanism to control massive and unregulated protein S-nitrosylation could be operating in plant cells. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Punching loan sharks on the nose: effective interventions to reduce financial hardship in New Zealand.

PubMed

Signal, Louise; Lanumata, Tolotea; Bowers, Sharron

2012-08-01

Growth in the high-cost, unregulated fringe lender market (with these lenders commonly referred to as loan sharks) has occurred both internationally and in New Zealand in recent years. The credit practices of loan sharks create financial hardship for many people including Māori, Pacific and low-income New Zealanders. This paper reports on research that explored strategies for reducing the impact of the fringe lender market on Māori, Pacific and low-income New Zealanders. A narrative literature review and 10 key informant interviews were conducted to provide information on how best to intervene to reduce the impact of the fringe lender market for these people. The main interventions identified were: two regulatory approaches, one for capping interest rates and another to create codes of responsible lending; access to safe affordable micro-finance options; financial literacy education; and Pacific cultural change around fa'alavelave, which are the 'obligations' of giving. Protecting consumers from the unsafe practices of fringe lenders requires a combined approach of discouraging the undesirable practices of fringe lenders through regulation and encouraging the growth of safe, affordable micro-finance options. Financial literacy education is a valuable activity for directing consumer attention to the safest options, but in isolation will have limited effect if options are limited. Health promoters have a valuable role to play in implementing these interventions.

Cuf2 Is a Novel Meiosis-Specific Regulatory Factor of Meiosis Maturation

PubMed Central

Ioannoni, Raphael; Beaudoin, Jude; Lopez-Maury, Luis; Codlin, Sandra; Bahler, Jurg; Labbe, Simon

2012-01-01

Background Meiosis is the specialized form of the cell cycle by which diploid cells produce the haploid gametes required for sexual reproduction. Initiation and progression through meiosis requires that the expression of the meiotic genes is precisely controlled so as to provide the correct gene products at the correct times. During meiosis, four temporal gene clusters are either induced or repressed by a cascade of transcription factors. Principal Findings In this report a novel copper-fist-type regulator, Cuf2, is shown to be expressed exclusively during meiosis. The expression profile of the cuf2+ mRNA revealed that it was induced during middle-phase meiosis. Both cuf2+ mRNA and protein levels are unregulated by copper addition or starvation. The transcription of cuf2+ required the presence of a functional mei4+ gene encoding a key transcription factor that activates the expression of numerous middle meiotic genes. Microscopic analyses of cells expressing a functional Cuf2-GFP protein revealed that Cuf2 co-localized with both homologous chromosomes and sister chromatids during the meiotic divisions. Cells lacking Cuf2 showed an elevated and sustained expression of several of the middle meiotic genes that persisted even during late meiosis. Moreover, cells carrying disrupted cuf2Δ/cuf2Δ alleles displayed an abnormal morphology of the forespore membranes and a dramatic reduction of spore viability. Significance Collectively, the results revealed that Cuf2 functions in the timely repression of the middle-phase genes during meiotic differentiation. PMID:22558440

Temperature effects on particulate matter emissions from light-duty, gasoline-powered motor vehicles

EPA Science Inventory

The Kansas City Light-Duty Vehicle Emissions study measured exhaust emissions of regulated and unregulated pollutants from over 500 vehicles randomly recruited in the Kansas City metropolitan area in 2004 and 2005. Vehicle emissions testing occurred during the summer and winter, ...

78 FR 58296 - Commission Information Collection Activities (FERC-604); Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

... collection requirements with no changes to the reporting requirements. Abstract: Cash management or ``money... unregulated) pools of money in cash management programs could detrimentally affect regulated rates. To protect... submitting the information collection FERC-604 (Cash Management Agreements) to the Office of Management and...

REMOVING ORGANIC CONTAMINANTS OF REGULATORY INTEREST WITH MEMBRANE PROCESSES: USEPA'S SCREENING STUDIES

EPA Science Inventory

The 1996 amendments to the Safe Drinking Water Act require the US Environmental Protection Agency (USEPA) to establish a list of unregulated microbiological and chemical contaminants to aid in priority-setting for the Agency's drinking water program. This list, known as the Cont...

American Attitudes Toward the Land

ERIC Educational Resources Information Center

Miller, Charles A.

1975-01-01

The colonial attitude toward land depended on the climate of the area and the culture of the settlers. With independence came a national attitude that land represented economic and political freedom for the individual. Abundant land fostered unregulated lumbering, mining, and farming. Today environmental awareness has created the conservation…

Chloride Released from Three Permeable Pavement Surfaces after Winter Salt Application - journal

EPA Science Inventory

EPA does not classify chloride as a priority pollutant. It is often unregulated in stormwater runoff but has been a target stressor for Total Maximum Daily Load (TMDL) allotments developed for multiple waterbodies. Previous research has shown that road salt applications increas...

ESTIMATING DIFFUSE STORMWATER NUTRIENT LOADS FROM SUBURBAN LANDSCAPES TO THE NAVESINK ESTUARY, NEW JERSEY

EPA Science Inventory

Hitherto, stormwater runoff from suburban land-uses has been largely unregulated and designated as a non-point source. Phase II of the Clean Water Act will require permits under the National Pollutant Discharge Elimination System for stormwater discharges from municipal separate ...

ESTIMATING DIFFUSE STORMWATER NUTRIENT LOADS FROM SUBURBAN LANDSCAPES IN THE NAVESINK ESTUARY, NEW JERSEY

EPA Science Inventory

Hitherto, stormwater runoff from suburban land-uses has been largely unregulated and designated as a non-point source. Phase II of the Clean Water Act now requires permits under the National Pollutant Discharge Elimination System for stormwater discharges from municipal separate...

From Theory to Practice: Considerations for Implementing a Statewide Voucher System.

ERIC Educational Resources Information Center

Doyle, Denis P.

This monograph analyzes trends in American educational philosophy and history in its proposal to implement an all-public statewide school voucher system. Following an introduction, section 1, "Alternative Voucher Systems," discusses three concepts: universal unregulated vouchers, favored by Milton Friedman; regulated compensatory vouchers,…

Save the Bay's "Toxic Diet" Project.

ERIC Educational Resources Information Center

Wilder, Diana

1994-01-01

Although progress has been made in curbing industrial pollutants in larger communities, small, nonindustrial communities lack strategies for reducing unregulated toxic sources to the influent stream. This article outlines one environmental organization's model for reducing these toxic sources that can be used to help small communities nationwide.…

ANALYTICAL PROCEDURES FOR CHARACTERIZING UNREGULATED EMISSIONS FROM VEHICLES USING MIDDLE-DISTILLATE FUELS

EPA Science Inventory

This research program was initiated with the objective of developing, codifying and testing a group of chemical analytical methods for measuring toxic compounds in the exhaust of distillate-fueled engines (i.e. diesel, gas turbine, Stirling, or Rankin cycle powerplants). It is a ...

Analysis of the streamflow-gaging station network in Ohio for effectiveness in providing regional streamflow information

USGS Publications Warehouse

Straub, D.E.

1998-01-01

The streamflow-gaging station network in Ohio was evaluated for its effectiveness in providing regional streamflow information. The analysis involved application of the principles of generalized least squares regression between streamflow and climatic and basin characteristics. Regression equations were developed for three flow characteristics: (1) the instantaneous peak flow with a 100-year recurrence interval (P100), (2) the mean annual flow (Qa), and (3) the 7-day, 10-year low flow (7Q10). All active and discontinued gaging stations with 5 or more years of unregulated-streamflow data with respect to each flow characteristic were used to develop the regression equations. The gaging-station network was evaluated for the current (1996) condition of the network and estimated conditions of various network strategies if an additional 5 and 20 years of streamflow data were collected. Any active or discontinued gaging station with (1) less than 5 years of unregulated-streamflow record, (2) previously defined basin and climatic characteristics, and (3) the potential for collection of more unregulated-streamflow record were included in the network strategies involving the additional 5 and 20 years of data. The network analysis involved use of the regression equations, in combination with location, period of record, and cost of operation, to determine the contribution of the data for each gaging station to regional streamflow information. The contribution of each gaging station was based on a cost-weighted reduction of the mean square error (average sampling-error variance) associated with each regional estimating equation. All gaging stations included in the network analysis were then ranked according to their contribution to the regional information for each flow characteristic. The predictive ability of the regression equations developed from the gaging station network could be improved for all three flow characteristics with the collection of additional streamflow data. The addition of new gaging stations to the network would result in an even greater improvement of the accuracy of the regional regression equations. Typically, continued data collection at stations with unregulated streamflow for all flow conditions that had less than 11 years of record with drainage areas smaller than 200 square miles contributed the largest cost-weighted reduction to the average sampling-error variance of the regional estimating equations. The results of the network analyses can be used to prioritize the continued operation of active gaging stations or the reactivation of discontinued gaging stations if the objective is to maximize the regional information content in the streamflow-gaging station network.

Masters of the Universe: The Passively Multiplayer Online Game

ERIC Educational Resources Information Center

Harris, Christopher

2008-01-01

The digital age has freed information from the restrictive hierarchies of traditional cataloging methods, notably Dewey. Although libraries still deal with the challenge of physical books, online content is a different matter. Thanks to the unregulated, grassroots cataloging effort known as tagging, the Web presents a glorious chaos of…

50 CFR 300.202 - Identification and certification of nations engaged in illegal, unreported, or unregulated...

Code of Federal Regulations, 2011 CFR

2011-10-01

... into account whether an international fishery management organization exists with a mandate to regulate... will consider whether the relevant international fishery management organization has adopted measures... international fishery management organization of actions taken by the United States to identify nations whose...

EPA Treatability Database Digs Deep for Data on Drinking Water Contaminants and Treatment Processes

EPA Science Inventory

The TDB is an interactive database that was initially developed in 2006-2007. The TDB currently contains more than 60 regulated and unregulated contaminants and 28 treatment processes that are known to be effective and are commonly employed at drinking water utilities. TDB lite...

75 FR 10213 - Identification of Nations Whose Fishing Vessels are Engaged in Illegal, Unreported, or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... Identification of Nations Whose Fishing Vessels are Engaged in Illegal, Unreported, or Unregulated Fishing and/or..., or unreported (IUU) fishing or bycatch of protected living marine resources (PLMRs). Such information... Fishing Moratorium Protection Act (Moratorium Protection Act). DATES: Information should be received on or...

REMOVAL OF ORGANIC CCL CONTAMINANTS FROM DRINKING WATERS BY GAC, AIR STRIPPING, AND MEMBRANE PROCESSES

EPA Science Inventory

The 1996 amendments to the Safe Drinking Water Act (SWDA) require the US Environmental Protection Agency (USEPA) to establish a list of unregulated microbiological and chemical contaminants to aid in priority-setting for the Agency's drinking water program. This list, known as t...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2010 CFR

2010-07-01

... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which...

Development of a U.S. EPA Method for the Analysis of Selected Drinking Water Contaminants by LC/MS/MS

EPA Science Inventory

The U.S. Environmental Protection Agency’s (U.S. EPA) Office of Ground Water and Drinking Water (OGWDW) collects national occurrence data on drinking water contaminants using Unregulated Contaminant Monitoring Regulations (UCMRs). These contaminants may be selected from the Drin...

USEPA'S APPROACH TO THE DEVELOPMENT OF NEW ANALYTICAL METHODS FOR EMERGING CONTAMINANTS IN DRINKING WATER

EPA Science Inventory

The 1996 Amendments to the Safe Drinking Water Act require USEPA to perform Unregulated Contaminant Monitoring (UCM) for chemicals of interest to the Agency for possible future regulation. Many of these chemicals fall into the category of "emerging contaminants". An important e...

5 Key Ways Your Electronic Data May Be at Risk

ERIC Educational Resources Information Center

Titus, Aaron

2008-01-01

This article describes five organizational policies and behavior that put personal information in jeopardy. These are: (1) Inadequate security for old data; (2) Shadow systems and unregulated servers; (3) Unsophisticated privacy policies; (4) Improper use of Social Security numbers; and (5) Unsanitized old hard drives. Although the academic…

40 CFR 141.35 - Reporting for unregulated contaminant monitoring results.

Code of Federal Regulations, 2014 CFR

2014-07-01

... up to 30 characters assigned by the laboratory to uniquely identify containers, or groups of containers, containing water samples collected at the same sampling location for the same sampling date. 9... each sample event. This will associate samples with the PWS monitoring plan to allow EPA to track...

40 CFR 141.35 - Reporting for unregulated contaminant monitoring results.

Code of Federal Regulations, 2012 CFR

2012-07-01

... up to 30 characters assigned by the laboratory to uniquely identify containers, or groups of containers, containing water samples collected at the same sampling location for the same sampling date. 9... each sample event. This will associate samples with the PWS monitoring plan to allow EPA to track...

40 CFR 141.35 - Reporting for unregulated contaminant monitoring results.

Code of Federal Regulations, 2013 CFR

2013-07-01

... up to 30 characters assigned by the laboratory to uniquely identify containers, or groups of containers, containing water samples collected at the same sampling location for the same sampling date. 9... each sample event. This will associate samples with the PWS monitoring plan to allow EPA to track...

Methods for estimating annual exceedance-probability discharges and largest recorded floods for unregulated streams in rural Missouri.

DOT National Transportation Integrated Search

2014-01-01

Regression analysis techniques were used to develop a : set of equations for rural ungaged stream sites for estimating : discharges with 50-, 20-, 10-, 4-, 2-, 1-, 0.5-, and 0.2-percent : annual exceedance probabilities, which are equivalent to : ann...

Clandestine Employment: A Problem of Our Times.

ERIC Educational Resources Information Center

De Grazia, Raffaele

1980-01-01

Explores the causes and effects of clandestine and illegal employment, which is therefore unregulated by the authorities, and analyzes the attitudes of those involved. Refers to measures that have been taken to combat the phenomenon, which some regard as beneficial, and which call for further investigation and elucidation. (Editor/ JOW)

40 CFR 141.40 - Monitoring requirements for unregulated contaminants.

Code of Federal Regulations, 2011 CFR

2011-07-01

... monitoring to be completed Reserved i Reserved i Reserved i Reserved i Reserved i Reserved i Column headings... Pesticides and Flame Retardants in Drinking Water by Solid Phase Extraction and Capillary Column Gas... Water by Solid Phase Extraction and Capillary Column Gas Chromatography/Mass Spectrometry (GC/MS...

Elevated systemic hepcidin and iron depletion in obese pre-menopausal females.

USDA-ARS?s Scientific Manuscript database

Hepcidin, the body’s main regulator of systemic iron homeostasis, is unregulated in response to inflammation, and is thought to play a role in the manifestation of iron deficiency (ID) observed in obese populations. We determined systemic hepcidin levels and its association with body mass, inflammat...

75 FR 678 - Federal Home Loan Bank Membership for Community Development Financial Institutions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... substantive issues raised by the comment letters focused principally on the criteria that FHFA had proposed... and business lines. The four categories of institutions eligible for CDFI certification and CDFI Fund... are unregulated institutions specializing in financing of housing, businesses or community facilities...

Stochastic model for simulating Souris River Basin precipitation, evapotranspiration, and natural streamflow

USGS Publications Warehouse

Kolars, Kelsey A.; Vecchia, Aldo V.; Ryberg, Karen R.

2016-02-24

The Souris River Basin is a 61,000-square-kilometer basin in the Provinces of Saskatchewan and Manitoba and the State of North Dakota. In May and June of 2011, record-setting rains were seen in the headwater areas of the basin. Emergency spillways of major reservoirs were discharging at full or nearly full capacity, and extensive flooding was seen in numerous downstream communities. To determine the probability of future extreme floods and droughts, the U.S. Geological Survey, in cooperation with the North Dakota State Water Commission, developed a stochastic model for simulating Souris River Basin precipitation, evapotranspiration, and natural (unregulated) streamflow. Simulations from the model can be used in future studies to simulate regulated streamflow, design levees, and other structures; and to complete economic cost/benefit analyses.Long-term climatic variability was analyzed using tree-ring chronologies to hindcast precipitation to the early 1700s and compare recent wet and dry conditions to earlier extreme conditions. The extended precipitation record was consistent with findings from the Devils Lake and Red River of the North Basins (southeast of the Souris River Basin), supporting the idea that regional climatic patterns for many centuries have consisted of alternating wet and dry climate states.A stochastic climate simulation model for precipitation, temperature, and potential evapotranspiration for the Souris River Basin was developed using recorded meteorological data and extended precipitation records provided through tree-ring analysis. A significant climate transition was seen around1970, with 1912–69 representing a dry climate state and 1970–2011 representing a wet climate state. Although there were some distinct subpatterns within the basin, the predominant differences between the two states were higher spring through early fall precipitation and higher spring potential evapotranspiration for the wet compared to the dry state.A water-balance model was developed for simulating monthly natural (unregulated) mean streamflow based on precipitation, temperature, and potential evapotranspiration at select streamflow-gaging stations. The model was calibrated using streamflow data from the U.S. Geological Survey and Environment Canada, along with natural (unregulated) streamflow data from the U.S. Army Corps of Engineers. Correlation coefficients between simulated and natural (unregulated) flows generally were high (greater than 0.8), and the seasonal means and standard deviations of the simulated flows closely matched the means and standard deviations of the natural (unregulated) flows. After calibrating the model for a monthly time step, monthly streamflow for each subbasin was disaggregated into three values per month, or an approximately 10-day time step, and a separate routing model was developed for simulating 10-day streamflow for downstream gages.The stochastic climate simulation model for precipitation, temperature, and potential evapotranspiration was combined with the water-balance model to simulate potential future sequences of 10-day mean streamflow for each of the streamflow-gaging station locations. Flood risk, as determined by equilibrium flow-frequency distributions for the dry (1912–69) and wet (1970–2011) climate states, was considerably higher for the wet state compared to the dry state. Future flood risk will remain high until the wet climate state ends, and for several years after that, because there may be a long lag-time between the return of drier conditions and the onset of a lower soil-moisture storage equilibrium.

Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1.

PubMed

Manuel, Sharrón L; Sehgal, Mohit; Connolly, John; Makedonas, George; Khan, Zafar K; Gardner, Jay; Betts, Michael R; Jain, Pooja

2013-10-01

The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. Quality of cytotoxic T lymphocytes (CTLs) is being increasingly associated with the outcome of persistent HTLV-1 infection. In this respect, a patient cohort (from HTLV-1 endemic region) consisting of seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8(+) T cells polyfunctionality in response to the viral antigen Tax. Compared to ACs, ATL and HAM/TSP patients had lower frequency and polyfunctionality of CTLs in response to Tax suggesting dysfunction of CD8(+) T cells in these individuals. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive as well as total CD8(+) T cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, PD-1 expression showed a direct whereas MIP-1α expression had an indirect correlation with the proviral load providing new insights about the immunopathogenesis of HTLV-associated diseases. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex assay. Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway are potential approaches for immunotherapy / therapeutic vaccine against HTLV-mediated diseases.

Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1

PubMed Central

Manuel, Sharrón L.; Sehgal, Mohit; Connolly, John; Makedonas, George; Khan, Zafar K.; Gardner, Jay; Goedert, James J.; Betts, Michael R.; Jain, Pooja

2013-01-01

Purpose & methods The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. In this respect, a patient cohort from HTLV-1 endemic region that included seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8+ T cells polyfunctionality in response to the viral antigen Tax. Results Compared to ACs, ATL and HAM/TSP patients had lower frequency and polyfunctionality of CTLs in response to Tax suggesting dysfunction of CD8+ T cells in these individuals. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive as well as total CD8+ T cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, PD-1 expression showed a direct whereas MIP-1α expression had an indirect correlation with the proviral load providing new insights about the immunopathogenesis of HTLV-associated diseases. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex assay. Conclusions Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway are potential approaches for immunotherapy and therapeutic vaccine against HTLV-mediated diseases. PMID:23888327

The Physics of Amyloid Aggregation and Templating in Prions

NASA Astrophysics Data System (ADS)

Cox, Daniel

2012-02-01

The problem of self-assembled amyloid aggregation of proteins in structures with beta-strands perpendicular to a one dimensional grown axis is interesting at a fundamental level (is this the most generic end state of proteins?), from a biological level (if the self-assembly can be regulated it is of use in contexts like spider silk and bacterial colony formation), for human public health (aggregation unregulated induces diseases like mad cow and Alzheimer's), and for possible materials applications (e.g., in tissue scaffolding). In this presentation, I will review the work of my group in examining the possibility that the left-handed beta helix (LHBH) structure can be the building block of the aggregates of mammalian prion and yeast prion proteins. I will also discuss our efforts to assess the possibility of a novel pH driven structural switch between LHBH and alpha-helical forms in the ordered half of the mammalian prion protein, and now the possibly pH stabilized LHBH structure can template aggregate growth of the disordered half of the protein, identified in numerous experimental studies as most relevant to disease.

"Save 30% if you buy today". Online pharmacies and the enhancement of peripheral thinking in consumers.

PubMed

Orizio, Grazia; Rubinelli, Sara; Schulz, Peter J; Domenighini, Serena; Bressanelli, Maura; Caimi, Luigi; Gelatti, Umberto

2010-09-01

Online pharmacies (OPs) are recognized as a potential threat to public health. The growth of an unregulated global drugs market risks increasing the spread of counterfeit medicines which are often delivered to consumers without a medical prescription. The aim of the study was to assess the strategies of argumentation that OPs adopt in their marketing. A sample of 175 OPs was analyzed using the content-analysis method, and evaluated by relying on the Elaboration Likelihood Model (ELM) of persuasion. Almost 80% of the sample of OPs did not ask for a medical prescription by the consumer's physician. The selling arguments used included privacy policy, economic, quality, and service issues. About one-third of the OPs did not declare any side-effects regarding the drugs offered. Our results show that OPs advertise their products in an argumentative fashion that enhances consumers' peripheral reflection: by analogically playing with the selling of other commodities, they magnify aspects of the online trade that consumers might find convenient, but overshadow the nature and risks of the actual products they sell. (c) 2010 John Wiley & Sons, Ltd.

An historical perspective on eutrophication in the Pensacola ...

