Current umbilical cord clamping practices and attitudes of obstetricians and midwives toward delayed cord clamping in Saudi Arabia.

PubMed

Ibrahim, Nadia O; Sukkarieh, Hatouf H; Bustami, Rami T; Alshammari, Elaf A; Alasmari, Lama Y; Al-Kadri, Hanan M

2017-01-01

In Saudi Arabia, as in many countries, there is usually no clear definition of the timing of umbilical cord clamping (UCC) in the policies and procedures used by hospitals. The World Health Organization (WHO) recommends delayed cord clamping (DCC) ( > 1 minute after birth) as it can significantly improve hemodynamics and long-term neurodevelopment. To investigate current practices of healthcare professionals on the timing of UCC in Saudi Arabia. Cross-sectional survey. Five tertiary hospitals in Riyadh, Saudi Arabia, during May to October 2016. Obstetricians and midwives completed a widely-used questionnaire on UCC practices. Current UCC practices and attitudes of obstetricians and midwives toward DCC. Eighty-two obstetricians and 75 midwives completed the questionnaire for a response rate of 80%. The majority of respondents were aged 30 years or older (81%) and 84% were females. Most respondents were non-Saudi (66%) and had an educational level of bachelor's degree or higher (72%). Only 42% of respondents reported the existence of UCC guidelines in their practice; 38% reported the existence of a set time for UCC when the neonate was term and healthy, and only 32% had a set time for UCC in preterm neonates. While lower levels of agreement were reported among obstetricians and midwives on the benefits of DCC for babies requiring positive pressure ventilation, the majority of respondents (69-71%) thought that DCC was generally good for both term and preterm babies and that its benefits extend beyond the neonatal period. While the majority of obstetricians and midwives that participated in this study had a positive perception toward DCC, this did not translate to their daily practice as most of these professionals reported a lack of existing UCC guidelines in their institutions. Further studies are warranted to confirm these findings. Participant selection by convenience sampling.

Role of Netrin-1 Signaling in Nerve Regeneration

PubMed Central

Dun, Xin-Peng; Parkinson, David B.

2017-01-01

Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

A novel DCC mutation and genetic heterogeneity in congenital mirror movements.

PubMed

Depienne, C; Cincotta, M; Billot, S; Bouteiller, D; Groppa, S; Brochard, V; Flamand, C; Hubsch, C; Meunier, S; Giovannelli, F; Klebe, S; Corvol, J C; Vidailhet, M; Brice, A; Roze, E

2011-01-18

DCC is the receptor for netrin, a protein that guides axon migration of developing neurons across the body's midline. Mutations in the DCC gene were recently identified in 2 families with congenital mirror movements (MM). The objective was to study clinical and genetic characteristics of 3 European families with MM and to test whether this disorder is genetically homogeneous. We studied 3 MM families with a total of 13 affected subjects. Each patient had a standardized interview and neurologic examination, focusing on the phenomenology and course of the MM. The severity of MM was also assessed. Molecular analysis of DCC was performed in the index cases. In addition, linkage analysis of the DCC locus was performed in a large French family. The clinical expression and course of MM were very similar in all the affected subjects, regardless of DCC mutational status. However, slight intersubject variability in the severity of MM was noted within each family. Onset always occurred in infancy or early childhood, and MM did not deteriorate over time. Motor disability due to MM was mild and restricted to activities that require independent movements of the 2 hands. We found a novel mutation in the DCC gene in an Italian family with MM associated with abnormal ipsilateral corticospinal projection. The DCC locus was excluded in the French family. DCC has a crucial role in the development of corticospinal tracts in humans. Congenital MM is genetically heterogeneous, despite its clinical homogeneity.

Anchoring of protein kinase A by ERM (ezrin-radixin-moesin) proteins is required for proper netrin signaling through DCC (deleted in colorectal cancer).

PubMed

Deming, Paula B; Campbell, Shirley L; Stone, Jamie B; Rivard, Robert L; Mercier, Alison L; Howe, Alan K

2015-02-27

Netrin-1, acting through its principal receptor DCC (deleted in colorectal cancer), serves as an axon guidance cue during neural development and also contributes to vascular morphogenesis, epithelial migration, and the pathogenesis of some tumors. Several lines of evidence suggest that netrin-DCC signaling can regulate and be regulated by the cAMP-dependent protein kinase, PKA, although the molecular details of this relationship are poorly understood. Specificity in PKA signaling is often achieved through differential subcellular localization of the enzyme by interaction with protein kinase A anchoring proteins (AKAPs). Here, we show that AKAP function is required for DCC-mediated activation of PKA and phosphorylation of cytoskeletal regulatory proteins of the Mena/VASP (vasodilator-stimulated phosphoprotein) family. Moreover, we show that DCC and PKA physically interact and that this association is mediated by the ezrin-radixin-moesin (ERM) family of plasma membrane-actin cytoskeleton cross-linking proteins. Silencing of ERM protein expression inhibits DCC-PKA interaction, DCC-mediated PKA activation, and phosphorylation of Mena/VASP proteins as well as growth cone morphology and neurite outgrowth. Finally, although expression of wild-type radixin partially rescued growth cone morphology and tropism toward netrin in ERM-knockdown cells, expression of an AKAP-deficient mutant of radixin did not fully rescue growth cone morphology and switched netrin tropism from attraction to repulsion. These data support a model in which ERM-mediated anchoring of PKA activity to DCC is required for proper netrin/DCC-mediated signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Dermatology discharge continuity clinic enhances resident autonomy and insight into transitions-of-care competencies: a cross-sectional survey study.

PubMed

Rana, Jasmine; Mostaghimi, Arash

2017-05-15

Dermatology residents perform consults on hospitalized patients, but are often limited in their ability to follow-up with these patients after discharge, leading to inadequate follow-up and understanding of post-discharge transitions of care. In 2013, a discharge continuity clinic (DCC) staffed by the inpatient consult dermatology resident and attending dermatologist was established at one of the four adult hospital sites residents rotate through in the Harvard Combined Dermatology Residency Program. Resident perceptions about the DCC and their educational experience on inpatient consult rotations with a DCC and without a DCC were obtained using a cross-sectional survey instrument in June 2016. Self-reported data from a multi-year cohort of dermatology residents (n = 14 of 20, 70% response rate) reveals that the DCC enabled resident autonomy and resident satisfaction in care of their patients,insight into the disease-related challenges and the broader social context during transitions of care from inpatient to outpatient settings, and more enriching learning experiences than inpatient consult rotations without a DCC. Dermatology residents self-report participation in an inpatient consult rotation with aDCC supports their autonomy and achievement of post-discharge transitions-of-care competencies.

X-Chromosome dosage compensation.

PubMed

Meyer, Barbara J

2005-06-25

In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the global, epigenetic regulation of X chromosomes that is maintained throughout the lifetime of hermaphrodites.

Microsphere-based scaffolds encapsulating chondroitin sulfate or decellularized cartilage

PubMed Central

Gupta, Vineet; Tenny, Kevin M; Barragan, Marilyn; Berkland, Cory J; Detamore, Michael S

2016-01-01

Extracellular matrix materials such as decellularized cartilage (DCC) and chondroitin sulfate (CS) may be attractive chondrogenic materials for cartilage regeneration. The goal of the current study was to investigate the effects of encapsulation of DCC and CS in homogeneous microsphere-based scaffolds, and to test the hypothesis that encapsulation of these extracellular matrix materials would induce chondrogenesis of rat bone marrow stromal cells. Four different types of homogeneous scaffolds were fabricated from microspheres of poly(D,L-lactic-co-glycolic acid): Blank (poly(D,L-lactic-co-glycolic acid) only; negative control), transforming growth factor-β3 encapsulated (positive control), DCC encapsulated, and CS encapsulated. These scaffolds were then seeded with rat bone marrow stromal cells and cultured for 6 weeks. The DCC and CS encapsulation altered the morphological features of the microspheres, resulting in higher porosities in these groups. Moreover, the mechanical properties of the scaffolds were impacted due to differences in the degree of sintering, with the CS group exhibiting the highest compressive modulus. Biochemical evidence suggested a mitogenic effect of DCC and CS encapsulation on rat bone marrow stromal cells with the matrix synthesis boosted primarily by the inherently present extracellular matrix components. An important finding was that the cell seeded CS and DCC groups at week 6 had up to an order of magnitude higher glycosaminoglycan contents than their acellular counterparts. Gene expression results indicated a suppressive effect of DCC and CS encapsulation on rat bone marrow stromal cell chondrogenesis with differences in gene expression patterns existing between the DCC and CS groups. Overall, DCC and CS were easily included in microsphere-based scaffolds; however, there is a requirement to further refine their concentrations to achieve the differentiation profiles we seek in vitro. PMID:27358376

dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients.

PubMed

Manitt, C; Eng, C; Pokinko, M; Ryan, R T; Torres-Berrío, A; Lopez, J P; Yogendran, S V; Daubaras, M J J; Grant, A; Schmidt, E R E; Tronche, F; Krimpenfort, P; Cooper, H M; Pasterkamp, R J; Kolb, B; Turecki, G; Wong, T P; Nestler, E J; Giros, B; Flores, C

2013-12-17

Adolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide.

Radiative Effects of the Diurnal Cycle of Clouds and their Response to Climate Change

NASA Astrophysics Data System (ADS)

Yin, J.; Porporato, A. M.

2017-12-01

Clouds effectively control the Earth's energy budget by reflecting solar radiation and restricting the terrestrial one. While these dynamics have been regarded as one of vexing problem in understanding the climate system and have thus attracted much attention in the literature, less research has been devoted to the diurnal cycle of clouds (DCC). Here we first quantify the mean, amplitude, and phase of the cloud cycles in current climate models and compare them with satellite observations and reanalysis data. We show that the mean values appear to be reliable but the amplitude and phase of the DCC are less consistent. These inconsistencies are interpreted using a minimalist radiative balance model to demonstrate their impacts on surface temperature. The DCC radiative impacts are then analyzed in terms of phase shift and amplitude modulation of DCC and their so-called cloud radiative effects are estimated directly from climate model outputs. This allows us to show that DCC variations may account for up to 10-20% of the total cloud radiative impacts, calling for increased attention to the temporal evolution of the DCC in climate models.

The Characterization of Deep Convective Clouds as an Invariant Calibration Target and as a Visible Calibration Technique

NASA Technical Reports Server (NTRS)

Doelling, David R.; Morstad, Daniel; Scarino, Benjamin R.; Bhatt, Rajendra; Gopalan, Arun

2012-01-01

Deep convective clouds (DCCs) are ideal visible calibration targets because they are bright nearly isotropic solar reflectors located over the tropics and they can be easily identified using a simple infrared threshold. Because all satellites view DCCs, DCCs provide the opportunity to uniformly monitor the stability of all operational sensors, both historical and present. A collective DCC anisotropically corrected radiance calibration approach is used to construct monthly probability distribution functions (PDFs) to monitor sensor stability. The DCC calibration targets were stable to within 0.5% and 0.3% per decade when the selection criteria were optimized based on Aqua MODerate Resolution Imaging Spectroradiometer 0.65-micrometer-band radiances. The Tropical Western Pacific (TWP), African, and South American regions were identified as the dominant DCC domains. For the 0.65-micrometer band, the PDF mode statistic is preferable, providing 0.3%regional consistency and 1%temporal uncertainty over land regions. It was found that the DCC within the TWP had the lowest radiometric response and DCC over land did not necessarily have the highest radiometric response. For wavelengths greater than 1 micrometer, the mean statistic is preferred, and land regions provided a regional variability of 0.7%with a temporal uncertainty of 1.1% where the DCC land response was higher than the response over ocean. Unlike stratus and cirrus clouds, the DCC spectra were not affected by water vapor absorption.

Comparative evaluation of effectiveness of sodium dichloroisocyanurate and calcium hydroxide against Candida albicans.

PubMed

Kurian, Jacob; Bolla, Nagesh; Damaraju, Bhargavi

2012-09-01

Candida albicans is the most commonly isolated fungi from the oral cavity. It is the most infective to various intracanal medicaments and is considered as invasive yeast. Sodium dichloroisocyanurate (NaDCC) which is used as a disinfectant and as a biocide in treating potable water has similar action to that of sodium hypochlorite against microbes. The aim of the present study is to compare the effectiveness of calcium hydroxide and NaDCC against Candida albicans. After obtaining the stock cultures of Candida, the isolates were divided into six groups which were exposed to different concentrations of NaDCC and calcium hydroxide Ca(OH)₂. Group 1 consisted of the isolates which were subdivided into three groups, subjected to three different concentrations of NaDCC. Group 2 also consisted of three subgroups exposed to three different concentrations of Ca(OH)₂. Group three consisted of three subgroups which were exposed to three different concentrations of combinations of both NaDCC and Ca(OH)₂. The results of the present study show that calcium hydroxide was totally ineffective at all concentrations and NaDCC was effective and also the combination of both was shown to be effective. NaDCC alone was effective at all concentrations and the combination with Ca(OH)₂ was found to be less effective. Ca(OH)₂ was totally ineffective.

Quality of life assessment in advanced cancer patients treated at home, an inpatient unit, and a day care center

PubMed Central

Leppert, Wojciech; Majkowicz, Mikolaj; Forycka, Maria; Mess, Eleonora; Zdun-Ryzewska, Agata

2014-01-01

Aim of the study To assess quality of life (QoL) in cancer patients treated at home, at an in-patient palliative care unit (PCU), and at a day care center (DCC). Patients and methods QoL was assessed in advanced cancer patients at baseline and after 7 days of symptomatic treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL), the Edmonton Symptom Assessment System (ESAS), and the Karnofsky Performance Status (KPS) scale. Results A total of 129 patients completed the study, with 51 patients treated at home, 51 patients treated at the PCU, and 27 patients at DCC. In the EORTC QLQ-C15-PAL, improvement in functional and symptom scales was observed except in physical functioning and fatigue levels; patients at DCC had a better physical functioning, global QoL, appetite, and fatigue levels. In the ESAS, improvement in all items was found except for drowsiness levels, which was stable in patients treated at DCC and deteriorated in home and PCU patients. Higher activity, better appetite and well-being, and less drowsiness were observed in patients treated at DCC. KPS was better in DCC patients compared to those treated at home and at the PCU; the latter group deteriorated. Conclusions QoL improved in all patient groups, with better results in DCC patients and similar scores in those staying at home and at the PCU. Along with clinical assessment, baseline age, KPS, physical and emotional functioning may be considered when assigning patients to care at a DCC, PCU, or at home. PMID:24855379

Diel activity patterns of juvenile late fall-run Chinook salmon with implications for operation of a gated water diversion in the Sacramento–San Joaquin River Delta

USGS Publications Warehouse

Plumb, John M.; Adams, Noah S.; Perry, Russell W.; Holbrook, Christopher; Romine, Jason G.; Blake, Aaron R.; Burau, Jon R.

2016-01-01

In the Sacramento-San Joaquin River Delta, California, tidal forces that reverse river flows increase the proportion of water and juvenile late fall-run Chinook salmon diverted into a network of channels that were constructed to support agriculture and human consumption. This area is known as the interior delta, and it has been associated with poor fish survival. Under the rationale that the fish will be diverted in proportion to the amount of water that is diverted, the Delta Cross Channel (DCC) has been prescriptively closed during the winter out-migration to reduce fish entrainment and mortality into the interior delta. The fish are thought to migrate mostly at night, and so daytime operation of the DCC may allow for water diversion that minimizes fish entrainment and mortality. To assess this, the DCC gate was experimentally opened and closed while we released 2983 of the fish with acoustic transmitters upstream of the DCC to monitor their arrival and entrainment into the DCC. We used logistic regression to model night-time arrival and entrainment probabilities with covariates that included the proportion of each diel period with upstream flow, flow, rate of change in flow and water temperature. The proportion of time with upstream flow was the most important driver of night-time arrival probability, yet river flow had the largest effect on fish entrainment into the DCC. Modelling results suggest opening the DCC during daytime while keeping the DCC closed during night-time may allow for water diversion that minimizes fish entrainment into the interior delta.

Sodium dichloroisocyanurate (NaDCC) tablets as an alternative to sodium hypochlorite for the routine treatment of drinking water at the household level.

PubMed

Clasen, Thomas; Edmondson, Paul

2006-03-01

Household water treatment using sodium hypochlorite (NaOCl) has been recognized as a cost-effective means of reducing the heavy burden of diarrhea and other waterborne diseases, especially among populations without access to improved water supplies. Sodium dichloroisocyanurate (NaDCC), which is widely used in emergencies, is an alternative source of chlorine that may present certain advantages over NaOCl for household-based interventions in development settings. We summarize the basic chemistry and possible benefits of NaDCC, and review the available literature concerning its safety and regulatory treatment and microbiological effectiveness. We review the evidence concerning NaDCC in field studies, including microbiological performance and health outcomes. Finally, we examine studies and data to compare NaDCC with NaOCl in terms of compliance, acceptability, affordability and sustainability, and suggest areas for further research.

Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution

PubMed Central

Wheeler, Bayly S; Anderson, Erika; Frøkjær-Jensen, Christian; Bian, Qian; Jorgensen, Erik; Meyer, Barbara J

2016-01-01

Changes in chromosome number impair fitness by disrupting the balance of gene expression. Here we analyze mechanisms to compensate for changes in gene dose that accompanied the evolution of sex chromosomes from autosomes. Using single-copy transgenes integrated throughout the Caenorhabditis elegans genome, we show that expression of all X-linked transgenes is balanced between XX hermaphrodites and XO males. However, proximity of a dosage compensation complex (DCC) binding site (rex site) is neither necessary to repress X-linked transgenes nor sufficient to repress transgenes on autosomes. Thus, X is broadly permissive for dosage compensation, and the DCC acts via a chromosome-wide mechanism to balance transcription between sexes. In contrast, no analogous X-chromosome-wide mechanism balances transcription between X and autosomes: expression of compensated hermaphrodite X-linked transgenes is half that of autosomal transgenes. Furthermore, our results argue against an X-chromosome dosage compensation model contingent upon rex-directed positioning of X relative to the nuclear periphery. DOI: http://dx.doi.org/10.7554/eLife.17365.001 PMID:27572259

Respiratory infection with Francisella novicida induces rapid dystrophic cardiac calcinosis (DCC).

PubMed

Roth, Kimberly M; Oghumu, Steve; Satoskar, Anjali A; Gunn, John S; van Rooijen, Nico; Satoskar, Abhay R

2008-06-01

Francisella tularensis causes pulmonary tularemia and death in humans when left untreated. Here, using a novel aerosol infection model, we show that acute pulmonary Francisella novicida infection not only causes pneumonia and liver damage, but also induces dystrophic cardiac calcinosis (DCC) in BALB/c mice. C57BL/6 mice also develop pneumonia and hepatic damage, but fail to develop DCC. Development of DCC in BALB/c mice is associated with significant induction of RANKL but not osteopontin in their organs. Depletion of lung macrophages prior to infection markedly reduces pericarditis and calcification in BALB/c mice but does not increase their susceptibility to infection.

Frequency of Tropical Ocean Deep Convection and Global Warming

NASA Astrophysics Data System (ADS)

Aumann, H. H.; Behrangi, A.; Ruzmaikin, A.

2017-12-01

The average of 36 CMIP5 models predicts about 3K of warming and a 4.7% increase in precipitation for the tropical oceans with a doubling of the CO2 by the end of this century. For this scenario we evaluate the increase in the frequency of Deep Convective Clouds (DCC) in the tropical oceans. We select only DCC which reach or penetrate the tropopause in the 15 km AIRS footprint. The evaluation is based on Probability Distribution Functions (PDFs) of the current temperatures of the tropical oceans, those predicted by the mean of the CMIP5 models and the PDF of the DCC process. The PDF of the DCC process is derived from the Atmospheric Infrared Sounder (AIRS) between the years 2003 and 2016. During this time the variability due Enso years provided a 1 K p-p change in the mean tropical SST. The key parameter is the SST associated with the onset of the DCC process. This parameter shifts only 0.5 K for each K of warming of the oceans. As a result the frequency of DCC is expected to increases by the end of this century by about 50% above the current frequency.

Disinfection efficacy of sodium dichloroisocyanurate (NADCC) against common food-borne intestinal protozoa.

PubMed

El Zawawy, Lobna A; El-Said, Doaa; Ali, Safia M; Fathy, Fouad M

2010-04-01

The present study was conducted to investigate the efficacy of sodium dichloroisocyanurate (NaDCC) on the infective stages of common food-borne intestinal protozoa; Entamoeba histolytica (E. histolytica), Giardia lamblia (G. lamblia), Cryptosporidium, Cyclospora and Microsporidia; beside its effect on raw green vegetables and fruits. Parasites, isolated from stool of patients with diarrhea or dysentery, were exposed to NaDCC solution (1g/l) for one and two hours. Disinfection effect of NaDCC was assessed by in-vitro viability, using trypan blue stain, and infectivity bioassay in laboratory animals as indicated by fecal and intestinal parasitic counts. Raw vegetables and fruits were dipped in NaDCC solution in the same concentration and exposure time as used for treatment of the parasites. Results revealed statistically significant reductions in viability and infectivity of all examined parasites indicating their susceptibility to NaDCC. Relative variations in susceptibility were revealed; E. histolytica and G. lamblia were most susceptible (100% reduction) followed by Microsporidia then Cryptospridium and Cyclospora. NaDCC did not affect the consistency, color, taste or flavor of raw green vegetables and fruits. The proved efficacy of NaDCC, in cheap and convenient dry tablet form, makes it a promising tool in decontaminating raw vegetables and fruits from food-borne protozoan parasites at household and restaurant levels as well as in catering and fresh produce industry. It is also recommended for disinfection of food preparation surfaces and equipment.

Timing of umbilical cord clamping among infants born at 22 through 27 weeks' gestation.

PubMed

Backes, C H; Huang, H; Iams, J D; Bauer, J A; Giannone, P J

2016-01-01

To investigate the safety, feasibility and efficacy of delayed cord clamping (DCC) compared with immediate cord clamping (ICC) at delivery among infants born at 22 to 27 weeks' gestation. This was a pilot, randomized, controlled trial in which women in labor with singleton pregnancies at 22 to 27 weeks' gestation were randomly assigned to ICC (cord clamped at 5 to 10 s) or DCC (30 to 45 s). Forty mother-infant pairs were randomized. Infants in the ICC and DCC groups had mean gestational ages (GA) of 24.6 and 24.4 weeks, respectively. No differences were observed between the groups across all available safety measures, although infants in the DCC group had higher admission temperatures than infants in the ICC group (97.4 vs. 96.2 °F, P=0.04). During the first 24 h of life, blood pressures were lower in the ICC group than in the DCC group (P<0.05), despite a threefold greater incidence of treatment for hypotension (45% vs. 12%, P<0.01). Infants in the ICC group had increased numbers of red blood transfusions (in first 28 days of life) than infants in DCC group (4.1±3.9 vs. 2.8±2.2, P=0.04). Among infants born at an average GA of 24 weeks', DCC appears safe, logistically feasible, and offers hematological and circulatory advantages compared with ICC. A more comprehensive appraisal of this practice is needed.

Role of the DIP Molecules in DCC Signaling

DTIC Science & Technology

2001-03-01

DIP13 interacts with AKT , a key molecule for cell survival. Our results suggest that the DCC apoptotic signal is mediated by DIP13 that interferes with... AKT cell survival pathway, resulting in cell death. Finally, we have cloned DIP13 beta, suggesting that DIP13 represents a family of molecules with at...interacts with DCC through its PTB domain (Fig. 4). Interestingly, Mitsuuchi et al. (1999) identified a gene dubbed APPL that interacts with AKT , a key

ESCRT-II controls retinal axon growth by regulating DCC receptor levels and local protein synthesis

PubMed Central

Konopacki, Filip A.; Dwivedy, Asha; Bellon, Anaïs; Blower, Michael D.

2016-01-01

Endocytosis and local protein synthesis (LPS) act coordinately to mediate the chemotropic responses of axons, but the link between these two processes is poorly understood. The endosomal sorting complex required for transport (ESCRT) is a key regulator of cargo sorting in the endocytic pathway, and here we have investigated the role of ESCRT-II, a critical ESCRT component, in Xenopus retinal ganglion cell (RGC) axons. We show that ESCRT-II is present in RGC axonal growth cones (GCs) where it co-localizes with endocytic vesicle GTPases and, unexpectedly, with the Netrin-1 receptor, deleted in colorectal cancer (DCC). ESCRT-II knockdown (KD) decreases endocytosis and, strikingly, reduces DCC in GCs and leads to axon growth and guidance defects. ESCRT-II-depleted axons fail to turn in response to a Netrin-1 gradient in vitro and many axons fail to exit the eye in vivo. These defects, similar to Netrin-1/DCC loss-of-function phenotypes, can be rescued in whole (in vitro) or in part (in vivo) by expressing DCC. In addition, ESCRT-II KD impairs LPS in GCs and live imaging reveals that ESCRT-II transports mRNAs in axons. Collectively, our results show that the ESCRT-II-mediated endocytic pathway regulates both DCC and LPS in the axonal compartment and suggest that ESCRT-II aids gradient sensing in GCs by coupling endocytosis to LPS. PMID:27248654

Probing the dynamic reversibility and generation of dynamic combinatorial libraries in the presence of bacterial model oligopeptides as templating guests of tetra-carbohydrazide macrocycles using electrospray mass spectrometry.

PubMed

Nour, Hany F; Islam, Tuhidul; Fernández-Lahore, Marcelo; Kuhnert, Nikolai

2012-12-30

Over the past few decades, bacterial resistance to antibiotics has emerged as a real threat to human health. Accordingly, there is an urgent demand for the development of innovative strategies for discovering new antibiotics. We present the first use of tetra-carbohydrazide cyclophane macrocycles in dynamic combinatorial chemistry (DCC) and molecular recognition as chiral hosts binding oligopeptides, which mimic bacterial cell wall. This study introduces an innovative application of electrospray ionisation time-of-flight mass spectrometry (ESI-TOF MS) to oligopeptides recognition using DCC. A small dynamic library composed of eight functionalised macrocycles has been generated in solution and all members were characterised by ESI-TOF MS. We also probed the dynamic reversibility and mechanism of formation of tetra-carbohydrazide cyclophanes in real-time using ESI-TOF MS. Dynamic reversibility of tetra-carbohydrazide cyclophanes is favored under thermodynamic control. The mechanism of formation of tetra-carbohydrazide cyclophanes involves key dialdehyde intermediates, which have been detected and assigned according to their high-resolution m/z values. Three members of the dynamic library bind efficiently in the gas phase to a selection of oligopeptides, unique to bacteria, allowing observation of host/guest complex ions in the gas phase. We probed the mechanism of the [2+2]-cyclocondensation reaction forming library members, proved dynamic reversibility of tetra-carbohydrazide cyclophanes and showed that complex ions formed between library members and hosts can be observed in the gas phase, allowing the solution of an important problem of biological interest. Copyright © 2012 John Wiley & Sons, Ltd.

Automatic control of clock duty cycle

NASA Technical Reports Server (NTRS)

Feng, Xiaoxin (Inventor); Roper, Weston (Inventor); Seefeldt, James D. (Inventor)

2010-01-01

In general, this disclosure is directed to a duty cycle correction (DCC) circuit that adjusts a falling edge of a clock signal to achieve a desired duty cycle. In some examples, the DCC circuit may generate a pulse in response to a falling edge of an input clock signal, delay the pulse based on a control voltage, adjust the falling edge of the input clock signal based on the delayed pulse to produce an output clock signal, and adjust the control voltage based on the difference between a duty cycle of the output clock signal and a desired duty cycle. Since the DCC circuit adjusts the falling edge of the clock cycle to achieve a desired duty cycle, the DCC may be incorporated into existing PLL control loops that adjust the rising edge of a clock signal without interfering with the operation of such PLL control loops.

Investigation of Pinus mugo essential oil oxygenated fraction by combined use of gas chromatography and dry column chromatography.

PubMed

A, M B; Coran, S A; Giannellini, V; Vincieri, F F; Moneti, G

1981-09-01

The oxygenated compounds of Pinus mugo Turra essential oil were investigated by a combination of GC and dry column chromatography (DCC) coordinated by GC data processing. The collected data resulted in a bar graph ("normalized" gas chromatogram) giving the RRT's and relative amounts of 68 components; 38 of them were identified by MS and IR. The described procedure may be used for essential oil analysis in general.

Frequency of Deep Convective Clouds and Global Warming

NASA Technical Reports Server (NTRS)

Aumann, Hartmut H.; Teixeira, Joao

2008-01-01

This slide presentation reviews the effect of global warming on the formation of Deep Convective Clouds (DCC). It concludes that nature responds to global warming with an increase in strong convective activity. The frequency of DCC increases with global warming at the rate of 6%/decade. The increased frequency of DCC with global warming alone increases precipitation by 1.7%/decade. It compares the state of the art climate models' response to global warming, and concludes that the parametrization of climate models need to be tuned to more closely emulate the way nature responds to global warming.

Numerical investigations on unstable direct contact condensation of cryogenic fluids

NASA Astrophysics Data System (ADS)

Jayachandran, K. N.; Arnab, Roy; Parthasarathi, Ghosh

2017-02-01

A typical problem of Direct Contact Condensation (DCC) occurs at the liquid oxygen (LOX) booster turbopump exit of oxidiser rich staged combustion cycle based semi-cryogenic rocket engines, where the hot gas mixture (predominantly oxygen and small amounts of combustion products) that runs the turbine mixes with LOX from the pump exit. This complex multiphase phenomena leads to the formation of solid CO2 & H2O, which is undesirable for the functioning of the main LOX turbopump. As a starting point for solving this complex problem, in this study, the hot gas mixture is taken as pure oxygen and hence, DCC of pure oxygen vapour jets in subcooled liquid oxygen is simulated using the commercial CFD package ANSYS CFX®. A two fluid model along with the thermal phase change model is employed for capturing the heat and mass transfer effects. The study mainly focuses on the subsonic DCC bubbling regime, which is reported as unstable with bubble formation, elongation, necking and collapsing effects. The heat transfer coefficients over a period of time have been computed and the various stages of bubbling have been analysed with the help of vapour volume fraction and pressure profiles. The results obtained for DCC of oxygen vapour-liquid mixtures is in qualitative agreement with the experimental results on DCC of steam-water mixtures.

Progress on thermobrachytherapy surface applicator for superficial tissue disease

NASA Astrophysics Data System (ADS)

Arunachalam, Kavitha; Craciunescu, Oana I.; Maccarini, Paolo F.; Schlorff, Jaime L.; Markowitz, Edward; Stauffer, Paul R.

2009-02-01

This work reports the ongoing development of a combination applicator for simultaneous heating of superficial tissue disease using a 915 MHz DCC (dual concentric conductor) array and High Dose Rate (HDR) brachytherapy delivered via an integrated conformal catheter array. The progress includes engineering design changes in the waterbolus, DCC configurations and fabrication techniques of the conformal multilayer applicator. The dosimetric impact of the thin copper DCC array is also assessed. Steady state fluid dynamics of the new waterbolus bag indicates nearly uniform flow with less than 1°C variation across a large (19×32cm) bolus. Thermometry data of the torso phantom acquired with computer controlled movement of fiberoptic temperature probes inside thermal mapping catheters indicate feasibility of real time feedback control for the DCC array. MR (magnetic resonance) scans of a torso phantom indicate that the waterbolus thickness across the treatment area is controlled by the pressure applied by the surrounding inflatable airbladder and applicator securing straps. The attenuation coefficient of the DCC array was measured as 3+/- 0.001% and 2.95+/-0.03 % using an ion chamber and OneDose dosimeters respectively. The performance of the combination applicator on patient phantoms provides valuable feedback to optimize the applicator prior use in the patient clinic.

Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord.

PubMed

Junge, Harald J; Yung, Andrea R; Goodrich, Lisa V; Chen, Zhe

2016-10-26

Newborn neurons often migrate before undergoing final differentiation, extending neurites, and forming synaptic connections. Therefore, neuronal migration is crucial for establishing neural circuitry during development. In the developing spinal cord, neuroprogenitors first undergo radial migration within the ventricular zone. Differentiated neurons continue to migrate tangentially before reaching the final positions. The molecular pathways that regulate these migration processes remain largely unknown. Our previous study suggests that the DCC receptor is important for the migration of the dorsal spinal cord progenitors and interneurons. In this study, we determined the involvement of the Netrin1 ligand and the ROBO3 coreceptor in the migration. By pulse labeling neuroprogenitors with electroporation, we examined their radial migration in Netrin1 (Ntn1), Dcc, and Robo3 knockout mice. We found that all three mutants exhibit delayed migration. Furthermore, using immunohistochemistry of the BARHL2 interneuron marker, we found that the mediolateral and dorsoventral migration of differentiated dorsal interneurons is also delayed. Together, our results suggest that Netrin1/DCC signaling induce neuronal migration in the dorsal spinal cord. Netrin1, DCC, and ROBO3 have been extensively studied for their functions in regulating axon guidance in the spinal commissural interneurons. We reveal that during earlier development of dorsal interneurons including commissural neurons, these molecules play an important role in promoting cell migration.

Faster-X Evolution of Gene Expression in Drosophila

PubMed Central

Meisel, Richard P.; Malone, John H.; Clark, Andrew G.

2012-01-01

DNA sequences on X chromosomes often have a faster rate of evolution when compared to similar loci on the autosomes, and well articulated models provide reasons why the X-linked mode of inheritance may be responsible for the faster evolution of X-linked genes. We analyzed microarray and RNA–seq data collected from females and males of six Drosophila species and found that the expression levels of X-linked genes also diverge faster than autosomal gene expression, similar to the “faster-X” effect often observed in DNA sequence evolution. Faster-X evolution of gene expression was recently described in mammals, but it was limited to the evolutionary lineages shortly following the creation of the therian X chromosome. In contrast, we detect a faster-X effect along both deep lineages and those on the tips of the Drosophila phylogeny. In Drosophila males, the dosage compensation complex (DCC) binds the X chromosome, creating a unique chromatin environment that promotes the hyper-expression of X-linked genes. We find that DCC binding, chromatin environment, and breadth of expression are all predictive of the rate of gene expression evolution. In addition, estimates of the intraspecific genetic polymorphism underlying gene expression variation suggest that X-linked expression levels are not under relaxed selective constraints. We therefore hypothesize that the faster-X evolution of gene expression is the result of the adaptive fixation of beneficial mutations at X-linked loci that change expression level in cis. This adaptive faster-X evolution of gene expression is limited to genes that are narrowly expressed in a single tissue, suggesting that relaxed pleiotropic constraints permit a faster response to selection. Finally, we present a conceptional framework to explain faster-X expression evolution, and we use this framework to examine differences in the faster-X effect between Drosophila and mammals. PMID:23071459

The use of deep convective clouds to uniformly calibrate the next generation of geostationary reflective solar imagers

NASA Astrophysics Data System (ADS)

Doelling, David R.; Bhatt, Rajendra; Haney, Conor O.; Gopalan, Arun; Scarino, Benjamin R.

2017-09-01

The new 3rd generation geostationary (GEO) imagers will have many of the same NPP-VIIRS imager spectral bands, thereby offering the opportunity to apply the VIIRS cloud, aerosol, and land use retrieval algorithms on the new GEO imager measurements. Climate quality retrievals require multi-channel calibrated radiances that are stable over time. The deep convective cloud calibration technique (DCCT) is a large ensemble statistical technique that assumes that the DCC reflectance is stable over time. Because DCC are found in sufficient numbers across all GEO domains, they provide a uniform calibration stability evaluation across the GEO constellation. The baseline DCCT has been successful in calibrating visible and near-infrared channels. However, for shortwave infrared (SWIR) channels the DCCT is not as effective to monitor radiometric stability. The DCCT was optimized as a function wavelength in this paper. For SWIR bands, the greatest reduction of the DCC response trend standard error was achieved through deseasonalization. This is effective because the DCC reflectance exhibits small regional seasonal cycles that can be characterized on a monthly basis. On the other hand, the inter-annually variability in DCC response was found to be extremely small. The Met-9 0.65-μm channel DCC response was found to have a 3% seasonal cycle. Deseasonalization reduced the trend standard error from 1% to 0.4%. For the NPP-VIIRS SWIR bands, deseasonalization reduced the trend standard error by more than half. All VIIRS SWIR band trend standard errors were less than 1%. The DCCT should be able to monitor the stability of all GEO imager solar reflective bands across the tropical domain with the same uniform accuracy.

FACTORS ASSOCIATED WITH THE UPTAKE OF SODIUM DICHLOROISOCYANURATE (NADCC) TABLETS AS HOUSEHOLD WATER-TREATMENT PRODUCT AMONG CAREGIVERS OF CHILDREN UNDER FIVE IN BENIN, WEST AFRICA.

PubMed

Inungu, Joseph N; Zinsou, Cyprien E; Mustafa, Younis; Singbo, Narcisse

2016-01-01

Improving access to safe drinking water is a critical step in mitigating diarrheal diseases that affect millions of children under 5 years throughout the developing world each year. While the delivery of safe water is out of the reach of many countries, the utilization of Sodium dichloroisocyanurate (NaDCC) is a proven cost-effective alternative to prevent diarrhea caused by waterborne pathogens. However, its uptake remains low in many developing countries, such as the Republic of Benin. This study examines the trends and the determinants of NaDCC uptake in Benin. Population Services International and its affiliate conducted two multistage household surveys among caregivers of children under five in Benin to examine the practices towards diarrheal disease in children under five and identify the factors associated with the use of NaDCC in this population. 2912 respondents/caregivers of children under five were interviewed in 2009 versus 3196 in 2011. The proportion of caregivers who reported ever treating water with NaDCC increased from 5.8% in 2009 to 11.5% in 2011, p < 0.001. The logistic regression model showed that caregivers who knew places that sell NaDCC in the community; those who felt capable of utilizing NADCC correctly to treat drinking water as well as caregivers who reported to be Muslim were more likely than their counterparts to use NaDCC as water treatment product. In order to increase the use of NADCC among caregivers, the Government of Benin and its development partners should focus not only on making NADCC available in the community and informing the community members about the different points of sale, but also in building up the capacity and confidence of caregivers in utilizing it.

Mouse genome-wide association study identifies polymorphisms on chromosomes 4, 11, and 15 for age-related cardiac fibrosis.

PubMed

Li, Qiaoli; Berndt, Annerose; Sundberg, Beth A; Silva, Kathleen A; Kennedy, Victoria E; Cario, Clinton L; Richardson, Matthew A; Chase, Thomas H; Schofield, Paul N; Uitto, Jouni; Sundberg, John P

2016-06-01

Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC-resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscalc loci 1 through 4. Here, we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. Using genotype and phenotype information of the 28 investigated strains, we performed genome-wide association studies (GWAS) and identified the most significant associations on chromosome (Chr) 15 at 72 million base pairs (Mb) (P < 10(-13)) and Chr 4 at 122 Mb (P < 10(-11)) and 134 Mb (P < 10(-7)). At the Chr 15 locus, Col22a1 and Kcnk9 were identified. Both have been reported to be morphologically and functionally important in the heart muscle. The strongest Chr 4 associations were located approximately 6 Mb away from the Dyscalc 2 quantitative trait locus peak within the boundaries of the Extl1 gene and in close proximity to the Trim63 and Cap1 genes. In addition, a single-nucleotide polymorphism association was found on chromosome 11. This study provides evidence for more than the previously reported 4 genetic loci determining cardiac fibrosis and DCC. The study also highlights the power of GWAS in the mouse for dissecting complex genetic traits.

Mouse genome-wide association study identifies polymorphisms on chromosomes 4, 11 and 15 for age-related cardiac fibrosis

PubMed Central

Li, Qiaoli; Berndt, Annerose; Sundberg, Beth A.; Silva, Kathleen A.; Kennedy, Victoria E.; Cario, Clinton L; Richardson, Matthew A.; Chase, Thomas H.; Schofield, Paul N.; Uitto, Jouni; Sundberg, John P.

2017-01-01

Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscal loci 1 through 4. Here we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. Using genotype and phenotype information of the 28 investigated strains we performed genome-wide association studies (GWAS) and identified the most significant associations on chromosome (Chr) 15 at 72 million base pairs (Mb) (P < 10−13) and Chr 4 at 122 Mb (P < 10−11) and 134 Mb (P < 10−7). At the Chr 15 locus Col22a1 and Kcnk9 were identified. Both have been reported to be morphologically and functionally important in the heart muscle. The strongest Chr 4 associations were located approximate 6 Mb away from the Dyscal 2 quantitative trait locus peak within the boundaries of the Extl1 gene and in close proximity to the Trim63 and Cap1 genes. In addition, a single nucleotide polymorphism association was found on chromosome 11. This study provides evidence for more than the previously reported 4 genetic loci determining cardiac fibrosis and DCC. The study also highlights the power of GWAS in the mouse for dissecting complex genetic traits. PMID:27126641

Association of gingivitis with dental calculus thickness or dental calculus coverage and subgingival bacteria in feline leukemia virus- and feline immunodeficiency virus-negative cats.

PubMed

Thengchaisri, Naris; Steiner, Jörg M; Suchodolski, Jan S; Sattasathuchana, Panpicha

2017-01-01

Periodontal disease is the most common oral disease in cats. The objectives of this study were to determine the relationships between gingivitis and dental calculus thickness (DCT), or dental calculus coverage (DCC); determine the association of gingivitis scores and types of oral bacteria; and to evaluate bacterial co-infection in cats with periodontal disease. Twelve cats that were not infected with feline leukemia or feline immunodeficiency viruses were enrolled in the study. Gingivitis, DCT, and DCC were scored and recorded. A Kruskal-Wallis test was used to compare scores among canine, 2nd premolar, 3rd premolar, 4th premolar, and 1st molar teeth. The relationship between gingivitis and DCT or DCC scores was determined using the Spearman rank sum test (ρ). Subgingival bacteria were cultured and the association between bacterial species and gingivitis score was evaluated using a Fisher's exact test. The average gingivitis, DCT, and DCC scores for the caudal maxillary teeth were higher for the caudal mandibular teeth and more severe for the 3rd premolar, 4th premolar, and 1st molar teeth than for the canine teeth. A strong relationship between average DCT or DCC score and average gingivitis score was found (ρ = 0.96 and 1, respectively). Aerobic and anaerobic bacterial infections were identified in a large number of cats with periodontal disease (71.1% and 28.9%, respectively). In conclusion, severe gingivitis scores were associated with anaerobic bacterial infection. The caudal teeth are affected with more severe gingivitis, DCT, and DCC than the other teeth. Antibiotic prophylaxis should be prescribed in cats with periodontal disease.

Assessing the growth and recovery of Salmonella Enteritidis SE86 after sodium dichloroisocyanurate exposure

PubMed Central

Ferreira, Fernanda Stoduto; Horvath, Mariana Bandeira; Tondo, Eduardo Cesar

2013-01-01

The objective of the present study was to assess the growth and the recovery of Salmonella (S.) Enteritidis SE86 in different diluents, culture media and using different plating methods after the exposure to 200 mg/kg sodium dichloroisocyanurate (NaDCC). Before and after NaDCC exposure, SE86 was cultured at 30 °C and 7 °C in the following diluents: Peptone water (P), Saline solution (SaS), Peptone water+Saline solution (P+SaS), Peptone water+Tween 80+Lecithin+Sodium thiosulfate (P+N) and Saline solution+Tween 80+Lecithin+Sodium thiosulfate (SaS+N). The SaS diluent was chosen because it was able to maintain cells viable without growth and was further used for plating SE86 on non selective medium (Tryptic Soy Agar-TSA) and on selective media (Mannitol Lysine Crystal Violet Brilliant Green Agar-MLCB; Brilliant Green Agar-BGA; Salmonella Shigella Agar-SS and Xylose Lysine Dextrose–XLD). The Thin Agar Layer method (TAL) i.e., selective media overlayed with non selective TSA was also evaluated. Results indicated that SE86 not exposed to NaDCC was able to grow in P, P+N, SaS+N and P+SaS, but not in SaS, that was able to maintain cells viable. SE86 exposed to NaDCC demonstrated similar counts after dilution in SaS and the plating on non selective TSA, selective media MLCB, BGA, SS and XLD and on TAL media. SE86, S. Typhimurium and S. Bredeney, exposed or not exposed to NaDCC, showed no significant differences in counts on TSA, XLD and XLD overlayed with TSA, suggesting that all those media may be used to quantify NaDCC-exposed Salmonella by plating method. PMID:24516446

Sodium Dichloroisocyanurate Tablets for Routine Treatment of Household Drinking Water in Periurban Ghana: A Randomized Controlled Trial

PubMed Central

Jain, Seema; Sahanoon, Osman K.; Blanton, Elizabeth; Schmitz, Ann; Wannemuehler, Kathleen A.; Hoekstra, Robert M.; Quick, Robert E.

2010-01-01

We conducted a randomized, placebo-controlled, triple-blinded trial to determine the health impact of daily use of sodium dichloroisocyanurate (NaDCC) tablets for household drinking water treatment in periurban Ghana. We randomized 240 households (3,240 individuals) to receive either NaDCC or placebo tablets. All households received a 20-liter safe water storage vvessel. Over 12 weeks, 446 diarrhea episodes (2.2%) occurred in intervention and 404 (2.0%) in control households (P = 0.38). Residual free chlorine levels indicated appropriate tablet use. Escherichia coli was found in stored water at baseline in 96% of intervention and 88% of control households and at final evaluation in 8% of intervention and 54% of control households (P = 0.002). NaDCC use did not prevent diarrhea but improved water quality. Diarrhea rates were low and water quality improved in both groups. Safe water storage vessels may have been protective. A follow-up health impact study of NaDCC tablets is warranted. PMID:20064989

Disinfection By-Product Formation and Mitigation Strategies in Point-of-Use Chlorination with Sodium Dichloroisocyanurate in Tanzania

PubMed Central

Lantagne, Daniele S.; Cardinali, Fred; Blount, Ben C.

2010-01-01

Almost a billion persons lack access to improved drinking water, and diarrheal diseases cause an estimated 1.87 million deaths per year. Sodium dichloroisocyanurate (NaDCC) tablets are widely recommended for household water treatment to reduce diarrhea. Because NaDCC is directly added to untreated water sources, concerns have been raised about the potential health impact of disinfection by-products. This study investigated trihalomethane (THM) production in water from six sources used for drinking (0.6–888.5 nephelometric turbidity units) near Arusha, Tanzania. No sample collected at 1, 8, and 24 hours after NaDCC addition exceeded the World Health Organization guideline values for either individual or total THMs. Ceramic filtration, sand filtration, cloth filtration, and settling and decanting were not effective mitigation strategies to reduce THM formation. Chlorine residual and THM formation were not significantly different in NaDCC and sodium hypochlorite treatment. Household chlorination of turbid and non-turbid waters did not create THM concentrations that exceeded health risk guidelines. PMID:20595492

GTC and Swift observations of SN 2017dcc: Revised redshift & X-ray upper limit

NASA Astrophysics Data System (ADS)

Kann, D. A.; Izzo, L.; Cano, Z.; Postigo, A. de Ugarte; Thoene, C. C.; Schulze, S.

2017-04-01

We obtained observations of the broad-lined type Ic SN 2017dcc (Guiterrez et al., ATel #10313) with the 10.4m GTC on La Palma, Canary Islands, Spain, as well as with XRT and UVOT on the Swift space telescope.

Optimization of a Deep Convective Cloud Technique in Evaluating the Long-Term Radiometric Stability of MODIS Reflective Solar Bands

NASA Technical Reports Server (NTRS)

Mu, Qiaozhen; Wu, Aisheng; Xiong, Xiaoxiong; Doelling, David R.; Angal, Amit; Chang, Tiejun; Bhatt, Rajendra

2017-01-01

MODIS reflective solar bands are calibrated on-orbit using a solar diffuser and near-monthly lunar observations. To monitor the performance and effectiveness of the on-orbit calibrations, pseudo-invariant targets such as deep convective clouds (DCCs), Libya-4, and Dome-C are used to track the long-term stability of MODIS Level 1B product. However, the current MODIS operational DCC technique (DCCT) simply uses the criteria set for the 0.65- m band. We optimize several critical DCCT parameters including the 11- micrometer IR-band Brightness Temperature (BT11) threshold for DCC identification, DCC core size and uniformity to help locate DCCs at convection centers, data collection time interval, and probability distribution function (PDF) bin increment for each channel. The mode reflectances corresponding to the PDF peaks are utilized as the DCC reflectances. Results show that the BT11 threshold and time interval are most critical for the Short Wave Infrared (SWIR) bands. The Bidirectional Reflectance Distribution Function model is most effective in reducing the DCC anisotropy for the visible channels. The uniformity filters and PDF bin size have minimal impacts on the visible channels and a larger impact on the SWIR bands. The newly optimized DCCT will be used for future evaluation of MODIS on-orbit calibration by MODIS Characterization Support Team.

A Multiple Ejecta-circumstellar Medium Interaction Model and Its Implications for Superluminous Supernovae iPTF15esb and iPTF13dcc

NASA Astrophysics Data System (ADS)

Liu, Liang-Duan; Wang, Ling-Jun; Wang, Shan-Qin; Dai, Zi-Gao

2018-03-01

In this paper, we investigate two hydrogen-poor superluminous supernovae (SLSNe), iPTF15esb and iPTF13dcc, whose light curves (LCs) show significant deviation from the smooth rise and fall. The LC of iPTF15esb exhibits two peaks and a post-peak plateau, and furthermore the late-time spectrum of iPTF15esb shows a strong, broad Hα emission line. The early-time LC of iPTF13dcc shows a long-duration bump followed by the second peak. Here, we propose an ejecta-circumstellar medium interaction model involving multiple shells/winds and use it to explain the LCs of iPTF15esb and iPTF13dcc. We find that the theoretical LCs reproduced by this model can match observations of iPTF15esb and iPTF13dcc. Based on our results, we infer that the progenitors have undergone multiple violent mass-loss processes before the SN explosion. In addition, we find that the variation trend of our inferred densities of the shells is consistent with that predicted by the stellar mass-loss history before an SN explosion. Further investigations for other bumpy SLSNe/SNe would shed light on their nature and provide a probe for the mass-loss history of their progenitors.

Growth phase-dependent activation of the DccRS regulon of Campylobacter jejuni

USDA-ARS?s Scientific Manuscript database

Two-component systems are widespread prokaryotic signal transduction devices which allow the regulation of cellular functions in response to changing environmental conditions. The two-component system DccRS (Cj1223-Cj1222) of Campylobacter jejuni is important for the colonization of chickens. Here w...

Marketing Segmentation Analysis.

ERIC Educational Resources Information Center

Weeks, Ann A.

A study was conducted to differentiate by cities and towns the various demographic characteristics of students that Dutchess Community College (DCC) was receiving from its major service area, Dutchess County, in order to ascertain if DCC was receiving its expected share of students from these cities and towns. All the students enrolling at DCC…

Pervasive and largely lineage-specific adaptive protein evolution in the dosage compensation complex of Drosophila melanogaster.

PubMed

Levine, Mia T; Holloway, Alisha K; Arshad, Umbreen; Begun, David J

2007-11-01

Dosage compensation refers to the equalization of X-linked gene transcription among heterogametic and homogametic sexes. In Drosophila, the dosage compensation complex (DCC) mediates the twofold hypertranscription of the single male X chromosome. Loss-of-function mutations at any DCC protein-coding gene are male lethal. Here we report a population genetic analysis suggesting that four of the five core DCC proteins--MSL1, MSL2, MSL3, and MOF--are evolving under positive selection in D. melanogaster. Within these four proteins, several domains that range in function from X chromosome localization to protein-protein interactions have elevated, D. melanogaster-specific, amino acid divergence.

Alumni Survey, 1973-1983.

ERIC Educational Resources Information Center

Weeks, Ann A.; Sillin, Andrew

A study was conducted at Dutchess Community College (DCC) to provide a broad picture of the further education and employment status of DCC alumni several years after graduation and to determine how satisfied alumni were with the education and services provided by the college. Survey questionnaires were mailed to a random sample of 20% of DCC…

Compliant Buckled Foam Actuators and Application in Patient-Specific Direct Cardiac Compression.

PubMed

Mac Murray, Benjamin C; Futran, Chaim C; Lee, Jeanne; O'Brien, Kevin W; Amiri Moghadam, Amir A; Mosadegh, Bobak; Silberstein, Meredith N; Min, James K; Shepherd, Robert F

2018-02-01

We introduce the use of buckled foam for soft pneumatic actuators. A moderate amount of residual compressive strain within elastomer foam increases the applied force ∼1.4 × or stroke ∼2 × compared with actuators without residual strain. The origin of these improved characteristics is explained analytically. These actuators are applied in a direct cardiac compression (DCC) device design, a type of implanted mechanical circulatory support that avoids direct blood contact, mitigating risks of clot formation and stroke. This article describes a first step toward a pneumatically powered, patient-specific DCC design by employing elastomer foam as the mechanism for cardiac compression. To form the device, a mold of a patient's heart was obtained by 3D printing a digitized X-ray computed tomography or magnetic resonance imaging scan into a solid model. From this model, a soft, robotic foam DCC device was molded. The DCC device is compliant and uses compressed air to inflate foam chambers that in turn apply compression to the exterior of a heart. The device is demonstrated on a porcine heart and is capable of assisting heart pumping at physiologically relevant durations (∼200 ms for systole and ∼400 ms for diastole) and stroke volumes (∼70 mL). Although further development is necessary to produce a fully implantable device, the material and processing insights presented here are essential to the implementation of a foam-based, patient-specific DCC design.

The Fat-like Cadherin CDH-4 Acts Cell-Non-Autonomously in Anterior-Posterior Neuroblast Migration

PubMed Central

Sundararajan, Lakshmi; Norris, Megan L.; Schöneich, Sebastian; Ackley, Brian D.; Lundquist, Erik A.