EPA Pesticide Factsheets

In this chapter, we provide a brief description of the Pensacola Bay estuary, examining the available historical data for evidence of trends in eutrophication within the estuary. Common to many industrialized estuaries, Pensacola Bay has been subjected to unregulated point sources of nutrients and other contaminants, peaking during the 1950s and 1960s. Also, over the past 60 years, the region has experienced a 5-fold increase in population in the watershed and a doubling of river nitrate concentrations. Today, the estuary exhibits classical symptoms of eutrophication, including extensive summer hypoxia, significant loss of seagrass habitat, and phytoplankton dynamics that respond strongly to seasonal and interannual variation in freshwater flow. Surprisingly, Pensacola Bay appears to have low nutrient concentrations, moderate productivity, and high water transparency; characteristics that appear to have persisted during a period of rapid human population growth. We find the lack of demonstrable changes in the distribution of phytoplankton biomass or distribution and severity of hypoxia during a period of increasing human population pressures enigmatic. This brief manuscript summarizes historical water quality data from Pensacola Bay Florida

The Allosterically Unregulated Isoform of ADP-Glucose Pyrophosphorylase from Barley Endosperm Is the Most Likely Source of ADP-Glucose Incorporated into Endosperm Starch.

PubMed

Doan; Rudi; Olsen

1999-11-01

We present the results of studies of an unmodified version of the recombinant major barley (Hordeum vulgare) endosperm ADP-glucose pyrophoshorylase (AGPase) expressed in insect cells, which corroborate previous data that this isoform of the enzyme acts independently of the allosteric regulators 3-phosphoglycerate and inorganic phosphate. We also present a characterization of the individual subunits expressed separately in insect cells, showing that the SS AGPase is active in the presence of 3-phosphoglycerate and is inhibited by inorganic phosphate. As a step toward the elucidation of the role of the two AGPase isoforms in barley, the temporal and spatial expression profile of the four barley AGPase transcripts encoding these isoforms were studied. The results show that the steady-state level of beps and bepl, the transcripts encoding the major endosperm isoform, correlated positively with the rate of endosperm starch accumulation. In contrast, blps and blpl, the transcripts encoding the major leaf isoform, were constitutively expressed at a very low steady-state level throughout the barley plant. The implications of these findings for the evolution of plant AGPases are discussed.

The Allosterically Unregulated Isoform of ADP-Glucose Pyrophosphorylase from Barley Endosperm Is the Most Likely Source of ADP-Glucose Incorporated into Endosperm Starch1

PubMed Central

Doan, Danny N.P.; Rudi, Heidi; Olsen, Odd-Arne

1999-01-01

We present the results of studies of an unmodified version of the recombinant major barley (Hordeum vulgare) endosperm ADP-glucose pyrophoshorylase (AGPase) expressed in insect cells, which corroborate previous data that this isoform of the enzyme acts independently of the allosteric regulators 3-phosphoglycerate and inorganic phosphate. We also present a characterization of the individual subunits expressed separately in insect cells, showing that the SS AGPase is active in the presence of 3-phosphoglycerate and is inhibited by inorganic phosphate. As a step toward the elucidation of the role of the two AGPase isoforms in barley, the temporal and spatial expression profile of the four barley AGPase transcripts encoding these isoforms were studied. The results show that the steady-state level of beps and bepl, the transcripts encoding the major endosperm isoform, correlated positively with the rate of endosperm starch accumulation. In contrast, blps and blpl, the transcripts encoding the major leaf isoform, were constitutively expressed at a very low steady-state level throughout the barley plant. The implications of these findings for the evolution of plant AGPases are discussed. PMID:10557246

The Use of Biofuel for Sustainable Growth in Developing Countries

NASA Astrophysics Data System (ADS)

Tsang, J.

2014-12-01

The biofuel industry is divided into four categories comprising of feedstocks used in 1st and 2nd generation bioethanol and biodiesel. In order to identify and quantify each biofuel feedstock's potential for sustainable growth, each were evaluated according to self-developed social, financial, and environmental criteria. From the investigation and analysis carried out, 1st generation biodiesel and bioethanol were determined to be feedstocks not capable of facilitating sustainable growth. Results showed low earnings before interest, taxes, depreciation and amortization (EBITDA) of -0.5 to 1 USD per gallon for biodiesel and 0.25 to 0.5 USD per gallon for bioethanol. Results also showed a poor return on asset (ROA). The energy required to produce one MJ of 1st generation biofuel fuel was at least 0.4 MJ, showing poor energy balance. Furthermore, high land, water, pesticide, and fertilizer requirements strained surrounding ecosystems by affecting the food web, thus reducing biodiversity. Over 55% of land used by the biodiesel industry in Indonesia and Malaysia involved the deforestation of local rainforests. This not only displaced indigenous organisms from their habitat and decreased their scope of nutrition, but also contributed to soil erosion and increased the probability of flooding. If left unregulated, imbalances in the ecosystem due to unsustainable growth will result in a permanent reshaping of tropical rainforest ecosystems in Southeast Asia. Algae, an example of 2nd generation biodiesel feedstock, was concluded to be the biofuel feedstock most capable of supporting sustainable growth. This is due to its low production costs of $1-1.5/gal, high biological productivity of 5000 gallons of biodiesel per acre per year, and high ROA of 25-35%. Additionally, algae's adaptability to varying environmental conditions also makes it an appealing candidate for businesses in developing countries, where access to resource supplies is unstable. Additionally, its reduced net greenhouse gas emissions and low impact on biodiversity makes it a feedstock highly capable of stimulating economic growth yet simultaneously resolving environmental issues and infrastructural restraints in developing countries.

78 FR 22540 - Notice of Public Meeting/Webinar: EPA Method Development Update on Drinking Water Testing Methods...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

...: EPA Method Development Update on Drinking Water Testing Methods for Contaminant Candidate List... Division will describe methods currently in development for many CCL contaminants, with an expectation that several of these methods will support future cycles of the Unregulated Contaminant Monitoring Rule (UCMR...

50 CFR 635.41 - Products denied entry.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Products denied entry. (a) [Reserved] (b) All shipments of tuna or tuna-like species, or their products, in.... (c) All shipments of tuna or tuna-like species, or their products, in any form, harvested in the..., and unregulated fishing will be denied entry into the United States. (d) All shipments of tuna or tuna...

50 CFR 635.41 - Products denied entry.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Products denied entry. (a) [Reserved] (b) All shipments of tuna or tuna-like species, or their products, in.... (c) All shipments of tuna or tuna-like species, or their products, in any form, harvested in the..., and unregulated fishing will be denied entry into the United States. (d) All shipments of tuna or tuna...

Exploring Young Children's Understanding of Risks Associated with Internet Usage and Their Concepts of Management Strategies

ERIC Educational Resources Information Center

Ey, Lesley-Anne; Cupit, C. Glenn

2011-01-01

The Internet provides remarkable opportunities for children's learning and development. Nevertheless, it is unregulated and hard to control, which potentially places children at risk of exploitation. This study examined five-eight-year-old children's understanding of dangers associated with the Internet, management strategies and sources of their…

REMOVAL OF ORGANIC CCL CONTAMINANTS FROM DRINKING WATERS BY ENHANCED COAGULATION, POWDERED ACTIVATED CARBON, CHEMICAL SOFTENING, AND OXIDATION

EPA Science Inventory

The 1996 amendments to the Safe Drinking Water Act (SWDA) require the US Environmental Protection Agency (USEPA) to establish a list of unregulated microbiological and chemical contaminants to aid in priority-setting for the Agency's drinking water program. This list, known as t...

76 FR 77521 - California State Nonroad Engine Pollution Control Standards; Commercial Harbor Craft Regulations...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... emissions of particulate matter and oxides of nitrogen from new and in-use diesel-fueled engines on... enforcement provisions. The requirements are applicable to diesel propulsion and auxiliary engines on new and... operating in California are previously unregulated diesel engines, accounting for approximately 3.3 tons per...

Plant succession after hydrologic disturbance: Inferences from contemporary vegetation on a chronosequence of bars, Willamette River, Oregon, USA

EPA Science Inventory

Historic unconstrained, unregulated streamflow along the upper mainstem of the Willamette River, Oregon, produced a floodplain of coalescent bars supporting a mosaic of vegetation patches. We sampled the contemporary vegetation of 42 bars formed 3 to 64 + years ago in four, 1 km...

Bandwidth Problems ca. 1912: The Need for Federal Regulation

ERIC Educational Resources Information Center

Social Education, 2005

2005-01-01

In the United States the use of wireless radio initially was unregulated-anyone could operate a radio transmitter anywhere, at any time, on any wavelength. And most utilized the longwave signals that traveled so well across land and sea. Naturally, severe interference occurred with everyone trying to use the same wavelengths. Eventually it was…

The Changing Role of Government and Other Stakeholders in Vocational Education and Training.

ERIC Educational Resources Information Center

International Labour Office, Geneva (Switzerland).

Historically, the roles of the public and private sectors in VET have been characterized by the following broad stages: (1) unstructured and unregulated VET; (2) supply-driven, state dominated VET; and (3) market-driven VET. More recently, the combined forces of globalization, technological change, and liberalization of markets have forced…

The Death of Socrates: Managerialism, Metrics and Bureaucratisation in Universities

ERIC Educational Resources Information Center

Orr, Yancey; Orr, Raymond

2016-01-01

Neoliberalism exults the ability of unregulated markets to optimise human relations. Yet, as David Graeber has recently illustrated, it is paradoxically built on rigorous systems of rules, metrics and managers. The potential transition to a market-based tuition and research-funding model for higher education in Australia has, not surprisingly,…

40 CFR 141.40 - Monitoring requirements for unregulated contaminants.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Contaminant List, in paragraph (a)(3) of this section. EPA will provide sample containers, provide pre-paid... Testing to be Sampled After Notice of Analytical Methods Availability] 1—Contaminant 2—CAS registry number... Records Administration (NARA). For information on availability of this material at NARA, call 202-741-6030...

Development of a Gas Chromatography/Mass Spectrometry Method for the Analysis of the Solvent Stabilizer 1,4-Dioxane in Drinking Water

EPA Science Inventory

The solvent stabilizer 1,4-dioxane was named to the latest draft Drinking Water Contaminant Candidate List (CCL3) in February 2008 by the United States Environmental Protection Agency (USEPA). To collect occurrence data under the Unregulated Contaminant Monitoring Regulation (UC...

DETERMINATION OF ROXARSONE, AN ARSENIC ANIMAL-FEED ADDITIVE, AND ITS TRANSFORMATION PRODUCTS IN CHICKEN MANURE BY CE-ICPMS AND HPLC-ICPMS

EPA Science Inventory

Disposal of arsenic-bearing wastes from poultry houses is currently unregulated and poses a potential environmental concern. Determination of roxarsone and its transformation products in chicken manure is necessary to understand their possible impacts on human health and ...

Interaction Management Strategies on IRC and Virtual Chat Rooms.

ERIC Educational Resources Information Center

Altun, Arif

Internet Relay Chat (IRC) is an electronic medium that combines orthographic form with real time, synchronous transmission in an unregulated global multi-user environment. The orthographic letters mediate the interaction in that users can only access the IRC session through reading and writing; they have no access to any visual representations at…

Unregulated Autonomy: Uncredentialed Educational Interpreters in Rural Schools

ERIC Educational Resources Information Center

Fitzmaurice, Stephen

2017-01-01

Although many rural Deaf and Hard of Hearing students attend public schools most of the day and use the services of educational interpreters to gain access to the school environment, little information exists on what interpreters are doing in rural school systems in the absence of credentialing requirements. The researcher used ethnographic…

Wilderness campsite conditions under an unregulated camping policy: An eastern example

Treesearch

Yu-Fai Leung; Jeffrey L. Marion

2000-01-01

This study identified and assessed 110 campsites in seven designated wilderness areas in the Jefferson National Forest of Virginia. The campsites were unevenly distributed within each wilderness, concentrating along trail corridors and near popular destination areas. With a few exceptions, most campsites surveyed were in good condition. The findings indicate that...

Reactive oxidative species formation and unregulated particulate emissions from blended diesel and biodiesel light-duty engine emissions

USDA-ARS?s Scientific Manuscript database

It is well established that particulate matter (PM) continues to be a major air pollutant challenge for human health globally and vehicle exhaust PM emissions have been linked to many adverse health effects. However, the relative toxicity of biodiesel emissions compared to petroleum diesel remains u...

77 FR 56200 - Agency Information Collection Activities OMB Responses

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

... on 08/31/2015; Approved with change. EPA ICR Number 2192.05; Unregulated Contaminant Monitoring in Public Water Systems (Final Rule); 40 CFR 141.35 and 141.40; was approved on 08/06/2012; OMB Number 2040-0270; expires on 08/31/2015; Approved with change. EPA ICR Number 1560.10; National Water Quality...

Predicting nonpoint stormwater runoff quality from land use

PubMed Central

2018-01-01

Evaluating the impact of urban development on natural ecosystem processes has become an increasingly complex task for planners, environmental scientists, and engineers. As the built environment continues to grow, unregulated nonpoint pollutants from increased human activity and large-scale development severely stress urban streams and lakes resulting in their currently impaired or degraded state. In response, integrated water quality management programs have been adopted to address these unregulated nonpoint pollutants by utilizing best management practices (BMPs) that treat runoff as close to the source as possible. Knowing where to install effective BMPs is no trivial task, considering budget constraints and the spatially extensive nature of nonpoint stormwater runoff. Accordingly, this paper presents an initial, straightforward and cost-effective methodology to identify critical nonpoint pollutant source watersheds through correlation of water quality with land use. Through an illustrative application to metropolitan Denver, Colorado, it is shown how this method can be used to aid stormwater professionals to evaluate and specify retrofit locations in need of water quality treatment features reduce, capture and treat stormwater runoff prior to entering receiving waters. PMID:29742172

Using an introduction website to start a family: implications for users and health practitioners.

PubMed

Harper, Joyce; Jackson, Emily; Spoelstra-Witjens, Laura; Reisel, Dan

2017-06-01

Donor insemination treatment offered in licensed clinics protects the donor, recipient and offspring both medically and legally. The Internet has opened up novel, unregulated ways of donating sperm through 'introduction websites' and social media forums. Broadly, three categories of women use introduction websites: those who want to have a child with no further involvement of the donor; those who wish to know the identity of the donor from the start; and those who intend to electively co-parent, that is, to bring up the child together with the donor/father. Donors may choose to donate through introduction websites for altruistic reasons and/or in order to have greater involvement with the child. There are some donors who are motivated by the prospect of a sexual encounter, advertising their preference for 'natural insemination' - i.e. via sexual intercourse or partial intercourse. When people make their own arrangements online, they may do so in the absence of clear, accurate information. This article, sets out some of the issues that recipients and donors ought to consider before embarking on unregulated sperm donation.

Spatial clustering of metal and metalloid mixtures in unregulated water sources on the Navajo Nation - Arizona, New Mexico, and Utah, USA.

PubMed

Hoover, Joseph H; Coker, Eric; Barney, Yolanda; Shuey, Chris; Lewis, Johnnye

2018-08-15

Contaminant mixtures are identified regularly in public and private drinking water supplies throughout the United States; however, the complex and often correlated nature of mixtures makes identification of relevant combinations challenging. This study employed a Bayesian clustering method to identify subgroups of water sources with similar metal and metalloid profiles. Additionally, a spatial scan statistic assessed spatial clustering of these subgroups and a human health metric was applied to investigate potential for human toxicity. These methods were applied to a dataset comprised of metal and metalloid measurements from unregulated water sources located on the Navajo Nation, in the southwest United States. Results indicated distinct subgroups of water sources with similar contaminant profiles and that some of these subgroups were spatially clustered. Several profiles had metal and metalloid concentrations that may have potential for human toxicity including arsenic, uranium, lead, manganese, and selenium. This approach may be useful for identifying mixtures in water sources, spatially evaluating the clusters, and help inform toxicological research investigating mixtures. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Scaling properties reveal regulation of river flows in the Amazon through a forest reservoir

NASA Astrophysics Data System (ADS)

Salazar, Juan Fernando; Villegas, Juan Camilo; María Rendón, Angela; Rodríguez, Estiven; Hoyos, Isabel; Mercado-Bettín, Daniel; Poveda, Germán

2018-03-01

Many natural and social phenomena depend on river flow regimes that are being altered by global change. Understanding the mechanisms behind such alterations is crucial for predicting river flow regimes in a changing environment. Here we introduce a novel physical interpretation of the scaling properties of river flows and show that it leads to a parsimonious characterization of the flow regime of any river basin. This allows river basins to be classified as regulated or unregulated, and to identify a critical threshold between these states. We applied this framework to the Amazon river basin and found both states among its main tributaries. Then we introduce the forest reservoir hypothesis to describe the natural capacity of river basins to regulate river flows through land-atmosphere interactions (mainly precipitation recycling) that depend strongly on the presence of forests. A critical implication is that forest loss can force the Amazonian river basins from regulated to unregulated states. Our results provide theoretical and applied foundations for predicting hydrological impacts of global change, including the detection of early-warning signals for critical transitions in river basins.

Predicting nonpoint stormwater runoff quality from land use.

PubMed

Zivkovich, Brik R; Mays, David C

2018-01-01

Evaluating the impact of urban development on natural ecosystem processes has become an increasingly complex task for planners, environmental scientists, and engineers. As the built environment continues to grow, unregulated nonpoint pollutants from increased human activity and large-scale development severely stress urban streams and lakes resulting in their currently impaired or degraded state. In response, integrated water quality management programs have been adopted to address these unregulated nonpoint pollutants by utilizing best management practices (BMPs) that treat runoff as close to the source as possible. Knowing where to install effective BMPs is no trivial task, considering budget constraints and the spatially extensive nature of nonpoint stormwater runoff. Accordingly, this paper presents an initial, straightforward and cost-effective methodology to identify critical nonpoint pollutant source watersheds through correlation of water quality with land use. Through an illustrative application to metropolitan Denver, Colorado, it is shown how this method can be used to aid stormwater professionals to evaluate and specify retrofit locations in need of water quality treatment features reduce, capture and treat stormwater runoff prior to entering receiving waters.

Estimating the magnitude of annual peak discharges with recurrence intervals between 1.1 and 3.0 years for rural, unregulated streams in West Virginia

USGS Publications Warehouse

Wiley, Jeffrey B.; Atkins, John T.; Newell, Dawn A.

2002-01-01

Multiple and simple least-squares regression models for the log10-transformed 1.5- and 2-year recurrence intervals of peak discharges with independent variables describing the basin characteristics (log10-transformed and untransformed) for 236 streamflow-gaging stations were evaluated, and the regression residuals were plotted as areal distributions that defined three regions in West Virginia designated as East, North, and South. Regional equations for the 1.1-, 1.2-, 1.3-, 1.4-, 1.5-, 1.6-, 1.7-, 1.8-, 1.9-, 2.0-, 2.5-, and 3-year recurrence intervals of peak discharges were determined by generalized least-squares regression. Log10-transformed drainage area was the most significant independent variable for all regions. Equations developed in this study are applicable only to rural, unregulated streams within the boundaries of West Virginia. The accuracies of estimating equations are quantified by measuring the average prediction error (from 27.4 to 52.4 percent) and equivalent years of record (from 1.1 to 3.4 years).

Regulated and unregulated emissions from a diesel engine fueled with biodiesel and biodiesel blended with methanol

NASA Astrophysics Data System (ADS)

Cheung, C. S.; Zhu, Lei; Huang, Zhen

Experiments were carried out on a diesel engine operating on Euro V diesel fuel, pure biodiesel and biodiesel blended with methanol. The blended fuels contain 5%, 10% and 15% by volume of methanol. Experiments were conducted under five engine loads at a steady speed of 1800 rev min -1 to assess the performance and the emissions of the engine associated with the application of the different fuels. The results indicate an increase of brake specific fuel consumption and brake thermal efficiency when the diesel engine was operated with biodiesel and the blended fuels, compared with the diesel fuel. The blended fuels could lead to higher CO and HC emissions than biodiesel, higher CO emission but lower HC emission than the diesel fuel. There are simultaneous reductions of NO x and PM to a level below those of the diesel fuel. Regarding the unregulated emissions, compared with the diesel fuel, the blended fuels generate higher formaldehyde, acetaldehyde and unburned methanol emissions, lower 1,3-butadiene and benzene emissions, while the toluene and xylene emissions not significantly different.

Cosmeceuticals: undefined, unclassified, and unregulated.

PubMed

Draelos, Zoe Diana

2009-01-01

The cosmeceutical category is an undefined, unclassified, and unregulated area of dermatology that is yet in its infancy. Traditional cosmeceuticals involve the topical application of biologically active ingredients that affect the skin barrier and overall skin health. The ability of these ingredients to enhance skin functioning depends on how they are formulated into products that can maintain the integrity of the active ingredient, deliver it in a biologically active form to the skin, reach the target site in sufficient quantity to exert an effect, and properly release from the carrier vehicle. In the United States, cosmeceuticals are sold as cosmetics, making marketing, packaging, and aesthetic appeal important considerations. Ideally, the cosmeceutical should be clinically tested for efficacy to ensure a proven skin benefit and also to substantiate marketing claims. Governmental limitations of efficacy claims restrict cosmeceutical development because products can only be assessed in terms of their ability to improve skin appearance but not function. Improving function would remove the cosmeceutical from the cosmetic category and place it in the drug category. Herein lies the challenge of defining the cosmeceutical category.

Hyperreactive malarial splenomegaly is associated with low levels of antibodies against red blood cell and Plasmodium falciparum derived glycolipids in Yanomami Amerindians from Venezuela.

PubMed

Vivas, Livia; O'Dea, Kieran P; Noya, Oscar; Pabon, Rosalba; Magris, Magda; Botto, Carlos; Holder, Anthony A; Brown, K Neil

2008-03-01

The immunological basis of the aberrant immune response in hyperreactive malarial splenomegaly (HMS) is poorly understood, but believed to be associated with polyclonal B cell activation by an unidentified malaria mitogen, leading to unregulated immunoglobulin and autoantibody production. HMS has been previously reported in Yanomami communities in the Upper Orinoco region of the Venezuelan Amazon. To investigate a possible association between antibody responses against Plasmodium falciparum and uninfected red blood cell (URBC) glycolipids and splenomegaly, a direct comparison of the parasite versus host anti-glycolipid antibody responses was made in an isolated community of this area. The anti-P. falciparum glycolipid (Pfglp) response was IgG3 dominated, whereas the uninfected red blood cell glycolipid (URBCglp) response showed a predominance of IgG1. The levels of IgG1 against Pfglp, and of IgG4 and IgM against URBCglp were significantly higher in women, while the anti-Pfglp or URBCglp IgM levels were inversely correlated with the degree of splenomegaly. Overall, these results suggest differential regulation of anti-parasite and autoreactive responses and that these responses may be linked to the development and evolution of HMS in this population exposed to endemic malaria. The high mortality rates associated with HMS point out that its early diagnosis together with the implementation of malaria control measures in these isolated Amerindian communities are a priority.

Sticholysin II-mediated cytotoxicity involves the activation of regulated intracellular responses that anticipates cell death.