2014-01-01

Directed migration of neurons is critical in the normal and pathological development of the brain and central nervous system. In C. elegans, the bilateral Q neuroblasts, QR on the right and QL on the left, migrate anteriorly and posteriorly, respectively. Initial protrusion and migration of the Q neuroblasts is autonomously controlled by the transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21. As QL migrates posteriorly, it encounters and EGL-20/Wnt signal that induces MAB-5/Hox expression that drives QL descendant posterior migration. QR migrates anteriorly away from EGL-20/Wnt and does not activate MAB-5/Hox, resulting in anterior QR descendant migration. A forward genetic screen for new mutations affecting initial Q migrations identified alleles of cdh-4, which caused defects in both QL and QR directional migration similar to unc-40, ptp-3, and mig-21. Previous studies showed that in QL, PTP-3/LAR and MIG-21 act in a pathway in parallel to UNC-40/DCC to drive posterior QL migration. Here we show genetic evidence that CDH-4 acts in the PTP-3/MIG-21 pathway in parallel to UNC-40/DCC to direct posterior QL migration. In QR, the PTP-3/MIG-21 and UNC-40/DCC pathways mutually inhibit each other, allowing anterior QR migration. We report here that CDH-4 acts in both the PTP-3/MIG-21 and UNC-40/DCC pathways in mutual inhibition in QR, and that CDH-4 acts cell-non-autonomously. Interaction of CDH-4 with UNC-40/DCC in QR but not QL represents an inherent left-right asymmetry in the Q cells, the nature of which is not understood. We conclude that CDH-4 might act as a permissive signal for each Q neuroblast to respond differently to anterior-posterior guidance information based upon inherent left-right asymmetries in the Q neuroblasts. PMID:24954154

Estimating effective particle size of tropical deep convective clouds with a look-up table method using satellite measurements of brightness temperature differences

NASA Astrophysics Data System (ADS)

Hong, Gang; Minnis, Patrick; Doelling, David; Ayers, J. Kirk; Sun-Mack, Szedung

2012-03-01

A method for estimating effective ice particle radius Re at the tops of tropical deep convective clouds (DCC) is developed on the basis of precomputed look-up tables (LUTs) of brightness temperature differences (BTDs) between the 3.7 and 11.0 μm bands. A combination of discrete ordinates radiative transfer and correlated k distribution programs, which account for the multiple scattering and monochromatic molecular absorption in the atmosphere, is utilized to compute the LUTs as functions of solar zenith angle, satellite zenith angle, relative azimuth angle, Re, cloud top temperature (CTT), and cloud visible optical thickness τ. The LUT-estimated DCC Re agrees well with the cloud retrievals of the Moderate Resolution Imaging Spectroradiometer (MODIS) for the NASA Clouds and Earth's Radiant Energy System with a correlation coefficient of 0.988 and differences of less than 10%. The LUTs are applied to 1 year of measurements taken from MODIS aboard Aqua in 2007 to estimate DCC Re and are compared to a similar quantity from CloudSat over the region bounded by 140°E, 180°E, 0°N, and 20°N in the Western Pacific Warm Pool. The estimated DCC Re values are mainly concentrated in the range of 25-45 μm and decrease with CTT. Matching the LUT-estimated Re with ice cloud Re retrieved by CloudSat, it is found that the ice cloud τ values from DCC top to the vertical location where LUT-estimated Re is located at the CloudSat-retrieved Re profile are mostly less than 2.5 with a mean value of about 1.3. Changes in the DCC τ can result in differences of less than 10% for Re estimated from LUTs. The LUTs of 0.65 μm bidirectional reflectance distribution function (BRDF) are built as functions of viewing geometry and column amount of ozone above upper troposphere. The 0.65 μm BRDF can eliminate some noncore portions of the DCCs detected using only 11 μm brightness temperature thresholds, which result in a mean difference of only 0.6 μm for DCC Re estimated from BTD LUTs.

DARPA Improving Warfighter Information Intake Under Stress -- Augmented Cognition. Volume 1. Phase 2: Concept Validation Experiment

DTIC Science & Technology

2006-09-01

trademark of the Boeing Company. Mercedes - Benz ® is a registered trademark of DaimlerChrysler AG Corporation. Released by R. J. Smillie, Head...Team DCC CLIP architecture. 2.2.4 Methodology The test conditions for the DCC team consisted of an instrumented Mercedes Benz ® S class vehicle

Heat Transfer Analysis of an Optimized, Flexible Holder System for Freeze-Drying in Dual Chamber Cartridges Using Different State-of-the-Art PAT Tools.

PubMed

Korpus, Christoph; Pikal, Michael; Friess, Wolfgang

2016-11-01

The aim of this study was to determine the heat transfer characteristics of an optimized flexible holder device, using Tunable Diode Laser Absorption Spectroscopy, the Pressure Rise Test, and the gravimetric procedure. Two different controlled nucleation methods were tested, and an improved sublimation process, "preheated plate," was developed. Tunable Diode Laser Absorption Spectroscopy identified an initial sublimation burst phase. Accordingly, steady-state equations were adapted for the gravimetric procedure, to account for this initial non-steady-state period. The heat transfer coefficient, K DCC , describing the transfer from the holder to the DCC, was the only heat transfer coefficient showing a clear pressure dependence with values ranging from 3.81E-04 cal/(g·cm 2 ·K) at 40 mTorr to 7.38E-04 cal/(g·cm 2 ·K) at 200 mTorr. The heat transfer coefficient, K tot , reflecting the overall energy transfer via the holder, increased by around 24% from 40 to 200 mTorr. This resulted in a pressure-independent sublimation rate of around 42 ± 1.06 mg/h over the whole pressure range. Hence, this pressure-dependent increase in energy transfer completely compensated the decrease in driving force of sublimation. The "flexible holder" shows a substantially reduced impact of atypical radiation, improved drying homogeneity, and ultimately a better transferability of the freeze-drying cycle for process optimization. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

RESRAD for Radiological Risk Assessment. Comparison with EPA CERCLA Tools - PRG and DCC Calculators

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

Yu, C.; Cheng, J. -J.; Kamboj, S.

The purpose of this report is two-fold. First, the risk assessment methodology for both RESRAD and the EPA’s tools is reviewed. This includes a review of the EPA’s justification for 2 using a dose-to-risk conversion factor to reduce the dose-based protective ARAR from 15 to 12 mrem/yr. Second, the models and parameters used in RESRAD and the EPA PRG and DCC Calculators are compared in detail, and the results are summarized and discussed. Although there are suites of software tools in the RESRAD family of codes and the EPA Calculators, the scope of this report is limited to the RESRADmore » (onsite) code for soil contamination and the EPA’s PRG and DCC Calculators also for soil contamination.« less

The first new application of the mathematical theory of stochastic processes to lunar and planetary science: topography profile diagrams of Mars

NASA Astrophysics Data System (ADS)

Salamuniccar, G.

The Mathematical Statistics Theory (MST) and the Mathematical Theory of Stochastic Processes (MTSP) are different branches of the more general Mathematical Probability Theory (MPT) that represents different aspects of some physical processes we can analyze using mathematics. Each model of a stochastic process according to MTSP can provide one or more interpretations in MST domain. Large body of work on the impact crater statistics according to MST was already done many years ago, for e.g., where Cratering Chronology Diagrams (CCD) were shown in log/log scale, showing Cum. Crater Frequency [N km-2] that is the function of Age [years] for some particular crater diameter. However, all this is only one possible representation in MST domain, of the bombardment of the planetary surface modeled as stochastic process according to MTSP. The idea that other representations in MST domain of the same stochastic process from MTSP are possible was recently presented [G. Salamuniæcar, Adv. Space Res. in press]. The importance of the approach is that each such interpretation can provide large amount of new information. Topography Profile Diagrams (TPDs) are one example, that with MOLA data provide us with large amount of new information regarding history of Mars. TPDs consists of [34thLPS #1403]: (1) Topography-Profile Curve (TPC) that is representation of the planet topography, (2) Density-of-Craters Curve (DCC) that represents density of craters, (3) Filtered-DCC (FDCC) that represents DCC filtered by a low-pass filter included with the purpose of reducing the noise and (4) Level-of-Substance-Over-Time Curve (LSOTC). While definition of TPC uniquely corresponds to way we will compute it, the same is not also the case with DCC and FDCC. While DCC depends on algorithms for computing crater altitude according to the topography, center coordinates and radius of impact crater [34thLPS #1409], FDCC depends on the architecture of the custom designed low-pass filter for filtering DCC [34thLPS #1415]. However all variations of DCC and FDCC including the different input craters data-sets confirmed correlation between density of craters and topographic altitude over 70˜ 80% of the planet surface. For the assumption that ocean primarily caused noted correlation, LSOTC additionally for the first time offers mathematical approach how to compute how level of ocean was changing over time [6thMars #3187]. Accordingly, conclusion is that TPDs are the first new practical application of MTSP to the Lunar and Planetary Science (LPS).

On the Early-Time Excess Emission in Hydrogen-Poor Superluminous Supernovae

NASA Technical Reports Server (NTRS)

Vreeswijk, Paul M.; Leloudas, Giorgos; Gal-Yam, Avishay; De Cia, Annalisa; Perley, Daniel A.; Quimby, Robert M.; Waldman, Roni; Sullivan, Mark; Yan, Lin; Ofek, Eran O.;

On The Early-Time Excess Emission In Hydrogen-Poor Superluminous Supernovae

DOE PAGES

Vreeswijk, Paul M.; Leloudas, Giorgos; Gal-Yam, Avishay; ...

2017-01-18

Here, we present the light curves of the hydrogen-poor superluminous supernovae (SLSNe I) PTF 12dam and iPTF 13dcc, discovered by the (intermediate) Palomar Transient Factory. Both show excess emission at early times and a slowly declining light curve at late times. The early bump in PTF 12dam is very similar in duration (~10 days) and brightness relative to the main peak (2-3 mag fainter) compared to that observed in other SLSNe I. In contrast, the long-duration ( > 30 days) early excess emission in iPTF 13dcc, whose brightness competes with that of the main peak, appears to be of amore » different nature. We construct bolometric light curves for both targets, and fit a variety of light-curve models to both the early bump and main peak in an attempt to understand the nature of these explosions. Even though the slope of the late-time decline in the light curves of both SLSNe is suggestively close to that expected from the radioactive decay of 56Ni and 56Co, the amount of nickel required to power the full light curves is too large considering the estimated ejecta mass. The magnetar model including an increasing escape fraction provides a reasonable description of the PTF 12dam observations. However, neither the basic nor the double-peaked magnetar model is capable of reproducing the light curve of iPTF 13dcc. A model combining a shock breakout in an extended envelope with late-time magnetar energy injection provides a reasonable fit to the iPTF 13dcc observations. Finally, we find that the light curves of both PTF 12dam and iPTF 13dcc can be adequately fit with the model involving interaction with the circumstellar medium.« less

Dual-mode antenna design for microwave heating and noninvasive thermometry of superficial tissue disease.

PubMed

Jacobsen, S; Stauffer, P R; Neuman, D G

2000-11-01

Hyperthermia therapy of superficial skin disease has proven clinically useful, but current heating equipment is somewhat clumsy and technically inadequate for many patients. The present effort describes a dual-purpose, conformal microwave applicator that is fabricated from thin, flexible, multilayer printed circuit board (PCB) material to facilitate heating of surface areas overlaying contoured anatomy. Preliminary studies document the feasibility of combining Archimedean spiral microstrip antennas, located concentrically within the central region of square dual concentric conductor (DCC) annular slot antennas. The motivation is to achieve homogeneous tissue heating simultaneously with noninvasive thermometry by radiometric sensing of blackbody radiation from the target tissue under the applicator. Results demonstrate that the two antennas have complimentary regions of influence. The DCC ring antenna structure produces a peripherally enhanced power deposition pattern with peaks in the outer corners of the aperture and a broad minimum around 50% of maximum centrally. In contrast, the Archimedean spiral radiates (or receives) energy predominantly along the boresight axis of the spiral, thus confining the region of influence to tissue located within the central broad minimum of the DCC pattern. Analysis of the temperature-dependent radiometer signal (brightness temperature) showed linear correlation of radiometer output with test load temperature using either the spiral or DCC structure as the receive antenna. The radiometric performance of the broadband Archimedean antenna was superior compared to the DCC, providing improved temperature resolution (0.1 degree C-0.2 degree C) and signal sensitivity (0.3 degree C-0.8 degree C/degree C) at all four 500 MHz integration bandwidths tested within the frequency range from 1.2 to 3.0 GHz.

ON THE EARLY-TIME EXCESS EMISSION IN HYDROGEN-POOR SUPERLUMINOUS SUPERNOVAE

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

Vreeswijk, Paul M.; Leloudas, Giorgos; Gal-Yam, Avishay

2017-01-20

We present the light curves of the hydrogen-poor superluminous supernovae (SLSNe I) PTF 12dam and iPTF 13dcc, discovered by the (intermediate) Palomar Transient Factory. Both show excess emission at early times and a slowly declining light curve at late times. The early bump in PTF 12dam is very similar in duration (∼10 days) and brightness relative to the main peak (2–3 mag fainter) compared to that observed in other SLSNe I. In contrast, the long-duration (>30 days) early excess emission in iPTF 13dcc, whose brightness competes with that of the main peak, appears to be of a different nature. Wemore » construct bolometric light curves for both targets, and fit a variety of light-curve models to both the early bump and main peak in an attempt to understand the nature of these explosions. Even though the slope of the late-time decline in the light curves of both SLSNe is suggestively close to that expected from the radioactive decay of {sup 56}Ni and {sup 56}Co, the amount of nickel required to power the full light curves is too large considering the estimated ejecta mass. The magnetar model including an increasing escape fraction provides a reasonable description of the PTF 12dam observations. However, neither the basic nor the double-peaked magnetar model is capable of reproducing the light curve of iPTF 13dcc. A model combining a shock breakout in an extended envelope with late-time magnetar energy injection provides a reasonable fit to the iPTF 13dcc observations. Finally, we find that the light curves of both PTF 12dam and iPTF 13dcc can be adequately fit with the model involving interaction with the circumstellar medium.« less

Presence of Pathogenic Bacteria and Viruses in the Daycare Environment.

PubMed

Ibfelt, Tobias; Engelund, Eva Hoy; Permin, Anders; Madsen, Jonas Stenløkke; Schultz, Anna Charlotte; Andersen, Leif Percival

2015-10-01

The number of children in daycare centers (DCCs) is rising. This increases exposure to microorganisms and infectious diseases. Little is known about which bacteria and viruses are present in the DCC environment and where they are located. In the study described in this article, the authors set out to determine the prevalence of pathogenic bacteria and viruses and to find the most contaminated fomites in DCCs. Fifteen locations in each DCC were sampled for bacteria, respiratory viruses, and gastrointestinal viruses. The locations were in the toilet, kitchen, and playroom areas and included nursery pillows, toys, and tables, among other things. Coliform bacteria were primarily found in the toilet and kitchen areas whereas nasopharyngeal bacteria were found mostly on toys and fabric surfaces in the playroom. Respiratory viruses were omnipresent in the DCC environment, especially on the toys.

Mechanical gating of a mechanochemical reaction cascade

NASA Astrophysics Data System (ADS)

Wang, Junpeng; Kouznetsova, Tatiana B.; Boulatov, Roman; Craig, Stephen L.

2016-11-01

Covalent polymer mechanochemistry offers promising opportunities for the control and engineering of reactivity. To date, covalent mechanochemistry has largely been limited to individual reactions, but it also presents potential for intricate reaction systems and feedback loops. Here we report a molecular architecture, in which a cyclobutane mechanophore functions as a gate to regulate the activation of a second mechanophore, dichlorocyclopropane, resulting in a mechanochemical cascade reaction. Single-molecule force spectroscopy, pulsed ultrasonication experiments and DFT-level calculations support gating and indicate that extra force of >0.5 nN needs to be applied to a polymer of gated gDCC than of free gDCC for the mechanochemical isomerization gDCC to proceed at equal rate. The gating concept provides a mechanism by which to regulate stress-responsive behaviours, such as load-strengthening and mechanochromism, in future materials designs.

Three-Dimensional Color Code Thresholds via Statistical-Mechanical Mapping

NASA Astrophysics Data System (ADS)

Kubica, Aleksander; Beverland, Michael E.; Brandão, Fernando; Preskill, John; Svore, Krysta M.

2018-05-01

Three-dimensional (3D) color codes have advantages for fault-tolerant quantum computing, such as protected quantum gates with relatively low overhead and robustness against imperfect measurement of error syndromes. Here we investigate the storage threshold error rates for bit-flip and phase-flip noise in the 3D color code (3DCC) on the body-centered cubic lattice, assuming perfect syndrome measurements. In particular, by exploiting a connection between error correction and statistical mechanics, we estimate the threshold for 1D stringlike and 2D sheetlike logical operators to be p3DCC (1 )≃1.9 % and p3DCC (2 )≃27.6 % . We obtain these results by using parallel tempering Monte Carlo simulations to study the disorder-temperature phase diagrams of two new 3D statistical-mechanical models: the four- and six-body random coupling Ising models.

Exploring the formation pathways of donor-acceptor catenanes in aqueous dynamic combinatorial libraries.

PubMed

Cougnon, Fabien B L; Au-Yeung, Ho Yu; Pantoş, G Dan; Sanders, Jeremy K M

2011-03-09

The discovery through dynamic combinatorial chemistry (DCC) of a new generation of donor-acceptor [2]catenanes highlights the power of DCC to access unprecedented structures. While conventional thinking has limited the scope of donor-acceptor catenanes to strictly alternating stacks of donor (D) and acceptor (A) aromatic units, DCC is demonstrated in this paper to give access to unusual DAAD, DADD, and ADAA stacks. Each of these catenanes has specific structural requirements, allowing control of their formation. On the basis of these results, and on the observation that the catenanes represent kinetic bottlenecks in the reaction pathway, we propose a mechanism that explains and predicts the structures formed. Furthermore, the spontaneous assembly of catenanes in aqueous dynamic systems gives a fundamental insight into the role played by hydrophobic effect and donor-acceptor interactions when building such complex architectures.

Target Detection and Identification Using Canonical Correlations Analysis and Subspace Partitioning

DTIC Science & Technology

2008-04-01

Fig. 2. ROCs for DCC, DCC-P, NNLS, and NNLSP (Present chemical=t1, background= t56 , SNR= 5 dB) alarm, or 1−specificity, and PD is the probability of...discrimination values are given in each ROC plot. In Fig. 2, we use t56 as the background, and t1 as the target chemical. The SNR is 5 dB. For each

NEURAL NETWORK MODELLING OF CARDIAC DOSE CONVERSION COEFFICIENT FOR ARBITRARY X-RAY SPECTRA.

PubMed

Kadri, O; Manai, K

2016-12-01

In this article, an approach to compute the dose conversion coefficients (DCCs) is described for the computational voxel phantom 'High-Definition Reference Korean-Man' (HDRK-Man) using artificial neural networks (ANN). For this purpose, the voxel phantom was implemented into the Monte Carlo (MC) transport toolkit GEANT4, and the DCCs for more than 30 tissues and organs, due to a broad parallel beam of monoenergetic photons with energy ranging from 15 to 150 keV by a step of 5 keV, were calculated. To study the influence of patient size on DCC values, DCC calculation was performed, for a representative body size population, using five different sizes covering the range of 80-120 % magnification of the original HDRK-Man. The focus of the present study was on the computation of DCC for the human heart. ANN calculation and MC simulation results were compared, and good agreement was observed showing that ANNs can be used as an efficient tool for modelling DCCs for the computational voxel phantom. ANN approach appears to be a significant advance over the time-consuming MC methods for DCC calculation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Product Distribution from Precursor Bite Angle Variation in Multitopic Alkyne Metathesis: Evidence for a Putative Kinetic Bottleneck.

PubMed

Moneypenny, Timothy P; Yang, Anna; Walter, Nathan P; Woods, Toby J; Gray, Danielle L; Zhang, Yang; Moore, Jeffrey S

2018-05-02

In the dynamic synthesis of covalent organic frameworks and molecular cages, the typical synthetic approach involves heuristic methods of discovery. While this approach has yielded many remarkable products, the ability to predict the structural outcome of subjecting a multitopic precursor to dynamic covalent chemistry (DCC) remains a challenge in the field. The synthesis of covalent organic cages is a prime example of this phenomenon, where precursors designed with the intention of affording a specific product may deviate dramatically when the DCC synthesis is attempted. As such, rational design principles are needed to accelerate discovery in cage synthesis using DCC. Herein, we test the hypothesis that precursor bite angle contributes significantly to the energy landscape and product distribution in multitopic alkyne metathesis (AM). By subjecting a series of precursors with varying bite angles to AM, we experimentally demonstrate that the product distribution, and convergence toward product formation, is strongly dependent on this geometric attribute. Surprisingly, we discovered that precursors with the ideal bite angle (60°) do not afford the most efficient pathway to the product. The systematic study reported here illustrates how seemingly minor adjustments in precursor geometry greatly affect the outcome of DCC systems. This research illustrates the importance of fine-tuning precursor geometric parameters in order to successfully realize desirable targets.

Netrin-1 controls sympathetic arterial innervation.

PubMed

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J C; Kennedy, Timothy E; Zhuang, Zhen; Simons, Michael; Levy, Bernard I; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-07-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

Netrin-1 controls sympathetic arterial innervation

PubMed Central

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J.C.; Kennedy, Timothy E.; Zhuang, Zhen; Simons, Michael; Levy, Bernard I.; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-01-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type–specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs. PMID:24937433

Three-Dimensional Color Code Thresholds via Statistical-Mechanical Mapping.

PubMed

Kubica, Aleksander; Beverland, Michael E; Brandão, Fernando; Preskill, John; Svore, Krysta M

2018-05-04

Three-dimensional (3D) color codes have advantages for fault-tolerant quantum computing, such as protected quantum gates with relatively low overhead and robustness against imperfect measurement of error syndromes. Here we investigate the storage threshold error rates for bit-flip and phase-flip noise in the 3D color code (3DCC) on the body-centered cubic lattice, assuming perfect syndrome measurements. In particular, by exploiting a connection between error correction and statistical mechanics, we estimate the threshold for 1D stringlike and 2D sheetlike logical operators to be p_{3DCC}^{(1)}≃1.9% and p_{3DCC}^{(2)}≃27.6%. We obtain these results by using parallel tempering Monte Carlo simulations to study the disorder-temperature phase diagrams of two new 3D statistical-mechanical models: the four- and six-body random coupling Ising models.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

PubMed

Ahmed, Aijaz; Gonzalez, Stevan A; Cholankeril, George; Perumpail, Ryan B; McGinnis, Justin; Saab, Sammy; Beckerman, Rachel; Younossi, Zobair M

2017-07-01

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56). © 2017 by the American Association for the Study of Liver Diseases.

Distinct Impacts of Aerosols on an Evolving Continental Cloud Complex during the RACORO Field Campaign

DOE PAGES

Lin, Yun; Wang, Yuan; Pan, Bowen; ...

2016-08-26

In this study, a continental cloud complex, consisting of shallow cumuli, a deep convective cloud (DCC), and stratus, is simulated by a cloud-resolving Weather Research and Forecasting Model to investigate the aerosol microphysical effect (AME) and aerosol radiative effect (ARE) on the various cloud regimes and their transitions during the Department of Energy Routine Atmospheric Radiation Measurement Aerial Facility Clouds with Low Optical Water Depths Optical Radiative Observations (RACORO) campaign. Under an elevated aerosol loading with AME only, a reduced cloudiness for the shallow cumuli and stratus resulted from more droplet evaporation competing with suppressed precipitation, but an enhanced cloudinessmore » for the DCC is attributed to more condensation. With the inclusion of ARE, the shallow cumuli are suppressed owing to the thermodynamic effects of light-absorbing aerosols. The responses of DCC and stratus to aerosols are monotonic with AME only but nonmonotonic with both AME and ARE. The DCC is invigorated because of favorable convection and moisture conditions at night induced by daytime ARE, via the so-called aerosol-enhanced conditional instability mechanism. Finally, the results reveal that the overall aerosol effects on the cloud complex are distinct from the individual cloud types, highlighting that the aerosol–cloud interactions for diverse cloud regimes and their transitions need to be evaluated to assess the regional and global climatic impacts.« less

SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

PubMed

Hitz, Benjamin C; Rowe, Laurence D; Podduturi, Nikhil R; Glick, David I; Baymuradov, Ulugbek K; Malladi, Venkat S; Chan, Esther T; Davidson, Jean M; Gabdank, Idan; Narayana, Aditi K; Onate, Kathrina C; Hilton, Jason; Ho, Marcus C; Lee, Brian T; Miyasato, Stuart R; Dreszer, Timothy R; Sloan, Cricket A; Strattan, J Seth; Tanaka, Forrest Y; Hong, Eurie L; Cherry, J Michael

2017-01-01

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package.

SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata

PubMed Central

Podduturi, Nikhil R.; Glick, David I.; Baymuradov, Ulugbek K.; Malladi, Venkat S.; Chan, Esther T.; Davidson, Jean M.; Gabdank, Idan; Narayana, Aditi K.; Onate, Kathrina C.; Hilton, Jason; Ho, Marcus C.; Lee, Brian T.; Miyasato, Stuart R.; Dreszer, Timothy R.; Sloan, Cricket A.; Strattan, J. Seth; Tanaka, Forrest Y.; Hong, Eurie L.; Cherry, J. Michael

2017-01-01

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package. PMID:28403240

Piezoelectric ceramic (PZT) modulates axonal guidance growth of rat cortical neurons via RhoA, Rac1, and Cdc42 pathways.

PubMed

Wen, Jianqiang; Liu, Meili

2014-03-01

Electrical stimulation is critical for axonal connection, which can stimulate axonal migration and deformation to promote axonal growth in the nervous system. Netrin-1, an axonal guidance cue, can also promote axonal guidance growth, but the molecular mechanism of axonal guidance growth under indirect electric stimulation is still unknown. We investigated the molecular mechanism of axonal guidance growth under piezoelectric ceramic lead zirconate titanate (PZT) stimulation in the primary cultured cortical neurons. PZT induced marked axonal elongation. Moreover, PZT activated the excitatory postsynaptic currents (EPSCs) by increasing the frequency and amplitude of EPSCs of the cortical neurons in patch clamp assay. PZT downregulated the expression of Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC). Rho GTPase signaling is involved in interactions of Netrin-1 and DCC. PZT activated RhoA. Dramatic decrease of Cdc42 and Rac1 was also observed after PZT treatment. RhoA inhibitor Clostridium botulinum C3 exoenzyme (C3-Exo) prevented the PZT-induced downregulation of Netrin-1 and DCC. We suggest that PZT can promote axonal guidance growth by downregulation of Netrin-1 and DCC to mediate axonal repulsive responses via the Rho GTPase signaling pathway. Obviously, piezoelectric materials may provide a new approach for axonal recovery and be beneficial for clinical therapy in the future.

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

Goven, A.J.; Fitzpatrick, L.C.; Eyambe, G.S.

Acute toxicity in earthworms (Lumbricus terrestris) was assayed immediately after 5-d filter paper exposure to the polychlorinated biphenyl (PCB) Aroclor 1254, using coelomocyte viability, total extruded cell counts (ECC), differential cell counts (DCC), and formation of erythrocyte (ER) and secretory rosettes (SR) with, and phagocytosis of, antigenic rabbit red blood cells (RRBC). Chronic toxicity was assayed using rates by which earthworms replaced viable immunoactive coelomocytes, removed noninvasively immediately after exposure, over an 18-week depuration period. All cytological parameters, except ECC, were acutely affected immediately after exposure, when tissue concentrations were ([anti X] [plus minus] SE) 91.2 [plus minus] 8.19 [mu]gmore » PCB per gram dry mass. Replacement of viable immunoactive coelomocytes occurred within six weeks in unexposed control earthworms. Exposed earthworms showed significant alteration in viability, ECC, DCC, ER, and SR formation, and phagocytosis at 6 and 12 weeks when PCB tissue concentrations were 41 [plus minus] 0.31 and 30.2 [plus minus] 0.88 [mu]g/g dry mass, respectively. Replacement of extruded coelomocytes with normal DCC of viable immunocompetent cells was not observed until week 18, when PCB had decreased to 15.7 [plus minus] 0.83 [mu]g/g dry mass. Low inherent natural variability in coelomocyte viability, ECC, DCC, rosette formation, and phagocytosis, and their sensitivity to sublethal PCB body burdens, indicated that earthworm coelomocytes have potential as nonmammalian biomarkers for assaying acute and chronic sublethal toxicity of xenobiotics.« less

Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster

PubMed Central

Schunter, Sarah; Villa, Raffaella; Flynn, Victoria; Heidelberger, Jan B.; Classen, Anne-Kathrin; Beli, Petra; Becker, Peter B.

2017-01-01

The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the ‘Non-Specific-Lethal’ (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF’s overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies. PMID:28510597

Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.

PubMed

Schunter, Sarah; Villa, Raffaella; Flynn, Victoria; Heidelberger, Jan B; Classen, Anne-Kathrin; Beli, Petra; Becker, Peter B

2017-01-01

The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies.

Role of the DIP Molecules in DCC Signaling

DTIC Science & Technology

1999-09-01

to policies of applicable Federal Law 45 CFR 46. N/A In conducting research utilizing recombinant DNA technology , the investigator(s) adhered to...for 1 h, then with 0.1 mg/ml of proteinase K, 0.1% SDS at 50’C Ihle, 1995; Fraser and Evan, 1996). These molecules overnight. Samples were extracted ...incubated with 20 yg/ml of anti-DCC antibody diluted in PBS-0.1% saponin for 1 h, washed with PBS, blocked Western blotting with 5% normal donkey serum for 1

Modelling of volatility in monetary transmission mechanism

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

Dobešová, Anna; Klepáč, Václav; Kolman, Pavel

2015-03-10

The aim of this paper is to compare different approaches to modeling of volatility in monetary transmission mechanism. For this purpose we built time-varying parameter VAR (TVP-VAR) model with stochastic volatility and VAR-DCC-GARCH model with conditional variance. The data from three European countries are included in the analysis: the Czech Republic, Germany and Slovakia. Results show that VAR-DCC-GARCH system captures higher volatility of observed variables but main trends and detected breaks are generally identical in both approaches.

A dehydrogenative cross-coupling reaction between aromatic aldehydes or ketones and dialkyl H-phosphonates for formyl or acylphenylphosphonates.

PubMed

Huang, Xing-Fen; Wu, Qing-Lai; He, Jian-Shi; Huang, Zhi-Zhen

2015-04-21

A novel DCC reaction between aromatic aldehydes or ketones and H-phosphonates has been developed for the synthesis of p-formyl or p-acylphenylphosphonates. The synthetic method has excellent para regioselectivities, good yields, and broad substrate scopes and is more benign to the environment. The DCC reaction also tolerates many functional groups, and results in a series of new p-formyl and p-acylphenylphosphonates, which should be important building blocks for the synthesis of versatile arylphosphonate derivatives.

Investigation of High-Level Synthesis tools’ applicability to data acquisition systems design based on the CMS ECAL Data Concentrator Card example

NASA Astrophysics Data System (ADS)

HUSEJKO, Michal; EVANS, John; RASTEIRO DA SILVA, Jose Carlos

2015-12-01

High-Level Synthesis (HLS) for Field-Programmable Logic Array (FPGA) programming is becoming a practical alternative to well-established VHDL and Verilog languages. This paper describes a case study in the use of HLS tools to design FPGA-based data acquisition systems (DAQ). We will present the implementation of the CERN CMS detector ECAL Data Concentrator Card (DCC) functionality in HLS and lessons learned from using HLS design flow. The DCC functionality and a definition of the initial system-level performance requirements (latency, bandwidth, and throughput) will be presented. We will describe how its packet processing control centric algorithm was implemented with VHDL and Verilog languages. We will then show how the HLS flow could speed up design-space exploration by providing loose coupling between functions interface design and functions algorithm implementation. We conclude with results of real-life hardware tests performed with the HLS flow-generated design with a DCC Tester system.

Tail dependence and information flow: Evidence from international equity markets

NASA Astrophysics Data System (ADS)

Al Rahahleh, Naseem; Bhatti, M. Ishaq; Adeinat, Iman

2017-05-01

Bhatti and Nguyen (2012) used the copula approach to measure the tail dependence between a number of international markets. They observed that some country pairs exhibit only left-tail dependence whereas others show only right-tail. However, the flow of information from uni-dimensional (one-tail) to bi-dimensional (two-tails) between various markets was not accounted for. In this study, we address the flow of information of this nature by using the dynamic conditional correlation (DCC-GARCH) model. More specifically, we use various versions of the DCC models to explain the nexus between the information flow of international equity and to explain the stochastic forward vs. backward dynamics of financial markets based on data for a 15-year period comprising 3,782 observations. We observed that the information flow between the US and Hong Kong markets and between the US and Australian markets are bi-directional. We also observed that the DCC model captures a wider co-movement structure and inter-connectedness compared to the symmetric Joe-Clayton copula.

The Diesel Combustion Collaboratory: Combustion Researchers Collaborating over the Internet

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

C. M. Pancerella; L. A. Rahn; C. Yang

2000-02-01

The Diesel Combustion Collaborator (DCC) is a pilot project to develop and deploy collaborative technologies to combustion researchers distributed throughout the DOE national laboratories, academia, and industry. The result is a problem-solving environment for combustion research. Researchers collaborate over the Internet using DCC tools, which include: a distributed execution management system for running combustion models on widely distributed computers, including supercomputers; web-accessible data archiving capabilities for sharing graphical experimental or modeling data; electronic notebooks and shared workspaces for facilitating collaboration; visualization of combustion data; and video-conferencing and data-conferencing among researchers at remote sites. Security is a key aspect of themore » collaborative tools. In many cases, the authors have integrated these tools to allow data, including large combustion data sets, to flow seamlessly, for example, from modeling tools to data archives. In this paper the authors describe the work of a larger collaborative effort to design, implement and deploy the DCC.« less

Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes

PubMed Central

Reuten, Raphael; Patel, Trushar R.; McDougall, Matthew; Rama, Nicolas; Nikodemus, Denise; Gibert, Benjamin; Delcros, Jean-Guy; Prein, Carina; Meier, Markus; Metzger, Stéphanie; Zhou, Zhigang; Kaltenberg, Jennifer; McKee, Karen K.; Bald, Tobias; Tüting, Thomas; Zigrino, Paola; Djonov, Valentin; Bloch, Wilhelm; Clausen-Schaumann, Hauke; Poschl, Ernst; Yurchenco, Peter D.; Ehrbar, Martin; Mehlen, Patrick; Stetefeld, Jörg; Koch, Manuel

2016-01-01

Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interactions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin γ1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs. PMID:27901020

Biota Modeling in EPA's Preliminary Remediation Goal and Dose Compliance Concentration Calculators for Use in EPA Superfund Risk Assessment: Explanation of Intake Rate Derivation, Transfer Factor Compilation, and Mass Loading Factor Sources

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

Manning, Karessa L.; Dolislager, Fredrick G.; Bellamy, Michael B.

The Preliminary Remediation Goal (PRG) and Dose Compliance Concentration (DCC) calculators are screening level tools that set forth Environmental Protection Agency's (EPA) recommended approaches, based upon currently available information with respect to risk assessment, for response actions at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) sites, commonly known as Superfund. The screening levels derived by the PRG and DCC calculators are used to identify isotopes contributing the highest risk and dose as well as establish preliminary remediation goals. Each calculator has a residential gardening scenario and subsistence farmer exposure scenarios that require modeling of the transfer of contaminants frommore » soil and water into various types of biota (crops and animal products). New publications of human intake rates of biota; farm animal intakes of water, soil, and fodder; and soil to plant interactions require updates be implemented into the PRG and DCC exposure scenarios. Recent improvements have been made in the biota modeling for these calculators, including newly derived biota intake rates, more comprehensive soil mass loading factors (MLFs), and more comprehensive soil to tissue transfer factors (TFs) for animals and soil to plant transfer factors (BV's). New biota have been added in both the produce and animal products categories that greatly improve the accuracy and utility of the PRG and DCC calculators and encompass greater geographic diversity on a national and international scale.« less

Randomised control trial showed that delayed cord clamping and milking resulted in no significant differences in iron stores and physical growth parameters at one year of age.

PubMed

Agarwal, Shivam; Jaiswal, Vijay; Singh, Dharamveer; Jaiswal, Prateek; Garg, Amit; Upadhyay, Amit

2016-11-01

Placental redistribution has been shown to improve haematological outcomes in the immediate neonatal period and early infancy. This study compared the effects of delayed cord clamping (DCC) and umbilical cord milking (UCM) on haematological and growth parameters at 12 months of age. This was a follow-up study of a randomised control trial, conducted in a tertiary care paediatric centre from August 2013 to August 2014. We studied 200 apparently healthy Indian infants randomised at birth to receive DCC for 60-90 seconds or UCM. The outcome measures were iron status and physical growth parameters at 12 months. Of the 200 babies, 161 completed the follow-up and baseline characteristics were comparable in both groups. The mean haemoglobin in the DCC group (102.2 (17.2) g/L and serum ferritin 16.44 (2.77) μg/L) showed no significant differences to the UCM group (98.6 (17.1) g/L and 18.2 (2.8) μg/L) at one year. In addition, there were no significant differences in weight, height and mid-upper arm circumference in the two groups. Term-born Indian infants who had DCC at 60-90 seconds or UCM showed no significant differences in ferritin and haemoglobin levels and growth parameters at 12 months of age. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Costs and absence of HCV-infected employees by disease stage.

PubMed

Baran, Robert W; Samp, Jennifer C; Walker, David R; Smeeding, James E; Young, Jacob W; Kleinman, Nathan L; Brook, Richard A

2015-01-01

Quantify the costs and absenteeism associated with stages of the Hepatitis C virus (HCV). Retrospective analysis of the HCMS integrated database from multiple geographically diverse, US-based employers with employee information on medical, prescription, and absenteeism claims. Employee data were extracted from July 2001-March 2013. Employees with HCV were identified by ICD-9-CM codes and classified into disease severity cohorts using diagnosis/procedure codes assigning the first date of most severe claim as the index date. Non-HCV employees (controls) were assigned random index dates. Inclusion required 6-month pre-/post-index eligibility. Medical, prescription, and absenteeism cost and time were analyzed using two-part regression (logistic/generalized linear) models, controlling for potentially confounding factors. Costs were inflation adjusted to September 2013. All direct costs comparisons were statistically significant (p ≤ 0.05) with mean medical costs of $1813 [SE = $3] for controls (n = 727,588), $4611 [SE = $211] for non-cirrhotic (n = 1007), $4646 [SE = $721] for compensated cirrhosis (CC, n = 87), $12,384 [SE = $1122] for decompensated cirrhosis (DCC, n = 256), $33,494 [SE = $11,753] for hepatocellular carcinoma (HCC, n = 17) and $97,724 [SE = $32,437] for liver transplant (LT, n = 19) cohorts. Mean short-term disability days/costs were significantly greater for the non-cirrhotic (days = 2.03 [SE = 0.36]; $299 [SE = $53]), DCC (days = 6.20 [SE = 1.36]; $763 [SE = $169]), and LT cohorts (days = 21.98 [SE = 8.21]; $2537 [SE = $972]) compared to controls (days = 1.19 [SE = 0.01]; $155 [SE = $1]). Mean sick leave costs were significantly greater for non-cirrhotic ($373 [SE = $22]) and DCC ($460 [SE = $54]) compared to controls ($327 [SE = $1]). Employees with HCV were shown to have greater direct and indirect costs compared to non-HCV employee controls. Costs progressively increased in the more severe HCV disease categories. Slowing or preventing disease progression may avert the costs of more severe liver disease stages and enable employees with HCV to continue as productive members of the workforce.

User-Friendly Data-Sharing Practices for Fostering Collaboration within a Research Network: Roles of a Vanguard Center for a Community-Based Study

PubMed Central

Lee, Jae Eun; Sung, Jung Hye; Barnett, M. Edwina; Norris, Keith

2015-01-01

Although various attempts have been made to build collaborative cultures for data sharing, their effectiveness is still questionable. The Jackson Heart Study (JHS) Vanguard Center (JHSVC) at the NIH-funded Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN) Data Coordinating Center (DCC) may be a new concept in that the data are being shared with a research network where a plethora of scientists/researchers are working together to achieve their common goal. This study describes the current practices to share the JHS data through the mechanism of JHSVC. The JHS is the largest single-site cohort study to prospectively investigate the determinants of cardiovascular disease among African-Americans. It has adopted a formal screened access method through a formalized JHSVC mechanism, in which only a qualified scientist(s) can access the data. The role of the DCC was to help RTRN researchers explore hypothesis-driven ideas to enhance the output and impact of JHS data through customized services, such as feasibility tests, data querying, manuscript proposal development and data analyses for publication. DCC has implemented these various programs to facilitate data utility. A total of 300 investigators attended workshops and/or received training booklets. DCC provided two online and five onsite workshops and developed/distributed more than 250 copies of the booklet to help potential data users understand the structure of and access to the data. Information on data use was also provided through the RTRN website. The DCC efforts led to the production of five active manuscript proposals, seven completed publications, 11 presentations and four NIH grant proposals. These outcomes resulted from activities during the first four years; over the last couple of years, there were few new requests. Our study suggested that DCC-customized services enhanced the accessibility of JHS data and their utility by RTRN researchers and helped to achieve the principal goal of JHSVC of scientific productivity. In order to achieve long-term success, the following, but not limited to these, should be addressed in the current data sharing practices: preparation of new promotional strategies in response to changes in technology and users’ needs, collaboration with the Network statisticians, harmonization of the JHS data with the other local-based heart datasets to meet the needs of the potential users from the broader geographical areas, adoption of the RTRN comprehensive data-sharing policy to broaden the variety of research topics and implementation of an ongoing monitoring program to evaluate its success. PMID:26703645

Deciphering the Binding between Nupr1 and MSL1 and Their DNA-Repairing Activity

PubMed Central

Doménech, Rosa; Pantoja-Uceda, David; Gironella, Meritxell; Santoro, Jorge; Velázquez-Campoy, Adrián; Neira, José L.; Iovanna, Juan L.

2013-01-01

The stress protein Nupr1 is a highly basic, multifunctional, intrinsically disordered protein (IDP). MSL1 is a histone acetyl transferase-associated protein, known to intervene in the dosage compensation complex (DCC). In this work, we show that both Nupr1 and MSL1 proteins were recruited and formed a complex into the nucleus in response to DNA-damage, which was essential for cell survival in reply to cisplatin damage. We studied the interaction of Nupr1 and MSL1, and their binding affinities to DNA by spectroscopic and biophysical methods. The MSL1 bound to Nupr1, with a moderate affinity (2.8 µM) in an entropically-driven process. MSL1 did not bind to non-damaged DNA, but it bound to chemically-damaged-DNA with a moderate affinity (1.2 µM) also in an entropically-driven process. The Nupr1 protein bound to chemically-damaged-DNA with a slightly larger affinity (0.4 µM), but in an enthalpically-driven process. Nupr1 showed different interacting regions in the formed complexes with Nupr1 or DNA; however, they were always disordered (“fuzzy”), as shown by NMR. These results underline a stochastic description of the functionality of the Nupr1 and its other interacting partners. PMID:24205110

Pivot/Remote: a distributed database for remote data entry in multi-center clinical trials.

PubMed

Higgins, S B; Jiang, K; Plummer, W D; Edens, T R; Stroud, M J; Swindell, B B; Wheeler, A P; Bernard, G R

1995-01-01

1. INTRODUCTION. Data collection is a critical component of multi-center clinical trials. Clinical trials conducted in intensive care units (ICU) are even more difficult because the acute nature of illnesses in ICU settings requires that masses of data be collected in a short time. More than a thousand data points are routinely collected for each study patient. The majority of clinical trials are still "paper-based," even if a remote data entry (RDE) system is utilized. The typical RDE system consists of a computer housed in the CC office and connected by modem to a centralized data coordinating center (DCC). Study data must first be recorded on a paper case report form (CRF), transcribed into the RDE system, and transmitted to the DCC. This approach requires additional monitoring since both the paper CRF and study database must be verified. The paper-based RDE system cannot take full advantage of automatic data checking routines. Much of the effort (and expense) of a clinical trial is ensuring that study data matches the original patient data. 2. METHODS. We have developed an RDE system, Pivot/Remote, that eliminates the need for paper-based CRFs. It creates an innovative, distributed database. The database resides partially at the study clinical centers (CC) and at the DCC. Pivot/Remote is descended from technology introduced with Pivot [1]. Study data is collected at the bedside with laptop computers. A graphical user interface (GUI) allows the display of electronic CRFs that closely mimic the normal paper-based forms. Data entry time is the same as for paper CRFs. Pull-down menus, displaying the possible responses, simplify the process of entering data. Edit checks are performed on most data items. For example, entered dates must conform to some temporal logic imposed by the study. Data must conform to some acceptable range of values. Calculations, such as computing the subject's age or the APACHE II score, are automatically made as the data is entered. Data that is collected serially (BP, HR, etc.) can be displayed graphically in a trend form along with other related variables. An audit trail is created that automatically tracks all changes to the original data, making it possible to reconstruct the CRF to any point in time. On-line help provides information on the study protocol as well as assistance with the use of the system. Electronic security makes it possible to lock certain parts of the CRF once it has been monitored. Completed CRFs are transmitted to the DCC via electronic mail where it is reviewed and merged into the study database. Questions about subject data are transmitted back to the CC via electronic mail. This approach to maintaining the study database is unique in that the study data files are distributed among the CC and DCC. Until a subject's CRF is monitored (verified against the original patient data residing in the hospital record), it logically resides at the CC where it was collected. Copies are transmitted to the DCC and are only read there. Any pre-monitoring changes must be made to the data at the CC. Once the subject's CRF is monitored, it logically moves to the DCC, and any subsequent changes are made at the DCC with copies of the CRF flowing back to the CC. 3. DISCUSSION. Pivot/Remote eliminates the need for paper forms by utilizing portable computers that can be used at the patient bedside. A GUI makes it possible to quickly enter data. Because the user gets instant feedback on possible error conditions, time is saved because the original data is close at hand. The ability to display trended data or variables in the context of other data allows detection of erroneous conditions beyond simple range checks. The logical construction of the database minimizes the problem of managing dual databases (at the CC and DCC) and keeps CC personnel in the loop until all changes are made.

High blood lead levels are associated with lead concentrations in households and day care centers attended by Brazilian preschool children.

PubMed

da Rocha Silva, Júlia Prestes; Salles, Fernanda Junqueira; Leroux, Isabelle Nogueira; da Silva Ferreira, Ana Paula Sacone; da Silva, Agnes Soares; Assunção, Nilson Antonio; Nardocci, Adelaide Cassia; Sayuri Sato, Ana Paula; Barbosa, Fernando; Cardoso, Maria Regina Alves; Olympio, Kelly Polido Kaneshiro

2018-08-01

A previous study observed high blood lead levels (BLL) in preschool children attending 50 day care centers (DCC) in São Paulo, Brazil. To identify whether lead levels found in both homes and DCC environments are associated with high blood lead levels. Children attending 4 DCCs, quoted here as NR, VA, PS and PF, were divided into two groups according to BLL: high exposure (HE: ≥13.9 μg/dL; 97.5 percentile of the 2013 year sample) and low exposure (LE: <5 μg/dL). For in situ lead measurements (lead paint mode: mg/cm 2 and ROHS mode: μg/g) in the children's households and in the DCC environments, a field portable X-ray-fluorescence analyzer was used. Multiple logistic regressions were performed to control for confounding factors. Odds ratios were adjusted for age, sex, day care center's measured lead, and tobacco. In an NR DCC building, 33.8% of the measurements had lead levels >600 μg/g, whereas such levels were observed in 77.1% of NR playground measurements. In VA DCC, 22% and 23% of the measurements in the building and in the playgrounds had levels higher than 600 μg/g, respectively. The percentage of high lead levels in the children's houses of the LE group was 5.9% (95% CI: 4.3-7.6%) and 13.2 (95% CI: 8.3-18.0%) in the HE group. Moreover, a significant association was found between high BLLs and lead levels found both in households and DCCs (p < 0.001). Most of the high lead measurements were found in tiles and playground equipment. Lead exposure estimated from the DCCs, where children spend about 10 h/day, can be as relevant as their household exposure. Therefore, public authorities should render efforts to provide a rigorous surveillance for lead-free painting supplies and for all objects offered to children. Copyright © 2018 Elsevier Ltd. All rights reserved.

Shelf-Life of Chlorine Solutions Recommended in Ebola Virus Disease Response.

PubMed

Iqbal, Qais; Lubeck-Schricker, Maya; Wells, Emma; Wolfe, Marlene K; Lantagne, Daniele

2016-01-01

In Ebola Virus Disease (EVD) outbreaks, it is widely recommended to wash living things (handwashing) with 0.05% (500 mg/L) chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% (5,000 mg/L) chlorine solution. Chlorine solutions used in EVD response are primarily made from powdered calcium hypochlorite (HTH), granular sodium dichloroisocyanurate (NaDCC), and liquid sodium hypochlorite (NaOCl), and have a pH range of 5-11. Chlorine solutions degrade following a reaction highly dependent on, and unusually sensitive to, pH, temperature, and concentration. We determined the shelf-life of 0.05% and 0.5% chlorine solutions used in EVD response, including HTH, NaDCC, stabilized NaOCl, generated NaOCl, and neutralized NaOCl solutions. Solutions were stored for 30 days at 25, 30, and 35°C, and tested daily for chlorine concentration and pH. Maximum shelf-life was defined as days until initial concentration fell to <90% of initial concentration in ideal laboratory conditions. At 25-35°C, neutralized-NaOCl solutions (pH = 7) had a maximum shelf-life of a few hours, NaDCC solutions (pH = 6) 2 days, generated NaOCl solutions (pH = 9) 6 days, and HTH and stabilized NaOCl solutions (pH 9-11) >30 days. Models were developed for solutions with maximum shelf-lives between 1-30 days. Extrapolating to 40°C, the maximum predicted shelf-life for 0.05% and 0.5% NaDCC solutions were 0.38 and 0.82 hours, respectively; predicted shelf-life for 0.05% and 0.5% generated NaOCl solutions were >30 and 5.4 days, respectively. Each chlorine solution type offers advantages and disadvantages to responders, as: NaDCC is an easy-to-import high-concentration effervescent powder; HTH is similar, but forms a precipitate that may clog pipes; and, NaOCl solutions can be made locally, but are difficult to transport. We recommend responders chose the most appropriate source chlorine compound for their use, and ensure solutions are stored at appropriate temperatures and used or replaced before expiring.

Advanced Stirling Convertor Dual Convertor Controller Testing at NASA Glenn Research Center in the Radioisotope Power Systems System Integration Laboratory

NASA Technical Reports Server (NTRS)

Dugala, Gina M.; Taylor, Linda M.; Bell, Mark E.; Dolce, James L.; Fraeman, Martin; Frankford, David P.

2015-01-01

NASA Glenn Research Center developed a nonnuclear representation of a Radioisotope Power System (RPS) consisting of a pair of Advanced Stirling Convertors (ASCs), Dual Convertor Controller (DCC) EMs (engineering models) 2 and 3, and associated support equipment, which were tested in the Radioisotope Power Systems System Integration Laboratory (RSIL). The DCC was designed by the Johns Hopkins University Applied Physics Laboratory (JHU/APL) to actively control a pair of ASCs. The first phase of testing included a Dual Advanced Stirling Convertor Simulator (DASCS), which was developed by JHU/APL and simulates the operation and electrical behavior of a pair of ASCs in real time via a combination of hardware and software. RSIL provides insight into the electrical interactions between a representative radioisotope power generator, its associated control schemes, and realistic electric system loads. The first phase of integration testing included the following spacecraft bus configurations: capacitive, battery, and super-capacitor. A load profile, created based on data from several missions, tested the RPS's and RSIL's ability to maintain operation during load demands above and below the power provided by the RPS. The integration testing also confirmed the DCC's ability to disconnect from the spacecraft when the bus voltage dipped below 22 volts or exceeded 36 volts. Once operation was verified with the DASCS, the tests were repeated with actual operating ASCs. The goal of this integration testing was to verify operation of the DCC when connected to a spacecraft and to verify the functionality of the newly designed RSIL. The results of these tests are presented in this paper.

Promoter hypermethylation in Indian primary oral squamous cell carcinoma

PubMed Central

Kaur, Jatinder; Demokan, Semra; Tripathi, Satyendra Chandra; Macha, Muzafar Ahmad; Begum, Shahnaz; Califano, Joseph A.; Ralhan, Ranju

2010-01-01

We evaluated promoter hypermethylation of a panel of tumor suppressor genes as a means to detect epigenetic alterations in oral squamous cell carcinomas (OSCC) of Indian-origin and compare with North-American head and neck squamous cell carcinomas (HNSCC). Quantitative-methylation-specific PCR was used to investigate the promoter methylation status of DCC, EDNRB, p16INK4a and KIF1A in 92 OSCC, and compared to 48 paired normal tissues and 30 saliva and sera samples from healthy control subjects. Aberrant methylation of at-least one of these genes was detected in 74/92 (80.4%) OSCC; 72.8% at EDNRB, 71.7% at KIF1A, 47.8% at p16INK4a and 58.7% at DCC; and in 5 of 48 (10.4%) normal oral tissues. None of the saliva and sera samples from controls exhibited DNA methylation in these four target genes. Thirty-two of 72 node positive cases harbored p16INK4a and DCC hypermethylation (p = 0.005). Thus, promoter hypermethylation in genes analyzed herein is a common event in Indian OSCC and may represent promising markers for the molecular staging of OSCC patients. We found higher frequency of p16INK4a methylation (47.8%) in this Indian cohort in comparison with a North-American cohort (37.5%). In conclusion, aberrant methylation of EDNRB, KIF1A, DCC and p16INK4a genes is a common event in Indian OSCC, suggesting that epigenetic alterations of these genes warrant validation in larger studies for their potential use as biomarkers. PMID:20473870

The dynamic pattern of PLIN3 in pig oocytes and cumulus cells during in vitro maturation.

PubMed

Xu, Mingzhu; Zeng, Yaqiong; Chi, Daming; Si, Linan; Qu, Xiao; Li, Juan

2018-02-01

Lipid droplets (LDs) are the main energy resource for porcine preimplantation embryonic development. PLIN3 has been implicated in LD formation and regulation. Therefore, this study aimed to detect the dynamic pattern of PLIN3 in pig oocytes and cumulus cells (CC) during in vitro maturation (IVM), and to determine the relationship between PLIN3 and LD content. IVM with cumulus-enclosed oocytes (CEO), cumulus-denuded oocytes (DO) and the CCs denuded from the corresponding oocytes (DCC) was performed in porcine follicular fluid (PFF) or PFF-free optimized medium. DO and the DCC were cultured together under the same conditions as described above, while the DO was named DTO and the DCC was named DTCC in this group. Firstly, our results revealed LDs distributed widely in oocytes and CC, while the PLIN3 protein coated these LDs and spread out ubiquitously in the cytoplasm. Secondly, not only the mRNA level but also at protein level of PLIN3 in immature naked oocytes (IO) was higher than that in matured CEO, DO and DTO. Although PLIN3 was expressed at lower levels in CC from immature oocytes (ICC), the protein level of PLIN3 was comparably higher in the ECC and DCC groups. The triglyceride (TG) content in CEO and DO was significantly less abundant compared with that in IO. Therefore, our results indicated that co-culturing of oocytes and CC might affect PLIN3 expression levels in CC but not in oocytes. Lipid accumulation in pig oocytes during maturation might be affected by PLIN3 cross-talk between oocytes and CC.

Glypican Is a Modulator of Netrin-Mediated Axon Guidance

PubMed Central

Blanchette, Cassandra R.; Perrat, Paola N.; Thackeray, Andrea; Bénard, Claire Y.