PubMed

Soto, Carmen; Bergado, Gretchen; Blanco, Rancés; Griñán, Tania; Rodríguez, Hermis; Ros, Uris; Pazos, Fabiola; Lanio, María Eliana; Hernández, Ana María; Álvarez, Carlos

2018-05-01

Sticholysin II (StII) is a pore-forming toxin of biomedical interest that belongs to the actinoporin protein family. Sticholysins are currently under examination as an active immunomodulating component of a vaccinal platform against tumoral cells and as a key element of a nucleic acids delivery system to cell cytosol. These proteins form pores in the plasma membrane leading to ion imbalance and cell lysis. However, the intracellular mechanisms triggered by actinoporins upon binding to membranes and its consequences for cell death are barely understood. Here, we have examined the cytotoxicity and intracellular responses induced by StII upon binding to human B-cell lymphoma Raji in vitro. StII cytotoxicity involves a functional actin cytoskeleton, induces cellular swelling, lysis and the concomitant release of cytosol content. In addition, StII induces calcium release mainly from the Endoplasmic Reticulum, activates Mitogen-Activated Protein Kinase ERK and impairs mitochondrial membrane potential. Furthermore, StII stimulates the expression of receptor interacting protein kinase 1 (RIP1), normally related to different forms of regulated cell death such as apoptosis and necroptosis. In correspondence, necrostatin-1, an inhibitor of this kinase, reduces StII cytotoxicity. However, the mechanism of cell death activated by StII does not involve caspases activation, typical molecular features of apoptosis and pyroptosis. Our results suggest that, beyond pore-formation and cell lysis, StII-induced cytotoxicity could involve other regulated intracellular mechanisms connected to RIP1-MEK1/2 -ERK1/2- pathways. This opens new perspectives and challenges the general point of view that these toxins induce a completely unregulated mechanism of necrotic cell death. This study contributes to a better understanding of the molecular mechanisms involved in toxin-cell interaction and the implications for cell functioning, with connotation for the exploitations of these toxins in clinical settings. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Tyrosine kinase inhibitors and mesenchymal stromal cells: effects on self-renewal, commitment and functions

PubMed Central

Borriello, Adriana; Caldarelli, Ilaria; Bencivenga, Debora; Stampone, Emanuela; Perrotta, Silverio; Oliva, Adriana; Ragione, Fulvio Della

2017-01-01

The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish “normal” from “transformed” phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the “vanguard” of molecularly targeted therapy for human neoplasias. Imatinib and the successive generations of inhibitors of Bcr-Abl1 kinase, represent the major successful examples of TKI use in cancer treatment. Other tyrosine kinases have been selected as targets of therapy, but the efficacy of their inhibition, although evident, is less definite. Two major negative effects exist in this therapeutic strategy and are linked to the specificity of the drugs and to the role of the targeted kinase in non-malignant cells. In this review, we will discuss the data available on the TKIs effects on the metabolism and functions of mesenchymal stromal cells (MSCs). MSCs are widely distributed in human tissues and play key physiological roles; nevertheless, they might be responsible for important pathologies. At present, bone marrow (BM) MSCs have been studied in greater detail, for both embryological origins and functions. The available data are evocative of an unexpected degree of complexity and heterogeneity of BM-MSCs. It is conceivable that this grade of intricacy occurs also in MSCs of other organs. Therefore, in perspective, the negative effects of TKIs on MSCs might represent a critical problem in long-term cancer therapies based on such inhibitors. PMID:27750212

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.

Peak-flow frequency relations and evaluation of the peak-flow gaging network in Nebraska

USGS Publications Warehouse

Soenksen, Philip J.; Miller, Lisa D.; Sharpe, Jennifer B.; Watton, Jason R.

1999-01-01

Estimates of peak-flow magnitude and frequency are required for the efficient design of structures that convey flood flows or occupy floodways, such as bridges, culverts, and roads. The U.S. Geological Survey, in cooperation with the Nebraska Department of Roads, conducted a study to update peak-flow frequency analyses for selected streamflow-gaging stations, develop a new set of peak-flow frequency relations for ungaged streams, and evaluate the peak-flow gaging-station network for Nebraska. Data from stations located in or within about 50 miles of Nebraska were analyzed using guidelines of the Interagency Advisory Committee on Water Data in Bulletin 17B. New generalized skew relations were developed for use in frequency analyses of unregulated streams. Thirty-three drainage-basin characteristics related to morphology, soils, and precipitation were quantified using a geographic information system, related computer programs, and digital spatial data.For unregulated streams, eight sets of regional regression equations relating drainage-basin to peak-flow characteristics were developed for seven regions of the state using a generalized least squares procedure. Two sets of regional peak-flow frequency equations were developed for basins with average soil permeability greater than 4 inches per hour, and six sets of equations were developed for specific geographic areas, usually based on drainage-basin boundaries. Standard errors of estimate for the 100-year frequency equations (1percent probability) ranged from 12.1 to 63.8 percent. For regulated reaches of nine streams, graphs of peak flow for standard frequencies and distance upstream of the mouth were estimated.The regional networks of streamflow-gaging stations on unregulated streams were analyzed to evaluate how additional data might affect the average sampling errors of the newly developed peak-flow equations for the 100-year frequency occurrence. Results indicated that data from new stations, rather than more data from existing stations, probably would produce the greatest reduction in average sampling errors of the equations.

Estimating the magnitude of peak flows for streams in Kentucky for selected recurrence intervals

USGS Publications Warehouse

Hodgkins, Glenn A.; Martin, Gary R.

2003-01-01

This report gives estimates of, and presents techniques for estimating, the magnitude of peak flows for streams in Kentucky for recurrence intervals of 2, 5, 10, 25, 50, 100, 200, and 500 years. A flowchart in this report guides the user to the appropriate estimates and (or) estimating techniques for a site on a specific stream. Estimates of peak flows are given for 222 U.S. Geological Survey streamflow-gaging stations in Kentucky. In the development of the peak-flow estimates at gaging stations, a new generalized skew coefficient was calculated for the State. This single statewide value of 0.011 (with a standard error of prediction of 0.520) is more appropriate for Kentucky than the national skew isoline map in Bulletin 17B of the Interagency Advisory Committee on Water Data. Regression equations are presented for estimating the peak flows on ungaged, unregulated streams in rural drainage basins. The equations were developed by use of generalized-least-squares regression procedures at 187 U.S. Geological Survey gaging stations in Kentucky and 51 stations in surrounding States. Kentucky was divided into seven flood regions. Total drainage area is used in the final regression equations as the sole explanatory variable, except in Regions 1 and 4 where main-channel slope also was used. The smallest average standard errors of prediction were in Region 3 (from -13.1 to +15.0 percent) and the largest average standard errors of prediction were in Region 5 (from -37.6 to +60.3 percent). One section of this report describes techniques for estimating peak flows for ungaged sites on gaged, unregulated streams in rural drainage basins. Another section references two previous U.S. Geological Survey reports for peak-flow estimates on ungaged, unregulated, urban streams. Estimating peak flows at ungaged sites on regulated streams is beyond the scope of this report, because peak flows on regulated streams are dependent upon variable human activities.

Estimation of Flood-Frequency Discharges for Rural, Unregulated Streams in West Virginia

USGS Publications Warehouse

Wiley, Jeffrey B.; Atkins, John T.

2010-01-01

Flood-frequency discharges were determined for 290 streamgage stations having a minimum of 9 years of record in West Virginia and surrounding states through the 2006 or 2007 water year. No trend was determined in the annual peaks used to calculate the flood-frequency discharges. Multiple and simple least-squares regression equations for the 100-year (1-percent annual-occurrence probability) flood discharge with independent variables that describe the basin characteristics were developed for 290 streamgage stations in West Virginia and adjacent states. The regression residuals for the models were evaluated and used to define three regions of the State, designated as Eastern Panhandle, Central Mountains, and Western Plateaus. Exploratory data analysis procedures identified 44 streamgage stations that were excluded from the development of regression equations representative of rural, unregulated streams in West Virginia. Regional equations for the 1.1-, 1.5-, 2-, 5-, 10-, 25-, 50-, 100-, 200-, and 500-year flood discharges were determined by generalized least-squares regression using data from the remaining 246 streamgage stations. Drainage area was the only significant independent variable determined for all equations in all regions. Procedures developed to estimate flood-frequency discharges on ungaged streams were based on (1) regional equations and (2) drainage-area ratios between gaged and ungaged locations on the same stream. The procedures are applicable only to rural, unregulated streams within the boundaries of West Virginia that have drainage areas within the limits of the stations used to develop the regional equations (from 0.21 to 1,461 square miles in the Eastern Panhandle, from 0.10 to 1,619 square miles in the Central Mountains, and from 0.13 to 1,516 square miles in the Western Plateaus). The accuracy of the equations is quantified by measuring the average prediction error (from 21.7 to 56.3 percent) and equivalent years of record (from 2.0 to 70.9 years).

Primary emissions and secondary organic aerosol formation from the exhaust of a flex-fuel (ethanol) vehicle

NASA Astrophysics Data System (ADS)

Suarez-Bertoa, R.; Zardini, A. A.; Platt, S. M.; Hellebust, S.; Pieber, S. M.; El Haddad, I.; Temime-Roussel, B.; Baltensperger, U.; Marchand, N.; Prévôt, A. S. H.; Astorga, C.

2015-09-01

Incentives to use biofuels may result in increasing vehicular emissions of compounds detrimental to air quality. Therefore, regulated and unregulated emissions from a Euro 5a flex-fuel vehicle, tested using E85 and E75 blends (gasoline containing 85% and 75% of ethanol (vol/vol), respectively), were investigated at 22 and -7 °C over the New European Driving Cycle, at the Vehicle Emission Laboratory at the European Commission Joint Research Centre Ispra, Italy. Vehicle exhaust was comprehensively analyzed at the tailpipe and in a dilution tunnel. A fraction of the exhaust was injected into a mobile smog chamber to study the photochemical aging of the mixture. We found that emissions from a flex-fuel vehicle, fueled by E85 and E75, led to secondary organic aerosol (SOA) formation, despite the low aromatic content of these fuel blends. Emissions of regulated and unregulated compounds, as well as emissions of black carbon (BC) and primary organic aerosol (POA) and SOA formation were higher at -7 °C. The flex-fuel unregulated emissions, mainly composed of ethanol and acetaldehyde, resulted in very high ozone formation potential and SOA, especially at low temperature (860 mg O3 km-1 and up to 38 mg C kg-1). After an OH exposure of 10 × 106 cm-3 h, SOA mass was, on average, 3 times larger than total primary particle mass emissions (BC + POA) with a high O:C ratio (up to 0.7 and 0.5 at 22 and -7 °C, respectively) typical of highly oxidized mixtures. Furthermore, high resolution organic mass spectra showed high 44/43 ratios (ratio of the ions m/z 44 and m/z 43) characteristic of low-volatility oxygenated organic aerosol. We also hypothesize that SOA formation from vehicular emissions could be due to oxidation products of ethanol and acetaldehyde, both short-chain oxygenated VOCs, e.g. methylglyoxal and acetic acid, and not only from aromatic compounds.

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

A database of global marine commercial, small-scale, illegal and unreported fisheries catch 1950-2014

NASA Astrophysics Data System (ADS)

Watson, Reg A.

2017-04-01

Global fisheries landings data from a range of public sources was harmonised and mapped to 30-min spatial cells based on the distribution of the reported taxa and the fishing fleets involved. This data was extended to include the associated fishing gear used, as well as estimates of illegal, unregulated and unreported catch (IUU) and discards at sea. Expressed as catch rates, these results also separated small-scale fisheries from other fishing operations. The dataset covers 1950 to 2014 inclusive. Mapped catch allows study of the impacts of fisheries on habitats and fauna, on overlap with the diets of marine birds and mammals, and on the related use of fuels and release of greenhouse gases. The fine-scale spatial data can be aggregated to the exclusive economic zone claims of countries and will allow study of the value of landed marine products to their economies and food security, and to those of their trading partners.

A database of global marine commercial, small-scale, illegal and unreported fisheries catch 1950-2014.

PubMed

Watson, Reg A

2017-04-11

Global fisheries landings data from a range of public sources was harmonised and mapped to 30-min spatial cells based on the distribution of the reported taxa and the fishing fleets involved. This data was extended to include the associated fishing gear used, as well as estimates of illegal, unregulated and unreported catch (IUU) and discards at sea. Expressed as catch rates, these results also separated small-scale fisheries from other fishing operations. The dataset covers 1950 to 2014 inclusive. Mapped catch allows study of the impacts of fisheries on habitats and fauna, on overlap with the diets of marine birds and mammals, and on the related use of fuels and release of greenhouse gases. The fine-scale spatial data can be aggregated to the exclusive economic zone claims of countries and will allow study of the value of landed marine products to their economies and food security, and to those of their trading partners.

Targeting the FANCJ–BRCA1 interaction promotes a switch from recombination to polη-dependent bypass

PubMed Central

Xie, J; Litman, R; Wang, S; Peng, M; Guillemette, S; Rooney, T; Cantor, SB

2010-01-01

BRCA1 and the DNA helicase FANCJ (also known as BACH1 or BRIP1) have common functions in breast cancer suppression and DNA repair. However, the functional significance of the direct interaction between BRCA1 and FANCJ remains unclear. Here, we have discovered that BRCA1 binding to FANCJ regulates DNA damage repair choice. Thus, when FANCJ binding to BRCA1 is ablated, the molecular mechanism chosen for the repair of damaged DNA is dramatically altered. Specifically, a FANCJ protein that cannot be phosphorylated at serine 990 or bind BRCA1 inhibits DNA repair via homologous recombination and promotes polη-dependent bypass. Furthermore, the polη-dependent bypass promoted by FANCJ requires the direct binding to the mismatch repair (MMR) protein, MLH1. Together, our findings implicate that in human cells BRCA1 binding to FANCJ is critical to regulate DNA repair choice and promote genomic stability. Moreover, unregulated FANCJ function could be associated with cancer and/or chemoresistance. PMID:20173781

A database of global marine commercial, small-scale, illegal and unreported fisheries catch 1950–2014

PubMed Central

Watson, Reg A.

2017-01-01

Global fisheries landings data from a range of public sources was harmonised and mapped to 30-min spatial cells based on the distribution of the reported taxa and the fishing fleets involved. This data was extended to include the associated fishing gear used, as well as estimates of illegal, unregulated and unreported catch (IUU) and discards at sea. Expressed as catch rates, these results also separated small-scale fisheries from other fishing operations. The dataset covers 1950 to 2014 inclusive. Mapped catch allows study of the impacts of fisheries on habitats and fauna, on overlap with the diets of marine birds and mammals, and on the related use of fuels and release of greenhouse gases. The fine-scale spatial data can be aggregated to the exclusive economic zone claims of countries and will allow study of the value of landed marine products to their economies and food security, and to those of their trading partners. PMID:28398351

Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

PubMed Central

Senavirathne, Gayan; Bertram, Jeffrey G.; Jaszczur, Malgorzata; Chaurasiya, Kathy R.; Pham, Phuong; Mak, Chi H.; Goodman, Myron F.; Rueda, David

2015-01-01

Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ∼5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer. PMID:26681117

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.

Regulation of tattoo ink production and the tattoo business in the US.

PubMed

Haugh, I M; Laumann, S L; Laumann, Anne E

2015-01-01

The production of tattoo ink and pigments in the US is unregulated. There are no guidelines or standards issued by national agencies. However, the practice of tattooing is regulated at the state and local levels but varies widely. Adverse events are addressed when a problem is reported. © 2015 S. Karger AG, Basel.

Quantifying Channel Maintenance Instream Flows: An Approach for Gravel-Bed Streams in the Western United States

Treesearch

Larry J. Schmidt; John P. Potyondy

2004-01-01

This paper discusses one approach for quantifying channel maintenance instream flow necessary to achieve the Forest Service Organic Act purpose of securing favorable conditions of water flows. The approach is appropriate for quantifying channel maintenance flows on perennial, unregulated, snowmelt-dominated, gravel-bed streams with alluvial reaches. The approach...

Perceptions and Use of Electronic Cigarettes in Pregnancy

ERIC Educational Resources Information Center

McCubbin, Andrea; Fallin-Bennett, Amanda; Barnett, Janine; Ashford, Kristin

2017-01-01

Use of electronic cigarettes (e-cigs) is quickly growing in the United States, despite the unknown health implications and unregulated device contents. Although research is emerging around e-cigs in general, there continues to be a lack of scientific evidence regarding the safety and risks of e-cig use on maternal and fetal health, even though…

Mating strategy and breeding patterns of the foothill yellow-legged frog (Rana boylii)

Treesearch

Clara A. Wheeler; Hartwell H. Welsh Jr.

2008-01-01

The Foothill Yellow-legged Frog (Rana boylii) has declined across much of its native range in California. Improper stream management may lower egg mass survival and reduce the availability of suitable breeding habitats. We collected data during six breeding-seasons (2002-2007) along an unregulated stream in northwestern California. We monitored...

Risk and Protective Factors Associated with Gambling Products and Services: Indigenous Gamblers in North Queensland

ERIC Educational Resources Information Center

Breen, Helen

2012-01-01

As part of a larger study, this paper reports on findings into risk and protective factors associated with gambling products and services by Indigenous Australians. Both Indigenous card gambling (traditional or unregulated) and commercial gambling (regulated) were investigated. Permission was granted by Indigenous Elders and by a university ethics…

76 FR 11713 - Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... subject to possible selection for virus monitoring. If selected, these systems would be required to permit... selection of 800 small PWSs serving 10,000 or fewer people monitored for List 1 contaminants. This... health effects and occurrence data EPA used to make these selections are contained in ``Possible...

School Reform in a Global Society

ERIC Educational Resources Information Center

Segall, William E.

2006-01-01

School Reform in a Global Society is about how a silent, wealthy upper class in the United States waited until the end of the Twentieth Century to transform America into something it once was during the Age of the Robber Barons. Known today as neoliberals, this nostalgic elite, craving the return of the unregulated capitalism of the nineteenth…

76 FR 76259 - National Emissions Standards for Hazardous Air Pollutants: Primary Aluminum Reduction Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... Clean Air Act. If finalized, these proposed amendments would address previously unregulated emissions (i... instructions for submitting comments. Email: a-and-r[email protected] , Attention Docket ID Number EPA-HQ-OAR...://www.regulations.gov Web site is an ``anonymous access'' system, which means the EPA will not know your...

Development and Multi-laboratory Verification of U.S. EPA Method 540 for the Analysis of Drinking Water Contaminants by Solid Phase Extraction-LC/MS/MS

EPA Science Inventory

A drinking water method for 12 chemicals, predominately pesticides, is presented that addresses the occurrence monitoring needs of the U.S. Environmental Protection Agency (EPA) for a future Unregulated Contaminant Monitoring Regulation (UCMR). The method employs solid phase ext...

New York State School Facilities and Student Health, Achievement, and Attendance: A Data Analysis Report

ERIC Educational Resources Information Center

Boese, Stephen; Shaw, John

2005-01-01

Students who attend schools with environmental hazards that impact indoor air quality are more likely to miss class, and therefore lose learning opportunities. Yet school environmental health and safety remains largely unregulated and there is no state or federal agency in charge of protecting children's environmental health in schools. This…

40 CFR 141.35 - Reporting for unregulated contaminant monitoring results.

Code of Federal Regulations, 2011 CFR

2011-07-01

... logs or construction drawings indicating that the representative well(s) is/are at a representative... after the first sampling event, as specified in Table 2 of § 141.40(a)(4)(i)(B), no notification to EPA... before and one month after the month in which the second sampling event is scheduled (i.e., it is not...

Isolating causal pathways between flow and fish in the regulated river hierarchy

Treesearch

Ryan McManamay; Donald J. Orth; Charles A. Dolloff; David C. Mathews

2015-01-01

Unregulated river systems are organized in a hierarchy in which large scale factors (i.e. landscape and segment scales) influence local habitats (i.e. reach, meso- and microhabitat scales), and both differentially exert selective pressures on biota. Dams, however, create discontinua in these processes and change the hierarchical structure. We examined the relative...

50 CFR 300.202 - Identification and certification of nations engaged in illegal, unreported, or unregulated...

Code of Federal Regulations, 2013 CFR

2013-10-01

... vessels are engaged in IUU fishing (1) NMFS will identify and list, in a biennial report to Congress... biennial report to Congress, the Secretary of Commerce will notify the President of such identification. Within 60 days after submission of the biennial report to Congress, the Secretary of Commerce, acting...

ADVANCED OXIDATION PROCESSES (AOPS) FOR DESTRUCTION OF METHYL TERTIARY BUTYL ETHER (MTBE -AN UNREGULATED CONTAMINANT) IN DRINKING WATER

EPA Science Inventory

Advanced oxidation processes (AOPs) provide a promising treatment option for the destruction of MTBE directly in surface and ground waters. An ongoing study is evaluating the ability of three AOPs; hydrogen peroxide/ozone (H2O2/ O3), ultraviolet irradiation/ozone (UV/O3) and ultr...

An Assessment Arms Race and Its Fallout: High-Stakes Grading and the Case for Slow Scholarship

ERIC Educational Resources Information Center

Harland, Tony; McLean, Angela; Wass, Rob; Miller, Ellen; Sim, Kwong Nui

2015-01-01

This research questions the impact of assessment on university teaching and learning in circumstances where all student work is graded. Sixty-two students and lecturers were interviewed to explore their experiences of assessment at an institution that had adopted a modular course structure and largely unregulated numbers of internal assessments.…

Interference of peptone and tyrosine with the lignin peroxidase assay.

PubMed Central

ten Have, R; Hartmans, S; Field, J A

1997-01-01

The N-unregulated white rot fungus Bjerkandera sp. strain BOS55 was cultured in 1 liter of peptone-yeast extract medium to produce lignin peroxidase (LiP). During the LiP assay, the oxidation of veratryl alcohol to veratraldehyde was inhibited due to tyrosine present in the peptone and the yeast extract. PMID:9251220

Development and Multi-laboratory Verification of US EPA Method 543 for the Analysis of Drinking Water Contaminants by Online Solid Phase Extraction-LC–MS-MS

EPA Science Inventory

A drinking water method for seven pesticides and pesticide degradates is presented that addresses the occurrence monitoring needs of the US Environmental Protection Agency (EPA) for a future Unregulated Contaminant Monitoring Regulation (UCMR). The method employs online solid pha...

40 CFR 141.40 - Monitoring requirements for unregulated contaminants.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-12/31/2015 Column headings are: 1—Contaminant: The name of the contaminant to be analyzed. 2—CAS..., for List 2 Screening Survey, or List 3 Pre-Screen Testing, during the time frame indicated in column 6... paragraph (a)(3) of this section. Samples must be collected at each sample point that is specified in column...