2015-01-01

Netrin is a key axon guidance cue that orients axon growth during neural circuit formation. However, the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown. Here we demonstrate that in Caenorhabditis elegans, LON-2/glypican, a heparan sulfate proteoglycan, modulates UNC-6/netrin signaling and may do this through interactions with the UNC-40/DCC receptor. We show that developing axons misorient in the absence of LON-2/glypican when the SLT-1/slit guidance pathway is compromised and that LON-2/glypican functions in both the attractive and repulsive UNC-6/netrin pathways. We find that the core LON-2/glypican protein, lacking its heparan sulfate chains, and secreted forms of LON-2/glypican are functional in axon guidance. We also find that LON-2/glypican functions from the epidermal substrate cells to guide axons, and we provide evidence that LON-2/glypican associates with UNC-40/DCC receptor–expressing cells. We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration. PMID:26148345

Advanced Stirling Convertor Dual Convertor Controller Testing at NASA Glenn Research Center in the Radioisotope Power Systems System Integration Laboratory

NASA Technical Reports Server (NTRS)

Dugala, Gina M.; Taylor, Linda M.; Bell, Mark E.; Dolce, James L.; Fraeman, Martin; Frankford, David P.

2015-01-01

NASA Glenn Research Center (GRC) developed a non-nuclear representation of a Radioisotope Power System (RPS) consisting of a pair of Advanced Stirling Convertors (ASC), a Dual Convertor Controller (DCC) EM (engineering model) 2 & 3, and associated support equipment, which were tested in the Radioisotope Power Systems System Integration Laboratory (RSIL). The DCC was designed by the Johns Hopkins University/Applied Physics Laboratory (JHU/APL) to actively control a pair of Advanced Stirling Convertors (ASC). The first phase of testing included a Dual Advanced Stirling Convertor Simulator (DASCS) which was developed by JHU/APL and simulates the operation and electrical behavior of a pair of ASC's in real time via a combination of hardware and software. RSIL provides insight into the electrical interactions between a representative radioisotope power generator, its associated control schemes, and realistic electric system loads. The first phase of integration testing included the following spacecraft bus configurations: capacitive, battery, and supercapacitor. A load profile, created based on data from several missions, tested the RPS and RSIL ability to maintain operation during load demands above and below the power provided by the RPS. The integration testing also confirmed the DCC's ability to disconnect from the spacecraft when the bus voltage dipped below 22 V or exceeded 36 V. Once operation was verified with the DASCS, the tests were repeated with actual operating ASC's. The goal of this integration testing was to verify operation of the DCC when connected to a spacecraft and to verify the functionality of the newly designed RSIL. The results of these tests are presented in this paper.

Effect of indoor air quality of day care centers in children with different predisposition for asthma.

PubMed

Carreiro-Martins, Pedro; Papoila, Ana Luisa; Caires, Iolanda; Azevedo, Susana; Cano, Maria Manuela; Virella, Daniel; Leiria-Pinto, Paula; Teixeira, João Paulo; Rosado-Pinto, José; Annesi-Maesano, Isabella; Neuparth, Nuno

2016-05-01

Scarce information is available about the relationships between indoor air quality (IAQ) at day care centers (DCC), the estimated predisposition for asthma, and the actual wheezing susceptibility. In the Phase II of ENVIRH study, 19 DCC were recruited after cluster analysis. Children were evaluated firstly using the ISAAC questionnaire and later by a follow-up questionnaire about recent wheezing. A positive asthma predictive index (API) was considered as predisposition for asthma. Every DCC was audited for IAQ and monitored for chemical and biologic contaminants. We included 1191 children, with a median age of 43 (P25 -P75 : 25-58) months. Considering the overall sample, in the first questionnaire, associations were found between CO2 concentration (increments of 200 ppm) and diagnosis of asthma (OR: 1.10; 95% CI: 1.00-1.20). Each increment of 100 μg/m(3) of total volatile organic compounds (TVOC) and 1 μg of Der p1/g of dust were associated with wheezing in the previous 12 months (OR: 1.06; 95% CI: 1.01-1.11 and OR: 1.06; 95% CI: 0.99-1.12, respectively). In the follow-up questionnaire, TVOC were again associated with wheezing (OR: 1.05; 95% CI: 1.00-1.11). Children exposed to fungal concentration above the 75th percentile had also higher odds of wheezing at follow-up. TVOC were associated with wheezing in children with either negative or positive API. IAQ in DCC seems to be associated with wheezing, in children with and without predisposition for asthma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The burden of hepatitis C to the United States Medicare system in 2009: Descriptive and economic characteristics.

PubMed

Rein, David B; Borton, Joshua; Liffmann, Danielle K; Wittenborn, John S

2016-04-01

The aim of this work was to estimate and describe the Medicare beneficiaries diagnosed with hepatitis C virus (HCV) in 2009, incremental annual costs by disease stage, incremental total Medicare HCV payments in 2009 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data covering the years 2002 to 2009. We weighted the 2009 SEER-Medicare data to create estimates of the number of patients with an HCV diagnosis, used an inverse probability-weighted two-part, probit, and generalized linear model to estimate incremental per patient per month costs, and used simulation to estimate annual 2009 Medicare burden, presented in 2014 dollars. We summarized patient characteristics, diagnoses, and costs from SEER-Medicare files into a person-year panel data set. We estimated there were 407,786 patients with diagnosed HCV in 2009, of whom 61.4% had one or more comorbidities defined by the study. In 2009, 68% of patients were diagnosed with chronic HCV only, 9% with cirrhosis, 12% with decompensated cirrhosis (DCC), 2% with liver cancer, 2% with a history of transplant, and 8% who died. Annual costs for patients with chronic infection only and DCC were higher than the values used in many previous cost-effectiveness studies, and treatment of DCC accounted for 63.9% of total Medicare's HCV expenditures. Medicare paid $2.7 billion (credible interval: $0.7-$4.6 billion) in incremental costs for HCV in 2009. The costs of HCV to Medicare in 2009 were substantial and expected to increase over the next decade. Annual costs for patients with chronic infection only and DCC were higher than values used in many cost-effectiveness analyses. © 2015 by the American Association for the Study of Liver Diseases.

Decellularized Cartilage May Be a Chondroinductive Material for Osteochondral Tissue Engineering

PubMed Central

Sutherland, Amanda J.; Beck, Emily C.; Dennis, S. Connor; Converse, Gabriel L.; Hopkins, Richard A.; Berkland, Cory J.; Detamore, Michael S.

2015-01-01

Extracellular matrix (ECM)-based materials are attractive for regenerative medicine in their ability to potentially aid in stem cell recruitment, infiltration, and differentiation without added biological factors. In musculoskeletal tissue engineering, demineralized bone matrix is widely used, but recently cartilage matrix has been attracting attention as a potentially chondroinductive material. The aim of this study was thus to establish a chemical decellularization method for use with articular cartilage to quantify removal of cells and analyze the cartilage biochemical content at various stages during the decellularization process, which included a physically devitalization step. To study the cellular response to the cartilage matrix, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were cultured in cell pellets containing cells only (control), chondrogenic differentiation medium (TGF-β), chemically decellularized cartilage particles (DCC), or physically devitalized cartilage particles (DVC). The chemical decellularization process removed the vast majority of DNA and about half of the glycosaminoglycans (GAG) within the matrix, but had no significant effect on the amount of hydroxyproline. Most notably, the DCC group significantly outperformed TGF-β in chondroinduction of rBMSCs, with collagen II gene expression an order of magnitude or more higher. While DVC did not exhibit a chondrogenic response to the extent that DCC did, DVC had a greater down regulation of collagen I, collagen X and Runx2. A new protocol has been introduced for cartilage devitalization and decellularization in the current study, with evidence of chondroinductivity. Such bioactivity along with providing the ‘raw material’ building blocks of regenerating cartilage may suggest a promising role for DCC in biomaterials that rely on recruiting endogenous cell recruitment and differentiation for cartilage regeneration. PMID:25965981

VizieR Online Data Catalog: PTF 12dam & iPTF 13dcc follow-up (Vreeswijk+, 2017)

NASA Astrophysics Data System (ADS)

Vreeswijk, P. M.; Leloudas, G.; Gal-Yam, A.; De Cia, A.; Perley, D. A.; Quimby, R. M.; Waldman, R.; Sullivan, M.; Yan, L.; Ofek, E. O.; Fremling, C.; Taddia, F.; Sollerman, J.; Valenti, S.; Arcavi, I.; Howell, D. A.; Filippenko, A. V.; Cenko, S. B.; Yaron, O.; Kasliwal, M. M.; Cao, Y.; Ben-Ami, S.; Horesh, A.; Rubin, A.; Lunnan, R.; Nugent, P. E.; Laher, R.; Rebbapragada, U. D.; Wozniak, P.; Kulkarni, S. R.

2017-08-01

Spectroscopic follow-up observations of PTF 12dam were performed with the Kast Spectrograph at the Lick 3m Shane telescope, and the Low Resolution Imaging Spectrograph (LRIS) at the Keck-I 10m telescope (on Mauna Kea, Hawaii) on 2012 May 20, 21, and 22. The full spectroscopic sequence of PTF 12dam will be presented by R. M. Quimby et al. (2016, in preparation). PTF 12dam was imaged with the Palomar Oschin 48 inch (P48) (i)PTF survey telescope in the Mould R filter, the Palomar 60 inch (P60) and CCD camera in Johnson B and Sloan Digital Sky Survey (SDSS) gri, the Las Cumbres Observatory Global Telescope Network (LCOGT) in SDSS r, and LRIS mounted on the 10m Keck-I telescope in Rs. iPTF 13dcc has not had any exposure in the literature yet. It was flagged as a transient source on 2013 August 29. Spectroscopic follow-up observations spanning 2013 Nov 26 to 2014 Jan 16 were performed with the Double Spectrograph (DBSP) at the Palomar 200 inch (P200), LRIS at Keck-I, and the Inamori-Magellan Areal Camera & Spectrograph (IMACS) at the Magellan Baade telescope, showing iPTF 13dcc to be an SLSN at z=0.4305. iPTF 13dcc was imaged with the P48 Oschin (i)PTF survey telescope in the Mould R filter, the P60 in SDSS gri, the 4.3m Discovery Channel Telescope (DCT, at Lowell Observatory, Arizona) with the Large Monolithic Imager (LMI) in SDSS ri, and finally with the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) Wide-Field Camera using filter F625W (under program GO-13858; P.I. A. De Cia). (3 data files).

DNA-Encoded Dynamic Combinatorial Chemical Libraries.

PubMed

Reddavide, Francesco V; Lin, Weilin; Lehnert, Sarah; Zhang, Yixin

2015-06-26

Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Seasonality and Dynamic Spatial Contagion of Air Pollution in 42 Chinese Cities

PubMed Central

He, Zhanqiong; Sriboonchita, Songsak; He, Min

2013-01-01

To monitor and improve the urban air quality, the Chinese government has begun to make many efforts, and the interregional cooperation to cut and improve air quality has been required. In this paper, we focus on the seasonality of the first and second moments of the daily air pollution indexes (APIs) of 42 Chinese sample cities over 10 years, from June 5, 2000 to March 4, 2010, and investigate the dynamic correlation of air pollution indexes (APIs) between 42 Chinese cities and their corresponding regional and national levels; comparison with the model without seasonal consideration is made. By adopting a DCC-GARCH model that accounts for the seasonality, we found that (i) the transformed DCC-GARCH model including seasonality dummies improves the estimation result in this study; (ii) the seasonality feature of the second moment follows that of the first moment, with the condition mean and variance of the second and autumn significantly lower than spring, whereas that of winter is higher than spring; (iii) the correlation between local APIs and their corresponding regional and national levels is dynamic; (iv) comparing with the DCC-GARCH model estimation, the transformed model does not change the feature of the dynamic correlations very much. PMID:23533348

LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans

PubMed Central

Li, Pengpeng; Collins, Kevin M; Koelle, Michael R; Shen, Kang

2013-01-01

The diverse cell types and the precise synaptic connectivity between them are the cardinal features of the nervous system. Little is known about how cell fate diversification is linked to synaptic target choices. Here we investigate how presynaptic neurons select one type of muscles, vm2, as a synaptic target and form synapses on its dendritic spine-like muscle arms. We found that the Notch-Delta pathway was required to distinguish target from non-target muscles. APX-1/Delta acts in surrounding cells including the non-target vm1 to activate LIN-12/Notch in the target vm2. LIN-12 functions cell-autonomously to up-regulate the expression of UNC-40/DCC and MADD-2 in vm2, which in turn function together to promote muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in non-target vm1 muscle is sufficient to induce muscle arm extension from these cells. Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells. DOI: http://dx.doi.org/10.7554/eLife.00378.001 PMID:23539368

Netrin-1 rescues neuron loss by attenuating secondary apoptosis in ipsilateral thalamic nucleus following focal cerebral infarction in hypertensive rats.

PubMed

Liao, S-J; Gong, Q; Chen, X-R; Ye, L-X; Ding, Q; Zeng, J-S; Yu, J

2013-02-12

Neurological deficit following cerebral infarction correlates with not only primary injury, but also secondary neuronal apoptosis in remote loci connected to the infarction. Netrin-1 is crucial for axonal guidance by interacting with its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H (UNC5H). DCC and UNC5H are also dependence receptors inducing cell apoptosis when unbound by netrin-1. The present study is to investigate the role of netrin-1 and its receptors in ipsilateral ventroposterior thalamic nucleus (VPN) injury secondary to stroke in hypertensive rats. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO). Continuous intracerebroventricular infusion of netrin-1 (600 ng/d for 7 days) or vehicle (IgG/Fc) was given 24h after MCAO. Neurological function was evaluated by postural reflex 8 and 14 days after MCAO. Then, immunoreactivity was determined in the ipsilateral VPN for NeuN, glial fibrillary acidic protein, netrin-1 and its receptors (DCC and UNC5H2), apoptosis was detected with Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay, and the expressions of caspase-3, netrin-1, DCC, and UNC5H2 were quantified by western blot analysis. MCAO resulted in the impaired postural reflex after 8 and 14 days, with decreased NeuN marked neurons and increased TUNEL-positive cells, as well as an up-regulation in the levels of cleaved caspase-3 and UNC5H2 protein in the ipsilateral VPN, without significant change in DCC or netrin-1 expression. By exogenous netrin-1 infusion, the number of neurons was increased in the ipsilateral VPN, and both TUNEL-positive cell number and caspase-3 protein level were reduced, while UNC5H2 expression remained unaffected, simultaneously, the impairment of postural reflex was improved. Taken together, the present study indicates that exogenous netrin-1 could rescue neuron loss by attenuating secondary apoptosis in the ipsilateral VPN after focal cerebral infarction, possibly via its receptor UNC5H2, suggesting that relative insufficiency of endogenous netrin-1 be an underlying mechanism of secondary injury in the VPN post stroke. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Modeling inflation rates and exchange rates in Ghana: application of multivariate GARCH models.

PubMed

Nortey, Ezekiel Nn; Ngoh, Delali D; Doku-Amponsah, Kwabena; Ofori-Boateng, Kenneth

2015-01-01

This paper was aimed at investigating the volatility and conditional relationship among inflation rates, exchange rates and interest rates as well as to construct a model using multivariate GARCH DCC and BEKK models using Ghana data from January 1990 to December 2013. The study revealed that the cumulative depreciation of the cedi to the US dollar from 1990 to 2013 is 7,010.2% and the yearly weighted depreciation of the cedi to the US dollar for the period is 20.4%. There was evidence that, the fact that inflation rate was stable, does not mean that exchange rates and interest rates are expected to be stable. Rather, when the cedi performs well on the forex, inflation rates and interest rates react positively and become stable in the long run. The BEKK model is robust to modelling and forecasting volatility of inflation rates, exchange rates and interest rates. The DCC model is robust to model the conditional and unconditional correlation among inflation rates, exchange rates and interest rates. The BEKK model, which forecasted high exchange rate volatility for the year 2014, is very robust for modelling the exchange rates in Ghana. The mean equation of the DCC model is also robust to forecast inflation rates in Ghana.

Absorber modeling for NGCC carbon capture with aqueous piperazine.

PubMed

Zhang, Yue; Freeman, Brice; Hao, Pingjiao; Rochelle, Gary T

2016-10-20

A hybrid system combining amine scrubbing with membrane technology for carbon capture from natural gas combined cycle (NGCC) power plants is proposed in this paper. In this process, the CO 2 in the flue gas can be enriched from 4% to 18% by the membrane, and the amine scrubbing system will have lower capture costs. Aqueous piperazine (PZ) is chosen as the solvent. Different direct contact cooler (DCC) options, multiple absorber operating conditions, optimal intercooling designs, and different cooling options have been evaluated across a wide range of inlet CO 2 . Amine scrubbing without DCC is a superior design for NGCC carbon capture. Pump-around cooling at the bottom of the absorber can effectively manage the temperature of the hot flue gas, and still be effective for CO 2 absorption. The absorber gas inlet must be designed to avoid excessive localized temperature and solvent evaporation. When the inlet CO 2 increases from 4% to 18%, total absorber CAPEX decreases by 60%; another 10% of the total absorber CAPEX can be saved by eliminating the DCC. In-and-out intercooling works well for high CO 2 , while pump-around intercooling is more effective for low CO 2 . Dry cooling requires more packing and energy but appears to be technically and economically feasible if cooling water availability is limited.

The influence of day care centres for people with dementia on family caregivers: an integrative review of the literature.

PubMed

Tretteteig, Signe; Vatne, Solfrid; Rokstad, Anne Marie Mork

2016-01-01

Day care centres (DCC) for people with dementia (PWD) have received increased attention recently, due to a shift in policy from the use of residential care towards home-based services. The aim of this study is to provide an extended understanding of the influence of DCCs on family caregivers (FCs). An integrative review including 19 studies was used: qualitative (n = 2), quantitative non-randomised (n = 8), quantitative descriptive studies (n = 7), and with mixed-method design (n = 2). The quality of the studies was evaluated by the mixed-methods appraisal tool (MMAT). FC experienced the DCC both as a respite service, and to some extent as a support service, improving their competence in caring for the PWD. The quality of the DCC influenced its use, and the FC's motivation to care for the PWD. FC's gender, role, individual needs, PWD behavioural problems and need for assistance played an important role. As a respite and support service, DCCs have the potential to give FCs a feeling of safety and relief, reduce the caregiver's burden, and increase their motivation towards their role as caregivers. These outcomes depend on the quality of treatment, and how the service meets the FC's needs for flexibility, support, information, and responsibility sharing.

Interaction of Bacillus subtilis spores with sodium hypochlorite, sodium dichloroisocyanurate and chloramine-T.

PubMed

Bloomfield, S F; Arthur, M

1992-02-01

Solutions of chlorine-releasing agents (CRAs) show varying activity against Bacillus subtilis spores; sodium hypochlorite (NaOCl) shows higher activity than sodium dichloroisocyanurate (NaDCC) which is more active than chloramine-T. Investigations with coat- and cortex-extracted spores indicate that resistance to CRAs depends not only on the spore coat but also the cortex. Whereas extraction of alkali-soluble coat protein increased sensitivity to NaOCl and NaDCC, degradation of coat and cortex material was required to achieve significant activity with chloramine-T. NaOCl (in the presence and absence of NaOH) and NaDCC (in the presence of NaOH only) produced degradation of spore coat and cortex material which may be related to their rapid sporicidal action at low concentrations under these conditions. By contrast, chloramine-T produced no degradation of cortex peptidoglycan and was only effective against normal and alkali-treated spores at high concentrations, requiring extraction of peptidoglycan with urea/dithiothreitol/sodium lauryl sulphate (UDS) or UDS/lysozyme to achieve significant activity at low concentrations. Results suggest that the sporicidal action of CRAs is associated with spore coat and cortex degradation causing rehydration of the protoplast allowing diffusion to the site of action on the underlying protoplast.

Examining the impact of case management in Vancouver's downtown community court: a quasi-experimental design.

PubMed

Somers, Julian M; Moniruzzaman, Akm; Rezansoff, Stefanie N; Patterson, Michelle

2014-01-01

Problem solving courts (PSC) have been implemented internationally, with a common objective to prevent reoffending by addressing criminogenic needs and strengthening social determinants of health. There has been no empirical research on the effectiveness of community courts, which are a form of PSC designed to harness community resources and inter-disciplinary expertise to reduce recidivism in a geographic catchment area. We used the propensity score matching method to examine the effectiveness of Vancouver's Downtown Community Court (DCC). We focused on the subset of DCC participants who were identified as having the highest criminogenic risk and were assigned to a case management team (CMT). A comparison group was derived using one-to-one matching on a large array variables including static and dynamic criminogenic factors, geography, and time. Reductions in offences (one year pre minus one year post) were compared between CMT and comparison groups. Compared to other DCC offenders, those triaged to CMT (9.5% of the DCC population) had significantly higher levels of healthcare, social service use, and justice system involvement over the ten years prior to the index offence. Compared to matched offenders who received traditional court outcomes, those assigned to CMT (n=249) exhibited significantly greater reductions in overall offending (p<0.001), primarily comprised of significant reductions in property offences (p<0.001). Our findings indicate that CMT achieved significantly greater reductions in recidivism than traditional court among offenders with complex needs and high numbers of previous offences. Limitations of this research include a non-experimental design and one year follow up. Strengths include a robust matching process and extensive client level data spanning multiple sectors. Further research is needed to replicate the observed outcomes, to investigate the extension of community courts to settings with divergent offender needs and local resources, and to estimate potential cost avoidance attributable to this intervention.

Effectiveness of the Smoking Cessation and Reduction in Pregnancy Treatment (SCRIPT) dissemination project: a science to prenatal care practice partnership.

PubMed

Windsor, Richard; Clark, Jeannie; Cleary, Sean; Davis, Amanda; Thorn, Stephanie; Abroms, Lorien; Wedeles, John

2014-01-01

This study evaluated the effectiveness of the Smoking Cessation and Reduction in Pregnancy Treatment (SCRIPT) Program selected by the West Virginia-Right From The Start Project for state-wide dissemination. A process evaluation documented the fidelity of SCRIPT delivery by Designated Care Coordinators (DCC), licensed nurses and social workers who provide home-based case management to Medicaid-eligible clients in all 55 counties. We implemented a quasi-experimental, non-randomized, matched Comparison (C) Group design. The SCRIPT Experimental E Group (N = 259) were all clients in 2009-2010 that wanted to quit, provided a screening carbon monoxide (CO), and received a SCRIPT home visit. The (C) Group was derived from all clients in 2006-2007 who had the same CO assessments as E Group clients and reported receiving cessation counseling. We stratified the baseline CO of E Group clients into 10 strata, and randomly selected the same number of (C) Group clients (N = 259) from each matched strata to evaluate the effectiveness of the SCRIPT Program. There were no significant baseline differences in the E and (C) Group. A Process Evaluation documented a significant increase in the fidelity of DCC delivery of SCRIPT Program procedures: from 63 % in 2006 to 74 % in 2010. Significant increases were documented in the E Group cessation rate (+9.3 %) and significant reduction rate (+4.5 %), a ≥50 % reduction from a baseline CO. Perinatal health case management staff can deliver the SCRIPT Program, and Medicaid-supported clients can change smoking behavior, even very late in pregnancy. When multiple biases were analyzed, we concluded the SCRIPT Dissemination Project was the most plausible reason for the significant changes in behavior.

Synthesis, structure, and glutathione peroxidase-like activity of amino acid containing ebselen analogues and diaryl diselenides.

PubMed

Selvakumar, Karuthapandi; Shah, Poonam; Singh, Harkesh B; Butcher, Ray J

2011-11-04

The synthesis of some ebselen analogues and diaryl diselenides, which have amino acid functions as an intramolecularly coordinating group (Se···O) has been achieved by the DCC coupling procedure. The reaction of 2,2'-diselanediylbis(5-tert-butylisophthalic acid) or the activated ester tetrakis(2,5-dioxopyrrolidin-1-yl) 2,2'-diselanediylbis(5-tert-butylisophthalate) with different C-protected amino acids (Gly, L-Phe, L-Ala, and L-Trp) afforded the corresponding ebselen analogues. The used precursor diselenides have been found to undergo facile intramolecular cyclization during the amide bond formation reaction. In contrast, the DCC coupling of 2,2'-diselanediyldibenzoic acid with C-protected amino acids (Gly, L/D-Ala and L-Phe) affords the corresponding amide derivatives and not the ebselen analogues. Some of the representative compounds have been structurally characterized by single-crystal X-ray crystallography. The glutathione peroxidase (GPx)-like activities of the ebselen analogues and the diaryl diselenides have been evaluated by using the coupled reductase assay method. Intramolecularly stabilized ebselen analogues show slightly higher maximal velocity (V(max)) than ebselen. However, they do not show any GPx-like activity at low GSH concentrations at which ebselen and related diselenides are active. This could be attributed to the peroxide-mediated intramolecular cyclization of the corresponding selenenyl sulfide and diaryl diselenide intermediates generated during the catalytic cycle. Interestingly, the diaryl diselenides with alanine (L,L or D,D) amide moieties showed excellent catalytic efficiency (k(cat)/K(M)) with low K(M) values in comparison to the other compounds. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Co-movement measure of information transmission on international equity markets

NASA Astrophysics Data System (ADS)

Al Rahahleh, Naseem; Bhatti, M. Ishaq

2017-03-01

Recently, Bhatti and Nguyen (2012) used EVT and various stochastic copulas to study the cross-country co-movements diversification and asset pricing allocation. Weiss (2013) observed that Dynamic Conditional Correlation (DCC) models outperform various copula models. This paper attempts to contribute to the literature on multivariate models for capturing forward and backward return co-movement, spillover effects and volatility linkages. It reflects cross-country forward and backward co-movements more clearly among various coupled international stock markets relating to information transmission and price discovery for making investment decisions. Given the reality of fat-tail or skewed distribution of financial data, this paper proposes the use of VECM-DCC and VAR-DCC models which capture dynamic dependences between the Australian and other selected international financial stock markets. We observe that the return co-movement effects between Australian and Asian countries are bidirectional ((AUS ↔ Hong Kong), (AUS ↔ Japan)) with the exception of Taiwan (AUS → Taiwan). We also observe that the volatility spillover between the Australian and both the UK and the US markets are bidirectional with a larger volatility spillover from both toward the AUS market. Further, the UK market has a higher volatility spillover on the Australian market compared to the US market and the US market has a higher volatility spillover on the UK than that of the Australian market.

Deep convective cloud characterizations from both broadband imager and hyperspectral infrared sounder measurements

NASA Astrophysics Data System (ADS)

Ai, Yufei; Li, Jun; Shi, Wenjing; Schmit, Timothy J.; Cao, Changyong; Li, Wanbiao

2017-02-01

Deep convective storms have contributed to airplane accidents, making them a threat to aviation safety. The most common method to identify deep convective clouds (DCCs) is using the brightness temperature difference (BTD) between the atmospheric infrared (IR) window band and the water vapor (WV) absorption band. The effectiveness of the BTD method for DCC detection is highly related to the spectral resolution and signal-to-noise ratio (SNR) of the WV band. In order to understand the sensitivity of BTD to spectral resolution and SNR for DCC detection, a BTD to noise ratio method using the difference between the WV and IR window radiances is developed to assess the uncertainty of DCC identification for different instruments. We examined the case of AirAsia Flight QZ8501. The brightness temperatures (Tbs) over DCCs from this case are simulated for BTD sensitivity studies by a fast forward radiative transfer model with an opaque cloud assumption for both broadband imager (e.g., Multifunction Transport Satellite imager, MTSAT-2 imager) and hyperspectral IR sounder (e.g., Atmospheric Infrared Sounder) instruments; we also examined the relationship between the simulated Tb and the cloud top height. Results show that despite the coarser spatial resolution, BTDs measured by a hyperspectral IR sounder are much more sensitive to high cloud tops than broadband BTDs. As demonstrated in this study, a hyperspectral IR sounder can identify DCCs with better accuracy.

The impact of physicians' communication styles on evaluation of physicians and information processing: A randomized study with simulated video consultations on contraception with an intrauterine device.