40 CFR 141.40 - Monitoring requirements for unregulated contaminants.

Code of Federal Regulations, 2013 CFR

2013-07-01

...-12/31/2015 Column headings are: 1—Contaminant: The name of the contaminant to be analyzed. 2—CAS..., for List 2 Screening Survey, or List 3 Pre-Screen Testing, during the time frame indicated in column 6... paragraph (a)(3) of this section. Samples must be collected at each sample point that is specified in column...

40 CFR 141.40 - Monitoring requirements for unregulated contaminants.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-12/31/2015 Column headings are: 1—Contaminant: The name of the contaminant to be analyzed. 2—CAS..., for List 2 Screening Survey, or List 3 Pre-Screen Testing, during the time frame indicated in column 6... paragraph (a)(3) of this section. Samples must be collected at each sample point that is specified in column...

Cell division and endoreduplication: doubtful engines of vegetative growth.

PubMed

John, Peter C L; Qi, Ruhu

2008-03-01

Currently, there is little information to indicate whether plant cell division and development is the collective effect of individual cell programming (cell-based) or is determined by organ-wide growth (organismal). Modulation of cell division does not confirm cell autonomous programming of cell expansion; instead, final cell size seems to be determined by the balance between cells formed and subsequent tissue growth. Control of growth in regions of the plant therefore has great importance in determining cell, organ and plant development. Here, we question the view that formation of new cells and their programmed expansion is the driving force of growth. We believe there is evidence that division does not drive, but requires, cell growth and a similar requirement for growth is detected in the modified cycle termed endoreduplication.

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

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

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

Loss of PodJ in Agrobacterium tumefaciens Leads to Ectopic Polar Growth, Branching, and Reduced Cell Division

PubMed Central

Anderson-Furgeson, James C.; Zupan, John R.; Grangeon, Romain

2016-01-01

ABSTRACT Agrobacterium tumefaciens is a rod-shaped Gram-negative bacterium that elongates by unipolar addition of new cell envelope material. Approaching cell division, the growth pole transitions to a nongrowing old pole, and the division site creates new growth poles in sibling cells. The A. tumefaciens homolog of the Caulobacter crescentus polar organizing protein PopZ localizes specifically to growth poles. In contrast, the A. tumefaciens homolog of the C. crescentus polar organelle development protein PodJ localizes to the old pole early in the cell cycle and accumulates at the growth pole as the cell cycle proceeds. FtsA and FtsZ also localize to the growth pole for most of the cell cycle prior to Z-ring formation. To further characterize the function of polar localizing proteins, we created a deletion of A. tumefaciens podJ (podJAt). ΔpodJAt cells display ectopic growth poles (branching), growth poles that fail to transition to an old pole, and elongated cells that fail to divide. In ΔpodJAt cells, A. tumefaciens PopZ-green fluorescent protein (PopZAt-GFP) persists at nontransitioning growth poles postdivision and also localizes to ectopic growth poles, as expected for a growth-pole-specific factor. Even though GFP-PodJAt does not localize to the midcell in the wild type, deletion of podJAt impacts localization, stability, and function of Z-rings as assayed by localization of FtsA-GFP and FtsZ-GFP. Z-ring defects are further evidenced by minicell production. Together, these data indicate that PodJAt is a critical factor for polar growth and that ΔpodJAt cells display a cell division phenotype, likely because the growth pole cannot transition to an old pole. IMPORTANCE How rod-shaped prokaryotes develop and maintain shape is complicated by the fact that at least two distinct species-specific growth modes exist: uniform sidewall insertion of cell envelope material, characterized in model organisms such as Escherichia coli, and unipolar growth, which occurs in several alphaproteobacteria, including Agrobacterium tumefaciens. Essential components for unipolar growth are largely uncharacterized, and the mechanism constraining growth to one pole of a wild-type cell is unknown. Here, we report that the deletion of a polar development gene, podJAt, results in cells exhibiting ectopic polar growth, including multiple growth poles and aberrant localization of cell division and polar growth-associated proteins. These data suggest that PodJAt is a critical factor in normal polar growth and impacts cell division in A. tumefaciens. PMID:27137498

Natural Compounds as Occult Ototoxins? Ginkgo biloba Flavonoids Moderately Damage Lateral Line Hair Cells.

PubMed

Neveux, Sarah; Smith, Nicole K; Roche, Anna; Blough, Bruce E; Pathmasiri, Wimal; Coffin, Allison B

2017-04-01

Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine. Using the zebrafish lateral line, we screened a natural products library to identify potential ototoxins. We found that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant, demonstrated significant ototoxicity, killing up to 30 % of lateral line hair cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar levels of ototoxicity. After flavonoid treatment, surviving hair cells demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the health of the remaining hair cells was compromised. We then asked if these flavonoids enter hair cells through the mechanotransduction channel, which is the site of entry for many known ototoxins. High extracellular calcium or the quinoline derivative E6 berbamine significantly protected hair cells from flavonoid damage, implicating the transduction channel as a site of flavonoid uptake. Since known ototoxins activate cellular stress responses, we asked if reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment with the antioxidant D-methionine significantly protected hair cells from each flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How these products affect mammalian hair cells is still an open question and will be the target of future experiments. However, this research demonstrates the potential for ototoxic damage caused by unregulated herbal supplements and suggests that further supplement characterization is warranted.

Differential growth of pavement cells of Arabidopsis thaliana leaf epidermis as revealed by microbead labeling.

PubMed

Elsner, Joanna; Lipowczan, Marcin; Kwiatkowska, Dorota

2018-02-01

In numerous vascular plants, pavement cells of the leaf epidermis are shaped like a jigsaw-puzzle piece. Knowledge about the subcellular pattern of growth that accompanies morphogenesis of such a complex shape is crucial for studies of the role of the cytoskeleton, cell wall and phytohormones in plant cell development. Because the detailed growth pattern of the anticlinal and periclinal cell walls remains unknown, our aim was to measure pavement cell growth at a subcellular resolution. Using fluorescent microbeads applied to the surface of the adaxial leaf epidermis of Arabidopsis thaliana as landmarks for growth computation, we directly assessed the growth rates for the outer periclinal and anticlinal cell walls at a subcellular scale. We observed complementary tendencies in the growth pattern of the outer periclinal and anticlinal cell walls. Central portions of periclinal walls were characterized by relatively slow growth, while growth of the other wall portions was heterogeneous. Local growth of the periclinal walls accompanying lobe development after initiation was relatively fast and anisotropic, with maximal extension usually in the direction along the lobe axis. This growth pattern of the periclinal walls was complemented by the extension of the anticlinal walls, which was faster on the lobe sides than at the tips. Growth of the anticlinal and outer periclinal walls of leaf pavement cells is heterogeneous. The growth of the lobes resembles cell elongation via diffuse growth rather than tip growth. © 2018 Botanical Society of America.

Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

PubMed

Lee, Iris J; Hilliard, Brendan A; Ulas, Mehriban; Yu, Daohai; Vangala, Chandan; Rao, Swati; Lee, Jean; Gadegbeku, Crystal A; Cohen, Philip L

2015-06-01

Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel drug discovery strategies for atherosclerosis that target necrosis and necroptosis.

PubMed

Coornaert, Isabelle; Hofmans, Sam; Devisscher, Lars; Augustyns, Koen; Van Der Veken, Pieter; De Meyer, Guido R Y; Martinet, Wim

2018-06-01

Formation and enlargement of a necrotic core play a pivotal role in atherogenesis. Since the discovery of necroptosis, which is a regulated form of necrosis, prevention of necrotic cell death has become an attractive therapeutic goal to reduce plaque formation. Areas covered: This review highlights the triggers and consequences of (unregulated) necrosis and necroptosis in atherosclerosis. The authors discuss different pharmacological strategies to inhibit necrotic cell death in advanced atherosclerotic plaques. Expert opinion: Addition of a necrosis or necroptosis inhibitor to standard statin therapy could be a promising strategy for primary prevention of cardiovascular disease. However, a necrosis inhibitor cannot block all necrosis stimuli in atherosclerotic plaques. A necroptosis inhibitor could be more effective, because necroptosis is mediated by specific proteins, termed receptor-interacting serine/threonine-protein kinases (RIPK) and mixed lineage kinase domain-like pseudokinase (MLKL). Currently, only RIPK1 inhibitors have been successfully used in atherosclerotic mouse models to inhibit necroptosis. However, because RIPK1 is involved in both necroptosis and apoptosis, and also RIPK1-independent necroptosis can occur, we feel that targeting RIPK3 and MLKL could be a more attractive therapeutic approach to inhibit necroptosis. Therefore, future challenges will consist of developing RIPK3 and MLKL inhibitors applicable in both preclinical and clinical settings.

Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets.

PubMed

Vidaña, Beatriz; Martínez, Jorge; Martorell, Jaime; Montoya, María; Córdoba, Lorena; Pérez, Mónica; Majó, Natàlia

2016-11-08

Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3.

Sonic Hedgehog in pancreatic cancer: From bench to bedside, then back to the bench

PubMed Central

Rosow, David E.; Liss, Andrew S.; Strobel, Oliver; Fritz, Stefan; Bausch, Dirk; Valsangkar, Nakul P.; Alsina, Janivette; Kulemann, Birte; Park, Joo Kyung; Yamaguchi, Junpei; LaFemina, Jennifer; Thayer, Sarah P.

2013-01-01

Developmental genes are known to regulate cell proliferation, migration, and differentiation; thus, it comes as no surprise that the misregulation of developmental genes plays an important role in the biology of human cancers. One such pathway that has received an increasing amount of attention for its function in carcinogenesis is the Hedgehog (Hh) pathway. Initially the domain of developmental biologists, the Hh pathway and one of its ligands, Sonic Hedgehog (Shh), have been shown to play an important role in body planning and organ development, particularly in the foregut endoderm. Their importance in human disease became known to cancer biologists when germline mutations that resulted in the unregulated activity of the Hh pathway were found to cause basal cell carcinoma and medulloblastoma. Since then, misexpression of the Hh pathway has been shown to play an important role in many other cancers, including those of the pancreas. In many institutions, investigators are targeting misexpression of the Hh pathway in clinical trials, but there is still much fundamental knowledge to be gained about this pathway that can shape its clinical utility. This review will outline the evolution of our understanding of this pathway as it relates to the pancreas, as well as how the Hh pathway came to be a high-priority target for treatment. PMID:22770959

Deregulation of cell growth and malignant transformation.

PubMed

Sulić, Sanda; Panić, Linda; Dikić, Ivan; Volarević, Sinisa

2005-08-01

Cell growth and cell division are fundamental aspects of cell behavior in all organisms. Recent insights from many model organisms have shed light on the molecular mechanisms that control cell growth and cell division. A significant body of evidence has now been accumulated, showing a direct link between deregulation of components of cell cycle machinery and cancer. In addition, defects in one or more steps that control growth are important for malignant transformation, as many tumor suppressors and proto-oncogenes have been found to regulate cell growth. The importance of cell growth in tumor development is further supported by the discovery that rapamycin, an effective anticancer drug, inhibits a key regulator of protein synthetic machinery and cell growth, mammalian target of rapamycin (mTOR). In most cases, cell growth and cell division are coupled, thereby maintaining cell size within physiological limits. We believe that, in a long-term perspective, understanding how these two processes are coordinated in vivo and how their interplay is deregulated in a number of diseases, including cancer, may have a direct impact on the efficiency of modern therapeutics.

Health system reform and safe abortion: a case study of Mongolia.

PubMed

Beck, Christina; Berry, Nicole S; Choijil, Semjidmaa

2013-01-01

Unsafe abortion serves as a marker of global inequity as it is concentrated in the developing world where the poorest and most vulnerable women live. While liberalisation of abortion law is essential to the reduction of unsafe abortion, a number of challenges exist beyond this important step. This paper investigates how popular health system reforms consonant with neoliberal agendas can challenge access to safe abortion. We use Mongolia, a country that has liberalised abortion law, yet, limited access to safe abortion, as a case study. Mongolia embraced market reforms in 1990 and subsequently reformed its health system. We document how common reforms in the areas of finance and regulation can compromise the safety of abortions as they foster challenges that include inconsistencies in service delivery that further foment health inequities, adoption of reproductive health programmes that are incompatible with the local sociocultural context, unregulated growth of the private sector and poor enforcement of standards and technical guidelines for safe abortion. We then discuss how this case study suggests the conversations that reproductive health policy-makers must have with those engineering health sector reform to ensure access to safe abortion in a liberalised environment.

Acromegaly discovered during a routine out-patient surgical procedure: a case report.

PubMed

Chiaghana, Chukwudi O; Bauerfeind, Julia M; Sulek, Cheri A; Goldstein, J Christopher; Awoniyi, Caleb A

2017-06-24

Acromegaly is a rare syndrome in which there is unregulated hypersecretion of growth hormone. The anesthetic management of patients with this disorder is particularly challenging due to pre-existing cardiovascular and respiratory dysfunction, as well as recognized difficulties with airway management. Because of the insidious progression of the disease and the presence of nonspecific signs and symptoms, diagnosis is often made late when characteristic acromegalic features become apparent. We report the management of a 35-year-old African American man with previously undiagnosed acromegaly, who underwent a general anesthetic for same day surgery. Subtle physical features and difficult endotracheal intubation raised our suspicion for the diagnosis of acromegaly. Following an uncomplicated postoperative course he underwent workup for the disease, which was confirmed. In addition, brain magnetic resonance imaging showed a pituitary adenoma. A subsequent transsphenoidal hypophysectomy was performed successfully. This case underscores the notable absence of recognizing the clinical presentation of acromegaly in this patient by his primary care physician, and the value of thorough history taking, vigilance, and observation in making a new diagnosis that has the potential to alter a patient's health care and mitigate impending morbidity and/or mortality.

Muscular and Cardiorespiratory Fitness in Homeschool versus Public School Children.

PubMed

Kabiri, Laura S; Mitchell, Katy; Brewer, Wayne; Ortiz, Alexis

2017-08-01

The growth and unregulated structure of homeschooling creates an unknown population in regard to muscular and cardiorespiratory fitness. The purpose of this research was to compare muscular and cardiorespiratory fitness between elementary school aged homeschool and public school children. Homeschool children ages 8-11 years old (n = 75) completed the curl-up, 90° push-up, and Progressive Aerobic Capacity Endurance Run (PACER) portions of the FitnessGram to assess abdominal and upper body strength and endurance as well as cardiorespiratory fitness. Comparisons to public school children (n = 75) were made using t tests and chi-square tests. Homeschool children showed significantly lower abdominal (t(148) = -11.441, p < .001; χ 2 (1) = 35.503, p < .001) and upper body (t(148) = -3.610, p < .001; χ 2 (1) = 4.881, p = .027) strength and endurance. There were no significant differences in cardiorespiratory fitness by total PACER laps (t(108) = 0.879, p = .381) or estimated VO 2max (t(70) = 1.187, p = .239; χ 2 (1) = 1.444, p = .486). Homeschool children showed significantly lower levels of both abdominal and upper body muscular fitness compared with their age and gender matched public school peers but no difference in cardiorespiratory fitness.

Pakistan and the Millennium Development Goals for Maternal and Child Health: progress and the way forward.

PubMed

Rizvi, Arjumand; Bhatti, Zaid; Das, Jai K; Bhutta, Zulfiqar A

2015-04-03

The world has made substantial progress in reducing maternal and child mortality, but many countries are projected to fall short of achieving their Millennium Development Goals (MDGs) 4 and 5 targets. The major objective of this paper is to examine progress in Pakistan in reducing maternal and child mortality and malnutrition over the last two decades. Data from recent national and international surveys suggest that Pakistan lags behind on all of its MDGs related to maternal and child health and, for some indicators especially related to nutrition, the situation has worsened from the baseline of 1990. Progress in addressing key social determinants such as poverty, female education and empowerment has also been slow and unregulated population growth has further compromised progress. There is a need to integrate the various different sectors and programmes to achieve the desired results effectively and efficiently as many of the determinants and influencing factors are outside the health sector. Pakistan has to accelerate improvement of access to maternal health services, particularly contraception, emergency obstetric care and skilled birth attendance; the need to improve maternal and child nutrition cannot be over-emphasised.

Footprints near the Surf: Individual Privacy Decisions in Online Contexts

ERIC Educational Resources Information Center

McDonald, Aleecia M.

2010-01-01

As more people seek the benefits of going online, more people are exposed to privacy risks from their time online. With a largely unregulated Internet, self-determination about privacy risks must be feasible for people from all walks of life. Yet in many cases decisions are either not obvious or not accessible. As one example, privacy policies are…

Missing the Target: We Need to Focus on Informal Care Rather than Preschool. Evidence Speaks Reports, Vol 1, #19

ERIC Educational Resources Information Center

Loeb, Susanna

2016-01-01

Despite the widely-recognized benefits of early childhood experiences in formal settings that enrich the social and cognitive environments of children, many children--particularly infants and toddlers--spend their days in unregulated (or very lightly regulated) "informal" childcare settings. Over half of all one- and two-year-olds are…

Reconnaissance-Level Assessment of Water Quality Near Flandreau, South Dakota

DTIC Science & Technology

2002-01-01

associations with adverse health effects have been established. Con- centrations of some selected analytes were less than U.S. Environmental ...unregulated synthetic organic compounds in aquatic environments . This study provides information concerning the occurrence of selected organic compounds...water sites. Selected data from various other investigations also are described. A total of 15 environmental samples, which included two sets of

Fifty Educational Markets: A Playbook of State Laws and Regulations Governing Private Schools. School Choice Issues in Depth

ERIC Educational Resources Information Center

Hammons, Christopher

2008-01-01

There is a widespread misperception that private schools avoid government oversight or are "unregulated." In fact, private schools are subject to a wide variety of laws and regulations that run the gamut from reasonable rules to ensure health and safety to unreasonable rules that interfere with school curricula, preventing schools from pursuing…

Bleeding Hearts, Profiteers, or Both: Specialist Physician Fees in an Unregulated Market.

PubMed

Johar, Meliyanni; Mu, Chunzhou; Van Gool, Kees; Wong, Chun Yee

2017-04-01

This study shows that, in an unregulated fee-setting environment, specialist physicians practise price discrimination on the basis of their patients' income status. Our results are consistent with profit maximisation behaviour by specialists. These findings are based on a large population survey that is linked to administrative medical claims records. We find that, for an initial consultation, specialist physicians charge their high-income patients AU$26 more than their low-income patients. While this gap equates to a 19% lower fees for the poorest patients (bottom 25% of the household income distribution), it is unlikely to remove the substantial financial barriers they face in accessing specialist care. There are large variations across specialties, with neurologists exhibiting the largest fee gap between the high-income and low-income patients. Several possible channels for deducing the patient's income are examined. We find that patient characteristics such as age, health concession card status and private health insurance status are all used by specialists as proxies for income status. These characteristics are particularly important to further practise price discrimination among the low-income patients but are less relevant for the high-income patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Behavioural responses of spinner dolphins to human interactions.

PubMed

Fumagalli, Maddalena; Cesario, Amina; Costa, Marina; Harraway, John; Notarbartolo di Sciara, Giuseppe; Slooten, Elisabeth

2018-04-01

There is increasing evidence that whale and dolphin watching activities have detrimental effects on targeted cetacean populations. In Egypt, spinner dolphins regularly occur in the resting areas of Samadai, Satayah and Qubbat'Isa reefs. In-water human interactions with dolphins are regulated with a time-area closure system at Samadai, unregulated at Satayah and non-existent at Qubbat'Isa. This provided an ideal experimental setting to advance our understanding of the effects of tourism on a species highly sensitive to disturbances. Our study confirmed that the intensity and duration of interactions, and therefore, dolphin exposure to tourism, differed among the study sites. Compared with the Qubbat'Isa control site, behavioural reactions to boats and swimmers at the two tourism sites suggested that dolphin rest was disrupted, especially around the middle of the day and especially at Satayah, where dolphin tourism is unregulated. Our results indicate also that the dolphin protection measures at Samadai reduce the level of disturbance. We recommend that similar measures be implemented at other dolphin tourism locations, and that no new operations be initiated until the long-term impacts on dolphin populations are better understood. Our experience emphasizes the need to adopt precautionary approaches in research and management of whale and dolphin watching.

HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

PubMed

Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

2009-05-01

Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

Distal impacts of aquarium trade: Exploring the emerging sandhopper (Orchestoidea tuberculata) artisanal shore gathering fishery in Chile.

PubMed

Tapia-Lewin, Sebastián; Vergara, Karina; De La Barra, Christian; Godoy, Natalio; Castilla, Juan Carlos; Gelcich, Stefan

2017-10-01

Artisanal fishery activities support the livelihoods of millions of people worldwide, particularly in developing countries. Within these fisheries, distal global drivers can promote switching between alternative target resources. These drivers can promote the rapid development of new, unregulated and previously unexploited fisheries that pose a threat to the sustainability of ecosystems. In this paper, we describe a new artisanal shore gathering activity that targets a previously unexploited resource: the sandhopper (Orchestoidea tuberculata). The activity is driven by aquarium trade demand for food. We used mixed methods to describe the activity, assessed basic socio-economic incentives, and estimated Catches per Unit Effort. Results show that the sandhopper plays an important role for the livelihoods of shore gatherers engaged in the activity. Gatherers have adapted and developed two main extraction methods with different degrees of investment and extraction rates. Furthermore, gatherers have developed local knowledge regarding the ecology and management of the resource. Results show that economic incentives can motivate a rapid expansion of this unregulated activity. Future research gaps and management options to address the development of this fishery are discussed in light of these findings.

Secondary hemophagocytic lymphohistiocytosis in the setting of metastatic renal cell carcinoma: a case report.