PubMed

Bientzle, Martina; Fissler, Tim; Cress, Ulrike; Kimmerle, Joachim

2017-10-01

This study aimed at examining the impact of different types of physicians' communication styles on people's subsequent evaluation of physician attributes as well as on their information processing, attitude and decision making. In a between-group experiment, 80 participants watched one of three videos in which a gynaecologist displayed a particular communication style in a consultation situation on contraception with an intrauterine device. We compared doctor-centred communication (DCC) vs patient-centred communication (PCC) vs patient-centred communication with need-orientation (PCC-N). In the PCC condition, participants perceived the physician to be more empathetic and more competent than in the DCC condition. In the DCC condition, participants showed less attitude change compared to the other conditions. In the PCC-N condition, the physician was perceived as more empathetic and more socially competent than in the other conditions. However, participants acquired less knowledge in the PCC-N condition. We conclude that appropriate application of particular communication styles depends on specific consultation goals. Our results suggest that patients' needs should be addressed if the main goal is to build a good relationship, whereas a traditional PCC style appears to be more effective in communicating factual information. © 2016 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Principles of metadata organization at the ENCODE data coordination center

PubMed Central

Hong, Eurie L.; Sloan, Cricket A.; Chan, Esther T.; Davidson, Jean M.; Malladi, Venkat S.; Strattan, J. Seth; Hitz, Benjamin C.; Gabdank, Idan; Narayanan, Aditi K.; Ho, Marcus; Lee, Brian T.; Rowe, Laurence D.; Dreszer, Timothy R.; Roe, Greg R.; Podduturi, Nikhil R.; Tanaka, Forrest; Hilton, Jason A.; Cherry, J. Michael

2016-01-01

The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center (DCC) is responsible for organizing, describing and providing access to the diverse data generated by the ENCODE project. The description of these data, known as metadata, includes the biological sample used as input, the protocols and assays performed on these samples, the data files generated from the results and the computational methods used to analyze the data. Here, we outline the principles and philosophy used to define the ENCODE metadata in order to create a metadata standard that can be applied to diverse assays and multiple genomic projects. In addition, we present how the data are validated and used by the ENCODE DCC in creating the ENCODE Portal (https://www.encodeproject.org/). Database URL: www.encodeproject.org PMID:26980513

Design and Application of Synthetic Receptors for Recognition of Methylated Lysine and Supramolecular Affinity Labeling

NASA Astrophysics Data System (ADS)

Gober, Isaiah Nathaniel

This dissertation involves the design and synthesis of new synthetic receptors and their application in the molecular recognition of methylated lysine and their use as tools for chemical biology. The dissertation is divided into four parts. The first section focuses on the development of a novel labeling method that is based on ligand-directed affinity labeling principles. In this labeling method, a synthetic receptor that binds to trimethyl lysine (Kme3) is attached through a linker to an electrophilic tag group that can react with a nucleophilic amine in a histone peptide. This affinity labeling probe, which we called CX4-ONBD, is equipped with an electrophilic tag that allows for turn-on fluorescence labeling of Kme3 histone peitdes. We show that the probe gives a pronounced turn-on fluorescence response when it is incubated with a histone peptide that contains Kme3 and a nearby reactive lysine. This probe also displays >5-fold selectivity in covalent labeling over an unmethylated lysine peptide. This represents the first time a synthetic receptor has been used for affinity labeling purposes, and it also expands on the chemical toolkit that is available for sensing PTMs like lysine methylation. In the second section, the supramolecular affinity labeling method that was optimized using CX4-ONBD was applied to the development of a real-time assay for measuring enzymatic activity. More specifically, the probe was used to create a turn-on fluorescence assay for histone deacetylase (HDAC) activity and for inhibitor screening and IC50 determination. Most commercial kits for HDAC activity have limited substrate scope, and other common methods used for characterizing enzymatic activity often require chromatographic separation and are therefore not high-throughput. This small molecule receptor-mediated affinity labeling strategy allowed for facile readout of HDAC activity and inhibition. Overall, this application of supramolecular affinity labeling expands on the possible ways for detecting PTMs and may find use in the development of new assays for enzymes that lack robust methods for measuring their activity. The third section explores the development of new small molecule receptors capable of selectively binding hydrophilic guests in water, such as the lower methylation states of lysine. We identified a receptor, A2I, that has improved binding affinity and selectivity for dimethyllysine (Kme2). The receptor was discovered and synthesized by using dynamic combinatorial chemistry (DCC) to redesign a small molecule receptor (A2B ) that preferentially binds trimethyllysine (Kme3). Incorporating a biphenyl monomer with ortho-di-substituted carboxylates into the receptor lead to the formation of a salt bridge interaction with Kme2. These favorable electrostatic and hydrogen bonding interactions produced a receptor with 32-fold tighter binding to Kme2, which is the highest affinity synthetic receptor for Kme2 in the context of a peptide that has been reported. This work provides insight into effective strategies for binding hydrophilic, cationic guests in water and is an encouraging result toward a synthetic receptor that selectively binds Kme2 over other methylation states of lysine. In the final section, a small molecule receptor for Kme3 (A 2B) was redesigned using DCC to incorporate either aromatic or acidic amino acids into the receptor. We proposed that the incorporation of amino acids could introduce additional non-covalent interactions (such as cation-pi, electrostatic, and hydrogen bonding) with a guest bound inside the pocket of the receptor. However, selective non-covalent interactions between the amino acid side chain on the modified receptor and the bound methylated lysine guest could not be achieved. This is most likely due to the conformational flexibility of the amino acid-functionalized receptors. Furthermore, attaching amino acids to the receptor seemed to increase non-specific electrostatic interactions, resulting in tighter binding to the unmethylated lysine peptide (compared to A2B). Ultimately, this highlights the importance of incorporating monomers with less conformational flexibility that can rigidly place functional groups into the binding pocket.

Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings.

PubMed

Givon-Lavi, Noga; Fraser, Drora; Dagan, Ron

2003-06-01

We conducted a study to determine whether administration of a pneumococcal conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their younger siblings. In a double blind study, 262 DCC attendees ages 12 to 35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine (PnCRM9; n = 132), or a control vaccine (meningococcus C vaccine; n = 130). It was planned to follow the groups for 2 years with monthly nasopharyngeal pneumococcal cultures during the first follow-up year and every 2 months during the second year. Forty-six younger siblings of the above described children, age <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were also enrolled, and nasopharyngeal cultures were obtained monthly until the children reached the age of 18 months or started to attend DCC, if before the age of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic susceptibility. Of the 3748 cultures obtained from the DCC attendees, 2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures were significantly less frequently positive for the VT S. pneumoniae than among the controls (13% vs. 21%, respectively; P < 0.001). The same pattern was seen in the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs. 34%, respectively; P = 0.017). The reverse trend was seen for non-VT strains in both the DCC attendees (44% vs. 34%, respectively; P < 0.001) and their younger siblings (19% vs. 13%, respectively; P = 0.15). There was a significant decrease in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9 recipients and their younger siblings. The relative risks (and 95% confidence intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to > or =1, > or =2 and > or =3 antibiotic categories among younger siblings of PnCRM9 recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to 0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired, VT and antibiotic-resistant S. pneumoniae were carried for a significantly shorter period of time among siblings of PnCRM9 recipients than in siblings of controls. The marked effect of PnCRM9 administration to DCC attendees on carriage of VT and antibiotic-resistant S. pneumoniae among their younger household close contacts demonstrates a herd effect of the vaccine.

PHISICS/RELAP5-3D RESULTS FOR EXERCISES II-1 AND II-2 OF THE OECD/NEA MHTGR-350 BENCHMARK

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

Strydom, Gerhard

2016-03-01

The Idaho National Laboratory (INL) Advanced Reactor Technologies (ART) High-Temperature Gas-Cooled Reactor (HTGR) Methods group currently leads the Modular High-Temperature Gas-Cooled Reactor (MHTGR) 350 benchmark. The benchmark consists of a set of lattice-depletion, steady-state, and transient problems that can be used by HTGR simulation groups to assess the performance of their code suites. The paper summarizes the results obtained for the first two transient exercises defined for Phase II of the benchmark. The Parallel and Highly Innovative Simulation for INL Code System (PHISICS), coupled with the INL system code RELAP5-3D, was used to generate the results for the Depressurized Conductionmore » Cooldown (DCC) (exercise II-1a) and Pressurized Conduction Cooldown (PCC) (exercise II-2) transients. These exercises require the time-dependent simulation of coupled neutronics and thermal-hydraulics phenomena, and utilize the steady-state solution previously obtained for exercise I-3 of Phase I. This paper also includes a comparison of the benchmark results obtained with a traditional system code “ring” model against a more detailed “block” model that include kinetics feedback on an individual block level and thermal feedbacks on a triangular sub-mesh. The higher spatial fidelity that can be obtained by the block model is illustrated with comparisons of the maximum fuel temperatures, especially in the case of natural convection conditions that dominate the DCC and PCC events. Differences up to 125 K (or 10%) were observed between the ring and block model predictions of the DCC transient, mostly due to the block model’s capability of tracking individual block decay powers and more detailed helium flow distributions. In general, the block model only required DCC and PCC calculation times twice as long as the ring models, and it therefore seems that the additional development and calculation time required for the block model could be worth the gain that can be obtained in the spatial resolution« less

Principles of metadata organization at the ENCODE data coordination center.

PubMed

Hong, Eurie L; Sloan, Cricket A; Chan, Esther T; Davidson, Jean M; Malladi, Venkat S; Strattan, J Seth; Hitz, Benjamin C; Gabdank, Idan; Narayanan, Aditi K; Ho, Marcus; Lee, Brian T; Rowe, Laurence D; Dreszer, Timothy R; Roe, Greg R; Podduturi, Nikhil R; Tanaka, Forrest; Hilton, Jason A; Cherry, J Michael

2016-01-01

The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center (DCC) is responsible for organizing, describing and providing access to the diverse data generated by the ENCODE project. The description of these data, known as metadata, includes the biological sample used as input, the protocols and assays performed on these samples, the data files generated from the results and the computational methods used to analyze the data. Here, we outline the principles and philosophy used to define the ENCODE metadata in order to create a metadata standard that can be applied to diverse assays and multiple genomic projects. In addition, we present how the data are validated and used by the ENCODE DCC in creating the ENCODE Portal (https://www.encodeproject.org/). Database URL: www.encodeproject.org. © The Author(s) 2016. Published by Oxford University Press.

Dynamic combinatorial libraries: from exploring molecular recognition to systems chemistry.

PubMed

Li, Jianwei; Nowak, Piotr; Otto, Sijbren

2013-06-26

Dynamic combinatorial chemistry (DCC) is a subset of combinatorial chemistry where the library members interconvert continuously by exchanging building blocks with each other. Dynamic combinatorial libraries (DCLs) are powerful tools for discovering the unexpected and have given rise to many fascinating molecules, ranging from interlocked structures to self-replicators. Furthermore, dynamic combinatorial molecular networks can produce emergent properties at systems level, which provide exciting new opportunities in systems chemistry. In this perspective we will highlight some new methodologies in this field and analyze selected examples of DCLs that are under thermodynamic control, leading to synthetic receptors, catalytic systems, and complex self-assembled supramolecular architectures. Also reviewed are extensions of the principles of DCC to systems that are not at equilibrium and may therefore harbor richer functional behavior. Examples include self-replication and molecular machines.

A financial network perspective of financial institutions' systemic risk contributions

NASA Astrophysics Data System (ADS)

Huang, Wei-Qiang; Zhuang, Xin-Tian; Yao, Shuang; Uryasev, Stan

2016-08-01

This study considers the effects of the financial institutions' local topology structure in the financial network on their systemic risk contribution using data from the Chinese stock market. We first measure the systemic risk contribution with the Conditional Value-at-Risk (CoVaR) which is estimated by applying dynamic conditional correlation multivariate GARCH model (DCC-MVGARCH). Financial networks are constructed from dynamic conditional correlations (DCC) with graph filtering method of minimum spanning trees (MSTs). Then we investigate dynamics of systemic risk contributions of financial institution. Also we study dynamics of financial institution's local topology structure in the financial network. Finally, we analyze the quantitative relationships between the local topology structure and systemic risk contribution with panel data regression analysis. We find that financial institutions with greater node strength, larger node betweenness centrality, larger node closeness centrality and larger node clustering coefficient tend to be associated with larger systemic risk contributions.

Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target.

PubMed

Frei, Priska; Pang, Lijuan; Silbermann, Marleen; Eriş, Deniz; Mühlethaler, Tobias; Schwardt, Oliver; Ernst, Beat

2017-08-25

Target-directed dynamic combinatorial chemistry (DCC) is an emerging technique for the efficient identification of inhibitors of pharmacologically relevant targets. In this contribution, we present an application for a bacterial target, the lectin FimH, a crucial virulence factor of uropathogenic E. coli being the main cause of urinary tract infections. A small dynamic library of acylhydrazones was formed from aldehydes and hydrazides and equilibrated at neutral pH in presence of aniline as nucleophilic catalyst. The major success factors turned out to be an accordingly adjusted ratio of scaffolds and fragments, an adequate sample preparation prior to HPLC analysis, and the data processing. Only then did the ranking of the dynamic library constituents correlate well with affinity data. Furthermore, as a support of DCC applications especially to larger libraries, a new protocol for improved hit identification was established. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neutrino-induced meson productions off nucleon at forward limit in nucleon resonance region

NASA Astrophysics Data System (ADS)

Nakamura, S. X.; Kamano, H.; Lee, T.-S. H.; Sato, T.

2015-05-01

We study forward neutrino-induced meson production off the nucleon in the resonance region. Our calculation is based on a dynamical coupled-channels (DCC) model that reasonably describes π(γ)N → πN, ηN, KΛ, KΣ data in the resonance region. We apply the PCAC hypothesis to the DCC model to relate the πN reaction amplitude to the forward neutrino reaction amplitude. In this way, we give a prediction for νN → πN, ππN, ηN, KΛ, KΣ reaction cross sections. The predicted νN → ππN, ηN, KΛ, KΣ cross sections are, for the first time, based on a model extensively tested by data. We compare our results with those from the Rein-Sehgal model that has been very often used in the existing Monte Carlo simulators for neutrino experiments. We find a significant difference between them.

Digital intelligent booster for DCC miniature train networks

NASA Astrophysics Data System (ADS)

Ursu, M. P.; Condruz, D. A.

2017-08-01

Modern miniature trains are now driven by means of the DCC (Digital Command and Control) system, which allows the human operator or a personal computer to launch commands to each individual train or even to control different features of the same train. The digital command station encodes these commands and sends them to the trains by means of electrical pulses via the rails of the railway network. Due to the development of the miniature railway network, it may happen that the power requirement of the increasing number of digital locomotives, carriages and accessories exceeds the nominal output power of the digital command station. This digital intelligent booster relieves the digital command station from powering the entire railway network all by itself, and it automatically handles the multiple powered sections of the network. This electronic device is also able to detect and process short-circuits and overload conditions, without the intervention of the digital command station.

Lotus birth, a holistic approach on physiological cord clamping.

PubMed

Zinsser, Laura A

2018-04-01

The positive effects of delayed cord clamping (DCC) has been extensively researched. DCC means: waiting at least one minute after birth before clamping and cutting the cord or till the pulsation has stopped. With physiological clamping and cutting (PCC) the clamping and cutting can happen at the earliest after the pulsation has stopped. With a Lotus birth, no clamping and cutting of the cord is done. A woman called Clair Lotus Day imitated the holistic approach of PCC from an anthropoid ape in 1974. The chimpanzee did not separate the placenta from the newborn. The aim of this case report is to discuss and learn a different approach in the third stage of labour. Three cases of Lotus birth by human beings were observed. All three women gave birth in an out-of-hospital setting and had ambulant postnatal care. The placenta was washed, salted and herbs were put on 2-3h post partum. The placenta was wrapped in something that absorbs the moisture. The salting was repeated with a degreasing frequency depending on moistness of the placenta. On life day six all three Lotus babies experiences a natural separation of the cord. All three Lotus birth cases were unproblematic, no special incidence occurred. One should differentiate between early cord clamping (ECC), delayed cord clamping (DCC) and physiological cord clamping (PCC). Lotus birth might lead to an optimisation of the bonding and attachment. Research is needed in the areas of both PCC and Lotus birth. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Environment and Health in Children Day Care Centres (ENVIRH) - Study rationale and protocol.

PubMed

Araújo-Martins, J; Carreiro Martins, P; Viegas, J; Aelenei, D; Cano, M M; Teixeira, J P; Paixão, P; Papoila, A L; Leiria-Pinto, P; Pedro, C; Rosado-Pinto, J; Annesi-Maesano, I; Neuparth, N

2014-01-01

Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children's respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children's health. A building ventilation model will also be developed. This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Quantitative Reactivity Scales for Dynamic Covalent and Systems Chemistry.

PubMed

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

2016-01-13

Dynamic covalent chemistry (DCC) has become a powerful tool for the creation of molecular assemblies and complex systems in chemistry and materials science. Herein we developed for the first time quantitative reactivity scales capable of correlation and prediction of the equilibrium of dynamic covalent reactions (DCRs). The reference reactions are based upon universal DCRs between imines, one of the most utilized structural motifs in DCC, and a series of O-, N-, and S- mononucleophiles. Aromatic imines derived from pyridine-2-carboxyaldehyde exhibit capability for controlling the equilibrium through distinct substituent effects. Electron-donating groups (EDGs) stabilize the imine through quinoidal resonance, while electron-withdrawing groups (EWGs) stabilize the adduct by enhancing intramolecular hydrogen bonding, resulting in curvature in Hammett analysis. Notably, unique nonlinearity induced by both EDGs and EWGs emerged in Hammett plot when cyclic secondary amines were used. This is the first time such a behavior is observed in a thermodynamically controlled system, to the best of our knowledge. Unified quantitative reactivity scales were proposed for DCC and defined by the correlation log K = S(N) (R(N) + R(E)). Nucleophilicity parameters (R(N) and S(N)) and electrophilicity parameters (R(E)) were then developed from DCRs discovered. Furthermore, the predictive power of those parameters was verified by successful correlation of other DCRs, validating our reactivity scales as a general and useful tool for the evaluation and modeling of DCRs. The reactivity parameters proposed here should be complementary to well-established kinetics based parameters and find applications in many aspects, such as DCR discovery, bioconjugation, and catalysis.

Non-Intrusive Velocity Measurements with MTV During DCC Event in the HTTF

NASA Technical Reports Server (NTRS)

Andre, M. A.; Bardet, P. M.; Cadell, S. R.; Woods, B.; Burns, R. A.; Danehy, P. M.

2017-01-01

Velocity profiles are measured using molecular tagging velocimetry (MTV) in the high temperature test facility (HTTF) at Oregon State University during a depressurized conduction cooldown (DCC) event. The HTTF is a quarter scale electrically heated nuclear reactor simulator designed to replicate various accident scenarios. During a DCC, a double ended guillotine break results in the reactor pressure vessel (RPV) depressurizing into the reactor cavity and ultimately leading to air ingress in the reactor core (lock-exchange and gas diffusion). It is critical to understand the resulting buoyancy-driven flow to characterize the reactor self-cooling capacity through natural circulation. During tests conducted at ambient pressure and temperature, the RPV containing helium is opened (via the hot and cold legs) to a large vessel filled with nitrogen to simulate the atmosphere. The velocity profile on the hot leg pipe centerline is recorded at 10 Hz with MTV based on NO tracers. The precision of the velocimetry was measured to be 0.02 m/s in quiescent flow prior to the tests. A helium flow from the RPV is initially observed in the top quarter of the pipe. During the first 20 seconds of the event, helium flows out of the RPV with a maximum velocity below 2 m/s. The velocity profile transitions from parabolic to linear in character and decays slowly over the rest of the recording; peak velocities of 0.2 m/s are observed after 30 min. A counter-flow of nitrogen is also observed intermittently, which occurs at lower velocities (>0.1 m/s).

Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins.

PubMed

Hernandez-Fleming, Melissa; Rohrbach, Ethan W; Bashaw, Greg J

2017-01-03

Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin. In contrast to other examples of reverse signaling where Sema1a triggers repulsion through activation of Rho in response to Plexin binding, in commissural neurons Sema-1a acts independently of Plexins to inhibit Rho to promote attraction to the midline. These findings suggest that Sema-1a reverse signaling can elicit distinct axonal responses depending on differential engagement of distinct ligands and signaling effectors. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

MUC1 and colorectal cancer pathophysiology considerations.

PubMed

Niv, Yaron

2008-04-14

Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and co-investigators showed recently that MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through beta-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-beta-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound.

Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

PubMed Central

Akin, Orkun; Zipursky, S Lawrence

2016-01-01

Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it. Thus, despite the graded ligand distribution along the guidance path, Net-Fra is not used for chemoattraction. Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidance in vivo, thereby eroding the distinction between them. DOI: http://dx.doi.org/10.7554/eLife.20762.001 PMID:27743477

Comparing airborne and satellite retrievals of cloud optical thickness and particle effective radius using a spectral radiance ratio technique: two case studies for cirrus and deep convective clouds

NASA Astrophysics Data System (ADS)

Krisna, Trismono C.; Wendisch, Manfred; Ehrlich, André; Jäkel, Evelyn; Werner, Frank; Weigel, Ralf; Borrmann, Stephan; Mahnke, Christoph; Pöschl, Ulrich; Andreae, Meinrat O.; Voigt, Christiane; Machado, Luiz A. T.

2018-04-01

Solar radiation reflected by cirrus and deep convective clouds (DCCs) was measured by the Spectral Modular Airborne Radiation Measurement System (SMART) installed on the German High Altitude and Long Range Research Aircraft (HALO) during the Mid-Latitude Cirrus (ML-CIRRUS) and the Aerosol, Cloud, Precipitation, and Radiation Interaction and Dynamic of Convective Clouds System - Cloud Processes of the Main Precipitation Systems in Brazil: A Contribution to Cloud Resolving Modelling and to the Global Precipitation Measurement (ACRIDICON-CHUVA) campaigns. On particular flights, HALO performed measurements closely collocated with overpasses of the Moderate Resolution Imaging Spectroradiometer (MODIS) aboard the Aqua satellite. A cirrus cloud located above liquid water clouds and a DCC topped by an anvil cirrus are analyzed in this paper. Based on the nadir spectral upward radiance measured above the two clouds, the optical thickness τ and particle effective radius reff of the cirrus and DCC are retrieved using a radiance ratio technique, which considers the cloud thermodynamic phase, the vertical profile of cloud microphysical properties, the presence of multilayer clouds, and the heterogeneity of the surface albedo. For the cirrus case, the comparison of τ and reff retrieved on the basis of SMART and MODIS measurements yields a normalized mean absolute deviation of up to 1.2 % for τ and 2.1 % for reff. For the DCC case, deviations of up to 3.6 % for τ and 6.2 % for reff are obtained. The larger deviations in the DCC case are mainly attributed to the fast cloud evolution and three-dimensional (3-D) radiative effects. Measurements of spectral upward radiance at near-infrared wavelengths are employed to investigate the vertical profile of reff in the cirrus. The retrieved values of reff are compared with corresponding in situ measurements using a vertical weighting method. Compared to the MODIS observations, measurements of SMART provide more information on the vertical distribution of particle sizes, which allow reconstructing the profile of reff close to the cloud top. The comparison between retrieved and in situ reff yields a normalized mean absolute deviation, which ranges between 1.5 and 10.3 %, and a robust correlation coefficient of 0.82.

Design and implementation of co-operative control strategy for hybrid AC/DC microgrids

NASA Astrophysics Data System (ADS)

Mahmud, Rasel

This thesis is mainly divided in two major sections: 1) Modeling and control of AC microgrid, DC microgrid, Hybrid AC/DC microgrid using distributed co-operative control, and 2) Development of a four bus laboratory prototype of an AC microgrid system. At first, a distributed cooperative control (DCC) for a DC microgrid considering the state-of-charge (SoC) of the batteries in a typical plug-in-electric-vehicle (PEV) is developed. In DC microgrids, this methodology is developed to assist the load sharing amongst the distributed generation units (DGs), according to their ratings with improved voltage regulation. Subsequently, a DCC based control algorithm for AC microgrid is also investigated to improve the performance of AC microgrid in terms of power sharing among the DGs, voltage regulation and frequency deviation. The results validate the advantages of the proposed methodology as compared to traditional droop control of AC microgrid. The DCC-based control methodology for AC microgrid and DC microgrid are further expanded to develop a DCC-based power management algorithm for hybrid AC/DC microgrid. The developed algorithm for hybrid microgrid controls the power flow through the interfacing converter (IC) between the AC and DC microgrids. This will facilitate the power sharing between the DGs according to their power ratings. Moreover, it enables the fixed scheduled power delivery at different operating conditions, while maintaining good voltage regulation and improved frequency profile. The second section provides a detailed explanation and step-by-step design and development of an AC/DC microgrid testbed. Controllers for the three-phase inverters are designed and tested on different generation units along with their corresponding inductor-capacitor-inductor (LCL) filters to eliminate the switching frequency harmonics. Electric power distribution line models are developed to form the microgrid network topology. Voltage and current sensors are placed in the proper positions to achieve a full visibility over the microgrid. A running average filter (RAF) based enhanced phase-locked-loop (EPLL) is designed and implemented to extract frequency and phase angle information. A PLL-based synchronizing scheme is also developed to synchronize the DGs to the microgrid. The developed laboratory prototype runs on dSpace platform for real time data acquisition, communication and controller implementation.

Comparison of Promoter Hypermethylation Pattern in Salivary Rinses Collected with and without an Exfoliating Brush from Patients with HNSCC

PubMed Central

Sun, Wenyue; Zaboli, David; Liu, Yan; Arnaoutakis, Demetri; Khan, Tanbir; Wang, Hao; Koch, Wayne; Khan, Zubair; Califano, Joseph A.

2012-01-01

Background Salivary rinses have been recently proposed as a valuable resource for the development of epigenetic biomarkers for detection and monitoring of head and neck squamous cell carcinoma (HNSCC). Both salivary rinses collected with and without an exfoliating brush from patients with HNSCC are used in detection of promoter hypermethylation, yet their correlation of promoter hypermethylation has not been evaluated. This study was to evaluate the concordance of promoter hypermethylation between salivary rinses collected with and without an exfoliating brush from patients with HNSCC. Methodolgy 57 paired salivary rinses collected with or without an exfoliating brush from identical HNSCC patients were evaluated for promoter hypermethylation status using Quantitative Methylation-Specific PCR. Target tumor suppressor gene promoter regions were selected based on our previous studies describing a panel for HNSCC screening and surveillance, including P16, CCNA1, DCC, TIMP3, MGMT, DAPK and MINT31. Principal Findings In salivary rinses collected with and without brush, frequent methylation was detected in P16 (8.8% vs. 5.2%), CCNA1 (26.3% vs. 22.8%), DCC (33.3% vs. 29.8%), TIMP3 (31.6% vs. 36.8%), MGMT (29.8% vs. 38.6%), DAPK (14.0% vs. 19.2%), and MINT31 (10.5% vs. 8.8%). Spearman's rank correlation coefficient showed a positive correlation between salivary rinses collected with and without brush for P16 (ρ = 0.79), CCNA1 (ρ = 0.61), DCC (ρ = 0.58), TIMP3 (ρ = 0.10), MGMT (ρ = 0.70), DAPK (ρ = 0.51) and MINT31 (ρ = 0.72) (P<0.01). The percent agreement of promoter methylation between salivary rinses with brush and without brush were 96.5% for P16, 82.5% for CCNA1, 78.9% for DCC, 59.7% for TIMP3, 84.2% for MGMT, 84.2% for DAPK, and 94.7% for MINT31. Conclusions Our study demonstrated strong correlations of gene promoter hypermethylation between salivary rinses collected with and without an exfoliating brush. Salivary rinse collection without using an exfoliating brush may offer a cost effective, rapid, non-invasive, and reliable means for development of epigenetic salivary rinse biomarkers. PMID:22438973

Attenuation of neointimal formation with netrin-1 and netrin-1 preconditioned endothelial progenitor cells.