PubMed

El-Masry, Monica; Eisenbud, Lauren; Tran, Minh-Ha

2017-03-02

Hemophagocytic lymphohistiocytosis is a disease process characterized by unregulated hyperactivation of the immune system associated with multiorgan involvement and high mortality rates. Early recognition is crucial and a recently validated diagnostic schema, the H-Score, may facilitate diagnosis particularly in secondary hemophagocytic lymphohistiocytosis cases. We present a patient with secondary hemophagocytic lymphohistiocytosis in association with metastatic renal cell carcinoma in whom high-dose steroid therapy induced a remarkable response. A 35-year-old Vietnamese man with quiescent systemic lupus erythematosus was diagnosed 5 months prior to admission with left-sided renal cell carcinoma metastatic to the pancreas and spine. Ten days prior to admission, a febrile illness (temperatures to 39 °C) associated with flu-like symptoms unresponsive to levofloxacin developed. He took only two doses of pazopanib prior to admission. High fevers unresponsive to antimicrobial therapy, cytopenias, disseminated intravascular coagulation, and progressive multiorgan failure led to intubation and intensive care unit stay. Extensive infectious disease workup showed only negative results, but elevation of interleukin-2 receptor, exceedingly high ferritin levels and other features earned an H-Score of 302, consistent with >99% diagnostic probability for secondary hemophagocytic lymphohistiocytosis. High-dose steroid therapy produced a rapid clinical and biochemical response. Hemophagocytic lymphohistiocytosis is a life-threatening disorder which is likely to be under-recognized. Increased awareness of this disease entity and its diagnosis is crucial toward early recognition and treatment. To our knowledge, our patient is only the second reported with secondary hemophagocytic lymphohistiocytosis occurring in the setting of renal cell carcinoma.

Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.

PubMed

Hegedüs, Csilla; Truta-Feles, Krisztina; Antalffy, Géza; Várady, György; Német, Katalin; Ozvegy-Laczka, Csilla; Kéri, György; Orfi, László; Szakács, Gergely; Settleman, Jeffrey; Váradi, András; Sarkadi, Balázs

2012-08-01

Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side population that is characteristically enriched in normal and cancer stem cells. Numerous tumors depend on unregulated EGFR signaling, thus inhibition of this receptor by small molecular weight inhibitors such as gefitinib, and the novel second generation agents vandetanib, pelitinib and neratinib, is a promising therapeutic option. In the present study, we provide detailed biochemical characterization regarding the interaction of these EGFR inhibitors with ABCG2. We show that ABCG2 confers resistance to gefitinib and pelitinib, whereas the intracellular action of vandetanib and neratinib is unaltered by the presence of the transporter. At higher concentrations, however, all these EGFR inhibitors inhibit ABCG2 function, thereby promoting accumulation of ABCG2 substrate drugs. We also report enhanced expression of ABCG2 in gefitinib-resistant non-small cell lung cancer cells, suggesting potential clinical relevance of ABCG2 in acquired drug resistance. Since ABCG2 has important impact on both the pharmacological properties and anti-cancer efficiencies of drugs, our results regarding the novel EGFR inhibitors should provide useful information about their therapeutic applicability against ABCG2-expressing cancer cells depending on EGFR signaling. In addition, the finding that these EGFR inhibitors efficiently block ABCG2 function may help to design novel drug-combination therapeutic strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

Membrane cholesterol removal changes mechanical properties of cells and induces secretion of a specific pool of lysosomes.

PubMed

Hissa, Barbara; Pontes, Bruno; Roma, Paula Magda S; Alves, Ana Paula; Rocha, Carolina D; Valverde, Thalita M; Aguiar, Pedro Henrique N; Almeida, Fernando P; Guimarães, Allan J; Guatimosim, Cristina; Silva, Aristóbolo M; Fernandes, Maria C; Andrews, Norma W; Viana, Nathan B; Mesquita, Oscar N; Agero, Ubirajara; Andrade, Luciana O

2013-01-01

In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal.

Membrane Cholesterol Removal Changes Mechanical Properties of Cells and Induces Secretion of a Specific Pool of Lysosomes

PubMed Central

Roma, Paula Magda S.; Alves, Ana Paula; Rocha, Carolina D.; Valverde, Thalita M.; Aguiar, Pedro Henrique N.; Almeida, Fernando P.; Guimarães, Allan J.; Guatimosim, Cristina; Silva, Aristóbolo M.; Fernandes, Maria C.; Andrews, Norma W.; Viana, Nathan B.; Mesquita, Oscar N.; Agero, Ubirajara; Andrade, Luciana O.

2013-01-01

In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal. PMID:24376622

Separation of cell survival, growth, migration, and mesenchymal transdifferentiation effects of fibroblast secretome on tumor cells of head and neck squamous cell carcinoma.

PubMed

Metzler, Veronika Maria; Pritz, Christian; Riml, Anna; Romani, Angela; Tuertscher, Raphaela; Steinbichler, Teresa; Dejaco, Daniel; Riechelmann, Herbert; Dudás, József

2017-11-01

Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast-secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial-mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1.Tumor cell self-produced factors were sufficient to ensure tumor cell survival and basic cell growth, but fibroblast-secreted paracrine factors significantly increased cell proliferation, migration, and epithelial-mesenchymal transition-related phenotype changes in tumor cells. Transforming growth factor beta-1 generated individually migrating disseminating tumor cell groups or single cells separated from the tumor cell nest, which were characterized by reduced E-cadherin expression. At the same time, transforming growth factor beta-1 inhibited tumor cell proliferation under serum-starved conditions. Neutralizing transforming growth factor beta antibody reduced the cell migration support of fibroblast-conditioned medium. Transforming growth factor beta-1 as a single factor was sufficient for generation of disseminating tumor cells from epithelial tumor cell nests, while other fibroblast paracrine factors supported tumor nest outgrowth. Different fibroblast-released factors might support tumor cell proliferation and invasion, as two separate effects.

The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast

PubMed Central

2017-01-01

The size of nearly all cells is modulated by nutrients. Thus, cells growing in poor nutrients can be nearly half the size of cells in rich nutrients. In budding yeast, cell size is thought to be controlled almost entirely by a mechanism that delays cell cycle entry until sufficient growth has occurred in G1 phase. Here, we show that most growth of a new daughter cell occurs in mitosis. When the rate of growth is slowed by poor nutrients, the duration of mitosis is increased, which suggests that cells compensate for slow growth in mitosis by increasing the duration of growth. The amount of growth required to complete mitosis is reduced in poor nutrients, leading to a large reduction in cell size. Together, these observations suggest that mechanisms that control the extent of growth in mitosis play a major role in cell size control in budding yeast. PMID:28939614

System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells.

PubMed

Malina, Halina Z

2011-01-19

The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]). Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites). The formation of these polymers (aggregates) leads to an unregulated and, consequently, pathological protein network. The results suggest a mechanism for the involvement of small molecules in disease development. In the knockout cells, incorrect interactions between proteins were observed without the protein modification by small molecules, indicating the abnormality of the protein network in the transgenic system. The irreversible protein-protein interactions lead to protein aggregation and cell degeneration, which are observed in all aging-associated diseases.

System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells

PubMed Central

2011-01-01

Background The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Results Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]). Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. Conclusions The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites). The formation of these polymers (aggregates) leads to an unregulated and, consequently, pathological protein network. The results suggest a mechanism for the involvement of small molecules in disease development. In the knockout cells, incorrect interactions between proteins were observed without the protein modification by small molecules, indicating the abnormality of the protein network in the transgenic system. The irreversible protein-protein interactions lead to protein aggregation and cell degeneration, which are observed in all aging-associated diseases. PMID:21247434

Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis

PubMed Central

Skopova, Karolina; Tomalova, Barbora; Kanchev, Ivan; Rossmann, Pavel; Svedova, Martina; Adkins, Irena; Bibova, Ilona; Tomala, Jakub; Masin, Jiri; Guiso, Nicole; Osicka, Radim; Sedlacek, Radislav; Kovar, Marek

2017-01-01

ABSTRACT The adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, αMβ2 integrin, or CD11b/CD18). CyaA delivers into cells an N-terminal adenylyl cyclase (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cyclic AMP (cAMP), a key second messenger subverting bactericidal activities of phagocytes. In parallel, the hemolysin (Hly) moiety of CyaA forms cation-selective hemolytic pores that permeabilize target cell membranes. We constructed the first B. pertussis mutant secreting a CyaA toxin having an intact capacity to deliver the AC enzyme into CD11b-expressing (CD11b+) host phagocytes but impaired in formation of cell-permeabilizing pores and defective in cAMP elevation in CD11b− cells. The nonhemolytic AC+ Hly− bacteria inhibited the antigen-presenting capacities of coincubated mouse dendritic cells in vitro and skewed their Toll-like receptor (TLR)-triggered maturation toward a tolerogenic phenotype. The AC+ Hly− mutant also infected mouse lungs as efficiently as the parental AC+ Hly+ strain. Hence, elevation of cAMP in CD11b− cells and/or the pore-forming capacity of CyaA were not required for infection of mouse airways. The latter activities were, however, involved in bacterial penetration across the epithelial layer, enhanced neutrophil influx into lung parenchyma during sublethal infections, and the exacerbated lung pathology and lethality of B. pertussis infections at higher inoculation doses (>107 CFU/mouse). The pore-forming activity of CyaA further synergized with the cAMP-elevating activity in downregulation of major histocompatibility complex class II (MHC-II) molecules on infiltrating myeloid cells, likely contributing to immune subversion of host defenses by the whooping cough agent. PMID:28396322

Calcium signalling in salivary gland physiology and dysfunction

PubMed Central

2015-01-01

Abstract Studies over the past four decades have established that Ca2+ is a critical factor in control of salivary gland function and have led to identification of the critical components of this process. The major ion transport mechanisms and ion channels that are involved in fluid secretion have also been established. The key event in activation of fluid secretion is an increase in [Ca2+]i triggered by inositol 1,4,5‐trisphosphate (IP3)‐induced release of Ca2+ from ER via the IP3 receptor (IP3R). IP3Rs determine the site of initiation and the pattern of the [Ca2+]i signal in the cell. However, Ca2+ entry into the cell is required to sustain the elevation of [Ca2+]i and fluid secretion and is mediated by the store‐operated Ca2+ entry (SOCE) mechanism. Orai1, TRPC1, TRPC3 and STIM1 have been identified as critical components of SOCE in these cells. Cells finely tune the generation and amplification of [Ca2+]i signals for regulation of cell function. An important emerging area is the concept that unregulated [Ca2+]i signals in cells can directly cause cell damage, dysfunction and disease. Alternatively, aberrant [Ca2+]i signals can also amplify and increase the rates of cell damage. Such defects in Ca2+ signalling have been described in salivary glands in conjunction with radiation‐induced loss of salivary gland function as well as in the salivary defects associated with the autoimmune exocrinopathy Sjögren's syndrome. Such defects have been associated with altered function or expression of key Ca2+ signalling components, such as STIM proteins and TRP channels. These studies offer new avenues for examining the mechanisms underlying the disease and development of novel clinical targets and therapeutic strategies. PMID:26592972

Calcium signalling in salivary gland physiology and dysfunction.

PubMed

Ambudkar, Indu S

2016-06-01

Studies over the past four decades have established that Ca(2+) is a critical factor in control of salivary gland function and have led to identification of the critical components of this process. The major ion transport mechanisms and ion channels that are involved in fluid secretion have also been established. The key event in activation of fluid secretion is an increase in [Ca(2+) ]i triggered by inositol 1,4,5-trisphosphate (IP3 )-induced release of Ca(2+) from ER via the IP3 receptor (IP3 R). IP3 Rs determine the site of initiation and the pattern of the [Ca(2+) ]i signal in the cell. However, Ca(2+) entry into the cell is required to sustain the elevation of [Ca(2+) ]i and fluid secretion and is mediated by the store-operated Ca(2+) entry (SOCE) mechanism. Orai1, TRPC1, TRPC3 and STIM1 have been identified as critical components of SOCE in these cells. Cells finely tune the generation and amplification of [Ca(2+) ]i signals for regulation of cell function. An important emerging area is the concept that unregulated [Ca(2+) ]i signals in cells can directly cause cell damage, dysfunction and disease. Alternatively, aberrant [Ca(2+) ]i signals can also amplify and increase the rates of cell damage. Such defects in Ca(2+) signalling have been described in salivary glands in conjunction with radiation-induced loss of salivary gland function as well as in the salivary defects associated with the autoimmune exocrinopathy Sjögren's syndrome. Such defects have been associated with altered function or expression of key Ca(2+) signalling components, such as STIM proteins and TRP channels. These studies offer new avenues for examining the mechanisms underlying the disease and development of novel clinical targets and therapeutic strategies. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Characteristics of MIC-1 antlerogenic stem cells and their effect on hair growth in rabbits.

PubMed

Cegielski, Marek; Izykowska, Ilona; Chmielewska, Magdalena; Dziewiszek, Wojciech; Bochnia, Marek; Calkosinski, Ireneusz; Dziegiel, Piotr

2013-01-01

We characterized growth factors produced by MIC-1 antlerogenic stem cells and attempted to apply those cells to stimulate hair growth in rabbits. We evaluated the gene and protein expression of growth factors by immunocytochemical and molecular biology techniques in MIC-1 cells. An animal model was used to assess the effects of xenogenous stem cells on hair growth. In the experimental group, rabbits were intradermally injected with MIC-1 stem cells, whereas the control group rabbits were given vehicle-only. After 1, 2 and 4 weeks, skin specimen were collected for histological and immunohistochemical tests. MIC-1 antlerogenic stem cells express growth factors, as confirmed at the mRNA and protein levels. Histological and immunohistochemical analysis demonstrated an increase in the number of hair follicles, as well as the amount of secondary hair in the follicles, without an immune response in animals injected intradermally with MIC-1 cells, compared to animals receiving vehicle-alone. MIC-1 cells accelerated hair growth in rabbits due to the activation of cells responsible for the regulation of the hair growth cycle through growth factors. Additionally, the xenogenous cell implant did not induce immune response.

Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

PubMed Central

Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

2015-01-01

ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

Optimizing storage temperature of liquid bovine semen diluted in INRA96.

PubMed

Murphy, Edel M; O' Meara, Ciara; Eivers, Bernard; Lonergan, Patrick; Fair, Sean

2018-06-01

Temperature regulation of liquid bovine semen can be difficult in field situations. Two experiments were carried out to assess the effect of storage temperature on in vitro sperm characteristics and 60-d nonreturn rate (NRR) following artificial insemination (AI) of liquid bovine semen. In experiment 1, the effect of storage of liquid bovine semen in INRA96 diluent (IMV Technologies, L'Aigle, France) at 1 of 5 storage temperatures (5, 15, or 28°C, and fluctuating between 5 and 15°C or 5 and 28°C) on total and progressive motility and kinematic parameters was assessed objectively via computer-assisted sperm analyzer on d 0, 1, 2, 3, and 4 after collection. Fluctuating temperatures were designed to mimic day- to nighttime variation. In experiment 2, we assessed the field fertility of liquid semen stored at a constant 5 or 15°C or in an unregulated manner and compared with that of frozen-thawed semen (total of n = 106,738 inseminations). In experiment 1, we detected a linear decrease in motility with increased duration of storage. Semen stored at a constant 15°C or fluctuating between 5 and 15°C had greater total motility than semen held at 5 or 28°C or fluctuating between 5 and 28°C; however, semen stored at 15°C and fluctuating between 5 and 15°C did not differ from each other. Semen held at a constant 5 or 15°C or fluctuating between 5 and 15°C, although not differing from each other, had higher progressive motility scores than that held at 28°C or fluctuating between 5 and 28°C. Semen stored at a constant 28°C exhibited poor motility and velocity values but had high progressive motion values compared with that all other storage temperatures; however, the other storage temperatures did not differ from each other in relation to motility kinematics. In experiment 2, semen stored at a constant 5°C resulted in a lower 60-d NRR (62.5%) than storage at constant 15°C or unregulated temperature or frozen-thawed semen (73.6, 74.6, and 74.4%, respectively. In conclusion, sperm stored in IRNA96 are quite tolerant in terms of storage temperature, retaining acceptable motility between 5 and 15°C. Storing semen at a constant 15°C resulted in greater in vitro sperm motility and higher NRR rates than storage at 5°C and did not differ in NRR from frozen-thawed semen or semen stored at an unregulated temperature; however, lower storage temperatures were shown to be more detrimental to sperm in vivo than unregulated storage conditions. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Directed evolution of cell size in Escherichia coli.

PubMed

Yoshida, Mari; Tsuru, Saburo; Hirata, Naoko; Seno, Shigeto; Matsuda, Hideo; Ying, Bei-Wen; Yomo, Tetsuya

2014-12-17

In bacteria, cell size affects chromosome replication, the assembly of division machinery, cell wall synthesis, membrane synthesis and ultimately growth rate. In addition, cell size can also be a target for Darwinian evolution for protection from predators. This strong coupling of cell size and growth, however, could lead to the introduction of growth defects after size evolution. An important question remains: can bacterial cell size change and/or evolve without imposing a growth burden? The directed evolution of particular cell sizes, without a growth burden, was tested with a laboratory Escherichia coli strain. Cells of defined size ranges were collected by a cell sorter and were subsequently cultured. This selection-propagation cycle was repeated, and significant changes in cell size were detected within 400 generations. In addition, the width of the size distribution was altered. The changes in cell size were unaccompanied by a growth burden. Whole genome sequencing revealed that only a few mutations in genes related to membrane synthesis conferred the size evolution. In conclusion, bacterial cell size could evolve, through a few mutations, without growth reduction. The size evolution without growth reduction suggests a rapid evolutionary change to diverse cell sizes in bacterial survival strategies.

β-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche.

PubMed

Deschene, Elizabeth R; Myung, Peggy; Rompolas, Panteleimon; Zito, Giovanni; Sun, Thomas Yang; Taketo, Makoto M; Saotome, Ichiko; Greco, Valentina

2014-03-21

Wnt/β-catenin signaling is critical for tissue regeneration. However, it is unclear how β-catenin controls stem cell behaviors to coordinate organized growth. Using live imaging, we show that activation of β-catenin specifically within mouse hair follicle stem cells generates new hair growth through oriented cell divisions and cellular displacement. β-Catenin activation is sufficient to induce hair growth independently of mesenchymal dermal papilla niche signals normally required for hair regeneration. Wild-type cells are co-opted into new hair growths by β-catenin mutant cells, which non-cell autonomously activate Wnt signaling within the neighboring wild-type cells via Wnt ligands. This study demonstrates a mechanism by which Wnt/β-catenin signaling controls stem cell-dependent tissue growth non-cell autonomously and advances our understanding of the mechanisms that drive coordinated regeneration.

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells.

PubMed

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and increased necrosis in the tumor mass. The disparate molecular mechanisms of celecoxib-induced growth inhibition in human breast cancer cells depends upon the level of COX-2 expression and the invasive potential of the cell lines examined. Data suggest a role for COX-2 not only in the growth of cancer cells but also in activating the angiogenic pathway through regulating levels of vascular endothelial growth factor.

Anti-cell growth and anti-cancer stem cell activities of the non-canonical hedgehog inhibitor GANT61 in triple-negative breast cancer cells.

PubMed

Koike, Yoshikazu; Ohta, Yusuke; Saitoh, Wataru; Yamashita, Tetsumasa; Kanomata, Naoki; Moriya, Takuya; Kurebayashi, Junichi

2017-09-01

Triple-negative breast cancer (TNBC) exhibits biologically aggressive behavior and has a poor prognosis. Novel molecular targeting agents are needed to control TNBC. Recent studies revealed that the non-canonical hedgehog (Hh) signaling pathway plays important roles in the regulation of cancer stem cells (CSCs) in breast cancer. Therefore, the anti-cell growth and anti-CSC effects of the non-canonical Hh inhibitor GANT61 were investigated in TNBC cells. The effects of GANT61 on cell growth, cell cycle progression, apoptosis, and the proportion of CSCs were investigated in three TNBC cell lines. Four ER-positive breast cancer cell lines were also used for comparisons. The expression levels of effector molecules in the Hh pathway: glioma-associated oncogene (GLI) 1 and GLI2, were measured. The combined effects of GANT61 and paclitaxel on anti-cell growth and anti-CSC activities were also investigated. Basal expression levels of GLI1 and GLI2 were significantly higher in TNBC cells than in ER-positive breast cancer cells. GANT61 dose-dependently decreased cell growth in association with G1-S cell cycle retardation and increased apoptosis. GANT61 significantly decreased the CSC proportion in all TNBC cell lines. Paclitaxel decreased cell growth, but not the CSC proportion. Combined treatments of GANT61 and paclitaxel more than additively enhanced anti-cell growth and/or anti-CSC activities. The non-canonical Hh inhibitor GANT61 decreased not only cell growth, but also the CSC population in TNBC cells. GANT61 enhanced the anti-cell growth activity of paclitaxel in these cells. These results suggest for the first time that GANT61 has potential as a therapeutic agent in the treatment of patients with TNBC.

A non-inflammatory form of immune competence prevails in acute pre-pubescent malnutrition: new evidence based on critical mRNA transcripts in the mouse.

PubMed

Monk, Jennifer M; Richard, Cynthia L; Woodward, Bill

2012-05-01

The declining inflammatory immune competence of acute (i.e. wasting) pre-pubescent protein-energy malnutrition has been regarded as reflecting an unregulated immunological disintegration. Recent evidence, however, suggests that malnutrition stimulates a regulated immunological reconfiguration to achieve a non-inflammatory form of competence, perhaps offering protection against autoimmune reactions - the 'Tolerance Model'. Our objective was to determine the influence of acute pre-pubescent malnutrition on the expression of genes critical to tolerogenic regulation. Male and female C57BL/6J mice, initially 19 d old, consumed a complete purified diet either ad libitum (age-matched controls) or in restricted daily quantities (mimicking marasmus), or consumed an isoenergetic low-protein diet ad libitum (mimicking incipient kwashiorkor) for 14 d (six animals per dietary group). Gene expression in the spleen, typically an inflammatory organ, and in the small intestine, a site designed for non-inflammatory defence, was assessed by real-time quantitative RT-PCR, and normalised to β-actin. In the spleen of the malnourished groups, both IL-10 and transforming growth factor-β1 mRNA expression increased compared with controls (P < 0.05), whereas mRNA expression of IL-12p40 decreased (P < 0.05). Conversely, malnutrition exerted no influence on the expression of mRNA for these cytokines in the small intestine (P>0.05). Moreover, forkhead box P3 mRNA expression, indicative of cell-based tolerogenic potential, was sustained in both the spleen and intestine of the malnourished groups (P>0.05). Thus, despite limited supplies of energy and substrates, the spleen shifted towards a non-inflammatory character and the intestine was sustained in this mode in advanced pre-pubescent weight loss. These findings provide the first support for the Tolerance Model at the level of mRNA transcript expression.

Conditioned media from a renal cell carcinoma cell line demonstrates the presence of basic fibroblast growth factor.