PubMed

Liu, Norika Mengchia; Siu, Kin Lung; Youn, Ji Youn; Cai, Hua

2017-03-01

Restenosis after angioplasty is a serious clinical problem that can result in re-occlusion of the coronary artery. Although current drug-eluting stents have proved to be more effective in reducing restenosis, they have drawbacks of inhibiting reendothelialization to promote thrombosis. New treatment options are in urgent need. We have shown that netrin-1, an axon-guiding protein, promotes angiogenesis and cardioprotection via production of nitric oxide (NO). The present study examined whether and how netrin-1 attenuates neointimal formation in a femoral wire injury model. Infusion of netrin-1 into C57BL/6 mice markedly attenuated neointimal formation following wire injury of femoral arteries, measured by intimal to media ratio (from 1.94 ± 0.55 to 0.45 ± 0.86 at 4 weeks). Proliferation of VSMC in situ was largely reduced. This protective effect was absent in DCC +/- animals. NO production was increased by netrin-1 in both intact and injured femoral arteries, indicating netrin-1 stimulation of endogenous NO production from intact endothelium and remaining endothelial cells post-injury. VSMC migration was abrogated by netrin-1 via a NO/cGMP/p38 MAPK pathway, while timely EPC homing was induced. Injection of netrin-1 preconditioned wild-type EPCs, but not EPCs of DCC +/- animals, substantially attenuated neointimal formation. EPC proliferation, NO production, and resistance to oxidative stress induced apoptosis were augmented by netrin-1 treatment. In conclusion, our data for the first time demonstrate that netrin-1 is highly effective in reducing neointimal formation following vascular endothelial injury, which is dependent on DCC, and attributed to inhibition of VSMC proliferation and migration, as well as improved EPC function. These data may support usage of netrin-1 and netrin-1 preconditioned EPCs as novel therapies for post angioplasty restenosis. Netrin-1 attenuates neointimal formation following post endothelial injury via DCC and NO. Netrin-1 inhibits VSMC proliferation in situ following endothelial injury. Netrin-1 inhibits VSMC migration via a NO/cGMP/p38 MAPK pathway. Netrin-1 augments proliferation of endothelial progenitor cells (EPCs) and EPC eNOS/NO activation. Netrin-1 enhances resistance of EPCs to oxidative stress, improving re-endothelialization following injury.

Multifunctional Polymers and Composites for Self-Healing Applications

DTIC Science & Technology

2006-09-30

DCC) was obtained from Avocado . Reagent grade ether was purchased from Malinckrodt and anhydrous methylene chloride was purchased from Acros and...We have worked with several companies through sponsored research agreements to transition self-healing technology into the commercial market . These

Netrin-1 receptor antibodies in thymoma-associated neuromyotonia with myasthenia gravis.

PubMed

Torres-Vega, Estefanía; Mancheño, Nuria; Cebrián-Silla, Arantxa; Herranz-Pérez, Vicente; Chumillas, María J; Moris, Germán; Joubert, Bastien; Honnorat, Jérôme; Sevilla, Teresa; Vílchez, Juan J; Dalmau, Josep; Graus, Francesc; García-Verdugo, José Manuel; Bataller, Luis

2017-03-28

To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications. Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers). Immunoprecipitation studies identified 3 targets, including the Netrin-1 receptors DCC (deleted in colorectal carcinoma) and UNC5A (uncoordinated-5A) as well as Caspr2 (contactin-associated protein-like 2). Cell-based assays with these antigens showed that among the indicated patients, 9 had antibodies against Netrin-1 receptors (7 with additional Caspr2 antibodies) and 5 had isolated Caspr2 antibodies. Only one of the 219 controls had isolated Caspr2 antibodies with relapsing myelitis episodes. Among patients with neuromyotonia and/or myasthenia gravis, the presence of Netrin-1 receptor or Caspr2 antibodies predicted thymoma ( p < 0.05). Coexisting Caspr2 and Netrin-1 receptor antibodies were associated with concurrent thymoma, myasthenia gravis, and neuromyotonia, often with Morvan syndrome ( p = 0.009). Expression of DCC, UNC5A, and Caspr2 proteins was demonstrated in paraffin-embedded thymoma samples (3) and normal thymus. Antibodies against Netrin-1 receptors (DCC and UNC5a) and Caspr2 often coexist and associate with thymoma in patients with neuromyotonia and myasthenia gravis. This study provides Class III evidence that antibodies against Netrin-1 receptors can identify patients with thymoma (sensitivity 21.4%, specificity 100%). © 2017 American Academy of Neurology.

Unexpected role for dosage compensation in the control of dauer arrest, insulin-like signaling, and FoxO transcription factor activity in Caenorhabditis elegans.

PubMed

Dumas, Kathleen J; Delaney, Colin E; Flibotte, Stephane; Moerman, Donald G; Csankovszki, Gyorgyi; Hu, Patrick J

2013-07-01

During embryogenesis, an essential process known as dosage compensation is initiated to equalize gene expression from sex chromosomes. Although much is known about how dosage compensation is established, the consequences of modulating the stability of dosage compensation postembryonically are not known. Here we define a role for the Caenorhabditis elegans dosage compensation complex (DCC) in the regulation of DAF-2 insulin-like signaling. In a screen for dauer regulatory genes that control the activity of the FoxO transcription factor DAF-16, we isolated three mutant alleles of dpy-21, which encodes a conserved DCC component. Knockdown of multiple DCC components in hermaphrodite and male animals indicates that the dauer suppression phenotype of dpy-21 mutants is due to a defect in dosage compensation per se. In dpy-21 mutants, expression of several X-linked genes that promote dauer bypass is elevated, including four genes encoding components of the DAF-2 insulin-like pathway that antagonize DAF-16/FoxO activity. Accordingly, dpy-21 mutation reduced the expression of DAF-16/FoxO target genes by promoting the exclusion of DAF-16/FoxO from nuclei. Thus, dosage compensation enhances dauer arrest by repressing X-linked genes that promote reproductive development through the inhibition of DAF-16/FoxO nuclear translocation. This work is the first to establish a specific postembryonic function for dosage compensation in any organism. The influence of dosage compensation on dauer arrest, a larval developmental fate governed by the integration of multiple environmental inputs and signaling outputs, suggests that the dosage compensation machinery may respond to external cues by modulating signaling pathways through chromosome-wide regulation of gene expression.

Detection of triclocarban and two co-contaminating chlorocarbanilides in US aquatic environments using isotope dilution liquid chromatography tandem mass spectrometry.

PubMed

Sapkota, Amir; Heidler, Jochen; Halden, Rolf U

2007-01-01

The antimicrobial compound triclocarban (TCC; 3,4,4'-trichlorocarbanilide; CAS# 101-20-2) is a high-production-volume chemical, recently suggested to cause widespread contamination of US water resources. To test this hypothesis, we developed an isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry method for ultratrace analysis of TCC (0.9 ng/L detection limit) and analyzed low-volume water samples (200 mL) along with primary sludge samples from across the United States. All river water samples (100%) collected downstream of wastewater treatment plants had detectable levels of TCC, as compared to 56% of those taken upstream. Concentrations of TCC (mean+/-standard deviation) downstream of sewage treatment plants (84+/-110 ng/L) were significantly higher (P<0.05; Wilcoxon rank sum test) than those of samples taken upstream (12+/-15 ng/L). Compared to surface water, mean TCC concentrations found in dried, primary sludge obtained from municipal sewage treatment plants in five states were six orders of magnitude greater (19,300+/-7100 microg/kg). Several river samples contained a co-contaminant, identified based on its chromatographic retention time, molecular base ion, and MS/MS fragmentation behavior as 4,4'-dichlorocarbanilide (DCC; CAS# 1219-99-4). In addition to TCC and DCC, municipal sludge contained a second co-contaminant, 3,3',4,4'-tetrachlorocarbanilide (TetraCC; CAS# 4300-43-0). Both newly detected compounds were present as impurities (0.2%(w/w) each) in technical grade TCC (99%). Application of the new method for chlorocarbanilide analysis yielded TCC occurrence data for 13 US states, confirmed the role of sewage treatment plants as environmental inputs of TCC, and identified DCC and TetraCC as previously unrecognized pollutants released into the environment alongside TCC.

Comparative varicella vaccine effectiveness during outbreaks in day-care centres.

PubMed

Spackova, M; Wiese-Posselt, M; Dehnert, M; Matysiak-Klose, D; Heininger, U; Siedler, A

2010-01-08

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC). Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age<11 months, vaccinated at age<11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC). Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57-81, p<0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix (RR=2.8, 95%CI 1.0-7.8, p=0.05) or Priorix-Tetra (RR=2.4, 95%CI 0.7-8.3, p=0.18) but lower for 2 doses of Priorix-Tetra (RR=0.5, 95%CI 0.1-2.7, p=0.41) than for 1 dose of Varivax. Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.

Assessment of MODIS On-Orbit Calibration Using a Deep Convective Cloud Technique

NASA Technical Reports Server (NTRS)

Mu, Qiaozhen; Wu, Aisheng; Chang, Tiejun; Angal, Amit; Link, Daniel; Xiong, Xiaoxiong; Doelling, David R.; Bhatt, Rajendra

2016-01-01

The MODerate Resolution Imaging Spectroradiometer (MODIS) sensors onboard Terra and Aqua satellites are calibrated on-orbit with a solar diffuser (SD) for the reflective solar bands (RSB). The MODIS sensors are operating beyond their designed lifetime and hence present a major challenge to maintain the calibration accuracy. The degradation of the onboard SD is tracked by a solar diffuser stability monitor (SDSM) over a wavelength range from 0.41 to 0.94 micrometers. Therefore, any degradation of the SD beyond 0.94 micrometers cannot be captured by the SDSM. The uncharacterized degradation at wavelengths beyond this limit could adversely affect the Level 1B (L1B) product. To reduce the calibration uncertainties caused by the SD degradation, invariant Earth-scene targets are used to monitor and calibrate the MODIS L1B product. The use of deep convective clouds (DCCs) is one such method and particularly significant for the short-wave infrared (SWIR) bands in assessing their long-term calibration stability. In this study, we use the DCC technique to assess the performance of the Terra and Aqua MODIS Collection-6 L1B for RSB 1 3- 7, and 26, with spectral coverage from 0.47 to 2.13 micrometers. Results show relatively stable trends in Terra and Aqua MODIS reflectance for most bands. Careful attention needs to be paid to Aqua band 1, Terra bands 3 and 26 as their trends are larger than 1% during the study time period. We check the feasibility of using the DCC technique to assess the stability in MODIS bands 17-19. The assessment test on response versus scan angle (RVS) calibration shows substantial trend difference for Aqua band 1between different angles of incidence (AOIs). The DCC technique can be used to improve the RVS calibration in the future.

Tumor suppressor function of Betaig-H3 gene in radiation carcinogenesis

NASA Astrophysics Data System (ADS)

Zhao, Y. L.; Piao, C. Q.; Hei, T. K.

Interaction between cell and extracellular matrix (ECM) plays a crucial role in tumor invasiveness and metastasis. Using an immortalized human bronchial epithelial (BEP2D) cell model, we showed previously that expression of a list of genes including Betaig-h3 (induced by transforming growth factor-β) DCC (deleted in colorectal cancer), p21 cip1, c-fos , Heat shock protein (HSP27) and cytokeratin 14 were differentially expressed in several independently generated, radiation-induced tumor cell lines (TL1-TL5) relative to parental BEP2D cells. Our previous data further demonstrated that loss of tumor suppressor gene(s) as a likely mechanism of radiation carcinogenesis. In the present study, we chose Betaig-h3 and DCC that were downregulated in tumorigenic cells for further study. Restored expression of Betaig-h3 gene, not DCC gene, by transfecting cDNA into tumor cells resulted in a significant reduction in tumor growth. While integrin receptor α5β1 was overexpressed in tumor cells, its expression was corrected to the level found in control BEP2D cells after Betaig-h3 transfection. These data suggest that Betaig-h3 gene is involved in tumor progression by regulating integrin α5β1 receptor. Furthermore, exogenous TGF-β1 induced expression of Betaig-h3 gene and inhibited the growth of both control and tumorigenic BEP2D cells. Therefore, downregulation of Betaig-h3 gene may results from the decreased expression of upstream mediators such as TGF-β. The findings provide strong evidence that the Betaig-h3 gene has tumor suppressor function in radiation-induced tumorigenic human bronchial epithelial cells and suggest a potential target for interventional therapy.

An investigation of the speeding-related crash designation through crash narrative reviews sampled via logistic regression.

PubMed

Fitzpatrick, Cole D; Rakasi, Saritha; Knodler, Michael A

2017-01-01

Speed is one of the most important factors in traffic safety as higher speeds are linked to increased crash risk and higher injury severities. Nearly a third of fatal crashes in the United States are designated as "speeding-related", which is defined as either "the driver behavior of exceeding the posted speed limit or driving too fast for conditions." While many studies have utilized the speeding-related designation in safety analyses, no studies have examined the underlying accuracy of this designation. Herein, we investigate the speeding-related crash designation through the development of a series of logistic regression models that were derived from the established speeding-related crash typologies and validated using a blind review, by multiple researchers, of 604 crash narratives. The developed logistic regression model accurately identified crashes which were not originally designated as speeding-related but had crash narratives that suggested speeding as a causative factor. Only 53.4% of crashes designated as speeding-related contained narratives which described speeding as a causative factor. Further investigation of these crashes revealed that the driver contributing code (DCC) of "driving too fast for conditions" was being used in three separate situations. Additionally, this DCC was also incorrectly used when "exceeding the posted speed limit" would likely have been a more appropriate designation. Finally, it was determined that the responding officer only utilized one DCC in 82% of crashes not designated as speeding-related but contained a narrative indicating speed as a contributing causal factor. The use of logistic regression models based upon speeding-related crash typologies offers a promising method by which all possible speeding-related crashes could be identified. Published by Elsevier Ltd.

Copy number of the Adenomatous Polyposis Coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene.

PubMed

Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

2016-03-12

Changes in the number of alleles of a chromosome may have an impact upon gene expression. Loss of heterozygosity (LOH) indicates that one allele of a gene has been lost, and knowing the exact copy number of the gene would indicate whether duplication of the remaining allele has occurred. We were interested to determine the copy number of the Adenomatous Polyposis Coli (APC) gene in sporadic colorectal cancers with LOH. We selected 38 carcinomas with LOH for the APC gene region of chromosome 5, as determined by amplification of the CA repeat region within the D5S346 loci. The copy number status of APC was ascertained using the SALSA® MLPA® P043-B1 APC Kit. LOH for the DCC gene, KRAS gene mutation, and microsatellite instability were also evaluated for each tumor, utilizing standard polymerase chain reaction methods. No tumor demonstrated microsatellite instability. LOH of the DCC gene was also present in 33 of 36 (91.7%) informative tumors. A KRAS gene mutation was present in 16 of the 38 (42.1%) tumors. Twenty-four (63.2%) of the tumors were copy number neutral, 10 (26.3%) tumors demonstrated major loss, while two (5.3%) showed partial loss. Two tumors (5.3%) had copy number gain. Results of APC and DCC LOH, KRAS and microsatellite instability indicate our colorectal cancer cases were typical of sporadic cancers following the 'chromosomal instability' pathway. The majority of our colorectal carcinomas with LOH for APC gene are copy number neutral. However, one-third of our cases showed copy number loss, suggesting that duplication of the remaining allele is not required for the development of a colorectal carcinoma.

An Apprenticeship Rotation Teaches Chief Residents Nontechnical Skills and ACGME Core Competencies.

PubMed

Kwakye, Gifty; Chen, Xiaodong Phoenix; Havens, Joaquim M; Irani, Jennifer L; Yule, Steven; Smink, Douglas S

2015-01-01

Traditionally, surgical training has used an apprenticeship model but has more recently moved to a service-based model, with groups of residents working with groups of attending surgeons. We developed an apprenticeship rotation to enhance one-on-one interaction between chief residents and selected faculty. We hypothesized that the apprenticeship rotation would be effective for teaching nontechnical skills (NTS) and core competencies. An apprenticeship rotation was created at a university-based surgery residency in which each chief resident selected a single attending surgeon with whom to work exclusively with for a 4-week period. Emphasis was placed on teaching intraoperative NTS as well as the 4 difficult-to-teach Accreditation Council for Graduate Medical Education core competencies (DCC): Interpersonal and Communication Skills, Practice-Based Learning and Improvement, Professionalism, and Systems-Based Practice. Participants were surveyed afterwards about their rotation using a 5-point Likert scale. A Wilcoxon signed rank test was used to compare differences depending on data distribution. All (13/13) the chief residents and 67% (8/12) faculty completed the survey. Overall, 85% of residents and 87.5% of faculty would recommend the rotation to other residents/faculty members. Both residents and faculty reported improvement in trainees' technical skills and NTS. Residents reported improvement in all 4 DCC, particularly, Practice-Based Learning and Improvement, Professionalism, and Interpersonal and Communication Skills. The apprenticeship rotation is an effective means of teaching residents both NTS and DCC essential for independent practice. Consideration should be given to introducing this program into surgical curricula nationally. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Netrin-1 receptor antibodies in thymoma-associated neuromyotonia with myasthenia gravis

PubMed Central

Torres-Vega, Estefanía; Mancheño, Nuria; Cebrián-Silla, Arantxa; Herranz-Pérez, Vicente; Chumillas, María J.; Moris, Germán; Joubert, Bastien; Honnorat, Jérôme; Sevilla, Teresa; Vílchez, Juan J.; Dalmau, Josep; Graus, Francesc; García-Verdugo, José Manuel

2017-01-01

Objective: To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications. Methods: Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers). Results: Immunoprecipitation studies identified 3 targets, including the Netrin-1 receptors DCC (deleted in colorectal carcinoma) and UNC5A (uncoordinated-5A) as well as Caspr2 (contactin-associated protein-like 2). Cell-based assays with these antigens showed that among the indicated patients, 9 had antibodies against Netrin-1 receptors (7 with additional Caspr2 antibodies) and 5 had isolated Caspr2 antibodies. Only one of the 219 controls had isolated Caspr2 antibodies with relapsing myelitis episodes. Among patients with neuromyotonia and/or myasthenia gravis, the presence of Netrin-1 receptor or Caspr2 antibodies predicted thymoma (p < 0.05). Coexisting Caspr2 and Netrin-1 receptor antibodies were associated with concurrent thymoma, myasthenia gravis, and neuromyotonia, often with Morvan syndrome (p = 0.009). Expression of DCC, UNC5A, and Caspr2 proteins was demonstrated in paraffin-embedded thymoma samples (3) and normal thymus. Conclusions: Antibodies against Netrin-1 receptors (DCC and UNC5a) and Caspr2 often coexist and associate with thymoma in patients with neuromyotonia and myasthenia gravis. Classification of evidence: This study provides Class III evidence that antibodies against Netrin-1 receptors can identify patients with thymoma (sensitivity 21.4%, specificity 100%). PMID:28251919

LCRE and SNAP 50-DR-1 programs. Engineering progress report, October 1, 1962--December 31, 1962

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

None

Declassified 5 Sep 1973. Information is presented concerning LCRE specifications, reactor kinetics, fuel elements, primary coolant circuit, secondary coolant circuit, materials development, and fabrication; and SNAP50-DR- 1 specifications, primary pump, and materials development. (DCC)

LCRE and SNAP 50-DR-1 programs. Engineering progress report, January 1, 1963--March 31, 1963

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

None

Declassified 5 Sep 1973. Information is presented concerning LCRE specifications, primary coolant circuit, aaxiliary systems, fuel elements, instrumentation, materials development, and fabrication; and SNAP-50DR-1 specifications, fuel elements, pumps, steam generator, and materials development. (DCC)

Interactions between deep convective clouds and aerosols as observed by satellites

NASA Astrophysics Data System (ADS)

Yuan, T.; Li, Z. I.; Remer, L.; Martins, V.

2008-12-01

Major uncertainties regarding interactions between deep convective clouds (DCC) exist due partly to observational difficulty and partly to the entanglement among remotely sensed properties of aerosols and clouds and entanglement between meteorology and possible aerosol signals. In this study we adopt a novel, physically sound relationship between cloud crystal effective radius(CER) and brightness temperature (BT) and utilize ample sampling opportunity provided by MODIS instrument. We reveal aerosol impacts on DCCs by analyzing an ensemble data. Through a conceptual model we demonstrate how aerosol may affect DCC properties. We outline a few scenarios where aerosol signals are best separated and pronounced. Based on our results, anthropogenic pollutions and smokes are shown to effectively decrease CER and to elevate glaciation level of DCCs. On the other hand, dust particles from local sources have the opposite effects, namely, increasing cloud ice particle size and enhancing glaciation by acting possibly as giant CCN or IN. Implications of these effects for aerosols are discussed along with feedbacks of these effects to dynamics.

Theoretical and Experimental Study on Wide Range Optical Fiber Turbine Flow Sensor.

PubMed

Du, Yuhuan; Guo, Yingqing

2016-07-15

In this paper, a novel fiber turbine flow sensor was proposed and demonstrated for liquid measurement with optical fiber, using light intensity modulation to measure the turbine rotational speed for converting to flow rate. The double-circle-coaxial (DCC) fiber probe was introduced in frequency measurement for the first time. Through the divided ratio of two rings light intensity, the interference in light signals acquisition can be eliminated. To predict the characteristics between the output frequency and flow in the nonlinear range, the turbine flow sensor model was built. Via analyzing the characteristics of turbine flow sensor, piecewise linear equations were achieved in expanding the flow measurement range. Furthermore, the experimental verification was tested. The results showed that the flow range ratio of DN20 turbine flow sensor was improved 2.9 times after using piecewise linear in the nonlinear range. Therefore, combining the DCC fiber sensor and piecewise linear method, it can be developed into a strong anti-electromagnetic interference(anti-EMI) and wide range fiber turbine flowmeter.

Theoretical and Experimental Study on Wide Range Optical Fiber Turbine Flow Sensor

PubMed Central

Du, Yuhuan; Guo, Yingqing

2016-01-01

In this paper, a novel fiber turbine flow sensor was proposed and demonstrated for liquid measurement with optical fiber, using light intensity modulation to measure the turbine rotational speed for converting to flow rate. The double-circle-coaxial (DCC) fiber probe was introduced in frequency measurement for the first time. Through the divided ratio of two rings light intensity, the interference in light signals acquisition can be eliminated. To predict the characteristics between the output frequency and flow in the nonlinear range, the turbine flow sensor model was built. Via analyzing the characteristics of turbine flow sensor, piecewise linear equations were achieved in expanding the flow measurement range. Furthermore, the experimental verification was tested. The results showed that the flow range ratio of DN20 turbine flow sensor was improved 2.9 times after using piecewise linear in the nonlinear range. Therefore, combining the DCC fiber sensor and piecewise linear method, it can be developed into a strong anti-electromagnetic interference(anti-EMI) and wide range fiber turbine flowmeter. PMID:27428976

Robust forests of vertically aligned carbon nanotubes chemically assembled on carbon substrates.

PubMed

Garrett, David J; Flavel, Benjamin S; Shapter, Joseph G; Baronian, Keith H R; Downard, Alison J

2010-02-02

Forests of vertically aligned carbon nanotubes (VACNTs) have been chemically assembled on carbon surfaces. The structures show excellent stability over a wide potential range and are resistant to degradation from sonication in acid, base, and organic solvent. Acid-treated single-walled carbon nanotubes (SWCNTs) were assembled on amine-terminated tether layers covalently attached to pyrolyzed photoresist films. Tether layers were electrografted to the carbon substrate by reduction of the p-aminobenzenediazonium cation and oxidation of ethylenediamine. The amine-modified surfaces were incubated with cut SWCNTs in the presence of N,N'-dicyclohexylcarbodiimide (DCC), giving forests of vertically aligned carbon nanotubes (VACNTs). The SWCNT assemblies were characterized by scanning electron microscopy, atomic force microscopy, and electrochemistry. Under conditions where the tether layers slow electron transfer between solution-based redox probes and the underlying electrode, the assembly of VACNTs on the tether layer dramatically increases the electron-transfer rate at the surface. The grafting procedure, and hence the preparation of VACNTs, is applicable to a wide range of materials including metals and semiconductors.

Linear pi-Acceptor-Templated Dynamic Clipping to Macrobicycles and[2]Rotaxanes

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

Klivansky, Liana M.; Koshkakaryan, Gayane; Cao, Dennis

2009-04-30

Functional rotaxanes are one of the representative nanoscale molecular machines that have found applications in many areas, including molecular electronics, nanoelectromechanical systems (NEMS), photo controllable smart surfaces, and nanovalves. With the advent of molecular recognition and self-assembly, such molecular compounds can now be obtained efficiently through template-directed synthesis. One of the common strategies of making [2]rotaxanes involves the clipping of a macrocycle around a preformed dumbbell-shaped template in a [1+1] or [2+2] manner. While early examples were based on irreversible kinetic pathway through covalent bond formation, recent advances on reversible dynamic covalent chemistry (DCC) has attracted great attention to thismore » field. By virtue of thermodynamically controlled equilibria, DCC has provided highly efficient and versatile synthetic routes in the selection of specific products from a complex system. Among the several reversible reactions in the category of DCC reactions, the imine formation has proven to be very versatile in macrocyclization to give complex interlocked molecular compounds. Cryptands are three dimensional bicyclic hosts with preorganized cavities capable of inclusion of ions and small molecules. Replacing the nitrogen bridgeheads in common cryptands with aromatic ring systems gives cyclophane-based macrobicycles. The introduction of aromatic ring systems into a preorganized cage-like geometry facilitates ion-{pi} interactions and {pi}-{pi} interactions, resulting in novel metal sandwiches, fluoride receptors, and host-guest complexes. In particular, the seminal work by Gibson, Huang and coworkers on cryptand complexation with paraquat and diquat guests have resulted in the efficient synthesis of mechanically interlocked rotaxanes. The synthesis of cyclophane-based macrobicycles, however, was mostly realized through multiple reaction steps and in high-dilution conditions, which often suffered from low yield and tedious workup. Thus, a one-step, five-component [2+3] clipping reaction that can give the desired macrobicycle is highly desirable. We are motivated by a {pi}-guest templating protocol, because not only {pi}-{pi} interactions can contribute to the formation of macrobicycles, but also the resulting host-guest system holds great promise as a forerunner in the construction of interlocked molecules. (Scheme 1c) Very simple precursors, namely 1,3,5-benzenetrialdehyde (1) and 2,2{prime}-(ethylenedioxy)diethylamine (2) were chosen as the components for desired macrobicycle. (Scheme 2) The formation of six imine bonds would connect the five components to give a macrobicycle while extending the conjugation in the C{sub 3}-symmetric aromatic 'ceiling' and 'floor', which is suitable for enhancing the {pi}-{pi} interactions with a complementary aromatic template. Meanwhile, the ethylene glycol 'pillars' can provide sufficient flexibility, proper spacing, and polar binding sites to assist guest encapsulation. Initial screening of ?-templates engaged several C{sub 3} symmetric aromatic compounds in order to match the symmetry of the desired macrobicycle, which only resulted in nonspecific mixtures. It was found instead that linear bipyridinium (BPY) containing guests effectively templated the [2+3] clipping reaction. Based on this protocol, a [2]rotaxane was successfully assembled as the single product from the six-component reaction.« less

Developing Customized Programs for Steel and Other Heavy Industries.