PubMed

Mydlo, J H; Zajac, J; Macchia, R J

1993-09-01

In a previous report, we demonstrated the isolation and purification of a heparin binding growth factor from human renal carcinoma, and suggested that this growth factor may play a role in the neovascularity and growth of the tumor. In this report, we demonstrate that the growth of the renal cell carcinoma cell line RC29 is stimulated by the addition of exogenous fibroblast growth factor (FGF), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha). Also, media conditioned by this cell line was able to stimulate growth of the A431 vulvar tumor cell line, known for its high concentration of EGF receptors, 3T3 fibroblasts, human umbilical vein (HUV) cells and RC29 cells. Using heparin-sepharose chromatography and then SDS polyacrylamide gel electrophoresis (PAGE), we were able to demonstrate several proteins in the conditioned media of the RC29 cell line. Using Western blot analysis, we detected that at least one of the proteins expressed in this conditioned media was FGF and that it belongs to the basic, not acidic, family of fibroblast growth factors. These findings suggest that renal tumors may express growth factors that may play a direct role in maintaining their unrestricted proliferation.

Perchlorate Contamination of Drinking Water: Regulatory Issues and Legislative Actions

DTIC Science & Technology

2008-10-16

and water treatment costs, both of which are driven by federal and state standards. (California and Massachusetts have set standards.) EPA has spent... Hypothyroidism , Newborn Thyroid Function, and Environmental Perchlorate Exposure Among Residents of a Southern California Community,” Journal of Occupational... treatment technologies and for collecting occurrence data. In 1999, EPA required water systems to monitor for perchlorate under the Unregulated

The assistant practitioner role in healthcare.

PubMed

Dix, Ann

The assistant practitioner role is intended to free up nurses to make better use of their professional skills and improve patient outcomes. However, it can be perceived as a threat to nurses because it involves handing over clinical aspects of their work to unregistered and unregulated support workers. This article looks at how the role is developing, and the implications for nursing and quality of patient care.

Conditions of Storing the Documents as the Chief Means of Preserving the Library Holdings (As Shown by the Experience of the Russian State Library).

ERIC Educational Resources Information Center

Perminova, Olga; Stepanova, Tatiana

This report deals with problems of keeping the documents in the Russian state library tied up with their storage condition. Cited are results of the observation of temperature, humidity, sanitary, hygienic, and light conditions of storage in depositories with unregulated climate. The report shows the stabilization and research of documents carried…

Health and Safety Law over the Last 50 Years

ERIC Educational Resources Information Center

Whitcher, Ralph

2013-01-01

From a time when laws on health and safety applied only to some industries and much was unregulated, we have moved to a time when health and safety laws seem, if you believe some reports in the news, to pervade every aspect of working life with silly restrictions. This article looks at the development of the legislation from the 1960s and suggests…

Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

PubMed

Lee, J S; Kim, J M; Hong, E K; Kim, S-O; Yoo, Y-J; Cha, J-H

2009-02-01

A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the inhibition of p38 delayed the process. These results indicate that heparin-binding epidermal growth factor-like growth factor may constitute a critical factor in the wound healing of human periodontal ligament cells by a mechanism that requires the activation of Erk1/2 via specific interaction with epidermal growth factor receptor 1.

Methods for estimating selected low-flow frequency statistics for unregulated streams in Kentucky

USGS Publications Warehouse

Martin, Gary R.; Arihood, Leslie D.

2010-01-01

This report provides estimates of, and presents methods for estimating, selected low-flow frequency statistics for unregulated streams in Kentucky including the 30-day mean low flows for recurrence intervals of 2 and 5 years (30Q2 and 30Q5) and the 7-day mean low flows for recurrence intervals of 5, 10, and 20 years (7Q2, 7Q10, and 7Q20). Estimates of these statistics are provided for 121 U.S. Geological Survey streamflow-gaging stations with data through the 2006 climate year, which is the 12-month period ending March 31 of each year. Data were screened to identify the periods of homogeneous, unregulated flows for use in the analyses. Logistic-regression equations are presented for estimating the annual probability of the selected low-flow frequency statistics being equal to zero. Weighted-least-squares regression equations were developed for estimating the magnitude of the nonzero 30Q2, 30Q5, 7Q2, 7Q10, and 7Q20 low flows. Three low-flow regions were defined for estimating the 7-day low-flow frequency statistics. The explicit explanatory variables in the regression equations include total drainage area and the mapped streamflow-variability index measured from a revised statewide coverage of this characteristic. The percentage of the station low-flow statistics correctly classified as zero or nonzero by use of the logistic-regression equations ranged from 87.5 to 93.8 percent. The average standard errors of prediction of the weighted-least-squares regression equations ranged from 108 to 226 percent. The 30Q2 regression equations have the smallest standard errors of prediction, and the 7Q20 regression equations have the largest standard errors of prediction. The regression equations are applicable only to stream sites with low flows unaffected by regulation from reservoirs and local diversions of flow and to drainage basins in specified ranges of basin characteristics. Caution is advised when applying the equations for basins with characteristics near the applicable limits and for basins with karst drainage features.

1,4-Dioxane drinking water occurrence data from the third unregulated contaminant monitoring rule.

PubMed

Adamson, David T; Piña, Elizabeth A; Cartwright, Abigail E; Rauch, Sharon R; Hunter Anderson, R; Mohr, Thomas; Connor, John A

2017-10-15

This study examined data collected from U.S. public drinking water supplies in support of the recently-completed third round of the Unregulated Contaminant Monitoring Rule (UCMR3) to better understand the nature and occurrence of 1,4-dioxane and the basis for establishing drinking water standards. The purpose was to evaluate whether the occurrence data for this emerging but federally-unregulated contaminant fit with common conceptual models, including its persistence and the importance of groundwater contamination for potential exposure. 1,4-Dioxane was detected in samples from 21% of 4864 PWSs, and was in exceedance of the health-based reference concentration (0.35μg/L) at 6.9% of these systems. In both measures, it ranked second among the 28 UCMR3 contaminants. Although much of the focus on 1,4-dioxane has been its role as a groundwater contaminant, the detection frequency for 1,4-dioxane in surface water was only marginally lower than in groundwater (by a factor of 1.25; p<0.0001). However, groundwater concentrations were higher than those in surface water (p<0.0001) and contributed to a higher frequency of exceeding the reference concentration (by a factor of 1.8, p<0.0001), indicating that surface water sources tend to be more dilute. Sampling from large systems increased the likelihood that 1,4-dioxane was detected by a factor of 2.18 times relative to small systems (p<0.0001). 1,4-Dioxane detections in drinking water were highly associated with detections of other chlorinated compounds particularly 1,1-dichlorethane (odds ratio=47; p<0.0001), which is associated with the release of 1,4-dioxane as a chlorinated solvent stabilizer. Based on aggregated nationwide data, 1,4-dioxane showed evidence of a decreasing trend in concentration and detection frequency over time. These data suggest that the loading to drinking water supplies may be decreasing. However, in the interim, some water supply systems may need to consider improving their treatment capabilities in response to further regulatory review of this compound. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement and structure: A qualitative study of organizational change and sickness absence among women in the public sector in Sweden

PubMed Central

2011-01-01

Background Organizational changes in modern corporate life have become increasingly common and there are indications that they often fail to achieve their ends. An earlier study of 24,036 employees showed that those who had repeatedly been exposed to large increases in staffing during 1991-1996 had an excess risk of both long-term sickness absence and hospital admission during 1997-1999, while moderate expansion appeared to be protective. The former was most salient among female public sector employees. We used qualitative interviews to explore work environment factors underlying the impact of organizational changes (moderate and large expansions in staffing) on sickness absence from an employee perspective. Method We interviewed 21 strategically selected women from the earlier study using semi-structured telephone interviews focusing on working conditions during the organizational changes. We identified 22 themes which could explain the association between organizational changes and sickness absence. We then used Qualitative Comparative Analysis (QCA) to reduce the number of themes and discover patterns of possible causation. Results The themes that most readily explained the outcomes were Well Planned Process of Change (a clear structure for involvement of the employees in the changes), Agent of Change (an active role in the implementation of the changes), Unregulated Work (a lack of clear limits and guidelines regarding work tasks from the management and among the employees), and Humiliating Position (feelings of low status or of not being wanted at the workplace), which had been salient throughout the analytic process, in combination with Multiple Contexts (working in several teams in parallel) and Already Ill (having already had a debilitating illness at the beginning of 1991), which may indicate degree of individual exposure and vulnerability. Well Planned Process of Change, Agent of Change and Multiple Contexts are themes that were associated with low sickness absence. Unregulated Work, Humiliating Position and Already Ill were associated with high sickness absence. Conclusions These findings suggest that promising areas for future research and improvement in change management could be the structured involvement of the employees in the planning of organizational changes, and the development of methods to avoid highly unregulated working conditions. PMID:21575180

Involvement and structure: a qualitative study of organizational change and sickness absence among women in the public sector in Sweden.

PubMed

Baltzer, Maria; Westerlund, Hugo; Backhans, Mona; Melinder, Karin

2011-05-16

Organizational changes in modern corporate life have become increasingly common and there are indications that they often fail to achieve their ends. An earlier study of 24,036 employees showed that those who had repeatedly been exposed to large increases in staffing during 1991-1996 had an excess risk of both long-term sickness absence and hospital admission during 1997-1999, while moderate expansion appeared to be protective. The former was most salient among female public sector employees. We used qualitative interviews to explore work environment factors underlying the impact of organizational changes (moderate and large expansions in staffing) on sickness absence from an employee perspective. We interviewed 21 strategically selected women from the earlier study using semi-structured telephone interviews focusing on working conditions during the organizational changes. We identified 22 themes which could explain the association between organizational changes and sickness absence. We then used Qualitative Comparative Analysis (QCA) to reduce the number of themes and discover patterns of possible causation. The themes that most readily explained the outcomes were Well Planned Process of Change (a clear structure for involvement of the employees in the changes), Agent of Change (an active role in the implementation of the changes), Unregulated Work (a lack of clear limits and guidelines regarding work tasks from the management and among the employees), and Humiliating Position (feelings of low status or of not being wanted at the workplace), which had been salient throughout the analytic process, in combination with Multiple Contexts (working in several teams in parallel) and Already Ill (having already had a debilitating illness at the beginning of 1991), which may indicate degree of individual exposure and vulnerability. Well Planned Process of Change, Agent of Change and Multiple Contexts are themes that were associated with low sickness absence. Unregulated Work, Humiliating Position and Already Ill were associated with high sickness absence. These findings suggest that promising areas for future research and improvement in change management could be the structured involvement of the employees in the planning of organizational changes, and the development of methods to avoid highly unregulated working conditions.

Why do women choose an unregulated birth worker to birth at home in Australia: a qualitative study.

PubMed

Rigg, Elizabeth Christine; Schmied, Virginia; Peters, Kath; Dahlen, Hannah Grace

2017-03-28

In Australia the choice to birth at home is not well supported and only 0.4% of women give birth at home with a registered midwife. Recent changes to regulatory requirements for midwives have become more restrictive and there is no insurance product that covers private midwives for intrapartum care at home. Freebirth (planned birth at home with no registered health professional) with an unregulated birth worker who is not a registered midwife or doctor (e.g. Doula, ex-midwife, lay midwife etc.) appears to have increased in Australia. The aim of this study is to explore the reasons why women choose to give birth at home with an unregulated birth worker (UBW) from the perspective of women and UBWs. Nine participants (five women who had UBWs at their birth and four UBWs who had themselves used UBWs in the past for their births) were interviewed in-depth and the data analysed using thematic analysis. Four themes were found: 'A traumatising system', 'An inflexible system'; 'Getting the best of both worlds' and 'Treated with love and respect versus the mechanical arm on the car assembly line'. Women interviewed for this study either experienced or were exposed to mainstream care, which they found traumatising. They were not able to access their preferred birth choices, which caused them to perceive the system as inflexible. They interpreted this as having no choice when choice was important to them. The motivation then became to seek alternative options of care that would more appropriately meet their needs, and help avoid repeated trauma through mainstream care. Women who engaged UBWs viewed them as providing the best of both worlds - this was birthing at home with a knowledgeable person who was unconstrained by rules or regulations and who respected and supported the woman's philosophical view of birth. Women perceived UBWs as not only the best opportunity to achieve a natural birth but also as providing 'a safety net' in case access to emergency care was required.

The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast.

PubMed

Leitao, Ricardo M; Kellogg, Douglas R

2017-11-06

The size of nearly all cells is modulated by nutrients. Thus, cells growing in poor nutrients can be nearly half the size of cells in rich nutrients. In budding yeast, cell size is thought to be controlled almost entirely by a mechanism that delays cell cycle entry until sufficient growth has occurred in G1 phase. Here, we show that most growth of a new daughter cell occurs in mitosis. When the rate of growth is slowed by poor nutrients, the duration of mitosis is increased, which suggests that cells compensate for slow growth in mitosis by increasing the duration of growth. The amount of growth required to complete mitosis is reduced in poor nutrients, leading to a large reduction in cell size. Together, these observations suggest that mechanisms that control the extent of growth in mitosis play a major role in cell size control in budding yeast. © 2017 Leitao and Kellogg.

Hair-growth-promoting effect of conditioned medium of high integrin α6 and low CD 71 (α6bri/CD71dim) positive keratinocyte cells.

PubMed

Won, Chong Hyun; Jeong, Yun-Mi; Kang, Sangjin; Koo, Tae-Sung; Park, So-Hyun; Park, Ki-Young; Sung, Young-Kwan; Sung, Jong-Hyuk

2015-02-19

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells.

Computational modelling of the scaffold-free chondrocyte regeneration: a two-way coupling between the cell growth and local fluid flow and nutrient concentration.

PubMed

Hossain, Md Shakhawath; Bergstrom, D J; Chen, X B

2015-11-01

The in vitro chondrocyte cell culture process in a perfusion bioreactor provides enhanced nutrient supply as well as the flow-induced shear stress that may have a positive influence on the cell growth. Mathematical and computational modelling of such a culture process, by solving the coupled flow, mass transfer and cell growth equations simultaneously, can provide important insight into the biomechanical environment of a bioreactor and the related cell growth process. To do this, a two-way coupling between the local flow field and cell growth is required. Notably, most of the computational and mathematical models to date have not taken into account the influence of the cell growth on the local flow field and nutrient concentration. The present research aimed at developing a mathematical model and performing a numerical simulation using the lattice Boltzmann method to predict the chondrocyte cell growth without a scaffold on a flat plate placed inside a perfusion bioreactor. The model considers the two-way coupling between the cell growth and local flow field, and the simulation has been performed for 174 culture days. To incorporate the cell growth into the model, a control-volume-based surface growth modelling approach has been adopted. The simulation results show the variation of local fluid velocity, shear stress and concentration distribution during the culture period due to the growth of the cell phase and also illustrate that the shear stress can increase the cell volume fraction to a certain extent.

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN-depleted head and neck cancer tumor cells.

PubMed

Liu, Zhiyong; Hartman, Yolanda E; Warram, Jason M; Knowles, Joseph A; Sweeny, Larissa; Zhou, Tong; Rosenthal, Eben L

2011-08-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma-mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer, there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here, we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were cocultured with fibroblasts or inoculated with fibroblasts into severe combined immunodeficient mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Coculture experiments showed fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN-silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN-silenced cells compared with control vector-transfected cells, whereas inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast coculture, suggesting the importance of FGFR2 signaling in fibroblast-mediated tumor growth. Analysis of xenografted tumors revealed that EMMPRIN-silenced tumors had a larger stromal compartment compared with control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast-independent tumor growth.

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN depleted head and neck cancer tumor cells

PubMed Central

Liu, Zhiyong; Hartman, Yolanda E.; Warram, Jason M.; Knowles, Joseph A.; Sweeny, Larrisa; Zhou, Tong; Rosenthal, Eben L.

2011-01-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were co-cultured with fibroblasts or inoculated with fibroblasts into SCID mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Co-culture experiments demonstrated fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN silenced cells compared to control vector transfected cells, while inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast co-culture, suggesting the importance of FGFR2 signaling in fibroblast mediated tumor growth. Analysis of xenografted tumors revealed EMMPRIN silenced tumors had a larger stromal compartment compared to control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast independent tumor growth. PMID:21665938

Modular control of endothelial sheet migration

PubMed Central

Vitorino, Philip; Meyer, Tobias

2008-01-01

Growth factor-induced migration of endothelial cell monolayers enables embryonic development, wound healing, and angiogenesis. Although collective migration is widespread and therapeutically relevant, the underlying mechanism by which cell monolayers respond to growth factor, sense directional signals, induce motility, and coordinate individual cell movements is only partially understood. Here we used RNAi to identify 100 regulatory proteins that enhance or suppress endothelial sheet migration into cell-free space. We measured multiple live-cell migration parameters for all siRNA perturbations and found that each targeted protein primarily regulates one of four functional outputs: cell motility, directed migration, cell–cell coordination, or cell density. We demonstrate that cell motility regulators drive random, growth factor-independent motility in the presence or absence of open space. In contrast, directed migration regulators selectively transduce growth factor signals to direct cells along the monolayer boundary toward open space. Lastly, we found that regulators of cell–cell coordination are growth factor-independent and reorient randomly migrating cells inside the sheet when boundary cells begin to migrate. Thus, cells transition from random to collective migration through a modular control system, whereby growth factor signals convert boundary cells into pioneers, while cells inside the monolayer reorient and follow pioneers through growth factor-independent migration and cell–cell coordination. PMID:19056882

Development of a Monitoring Method for Nonlabeled Human Pluripotent Stem Cell Growth by Time-Lapse Image Analysis.

PubMed

Suga, Mika; Kii, Hiroaki; Niikura, Keiichi; Kiyota, Yasujiro; Furue, Miho K

2015-07-01

: Cell growth is an important criterion for determining healthy cell conditions. When somatic cells or cancer cells are dissociated into single cells for passaging, the cell numbers can be counted at each passage, providing information on cell growth as an indicator of the health conditions of these cells. In the case of human pluripotent stem cells (hPSCs), because the cells are usually dissociated into cell clumps of ∼50-100 cells for passaging, cell counting is time-consuming. In the present study, using a time-lapse imaging system, we developed a method to determine the growth of hPSCs from nonlabeled live cell phase-contrast images without damaging these cells. Next, the hPSC colony areas and number of nuclei were determined and used to derive equations to calculate the cell number in hPSC colonies, which were assessed on time-lapse images acquired using a culture observation system. The relationships between the colony areas and nuclei numbers were linear, although the equation coefficients were dependent on the cell line used, colony size, colony morphology, and culture conditions. When the culture conditions became improper, the change in cell growth conditions could be detected by analysis of the phase-contrast images. This method provided real-time information on colony growth and cell growth rates without using treatments that can damage cells and could be useful for basic research on hPSCs and cell processing for hPSC-based therapy. This is the first study to use a noninvasive method using images to systemically determine the growth of human pluripotent stem cells (hPSCs) without damaging or wasting cells. This method would be useful for quality control during cell culture of clinical hPSCs. ©AlphaMed Press.

Identification of interleukin-6 as an autocrine growth factor for Epstein-Barr virus-immortalized B cells.

PubMed Central

Tosato, G; Tanner, J; Jones, K D; Revel, M; Pike, S E

1990-01-01

Autocrine growth factors are believed to be important for maintenance of an immortalized state by Epstein-Barr virus (EBV), because cell-free supernatants of EBV-immortalized cell lines promote the proliferation of autologous cells and permit their growth at low cell density. In this study, we provide evidence for the existence of two autocrine growth factor activities produced by EBV-immortalized lines distinguished by size and biological activities. Much of the autocrine growth factor activity in lymphoblastoid cell line supernatants resided in a low-molecular-weight (less than 5,000) fraction. However, up to 20 to 30% of the autocrine growth factor activity resided in the high-molecular-weight (greater than 5,000) fraction. While the nature of the low-molecular-weight growth factor activity remains undefined, the high-molecular-weight growth factor activity was identified as interleukin-6 (IL-6). Culture supernatants from six EBV-induced lymphoblastoid cell lines tested contained IL-6 activity, because they promoted proliferation in the IL-6-dependent hybridoma cell line B9. In addition, a rabbit antibody to human IL-6 neutralized the capacity of the high-molecular-weight (greater than 5,000) fraction of a lymphoblastoid cell line supernatant to promote growth both in autologous EBV-immortalized cells and in B9 cells. Similarly, this high-molecular-weight autocrine growth factor activity was neutralized by a monoclonal antibody to human IL-6. Furthermore, characteristic bands, attributable to IL-6, were visualized in supernatants of each of four EBV-induced lymphoblastoid cell lines after immunoprecipitation with a rabbit antiserum to human IL-6. Thus, in addition to its previously reported properties, IL-6 is an autocrine growth factor for EBV-immortalized B cells cultured under serum-free conditions. Images PMID:2159561

Cytokinesis-Based Constraints on Polarized Cell Growth in Fission Yeast

PubMed Central

Bohnert, K. Adam; Gould, Kathleen L.

2012-01-01

The rod-shaped fission yeast Schizosaccharomyces pombe, which undergoes cycles of monopolar-to-bipolar tip growth, is an attractive organism for studying cell-cycle regulation of polarity establishment. While previous research has described factors mediating this process from interphase cell tips, we found that division site signaling also impacts the re-establishment of bipolar cell growth in the ensuing cell cycle. Complete loss or targeted disruption of the non-essential cytokinesis protein Fic1 at the division site, but not at interphase cell tips, resulted in many cells failing to grow at new ends created by cell division. This appeared due to faulty disassembly and abnormal persistence of the cell division machinery at new ends of fic1Δ cells. Moreover, additional mutants defective in the final stages of cytokinesis exhibited analogous growth polarity defects, supporting that robust completion of cell division contributes to new end-growth competency. To test this model, we genetically manipulated S. pombe cells to undergo new end take-off immediately after cell division. Intriguingly, such cells elongated constitutively at new ends unless cytokinesis was perturbed. Thus, cell division imposes constraints that partially override positive controls on growth. We posit that such constraints facilitate invasive fungal growth, as cytokinesis mutants displaying bipolar growth defects formed numerous pseudohyphae. Collectively, these data highlight a role for previous cell cycles in defining a cell's capacity to polarize at specific sites, and they additionally provide insight into how a unicellular yeast can transition into a quasi-multicellular state. PMID:23093943

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

PubMed Central

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Introduction Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. Methods MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. Results The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and increased necrosis in the tumor mass. Conclusion The disparate molecular mechanisms of celecoxib-induced growth inhibition in human breast cancer cells depends upon the level of COX-2 expression and the invasive potential of the cell lines examined. Data suggest a role for COX-2 not only in the growth of cancer cells but also in activating the angiogenic pathway through regulating levels of vascular endothelial growth factor. PMID:15987447

Spatial Patterning of Newly-Inserted Material during Bacterial Cell Growth

NASA Astrophysics Data System (ADS)

Ursell, Tristan

2012-02-01

In the life cycle of a bacterium, rudimentary microscopy demonstrates that cell growth and elongation are essential characteristics of cellular reproduction. The peptidoglycan cell wall is the main load-bearing structure that determines both cell shape and overall size. However, simple imaging of cellular growth gives no indication of the spatial patterning nor mechanism by which material is being incorporated into the pre-existing cell wall. We employ a combination of high-resolution pulse-chase fluorescence microscopy, 3D computational microscopy, and detailed mechanistic simulations to explore how spatial patterning results in uniform growth and maintenance of cell shape. We show that growth is happening in discrete bursts randomly distributed over the cell surface, with a well-defined mean size and average rate. We further use these techniques to explore the effects of division and cell wall disrupting antibiotics, like cephalexin and A22, respectively, on the patterning of cell wall growth in E. coli. Finally, we explore the spatial correlation between presence of the bacterial actin-like cytoskeletal protein, MreB, and local cell wall growth. Together these techniques form a powerful method for exploring the detailed dynamics and involvement of antibiotics and cell wall-associated proteins in bacterial cell growth.[4pt] In collaboration with Kerwyn Huang, Stanford University.

The Control of Growth Symmetry Breaking in the Arabidopsis Hypocotyl.

PubMed

Peaucelle, Alexis; Wightman, Raymond; Höfte, Herman

2015-06-29

Complex shapes in biology depend on the ability of cells to shift from isotropic to anisotropic growth during development. In plants, this growth symmetry breaking reflects changes in the extensibility of the cell walls. The textbook view is that the direction of turgor-driven cell expansion depends on the cortical microtubule (CMT)-mediated orientation of cellulose microfibrils. Here, we show that this view is incomplete at best. We used atomic force microscopy (AFM) to study changes in cell-wall mechanics associated with growth symmetry breaking within the hypocotyl epidermis. We show that, first, growth symmetry breaking is preceded by an asymmetric loosening of longitudinal, as compared to transverse, anticlinal walls, in the absence of a change in CMT orientation. Second, this wall loosening is triggered by the selective de-methylesterification of cell-wall pectin in longitudinal walls, and, third, the resultant mechanical asymmetry is required for the growth symmetry breaking. Indeed, preventing or promoting pectin de-methylesterification, respectively, increased or decreased the stiffness of all the cell walls, but in both cases reduced the growth anisotropy. Finally, we show that the subsequent CMT reorientation contributes to the consolidation of the growth axis but is not required for the growth symmetry breaking. We conclude that growth symmetry breaking is controlled at a cellular scale by bipolar pectin de-methylesterification, rather than by the cellulose-dependent mechanical anisotropy of the cell walls themselves. Such a cell asymmetry-driven mechanism is comparable to that underlying tip growth in plants but also anisotropic cell growth in animal cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anti-cancer stem cell activity of a hedgehog inhibitor GANT61 in estrogen receptor-positive breast cancer cells.

PubMed

Kurebayashi, Junichi; Koike, Yoshikazu; Ohta, Yusuke; Saitoh, Wataru; Yamashita, Tetsumasa; Kanomata, Naoki; Moriya, Takuya

2017-05-01

Estradiol (E2) increases not only the cell growth but also the cancer stem cell (CSC) proportion in estrogen receptor (ER)-positive breast cancer cells. It has been suggested that the non-canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER-positive breast cancer cells. We studied anti-CSC activity of a non-canonical Hh inhibitor GANT61 in ER-positive breast cancer cells. Effects of GANT61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER-positive breast cancer cell lines. CSC proportion was measured using either the mammosphere assay or CD44/CD24 assay. Expression levels of pivotal molecules in the Hh pathway were measured. Combined effects of GANT61 with antiestrogens on the anti-cell growth and anti-CSC activities were investigated. E2 significantly increased the cell growth and CSC proportion in all ER-positive cell lines. E2 increased the expression levels of glioma-associated oncogene (GLI) 1 and/or GLI2. GANT61 decreased the cell growth in association with a G1-S cell cycle retardation and increased apoptosis. GANT61 decreased the E2-induced CSC proportion measured by the mammosphere assay in all cell lines. Antiestrogens also decreased the E2-induced cell growth and CSC proportion. Combined treatments of GANT61 with antiestrogens additively enhanced anti-cell growth and/or anti-CSC activities in some ER-positive cell lines. In conclusion, the non-canonical Hh inhibitor GANT61 inhibited not only the cell growth but also the CSC proportion increased by E2 in ER-positive breast cancer cells. GANT61 enhanced anti-cell growth and/or anti-CSC activities of antiestrogens in ER-positive cell lines. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells

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

Montesano, Roberto; Sarkoezi, Rita; Schramek, Herbert

2008-09-12

Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hithertomore » unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.« less

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

PubMed

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Phosphate limitation induces sporulation in the chytridiomycete Blastocladiella emersonii.

PubMed

Bongiorno, Vagner Alexandre; Ferreira da Cruz, Angela; Nunis da Silva, Antonio; Corrêa, Luiz Carlos

2012-09-01

The cell cycle is controlled by numerous mechanisms that ensure correct cell division. If growth is not possible, cells may eventually promote autophagy, differentiation, or apoptosis. Microorganisms interrupt their growth and differentiate under general nutrient limitation. We analyzed the effects of phosphate limitation on growth and sporulation in the chytridiomycete Blastocladiella emersonii using kinetic data, phase-contrast, and laser confocal microscopy. Under phosphate limitation, zoospores germinated and subsequently formed 2-4 spores, regardless of the nutritional content of the medium. The removal of phosphate at any time during growth induced sporulation of vegetative cells. If phosphate was later added to the same cultures, growth was restored if the cells were not yet committed to sporulation. The cycles of addition and withdrawal of phosphate from growth medium resulted in cycles of germination-growth, germination-sporulation, or germination-growth-sporulation. These results show that phosphate limitation is sufficient to interrupt cell growth and to induce complete sporulation in B. emersonii. We concluded that the determination of growth or sporulation in this microorganism is linked to phosphate availability when other nutrients are not limiting. This result provides a new tool for the dissection of nutrient-energy and signal pathways in cell growth and differentiation.

Bridging the Timescales of Single-Cell and Population Dynamics

NASA Astrophysics Data System (ADS)

Jafarpour, Farshid; Wright, Charles S.; Gudjonson, Herman; Riebling, Jedidiah; Dawson, Emma; Lo, Klevin; Fiebig, Aretha; Crosson, Sean; Dinner, Aaron R.; Iyer-Biswas, Srividya

2018-04-01

How are granular details of stochastic growth and division of individual cells reflected in smooth deterministic growth of population numbers? We provide an integrated, multiscale perspective of microbial growth dynamics by formulating a data-validated theoretical framework that accounts for observables at both single-cell and population scales. We derive exact analytical complete time-dependent solutions to cell-age distributions and population growth rates as functionals of the underlying interdivision time distributions, for symmetric and asymmetric cell division. These results provide insights into the surprising implications of stochastic single-cell dynamics for population growth. Using our results for asymmetric division, we deduce the time to transition from the reproductively quiescent (swarmer) to the replication-competent (stalked) stage of the Caulobacter crescentus life cycle. Remarkably, population numbers can spontaneously oscillate with time. We elucidate the physics leading to these population oscillations. For C. crescentus cells, we show that a simple measurement of the population growth rate, for a given growth condition, is sufficient to characterize the condition-specific cellular unit of time and, thus, yields the mean (single-cell) growth and division timescales, fluctuations in cell division times, the cell-age distribution, and the quiescence timescale.

Hair-Growth-Promoting Effect of Conditioned Medium of High Integrin α6 and Low CD 71 (α6bri/CD71dim) Positive Keratinocyte Cells

PubMed Central

Won, Chong Hyun; Jeong, Yun-Mi; Kang, Sangjin; Koo, Tae-Sung; Park, So-Hyun; Park, Ki-Young; Sung, Young-Kwan; Sung, Jong-Hyuk

2015-01-01

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells. PMID:25706512

Stromal Cells Positively and Negatively Modulate the Growth of Cancer Cells: Stimulation via the PGE2-TNFα-IL-6 Pathway and Inhibition via Secreted GAPDH-E-Cadherin Interaction

PubMed Central

Kawada, Manabu; Inoue, Hiroyuki; Ohba, Shun-ichi; Yoshida, Junjiro; Masuda, Tohru; Yamasaki, Manabu; Usami, Ihomi; Sakamoto, Shuichi; Abe, Hikaru; Watanabe, Takumi; Yamori, Takao; Shibasaki, Masakatsu; Nomoto, Akio

2015-01-01

Fibroblast-like stromal cells modulate cancer cells through secreted factors and adhesion, but those factors are not fully understood. Here, we have identified critical stromal factors that modulate cancer growth positively and negatively. Using a cell co-culture system, we found that gastric stromal cells secreted IL-6 as a growth and survival factor for gastric cancer cells. Moreover, gastric cancer cells secreted PGE2 and TNFα that stimulated IL-6 secretion by the stromal cells. Furthermore, we found that stromal cells secreted glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Extracellular GAPDH, or its N-terminal domain, inhibited gastric cancer cell growth, a finding confirmed in other cell systems. GAPDH bound to E-cadherin and downregulated the mTOR-p70S6 kinase pathway. These results demonstrate that stromal cells could regulate cancer cell growth through the balance of these secreted factors. We propose that negative regulation of cancer growth using GAPDH could be a new anti-cancer strategy. PMID:25785838

Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

DTIC Science & Technology

2009-10-01

AD_________________ Award Number: W81XWH-08-1-0708 TITLE: Fibroblast Growth Factor 2: an...September 2008 – 14 September 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fibroblast Growth Factor 2: an Epithelial Ductal Cell Growth Inhibitor...9 Fibroblast Growth Factor -2: an Epithelial Ductal Cell Growth Inhibitor that Drops Out in Breast Cancer

A study of cell electrophoresis as a means of purifying growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Plank, Lindsay D.; Hymer, W. C.; Kunze, M. Elaine; Marks, Gary M.; Lanham, J. Wayne

1983-01-01

Growth hormone secreting cells of the rat anterior pituitary are heavily laden with granules of growth hormone and can be partialy purified on the basis of their resulting high density. Two methods of preparative cell electrophoresis were investigated as methods of enhancing the purification of growth hormone producing cells: density gradient electrophoresis and continuous flow electrophoresis. Both methods provided a two- to four-fold enrichment in growth hormone production per cell relative to that achieved by previous methods. Measurements of electrophoretic mobilities by two analytical methods, microscopic electrophoresis and laser-tracking electrophoresis, revealed very little distinction between unpurified anterior pituitary cell suspensions and somatotroph-enriched cell suspensions. Predictions calculated on the basis of analytical electrophoretic data are consistent with the hypothesis that sedimentation plays a significant role in both types of preparative electrophoresis and the electrophoretic mobility of the growth hormone secreting subpopulation of cells remains unknown.

Identification of growth phases and influencing factors in cultivations with AGE1.HN cells using set-based methods.

PubMed

Borchers, Steffen; Freund, Susann; Rath, Alexander; Streif, Stefan; Reichl, Udo; Findeisen, Rolf

2013-01-01

Production of bio-pharmaceuticals in cell culture, such as mammalian cells, is challenging. Mathematical models can provide support to the analysis, optimization, and the operation of production processes. In particular, unstructured models are suited for these purposes, since they can be tailored to particular process conditions. To this end, growth phases and the most relevant factors influencing cell growth and product formation have to be identified. Due to noisy and erroneous experimental data, unknown kinetic parameters, and the large number of combinations of influencing factors, currently there are only limited structured approaches to tackle these issues. We outline a structured set-based approach to identify different growth phases and the factors influencing cell growth and metabolism. To this end, measurement uncertainties are taken explicitly into account to bound the time-dependent specific growth rate based on the observed increase of the cell concentration. Based on the bounds on the specific growth rate, we can identify qualitatively different growth phases and (in-)validate hypotheses on the factors influencing cell growth and metabolism. We apply the approach to a mammalian suspension cell line (AGE1.HN). We show that growth in batch culture can be divided into two main growth phases. The initial phase is characterized by exponential growth dynamics, which can be described consistently by a relatively simple unstructured and segregated model. The subsequent phase is characterized by a decrease in the specific growth rate, which, as shown, results from substrate limitation and the pH of the medium. An extended model is provided which describes the observed dynamics of cell growth and main metabolites, and the corresponding kinetic parameters as well as their confidence intervals are estimated. The study is complemented by an uncertainty and outlier analysis. Overall, we demonstrate utility of set-based methods for analyzing cell growth and metabolism under conditions of uncertainty.

Identification of Growth Phases and Influencing Factors in Cultivations with AGE1.HN Cells Using Set-Based Methods

PubMed Central

Borchers, Steffen; Freund, Susann; Rath, Alexander; Streif, Stefan; Reichl, Udo; Findeisen, Rolf

2013-01-01

Production of bio-pharmaceuticals in cell culture, such as mammalian cells, is challenging. Mathematical models can provide support to the analysis, optimization, and the operation of production processes. In particular, unstructured models are suited for these purposes, since they can be tailored to particular process conditions. To this end, growth phases and the most relevant factors influencing cell growth and product formation have to be identified. Due to noisy and erroneous experimental data, unknown kinetic parameters, and the large number of combinations of influencing factors, currently there are only limited structured approaches to tackle these issues. We outline a structured set-based approach to identify different growth phases and the factors influencing cell growth and metabolism. To this end, measurement uncertainties are taken explicitly into account to bound the time-dependent specific growth rate based on the observed increase of the cell concentration. Based on the bounds on the specific growth rate, we can identify qualitatively different growth phases and (in-)validate hypotheses on the factors influencing cell growth and metabolism. We apply the approach to a mammalian suspension cell line (AGE1.HN). We show that growth in batch culture can be divided into two main growth phases. The initial phase is characterized by exponential growth dynamics, which can be described consistently by a relatively simple unstructured and segregated model. The subsequent phase is characterized by a decrease in the specific growth rate, which, as shown, results from substrate limitation and the pH of the medium. An extended model is provided which describes the observed dynamics of cell growth and main metabolites, and the corresponding kinetic parameters as well as their confidence intervals are estimated. The study is complemented by an uncertainty and outlier analysis. Overall, we demonstrate utility of set-based methods for analyzing cell growth and metabolism under conditions of uncertainty. PMID:23936299

Dual Insect specific virus infection limits Arbovirus replication in Aedes mosquito cells.

PubMed

Schultz, Michaela J; Frydman, Horacio M; Connor, John H

2018-05-01

Aedes mosquitoes are vectors for many pathogenic viruses. Cell culture systems facilitate the investigation of virus growth in the mosquito vector. We found Zika virus (ZIKV) growth to be consistent in A. albopictus cells but hypervariable in A. aegypti cell lines. As a potential explanation of this variability, we tested the hypothesis that our cells harbored opportunistic viruses. We screened Aedes cell lines for the presence of insect specific viruses (ISVs), Cell-fusing agent virus (CFAV) and Phasi charoen-like virus (PCLV). PCLV was present in the ZIKV-growth-variable A. aegypti cell lines but absent in A. albopictus lines, suggesting that these ISVs may interfere with ZIKV growth. In support of this hypothesis, PCLV infection of CFAV-positive A. albopictus cells inhibited the growth of ZIKV, dengue virus and La Crosse virus. These data suggest ISV infection of cell lines can impact arbovirus growth leading to significant changes in cell permissivity to arbovirus infection. Copyright © 2018 Elsevier Inc. All rights reserved.

Automated single cell microbioreactor for monitoring intracellular dynamics and cell growth in free solution†

PubMed Central

Johnson-Chavarria, Eric M.; Agrawal, Utsav; Tanyeri, Melikhan; Kuhlman, Thomas E.

2014-01-01

We report an automated microfluidic-based platform for single cell analysis that allows for cell culture in free solution with the ability to control the cell growth environment. Using this approach, cells are confined by the sole action of gentle fluid flow, thereby enabling non-perturbative analysis of cell growth away from solid boundaries. In addition, the single cell microbioreactor allows for precise and time-dependent control over cell culture media, with the combined ability to observe the dynamics of non-adherent cells over long time scales. As a proof-of-principle demonstration, we used the platform to observe dynamic cell growth, gene expression, and intracellular diffusion of repressor proteins while precisely tuning the cell growth environment. Overall, this microfluidic approach enables the direct observation of cellular dynamics with exquisite control over environmental conditions, which will be useful for quantifying the behaviour of single cells in well-defined media. PMID:24836754

Rod-like bacterial shape is maintained by feedback between cell curvature and cytoskeletal localization

PubMed Central

Ursell, Tristan S.; Nguyen, Jeffrey; Monds, Russell D.; Colavin, Alexandre; Billings, Gabriel; Ouzounov, Nikolay; Gitai, Zemer; Shaevitz, Joshua W.; Huang, Kerwyn Casey

2014-01-01

Cells typically maintain characteristic shapes, but the mechanisms of self-organization for robust morphological maintenance remain unclear in most systems. Precise regulation of rod-like shape in Escherichia coli cells requires the MreB actin-like cytoskeleton, but the mechanism by which MreB maintains rod-like shape is unknown. Here, we use time-lapse and 3D imaging coupled with computational analysis to map the growth, geometry, and cytoskeletal organization of single bacterial cells at subcellular resolution. Our results demonstrate that feedback between cell geometry and MreB localization maintains rod-like cell shape by targeting cell wall growth to regions of negative cell wall curvature. Pulse-chase labeling indicates that growth is heterogeneous and correlates spatially and temporally with MreB localization, whereas MreB inhibition results in more homogeneous growth, including growth in polar regions previously thought to be inert. Biophysical simulations establish that curvature feedback on the localization of cell wall growth is an effective mechanism for cell straightening and suggest that surface deformations caused by cell wall insertion could direct circumferential motion of MreB. Our work shows that MreB orchestrates persistent, heterogeneous growth at the subcellular scale, enabling robust, uniform growth at the cellular scale without requiring global organization. PMID:24550515

Biotechnological enhancement of capsaicin biosynthesis in cell suspension cultures of Naga King Chili (Capsicum chinense Jacq.).

PubMed

Kehie, Mechuselie; Kumaria, Suman; Tandon, Pramod

2016-01-01

Cell suspension cultures were initiated from hypocotyl derived callus to induce capsaicin biosynthesis in suspension cultures of Naga King Chili (Capsicum chinense Jacq.). Efficient capsaicin production with high growth index (GI) was obtained by exposing cells to salicylic acid (SA) and calcium channel modulators in suspension cultures. The time course of capsaicin formation is related to the cell growth profile in a batch culture. Cells cultivated in the standard medium (SM) initially showed low level of capsaicin yield during active growth. When the cells approached stationary phase, cell growth and cell viability decreased whereas capsaicin production increased continuously. In the fed-batch cultures, the highest capsaicin yield (567.4 ± 8.1 μgg(1) fresh weight) (f.wt) was obtained by feeding the cells with 1 mM SA. However, SA feeding during cultivation repressed the cell growth. Enhanced cell growth (3.1 ± 0.1 GI/culture) and capsaicin yield (534 ± 7.8 μgg(-1)f.wt) were obtained when the cells were fed with calcium ionophore A23187 (0.5 mM) on day 25 as compared to the control. Addition of the calcium channel blocker verapamil hydrochloride (100 mM) inhibited cell growth and capsaicin production in Naga King Chili suspension cell cultures.

Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes

PubMed Central

Lodish, Maya B.; Stratakis, Constantine A.

2010-01-01

Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumors. These hereditary cutaneous conditions affect the central nervous system and are characterized by the development of hamartomas. Over the past 20 years, there have been major advances in our understanding of the molecular basis of these diseases. Both NF-1 and TSC are disorders of unregulated progression through the cell cycle, in which causative genes behave as characteristic tumor suppressor genes. The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Additional related disorders that also converge on the mTOR pathway include Peutz-Jeghers syndrome and Cowden syndrome. All of these inherited cancer syndromes are associated with characteristic skin findings that offer a clue to their recognition and treatment. The discovery of mTOR inhibitors has led to a possible new therapeutic modality for patients with endocrine tumors as part of these familial syndromes. PMID:20833335

REVIEW ARTICLE: Emission measurement techniques for advanced powertrains

NASA Astrophysics Data System (ADS)

Adachi, Masayuki

2000-10-01

Recent developments in high-efficiency low-emission powertrains require the emission measurement technologies to be able to detect regulated and unregulated compounds with very high sensitivity and a fast response. For example, levels of a variety of nitrogen compounds and sulphur compounds should be analysed in real time in order to develop aftertreatment systems to decrease emission of NOx for the lean burning powertrains. Also, real-time information on the emission of particulate matter for the transient operation of diesel engines and direct injection gasoline engines is invaluable. The present paper reviews newly introduced instrumentation for such emission measurement that is demanded for the developments in advanced powertrain systems. They include Fourier transform infrared spectroscopy, mass spectrometry and fast response flame ionization detection. In addition, demands and applications of the fuel reformer developments for fuel cell electric vehicles are discussed. Besides the detection methodologies, sample handling techniques for the measurement of concentrations emitted from low emission vehicles for which the concentrations of the pollutants are significantly lower than the concentrations present in ambient air, are also described.

Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes.

PubMed

Lodish, Maya B; Stratakis, Constantine A

2010-06-01

Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumours. These hereditary cutaneous conditions affect the central nervous system and are characterised by the development of hamartomas. Over the past 20 years, there have been major advances in our understanding of the molecular basis of these diseases. Both NF-1 and TSC are disorders of unregulated progression through the cell cycle, in which causative genes behave as tumour suppressor genes. The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Additional related disorders that also converge on the mTOR pathway include Peutz-Jeghers syndrome and Cowden syndrome. All of these inherited cancer syndromes are associated with characteristic skin findings that offer a clue to their recognition and treatment. The discovery of mTOR inhibitors has led to a possible new therapeutic modality for patients with endocrine tumours as part of these familial syndromes. Published by Elsevier Ltd.

Switch on the engine: how the eukaryotic replicative helicase MCM2-7 becomes activated.

PubMed

Tognetti, Silvia; Riera, Alberto; Speck, Christian

2015-03-01

A crucial step during eukaryotic initiation of DNA replication is the correct loading and activation of the replicative DNA helicase, which ensures that each replication origin fires only once. Unregulated DNA helicase loading and activation, as it occurs in cancer, can cause severe DNA damage and genomic instability. The essential mini-chromosome maintenance proteins 2-7 (MCM2-7) represent the core of the eukaryotic replicative helicase that is loaded at DNA replication origins during G1-phase of the cell cycle. The MCM2-7 helicase activity, however, is only triggered during S-phase once the holo-helicase Cdc45-MCM2-7-GINS (CMG) has been formed. A large number of factors and several kinases interact and contribute to CMG formation and helicase activation, though the exact mechanisms remain unclear. Crucially, upon DNA damage, this reaction is temporarily halted to ensure genome integrity. Here, we review the current understanding of helicase activation; we focus on protein interactions during CMG formation, discuss structural changes during helicase activation, and outline similarities and differences of the prokaryotic and eukaryotic helicase activation process.

A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast

PubMed Central

Clarke, Jesse; Dephoure, Noah; Horecka, Ira; Gygi, Steven; Kellogg, Douglas

2017-01-01

In budding yeast, cell cycle progression and ribosome biogenesis are dependent on plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network appears to play an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together these discoveries provide new clues as to how growth-­dependent signals control cell growth and the cell cycle. PMID:28794263

CDP-Diacylglycerol Synthetase Coordinates Cell Growth and Fat Storage through Phosphatidylinositol Metabolism and the Insulin Pathway

PubMed Central

Liu, Yuan; Wang, Wei; Shui, Guanghou; Huang, Xun

2014-01-01

During development, animals usually undergo a rapid growth phase followed by a homeostatic stage when growth has ceased. The increase in cell size and number during the growth phase requires a large amount of lipids; while in the static state, excess lipids are usually stored in adipose tissues in preparation for nutrient-limited conditions. How cells coordinate growth and fat storage is not fully understood. Through a genetic screen we identified Drosophila melanogaster CDP-diacylglycerol synthetase (CDS/CdsA), which diverts phosphatidic acid from triacylglycerol synthesis to phosphatidylinositol (PI) synthesis and coordinates cell growth and fat storage. Loss of CdsA function causes significant accumulation of neutral lipids in many tissues along with reduced cell/organ size. These phenotypes can be traced back to reduced PI levels and, subsequently, low insulin pathway activity. Overexpressing CdsA rescues the fat storage and cell growth phenotypes of insulin pathway mutants, suggesting that CdsA coordinates cell/tissue growth and lipid storage through the insulin pathway. We also revealed that a DAG-to-PE route mediated by the choline/ethanolamine phosphotransferase Bbc may contribute to the growth of fat cells in CdsA RNAi. PMID:24603715

Modeling Surface Growth of Escherichia coli on Agar Plates

PubMed Central

Fujikawa, Hiroshi; Morozumi, Satoshi

2005-01-01

Surface growth of Escherichia coli cells on a membrane filter placed on a nutrient agar plate under various conditions was studied with a mathematical model. The surface growth of bacterial cells showed a sigmoidal curve with time on a semilogarithmic plot. To describe it, a new logistic model that we presented earlier (H. Fujikawa et al., Food Microbiol. 21:501-509, 2004) was modified. Growth curves at various constant temperatures (10 to 34°C) were successfully described with the modified model (model III). Model III gave better predictions of the rate constant of growth and the lag period than a modified Gompertz model and the Baranyi model. Using the parameter values of model III at the constant temperatures, surface growth at various temperatures was successfully predicted. Surface growth curves at various initial cell numbers were also sigmoidal and converged to the same maximum cell numbers at the stationary phase. Surface growth curves at various nutrient levels were also sigmoidal. The maximum cell number and the rate of growth were lower as the nutrient level decreased. The surface growth curve was the same as that in a liquid, except for the large curvature at the deceleration period. These curves were also well described with model III. The pattern of increase in the ATP content of cells grown on a surface was sigmoidal, similar to that for cell growth. We discovered several characteristics of the surface growth of bacterial cells under various growth conditions and examined the applicability of our model to describe these growth curves. PMID:16332768

Theileria parva infection induces autocrine growth of bovine lymphocytes.

PubMed Central

Dobbelaere, D A; Coquerelle, T M; Roditi, I J; Eichhorn, M; Williams, R O

1988-01-01

Bovine lymphocytes infected with the parasite Theileria parva continuously secrete a growth factor that is essential for their proliferation in vitro and also constitutively express interleukin 2 receptors on their surface. Dilution of the secreted growth factor, caused by culturing cells at low density, results in retardation of culture growth. Human recombinant interleukin 2, however, effectively substitutes for the diluted growth factor by restoring normal growth rates and also allows Theileria-infected cells to be grown at low density without the use of feeder layers. Secretion of the growth factor and expression of the interleukin 2 receptor depend on the presence of the parasite in the cytoplasm of the host cell. Elimination of the parasite from the cell cytoplasm by the specific antitheilerial drug BW 720c results in the arrest of growth factor secretion and the disappearance of interleukin 2 receptors from the cell surface. This is accompanied by growth arrest and reversion of the infected cells to the morphology of resting lymphocytes. We propose that the continuous proliferation of infected cells in vitro is mediated by autocrine receptor activation. Images PMID:3133661

Phenotypic indications of FtsZ inhibition in hok/sok-induced bacterial growth changes and stress response.

PubMed

Chukwudi, Chinwe Uzoma; Good, Liam

2018-01-01

The hok/sok locus has been shown to enhance the growth of bacteria in adverse growth conditions such as high temperature, low starting-culture densities and antibiotic treatment. This is in addition to their well-established plasmid-stabilization effect via post-segregational killing of plasmid-free daughter cells. It delays the onset of growth by prolonging the lag phase of bacterial culture, and increases the rate of exponential growth when growth eventually begins. This enables the cells adapt to the prevailing growth conditions and enhance their survival in stressful conditions. These effects functionally complement defective SOS response mechanism, and appear analogous to the growth effects of FtsZ in the SOS pathway. In this study, the role of FtsZ in the hok/sok-induced changes in bacterial growth and cell division was investigated. Morphologic studies of early growth-phase cultures and cells growing under temperature stress showed elongated cells typical of FtsZ inhibition/deficiency. Both ftsZ silencing and over-expression produced comparable growth effects in control cells, and altered the growth changes observed otherwise in the hok/sok + cells. These changes were diminished in SOS-deficient strain containing mutant FtsZ. The involvement of FtsZ in the hok/sok-induced growth changes may be exploited as drug target in host bacteria, which often propagate antibiotic resistance elements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inducible growth mode switches influence Valonia rhizoid differentiation.

PubMed

Elvira, Paul Rommel; Sekida, Satoko; Okuda, Kazuo

2013-02-01

Cell differentiation and cell type commitment are an integral part of plant growth and development. Investigations on how environmental conditions affect the formation of shoots, roots, and rhizoids can help illustrate how plants determine cell fate and overall morphology. In this study, we evaluated the role of substratum and light on rhizoid differentiation in the coenocytic green alga, Valonia aegagropila. Elongating rhizoids displayed varying growth modes and cell shape upon exposure to different substrata and light conditions. It was found that soft substrata and dark incubation promoted rhizoid elongation via tip growth while subsequent exposure to light prevented tip growth and instead induced swelling in the apical region of rhizoids. Swelling was accompanied by the accumulation of protoplasm in the rhizoid tip through expansion of the cell wall and uninhibited cytoplasmic streaming. Subsequent diffuse growth led to the transformation from slender, rod-shaped rhizoids into spherical thallus-like structures that required photosynthesis. Further manipulation of light regimes caused vacillating cell growth redirections. An elongating V. aegagropila rhizoid cell thus appears capable of growth mode switching that is regulated by immediate environmental conditions thereby influencing ultimate cell shape and function. This is the first description of inducible, multiple growth mode shifts in a single intact plant cell that directly impact its differentiation.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.

PubMed

Cheung, Laurence C; Strickland, Deborah H; Howlett, Meegan; Ford, Jette; Charles, Adrian K; Lyons, Karen M; Brigstock, David R; Goldschmeding, Roel; Cole, Catherine H; Alexander, Warren S; Kees, Ursula R

2014-07-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. Copyright© Ferrata Storti Foundation.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

PubMed Central

Cheung, Laurence C.; Strickland, Deborah H.; Howlett, Meegan; Ford, Jette; Charles, Adrian K.; Lyons, Karen M.; Brigstock, David R.; Goldschmeding, Roel; Cole, Catherine H.; Alexander, Warren S.; Kees, Ursula R.

2014-01-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. PMID:24727816

School Meal Programs: Competitive Foods Are Widely Available and Generate Substantial Revenues for Schools. Report to Congressional Requesters. GAO-05-563

ERIC Educational Resources Information Center

Bellis, David B.

2005-01-01

Recent increases in child obesity have sparked concerns about competitive foods--foods sold to students at school that are not part of federally reimbursable school meals. The nutritional value of these foods is largely unregulated, and students can often purchase these foods in addition to or instead of school meals. Nearly 9 out of 10 schools…

Cosmetics, categories, and the future.

PubMed

Draelos, Zoe Diana

2012-01-01

Cosmetics is an interesting unregulated category of over-the-counter products designed to enhance appearance and skin health. The coloring agents used in cosmetics are regulated along with their preservative constituents. New understandings of skin physiology have allowed cosmetics to advance beyond appearance issues into the functional arena. Cosmeceuticals is an unrecognized term from a regulatory perspective that conveys the new cosmetic formulations ability to improve skin health. © 2012 Wiley Periodicals, Inc.

Faunal assemblages and multi-scale habitat patterns in headwater tributaries of the South Fork Trinity River - an unregulated river embedded within a multiple-use landscape

Treesearch

H. H. Jr. Welsh; J. J. G. R. Hodgson; J. M. Emlen Duda

2010-01-01

Headwaters can represent 80% of stream kilometers in a watershed, and they also have unique physical and biological properties that have only recently been recognized for their importance in sustaining healthy functioning stream networks and their ecological services. We sampled 60 headwater tributaries in the South Fork Trinity River, a 2,430 km2...

Maine StreamStats: a water-resources web application

USGS Publications Warehouse

Lombard, Pamela J.

2015-01-01

Reports referenced in this fact sheet present the regression equations used to estimate the flow statistics, describe the errors associated with the estimates, and describe the methods used to develop the equations and to measure the basin characteristics used in the equations. Limitations of the methods are also described in the reports; for example, all of the equations are appropriate only for ungaged, unregulated, rural streams in Maine.

On Pecuniary Resiliency, Early Warning, and Market Imitation under Unrestricted Warfare

DTIC Science & Technology

2015-09-17

midnight oil finishing up our programs. I would also like to thank my brother for his insights as an economics instructor. His discussions provided...Unregulated Power; IOG-Integrated Oil & Gas; HCES-Health Care Equipment & Services; AMCB-Asset Man- agement & Custody Banks; and BT-Biotechnology. This suggests...Using Prediction Markets to Track Information Flows: Evidence from Google.” Lecture Notes of the Institute for Com- puter Sciences, Social Informatics

Towards a publicly available, map-based regional software tool to estimate unregulated daily streamflow at ungauged rivers

USGS Publications Warehouse

Archfield, Stacey A.; Steeves, Peter A.; Guthrie, John D.; Ries, Kernell G.

2013-01-01

Streamflow information is critical for addressing any number of hydrologic problems. Often, streamflow information is needed at locations that are ungauged and, therefore, have no observations on which to base water management decisions. Furthermore, there has been increasing need for daily streamflow time series to manage rivers for both human and ecological functions. To facilitate negotiation between human and ecological demands for water, this paper presents the first publicly available, map-based, regional software tool to estimate historical, unregulated, daily streamflow time series (streamflow not affected by human alteration such as dams or water withdrawals) at any user-selected ungauged river location. The map interface allows users to locate and click on a river location, which then links to a spreadsheet-based program that computes estimates of daily streamflow for the river location selected. For a demonstration region in the northeast United States, daily streamflow was, in general, shown to be reliably estimated by the software tool. Estimating the highest and lowest streamflows that occurred in the demonstration region over the period from 1960 through 2004 also was accomplished but with more difficulty and limitations. The software tool provides a general framework that can be applied to other regions for which daily streamflow estimates are needed.

Effect of mine discharge on the pattern of riverine habitat use of elephants Elephas maximus and other mammals in Singhbhum forests, Bihar, India

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

Singh, R.K.; Chowdhury, S.

The aim of this paper is to access the influence of water quality both on the occurrence of, and utilization by, elephants (Elephas maximus) in a riverine habitat. Mining operations and other anthropogenic changes to natural river systems have caused degradation of the ecosystem for elephants. A decline in their numbers has been seen throughout the Singhbhum Forests, India due to fragmentation and loss of habitat. The need to preserve and restore the habitat of the elephant is accepted, but until the factors that influence their distribution are known and understood, suitable management plans cannot be implemented. The study areamore » was the catchment of the river Koina where waste discharge from an iron oremine and processing plant impact upon water quality. The study period from April 1995 to March 1996 looked at sections of the river where unregulated mine discharge was made, and where regulation through tailing ponds controlled total suspended solids (TSS) output from the mine waste water to the river system. Various physico-chemical parameters recorded at seven sampling stations were quantified. Principal Component Analysis (PCA) segregated the key parameters in determining the discharge levels of both regulated and unregulated discharge at various sites.« less

Regulated and unregulated emissions from an internal combustion engine operating on ethanol-containing fuels

NASA Astrophysics Data System (ADS)

Poulopoulos, S. G.; Samaras, D. P.; Philippopoulos, C. J.

In the present work, the effect of ethanol addition to gasoline on regulated and unregulated emissions is studied. A 4-cylinder OPEL 1.6 L internal combustion engine equipped with a hydraulic brake dynamometer was used in all the experiments. For exhaust emissions treatment a typical three-way catalyst was used. Among the various compounds detected in exhaust emissions, the following ones were monitored at engine and catalyst outlet: methane, hexane, ethylene, acetaldehyde, acetone, benzene, 1,3-butadiene, toluene, acetic acid and ethanol. Addition of ethanol in the fuel up to 10% w/w had as a result an increase in the Reid vapour pressure of the fuel, which indicates indirectly increased evaporative emissions, while carbon monoxide tailpipe emissions were decreased. For ethanol-containing fuels, acetaldehyde emissions were appreciably increased (up to 100%), especially for fuel containing 3% w/w ethanol. In contrast, aromatics emissions were decreased by ethanol addition to gasoline. Methane and ethanol were the most resistant compounds to oxidation while ethylene was the most degradable compound over the catalyst. Ethylene, methane and acetaldehyde were the main compounds present at engine exhaust while methane, acetaldehyde and ethanol were the main compounds in tailpipe emissions for ethanol fuels after the catalyst operation.

Behavioural responses of spinner dolphins to human interactions

PubMed Central

Cesario, Amina; Costa, Marina; Harraway, John; Notarbartolo di Sciara, Giuseppe; Slooten, Elisabeth

2018-01-01

There is increasing evidence that whale and dolphin watching activities have detrimental effects on targeted cetacean populations. In Egypt, spinner dolphins regularly occur in the resting areas of Samadai, Satayah and Qubbat'Isa reefs. In-water human interactions with dolphins are regulated with a time-area closure system at Samadai, unregulated at Satayah and non-existent at Qubbat'Isa. This provided an ideal experimental setting to advance our understanding of the effects of tourism on a species highly sensitive to disturbances. Our study confirmed that the intensity and duration of interactions, and therefore, dolphin exposure to tourism, differed among the study sites. Compared with the Qubbat'Isa control site, behavioural reactions to boats and swimmers at the two tourism sites suggested that dolphin rest was disrupted, especially around the middle of the day and especially at Satayah, where dolphin tourism is unregulated. Our results indicate also that the dolphin protection measures at Samadai reduce the level of disturbance. We recommend that similar measures be implemented at other dolphin tourism locations, and that no new operations be initiated until the long-term impacts on dolphin populations are better understood. Our experience emphasizes the need to adopt precautionary approaches in research and management of whale and dolphin watching. PMID:29765660

Performance enhancement, elite athletes and anti doping governance: comparing human guinea pigs in pharmaceutical research and professional sports

PubMed Central

2014-01-01

In light of the World Anti Doping Agency’s 2013 Code Revision process, we critically explore the applicability of two of three criteria used to determine whether a method or substance should be considered for their Prohibited List, namely its (potential) performance enhancing effects and its (potential) risk to the health of the athlete. To do so, we compare two communities of human guinea pigs: (i) individuals who make a living out of serial participation in Phase 1 pharmacology trials; and (ii) elite athletes who engage in what is effectively 'unregulated clinical research’ by using untested prohibited or non-prohibited performance enhancing substances and methods, alone or in combination. Our comparison sheds light on norms of research ethics that these practices exacerbate with respect to the concepts of multiplicity, visibility, and consistency. We argue for the need to establish a proper governance framework to increase the accountability of these unregulated research practices in order to protect the human guinea pigs in elite sports contexts, and to establish reasonable grounds for the performance enhancing effects, and the risks to the health of the athlete, of the methods and substances that might justify their inclusion on the Prohibited List. PMID:24499536

Comparative effects of MTBE and ethanol additions into gasoline on exhaust emissions

NASA Astrophysics Data System (ADS)

Song, Chong-Lin; Zhang, Wen-Mei; Pei, Yi-Qiang; Fan, Guo-Liang; Xu, Guan-Peng

The effects of the additives of ethanol (EA) and methyl tert-butyl ether (MTBE) in various blend ratios into the gasoline fuel on the exhaust emissions and the catalytic conversion efficiencies were investigated in an EFI gasoline engine. The regulated exhaust emissions (CO, THC and NO X) and the unregulated exhaust emissions (benzene, formaldehyde, acetaldehyde, unburned EA and MTBE) before and after the three-way catalytic converter were measured. The experimental results showed that EA brought about generally lower regulated engine-out emissions than MTBE did. But, the comparison of the unregulated engine-out emissions between both additives was different. Concretely, the effect of EA on benzene emission was worse than that of MTBE on the whole, which was a contrast with formaldehyde emission. The difference in the acetaldehyde comparison depended much on the engine operating conditions, especially the engine speed. Both EA and MTBE were identified in the engine exhaust gases only when they were added to the fuel, and their volume fraction increased with blend ratios. The catalytic conversion efficiencies of the regulated emissions for the EA blends were in general lower than those for MTBE blends, especially at the low and high engine speeds. There was little difference in the catalytic conversion efficiencies for both benzene and formaldehyde, while distinct difference for acetaldehyde.

Management of unregulated agricultural nonpoint sources through water quality trading market.

PubMed

Mahjoobi, Emad; Sarang, Amin; Ardestani, Mojtaba

2016-11-01

Water quality trading (WQT) could be an innovative policy to incentivize farmers to implement best management practices (BMPs) for their activities. This study focused on assessment of involving unregulated agricultural nonpoint sources (NPS) into the WQT market in Gharesoo watershed in the west of Iran. It also proposes a methodology to determine location-based trading ratios as well as environmental penalty cost to achieve a more well-designed market structure. Trading activities in different scenarios were described by trading volume (TV), participation rate (PR), total exchanged value (TEV), and other market parameters in order to achieve a better comparison of market performance. Results showed that, by applying NPS to the Gharesoo watershed, total phosphorous (TP) trading market could increase TV, PR, and TEV up to 11, 1.7 and 7.5 times, respectively, depending on which level of BMPs are implemented by them. Additionally, it could save 29% of the total cost of implementing a TP total maximum daily load in this watershed compared to the 'command and control' approach. Furthermore, the agricultural sector could profit by $5.49 million (or $75/ha) by choosing solutions such as terrace systems and filter strips to register into the market. This profit can be allocated to the development of new agricultural technologies.

Effect of high electromagnetic fields on cellular growth

NASA Astrophysics Data System (ADS)

Albalawi, Abdullah; Mustafa, Mohammed; Masood, Samina

It is already known that high-intensity electromagnetic field affect the human lung growth and forces the T-cells to decrease by 20-30 percent. The electromagnetic field had a severe impact on human T-cells in contrast to lung cells. Due to the high-intensity electromagnetic field, the growth of T-cells becomes low and release of Ca+2 increases up to 3.5 times more than the lung cells. The high-intensity electromagnetic radiations do not directly produce cancer cells but had a severe impact on the growth of T-cells. It can also be said that electromagnetic field acts a role in the cancer initiation. It creates disordered in the structure of membranes and gesture transduction. The higher exposure to electromagnetic field increases PKC-alpha and this larger release from membranes cannot be controlled. It was concluded that greater exposure to the electromagnetic field is dangerous and had a severe impact on T-cells growth and lung cells growth and due to this greater possibility of leukemia occurrence. We show a similar effect of electromagnetic fields single celled bacteria to compare the bacterial cellular growth with the human cells using the bacteria strains which are commonly found in human body.

A quantitative life history of endangered humpback chub that spawn in the Little Colorado River: variation in movement, growth, and survival

USGS Publications Warehouse

Yackulic, Charles B.; Yard, Michael D.; Korman, Josh; Van Haverbeke, David R.

2014-01-01

While the ecology and evolution of partial migratory systems (defined broadly to include skip spawning) have been well studied, we are only beginning to understand how partial migratory populations are responding to ongoing environmental change. Environmental change can lead to differences in the fitness of residents and migrants, which could eventually lead to changes in the frequency of the strategies in the overall population. Here, we address questions concerning the life history of the endangered Gila cypha (humpback chub) in the regulated Colorado River and the unregulated tributary and primary spawning area, the Little Colorado River. We develop eight multistate models for the population based on three movement hypotheses, in which states are defined in terms of fish size classes and river locations. We fit these models to mark–recapture data collected in 2009–2012. We compare survival and growth estimates between the Colorado River and Little Colorado River and calculate abundances for all size classes. The best model supports the hypotheses that larger adults spawn more frequently than smaller adults, that there are residents in the spawning grounds, and that juveniles move out of the Little Colorado River in large numbers during the monsoon season (July–September). Monthly survival rates for G. cypha in the Colorado River are higher than in the Little Colorado River in all size classes; however, growth is slower. While the hypothetical life histories of life-long residents in the Little Colorado River and partial migrants spending most of its time in the Colorado River are very different, they lead to roughly similar fitness expectations when we used expected number of spawns as a proxy. However, more research is needed because our study period covers a period of years when conditions in the Colorado River for G. cypha are likely to have been better than has been typical over the last few decades.

Growth control of the eukaryote cell: a systems biology study in yeast.

PubMed

Castrillo, Juan I; Zeef, Leo A; Hoyle, David C; Zhang, Nianshu; Hayes, Andrew; Gardner, David Cj; Cornell, Michael J; Petty, June; Hakes, Luke; Wardleworth, Leanne; Rash, Bharat; Brown, Marie; Dunn, Warwick B; Broadhurst, David; O'Donoghue, Kerry; Hester, Svenja S; Dunkley, Tom Pj; Hart, Sarah R; Swainston, Neil; Li, Peter; Gaskell, Simon J; Paton, Norman W; Lilley, Kathryn S; Kell, Douglas B; Oliver, Stephen G

2007-01-01

Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.