ERIC Educational Resources Information Center

Day, Philip R., Jr.

1984-01-01

Describes Dundalk Community College's (DCC's) customized training programs for local industries. Looks at employment problems and outlook in Baltimore County, the development of a training agreement with Bethlehem Steel, the use of the Developing a Curriculum (DACUM) process to develop skill profiles, and future directions. (DMM)

NEW Work for Women: A Model Program for Nontraditional Careers.

ERIC Educational Resources Information Center

de Wit, Kathleen S.

The NEW (Nontraditional Employment for Women Act) Work for Women project at Dundalk Community College (DCC) encourages and assists women in entering nontraditional fields, especially the building and construction trades. The program provides comprehensive services in outreach and awareness of nontraditional careers, career counseling, education,…

LCRE and SNAP 50-DR-1 programs. Engineering and progress report, April 1, 1963--June 30, 1963

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

None

BS>Declassified 6 Sep 1973. Information is presented concerning the LCRE kinetics, auxiliary systems, fuel, primary cooling system components, instrumentation, secondary cooling system, materials development, and fabrication; and SNAP-50/SPUR kinetics, fuel, primary system pump, steam generator, and materials development. (DCC)

The Cutting Edge, 1999-2000.

ERIC Educational Resources Information Center

Cutting Edge, 2000

2000-01-01

The Cutting Edge is a bimonthly newsletter of the Regional Center for Applied Technology and Training at Danville Community College (DCC) (Virginia) that provides the latest information on a wide range of issues including technology, business, employment trends, and new legislation. Articles from the first five issues discuss: (1) the July 2000…

Air traffic control : good progress on interim replacement for outage-plagued system, but risks can be further reduced

DOT National Transportation Integrated Search

1996-10-01

Certain air traffic control(ATC) centers experienced a series of major outages, : some of which were caused by the Display Channel Complex or DCC-a mainframe : computer system that processes radar and other data into displayable images on : controlle...

Evaluation of the Virgin Mechanical and Thermal Properties of AVCO 3DCC Heatshield Materials

DTIC Science & Technology

1977-03-01

alumina or zirconia powder . Surrounding the guard is an annulus of distomaceous earth enclosed in an aluminum or transite shell. The specimens and...pa.-ked with either copper granules, graphite or zirconia powder . This packing provides a positive method for centering the calorimeter within the

MUC1 and colorectal cancer pathophysiology considerations

PubMed Central

Niv, Yaron

2008-01-01

Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and co-investigators showed recently that MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through β-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-β-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound. PMID:18407586

78 FR 28859 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

... Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; DCC MAPP Network. Date: June 12, 2013... Digestive and Kidney Diseases Special Emphasis Panel; NIDDK Bioengineering Interdisciplinary Training for...

77 FR 52750 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel HALT-PKD DCC. Date: October 17, [email protected] . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases...

The Economic Impact of Dutchess Community College.

ERIC Educational Resources Information Center

Dutchess Community Coll., Poughkeepsie, NY. Office of Planning and Institutional Research.

In an effort to measure the economic impact of Dutchess Community College (DCC), in Poughkeepsie, New York, on Dutchess County, a study was undertaken of expenditures and jobs created in the county during fiscal year 1991-92. To measure the tangible economic impact, three major financial components were examined: direct expenditures by the college…

Developing Clinical Leaders in Primary Care: The US Air Force Diabetes Champion Course

DTIC Science & Technology

2017-04-03

The US Air Force Diabetes Center of Excellence designed the Diabetes Champion Course (DCC), a semi-annual, 3-day course, to train primary care teams ...and patient flow in a team -based setting. Each team is tasked to identify local deficits and make a Plan of Action (POA) for implementation.

Bossier Parish Community College and Delgado Community College Collaborative Pharmacy Technician Program Distance Education Initiative.

ERIC Educational Resources Information Center

Bossier Parish Community Coll., Bossier City, LA.

Two Louisiana community colleges--Bossier Parish Community College (BPCC) and Delgado Community College (DCC)--proposed, developed, and implemented a collaborative Pharmacy Technician program for delivery through the use of two-way interactive video. The new program was inspired by new certification requirements instituted by the state of…

Impact Measures for a Marketing Intervention Strategy at a Two-Year College.

ERIC Educational Resources Information Center

Donsky, Aaron P.; And Others

In fall 1983, Dutchess Community College (DCC), Poughkeepsie, New York, implemented a strategic planning process which ultimately resulted in the development of short- and long-range marketing plans. The initial marketing approach began in spring 1985 and was directed toward a pilot project to affect summer 1985 enrollments utilizing a market…

Bypass Mechanisms of the Androgen Receptor Pathway in Therapy-Resistant Prostate Cancer Cell Models

PubMed Central

Marques, Rute B.; Dits, Natasja F.; Erkens-Schulze, Sigrun; van Weerden, Wytske M.; Jenster, Guido

2010-01-01

Background Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for late-stage tumors. However, despite initial remission, the cancer will inevitably recur. The present study was designed to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions. As model system, we used the androgen-responsive PC346C cell line and its therapy-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2. Methodology/Principal Findings Microarray technology was used to analyze differences in gene expression between the androgen-responsive and therapy-resistant PC346 cell lines. Microarray analysis revealed 487 transcripts differentially-expressed between the androgen-responsive and the therapy-resistant cell lines. Most of these genes were common to all three therapy-resistant sublines and only a minority (∼5%) was androgen-regulated. Pathway analysis revealed enrichment in functions involving cellular movement, cell growth and cell death, as well as association with cancer and reproductive system disease. PC346DCC expressed residual levels of androgen receptor (AR) and showed significant down-regulation of androgen-regulated genes (p-value = 10−7). Up-regulation of VAV3 and TWIST1 oncogenes and repression of the DKK3 tumor-suppressor was observed in PC346DCC, suggesting a potential AR bypass mechanism. Subsequent validation of these three genes in patient samples confirmed that expression was deregulated during prostate cancer progression. Conclusions/Significance Therapy-resistant growth may result from adaptations in the AR pathway, but androgen-independence may also be achieved by alternative survival mechanisms. Here we identified TWIST1, VAV3 and DKK3 as potential players in the bypassing of the AR pathway, making them good candidates as biomarkers and novel therapeutical targets. PMID:20976069

Effect of gamma irradiation and its convergent treatment for control of postharvest Botrytis cinerea of cut roses

NASA Astrophysics Data System (ADS)

Chu, Eun-Hee; Shin, Eun-Jung; Park, Hae-Jun; Jeong, Rae-Dong

2015-10-01

Postharvest diseases cause considerable losses to harvested crops. Among them, gray mold (Botrytis cinerea) is a major problem of exporting to cut rose flowers into Korea. Irradiation treatment is an alternative to phytosanitary purposes and a useful nonchemical approach to the control of postharvest diseases. Gamma irradiation was evaluated for its in vitro and in vivo antifungal activity against B. cinerea on cut rose varieties, 'Shooting Star' and 'Babe'. The irradiating dose required to reduce the population by 90%, D10, was 0.99 kGy. Gamma irradiation showed complete inhibition of spore germination and mycelial growth of B. cinerea, especially 4.0 kGy in vitro. Antifungal activity of gamma irradiation on rose B. cinerea is a dose-dependent manner. A significant phytotoxicity such as bent neck in cut rose quality was shown from gamma irradiation at over 0.4 kGy (p<0.05) in both varieties. Although there is no significant difference in both varieties for fresh weight, in the case of flower rate, 'Babe' shows more sensitivity than 'Shooting Star'. In vivo assays demonstrated that established doses in in vitro, over 4 kGy, could completely inactive fungal pathogens, but such high doses can cause severe flowers damage. Thus, to eliminate negative impact on their quality, gamma irradiation was evaluated at lower doses in combination with an eco-friendly chemical, sodium dichloroisocyanurate (NaDCC) to examine the inhibition of B. cinerea. Intriguingly, only the combined treatment with 0.2 kGy of gamma irradiation and 70 ppm of NaDCC exhibited significant synergistic antifungal activity against blue mold decay in both varieties. Together, these results suggest that a synergistic effect of the combined treatment with gamma irradiation and NaDCC can be efficiently used to control the postharvest diseases in cut rose flowers, and will provide a promising technology for horticulture products for exportation.

A uniform geostationary visible calibration approach to achieve a climate quality dataset

NASA Astrophysics Data System (ADS)

Haney, C.; Doelling, D.; Bhatt, R.; Scarino, B. R.; Gopalan, A.

2013-12-01

The geostationary (GEO) weather satellite visible and IR image record has surpassed 30 years. They have been preserved in the ISCCP-B1U 3-hourly dataset and other archives such as McIDAS, EUMETSAT, and NOAA CLASS. Since they were designed to aid in weather forecasting, long-term calibration stability was not a high priority. All GEO imagers lack onboard visible calibration and suffer from optical degradation after they are launched. In order to piece together the 35+ GEO satellite record both in time and space, a uniform calibration approach is desired to remove individual GEO temporal trends, as well as GEO spectral band differences. Otherwise, any artificial discontinuities caused by sequential GEO satellite records or spurious temporal trends caused by optical degradation may be interpreted as a change in climate. The approach relies on multiple independent methods to reduce the overall uncertainty of the GEO calibration coefficients. Consistency among methods validates the approach. During the MODIS record (2000 to the present) the GEO satellites are inter-calibrated against MODIS using ray-matched or bore-sighted radiance pairs. The MODIS and the VIIRS follow on instruments are equipped with onboard calibration thereby providing a stable calibration reference. The GEO spectral band differences are accounted for using a Spectral Band Adjustment Factor (SBAF) based on hyper-spectral SCIAMACHY data. During the pre-MODIS era, invariant earth targets of deserts and deep convective clouds (DCC) are used. Since GEO imagers have maintained their imaging scan schedules, GEO desert and DCC bidirectional reflectance distribution functions (BRDF) can be constructed and validated during the MODIS era. The BRDF models can then be applied to historical GEO imagers. Consistency among desert and DCC GEO calibration gains validates the approach. This approach has been applied to the GEO record beginning in 1985 and the results will be presented at the meeting.

Inhibitory effect of gamma irradiation and its application for control of postharvest green mold decay of Satsuma mandarins.

PubMed

Jeong, Rae-Dong; Chu, Eun-Hee; Lee, Gun Woong; Cho, Chuloh; Park, Hae-Jun

2016-10-03

Gamma irradiation has been shown to be effective for the control of postharvest fungi in vitro, but little is known regarding antifungal action, responses to gamma irradiation, and its application to fresh produce. Gamma irradiation was evaluated for its in vitro and in vivo antifungal activity against Penicillium digitatum on Satsuma mandarin fruits. Green mold was inhibited in a dose-dependent manner. Gamma irradiation showed a complete inhibition of spore germination, germ tube elongation, and mycelial growth of P. digitatum, particularly at 1.0kGy. To further investigate the mechanisms by which gamma irradiation inhibits fungal growth, the membrane integrity and cellular leakage of conidia were tested, indicating that gamma irradiation results in the loss of plasma membrane integrity, causing the release of intracellular contents such as soluble proteins. In vivo assays demonstrated that established doses can completely inhibit the growth of fungal pathogens, but such high doses cause severe fruit damage. Thus, to eliminate the negative impact on fruit quality, gamma irradiation at lower doses was evaluated for inhibition of P. digitatum, in combination with a chlorine donor, sodium dichloro-s-triazinetrione (NaDCC). Interestingly, only a combined treatment with 0.4kGy of gamma irradiation and 10ppm of NaDCC exhibited significant synergistic antifungal activity against green mold decay. The mechanisms by which the combined treatment decreased the green mold decay of mandarin fruits can be directly associated with the disruption of cell membrane of the fungal pathogen, which resulted in a loss of cytoplasmic material from the hyphae. These findings suggest that a synergistic effect of combining treatment with gamma irradiation with NaDCC has potential as an antifungal approach to reduce the severity of green mold in mandarin fruits. Copyright © 2016 Elsevier B.V. All rights reserved.

Loss of Chromosome 18 in Neuroendocrine Tumors of the Small Intestine: The Enigma Remains.

PubMed

Nieser, Maike; Henopp, Tobias; Brix, Joachim; Stoß, Laura; Sitek, Barbara; Naboulsi, Wael; Anlauf, Martin; Schlitter, Anna M; Klöppel, Günter; Gress, Thomas; Moll, Roland; Bartsch, Detlef K; Heverhagen, Anna E; Knoefel, Wolfram T; Kaemmerer, Daniel; Haybaeck, Johannes; Fend, Falko; Sperveslage, Jan; Sipos, Bence

2017-01-01

Neuroendocrine tumors of the small intestine (SI-NETs) exhibit an increasing incidence and high mortality rate. Until now, no fundamental molecular event has been linked to the tumorigenesis and progression of these tumors. Only the loss of chromosome 18 (Chr18) has been shown in up to two thirds of SI-NETs, whereby the significance of this alteration is still not understood. We therefore performed the first comprehensive study to identify Chr18-related events at the genetic, epigenetic and gene/protein expression levels. We did expression analysis of all seven putative Chr18-related tumor suppressors by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Next-generation exome sequencing and SNP array analysis were performed with five SI-NETs with (partial) loss of Chr18. Finally, we analyzed all microRNAs (miRNAs) located on Chr18 by qRT-PCR, comparing Chr18+/- and Chr18+/+ SI-NETs. Only DCC (deleted in colorectal cancer) revealed loss of/greatly reduced expression in 6/21 cases (29%). No relevant loss of SMAD2, SMAD4, elongin A3 and CABLES was detected. PMAIP1 and maspin were absent at the protein level. Next-generation sequencing did not reveal relevant recurrent somatic mutations on Chr18 either in an exploratory cohort of five SI-NETs, or in a validation cohort (n = 30). SNP array analysis showed no additional losses. The quantitative analysis of all 27 Chr18-related miRNAs revealed no difference in expression between Chr18+/- and Chr18+/+ SI-NETs. DCC seems to be the only Chr18-related tumor suppressor affected by the monoallelic loss of Chr18 resulting in a loss of DCC protein expression in one third of SI-NETs. No additional genetic or epigenetic alterations were present on Chr18. © 2016 S. Karger AG, Basel.

Impact of delayed umbilical cord clamping on public cord blood donations: can we help future patients and benefit infant donors?

PubMed

Ciubotariu, Rodica; Scaradavou, Andromachi; Ciubotariu, Ilinca; Tarnawski, Michal; Lloyd, Sara; Albano, Maria; Dobrila, Ludy; Rubinstein, Pablo; Grunebaum, Amos

2018-03-25

Cord blood (CB) is a widely accepted stem cell source and its clinical utilization depends, to a great extent, on its cell content. Birth-to-clamping (BTC) time of umbilical cord determines placental transfusion to the newborn, and the remaining blood that can be collected and banked. The 2017 Committee Opinion of the American College of Obstetrics and Gynecologists (ACOG) recommends a delay of "at least 30-60 seconds" before clamping the cord for all newborns to ensure adequate iron stores. The impact of delayed cord clamping (DCC) on public CB banking can be substantial. Cord blood units (CBUs) collected from 1210 mothers at one hospital were evaluated for total nucleated cells (TNCs) and weight/volume based on time to clamping. Bank staff recorded BTC time in seconds as reported by obstetricians; collections were performed ex utero. Immediate clamping was defined as BTC of less than 30 seconds, whereas DCC was defined as BTC of 30 seconds or more. Cord clamping was immediate in 903 (75%) and delayed in 307 (25%) deliveries. Successful recovery (% clinical CBUs) decreased 10-fold with DCC of more than 60 seconds (22% vs. 2.4%, p < 0.001). CBUs collected after DCC of more than 60 seconds had significantly lower TNC counts than those after DCC of less than 60 seconds (p < 0.0001). Furthermore, 38% to 46% of CBUs after DCC of more than 60 seconds had volume of less than 40 mL. Our study indicates that DCC of 30 to 60 seconds has a small negative impact on collection of high-TNC-count CBUs. However, increasing BTC to more than 60 seconds decreases significantly both TNC content and volume, reducing drastically the chances of obtaining clinically useful CBUs. © 2018 AABB.

Utilizing the Antarctic Master Directory to find orphan datasets

NASA Astrophysics Data System (ADS)

Bonczkowski, J.; Carbotte, S. M.; Arko, R. A.; Grebas, S. K.

2011-12-01

While most Antarctic data are housed at an established disciplinary-specific data repository, there are data types for which no suitable repository exists. In some cases, these "orphan" data, without an appropriate national archive, are served from local servers by the principal investigators who produced the data. There are many pitfalls with data served privately, including the frequent lack of adequate documentation to ensure the data can be understood by others for re-use and the impermanence of personal web sites. For example, if an investigator leaves an institution and the data moves, the link published is no longer accessible. To ensure continued availability of data, submission to long-term national data repositories is needed. As stated in the National Science Foundation Office of Polar Programs (NSF/OPP) Guidelines and Award Conditions for Scientific Data, investigators are obligated to submit their data for curation and long-term preservation; this includes the registration of a dataset description into the Antarctic Master Directory (AMD), http://gcmd.nasa.gov/Data/portals/amd/. The AMD is a Web-based, searchable directory of thousands of dataset descriptions, known as DIF records, submitted by scientists from over 20 countries. It serves as a node of the International Directory Network/Global Change Master Directory (IDN/GCMD). The US Antarctic Program Data Coordination Center (USAP-DCC), http://www.usap-data.org/, funded through NSF/OPP, was established in 2007 to help streamline the process of data submission and DIF record creation. When data does not quite fit within any existing disciplinary repository, it can be registered within the USAP-DCC as the fallback data repository. Within the scope of the USAP-DCC we undertook the challenge of discovering and "rescuing" orphan datasets currently registered within the AMD. In order to find which DIF records led to data served privately, all records relating to US data within the AMD were parsed. After identifying the records containing a URL leading to a national data center or other disciplinary data repository, the remaining records were individually inspected for data type, format, and quality of metadata and then assessed to determine how best to preserve. Of the records reviewed, those for which appropriate repositories could be identified were submitted. An additional 35 were deemed acceptable in quality of metadata to register in the USAP-DCC. The content of these datasets were varied in nature, ranging from penguin counts to paleo-geologic maps to results of meteorological models all of which are discoverable through our search interface, http://www.usap-data.org/search.php. The remaining 40 records linked to either no data or had inadequate documentation for preservation highlighting the danger of serving datasets on local servers where minimal metadata standards can not be enforced and long-term access can not be ensured.

Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

PubMed Central

2017-01-01

Conspectus Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular biodynamers are commonly produced in aqueous media under mild or even physiological conditions to suit their biorelated applications. In contrast to static biopolymers emphasizing structural stability and unity by using irreversible covalent bonds, molecular biodynamers are seeking relative structural adaptability and diversity through the formation of reversible covalent bonds. Based on these considerations, molecular biodynamers are capable of reorganizing their monomers, generating, identifying, and amplifying the fittest structures in response to environmental factors. Hence, molecular biodynamers have received considerable research attention over the past decades. Accordingly, the construction of molecular biodynamers through equilibrium polymerization of nucleobase-, carbohydrate- or amino-acid-based monomers can lead to the fabrication of dynamic analogues of nucleic acids (DyNAs), polysaccharides (glycodynamers), or proteins (dynamic proteoids), respectively. In this Account, we summarize recent advances in developing different types of molecular biodynamers as structural or functional biomimetics of biopolymers, including DyNAs, glycodynamers, and dynamic proteoids. We introduce how chemists utilize various reversible reactions to generate molecular biodynamers with specific sequences and well-ordered structures in aqueous medium. We also discuss and list their potential applications in various research fields, such as drug delivery, drug discovery, gene sensing, cancer diagnosis, and treatment. PMID:28169527

State Articulated Instructional Objectives Guide for Occupational Education Programs. State Pilot Model for Automotive Mechanics (DCC V-003) and Automotive Mechanics (High School).

ERIC Educational Resources Information Center

North Carolina State Dept. of Community Colleges, Raleigh.

This articulation instructional objective guide for automotive mechanics contains summary information on fifteen blocks (courses) of instruction. They are introduction to automotive technology; lubrication and vehicle operating maintenance; cooling system maintenance and repair; automobile heater maintenance and repair; braking system maintenance…

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia

PubMed Central

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P.; Snyder, David S.; Khoury, Jean; Bhalla, Kapil N.; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C.; Rutkoski, Thomas J.; Smith, Bryan D.; Flynn, Daniel L.; Kantarjian, Hagop M.; Rosen, Oliver; Van Etten, Richard A.

2017-01-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5′-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib (clinicaltrials.gov Identifier:00827138). PMID:27927766

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia.

PubMed

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P; Snyder, David S; Khoury, Jean; Bhalla, Kapil N; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C; Rutkoski, Thomas J; Smith, Bryan D; Flynn, Daniel L; Kantarjian, Hagop M; Rosen, Oliver; Van Etten, Richard A

2017-03-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5'-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib ( clinicaltrials.gov Identifier:00827138 ). Copyright© Ferrata Storti Foundation.

Report on Users' Satisfaction with Services Provided by Institutional Research. Research Report.

ERIC Educational Resources Information Center

Bashford, Joanne

The Office of Institutional Research (IR) at Miami-Dade Community College (M-DCC) (Florida) offers the results of a survey regarding the use of the office's services. Instead of using hard copy format as in the past, the current survey was conducted online. An e-mail message requesting participation was sent to the 3,498 employees with e-mail…

Transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 control anterior-posterior neuroblast migration with left-right functional asymmetry in Caenorhabditis elegans.

PubMed

Sundararajan, Lakshmi; Lundquist, Erik A

2012-12-01

Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left-right axis. Initial migration is independent of a Wnt signal that controls later anterior-posterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other's role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left-right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration.

Quantification of Methane and Ammonia Emissions in a Naturally Ventilated Barn by Using Defined Criteria to Calculate Emission Rates.

PubMed

Schmithausen, Alexander J; Schiefler, Inga; Trimborn, Manfred; Gerlach, Katrin; Südekum, Karl-Heinz; Pries, Martin; Büscher, Wolfgang

2018-05-16

Extensive experimentation on individual animals in respiration chambers has already been carried out to evaluate the potential of dietary changes and opportunities to mitigate CH₄ emissions from ruminants. Although it is difficult to determine the air exchange rate of open barn spaces, measurements at the herd level should provide similarly reliable and robust results. The primary objective of this study was (1) to define a validity range (data classification criteria (DCC)) for the variables of wind velocity and wind direction during long-term measurements at barn level; and (2) to apply this validity range to a feeding trial in a naturally cross-flow ventilated dairy barn. The application of the DCC permitted quantification of CH₄ and NH₃ emissions during a feeding trial consisting of four periods. Differences between the control group (no supplement) and the experimental group fed a ration supplemented with condensed Acacia mearnsii tannins (CT) became apparent. Notably, CT concentrations of 1% and 3% of ration dry matter did not reduce CH₄ emissions. In contrast, NH₃ emissions decreased 34.5% when 3% CT was supplemented. The data confirm that quantification of trace gases in a naturally ventilated barn at the herd level is possible.

[Receptor status (ER and PgR) determined with histochemical and biochemical methods in breast carcinoma].

PubMed

Simone, G; Paradiso, A; Cirillo, R; Mangia, A; Rella, G; Wiesel, S; Petroni, S; De Benedictis, G; De Lena, M

1991-01-01

Recently, a method similar to ER.ICA has been proposed for the progesterone receptor (PgR) using two monoclonal antibodies, JZB39 and KD68, specific for human PgR and characterized by a molecular weight of 95 and 120 Kd, respectively. A series of 73 breast cancer patients was studied with regards to ER and PgR using both immunocytochemical (ICA) and biochemical (DCC) assays. Results showed no substantial differences between the two methods when considering common clinical-pathological parameters. Overall agreement between ICA and DCC methods was found: 79% for PgR and 78% for ER. A slight quantitative correlation was also observed between the "score values" of the ICA method and the Fmol content of ER and PgR using the Brave-Pearson test (r = 0.49 for PgR; r = 0.43 for ER). Specificity of PgR.ICA method was 77% for PgR and 72% for ER; sensitivity was 82% and 83%, respectively. The ICA method is a reliable technique to assess PgR presence as well as ER. Further studies are necessary to evaluate the prognostic role of nuclear PgR.

Radiation patterns of dual concentric conductor microstrip antennas for superficial hyperthermia.

PubMed

Stauffer, P R; Rossetto, F; Leoncini, M; Gentilli, G B

1998-05-01

The finite difference time domain (FDTD) method has been used to calculate electromagnetic radiation patterns from 915-MHz dual concentric conductor (DCC) microwave antennas that are constructed from thin and flexible printed circuit board (PCB) materials. Radiated field distributions are calculated in homogeneous lossy muscle tissue loads located under variable thickness coupling bolus layers. This effort extends the results of previous investigations to consider more realistic applicator configurations with smaller 2-cm-square apertures and different coupling bolus materials and thicknesses, as well as various spacings of multiple-element arrays. Results are given for practical applicator designs with microstrip feedlines etched on the backside of the PCB antenna array instead of previously tested bulky coaxial-cable feedline connections to each radiating aperture. The results demonstrate that for an optimum coupling bolus thickness of 2.5-5 mm, the thin, flexible, and lightweight DCC antennas produce effective heating to the periphery of each aperture to a depth of approximately 1 cm, and may be combined into arrays for uniform heating of large area superficial tissue regions with the 50% power deposition contour conforming closely to the outer perimeter of the array.

Dichlorocarbene-Functionalized Fluorographene: Synthesis and Reaction Mechanism.

PubMed

Lazar, Petr; Chua, Chun Kiang; Holá, Kateřina; Zbořil, Radek; Otyepka, Michal; Pumera, Martin

2015-08-01

Halogen functionalization of graphene is an important branch of graphene research as it provides opportunities to tailor the band gap and catalytic properties of graphene. Monovalent C-X bond obviates pitfalls of functionalization with atoms of groups 13, 15, and 16, which can introduce various poorly defined groups. Here, the preparation of functionalized graphene containing both fluorine and chlorine atoms is shown. The starting material, fluorographite, undergoes a reaction with dichlorocarbene to provide dichlorocarbene-functionalized fluorographene (DCC-FG). The material is characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, and high-resolution transmission electron microscopy with X-ray dispersive spectroscopy. It is found that the chlorine atoms in DCC-FG are distributed homogeneously over the entire area of the fluorographene sheet. Further density functional theory calculations show that the mechanism of dichlorocarbene attack on fluorographene sheet is a two-step process. Dichlorocarbene detaches fluorine atoms from fluorographene sheet and subsequently adds to the newly formed sp(2) carbons. Halogenated graphene consisting of two (or eventually three) types of halogen atoms is envisioned to find its way as new graphene materials with tailored properties. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Indole-based novel small molecules for the modulation of bacterial signalling pathways.

PubMed

Biswas, Nripendra Nath; Kutty, Samuel K; Barraud, Nicolas; Iskander, George M; Griffith, Renate; Rice, Scott A; Willcox, Mark; Black, David StC; Kumar, Naresh

2015-01-21

Gram-negative bacteria such as Pseudomonas aeruginosa use N-acylated L-homoserine lactones (AHLs) as autoinducers (AIs) for quorum sensing (QS), a major regulatory and cell-to-cell communication system for social adaptation, virulence factor production, biofilm formation and antibiotic resistance. Some bacteria use indole moieties for intercellular signaling and as regulators of various bacterial phenotypes important for evading the innate host immune response and antimicrobial resistance. A range of natural and synthetic indole derivatives have been found to act as inhibitors of QS-dependent bacterial phenotypes, complementing the bactericidal ability of traditional antibiotics. In this work, various indole-based AHL mimics were designed and synthesized via the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N,N'-dicyclohexylcarbodiimide (DCC) mediated coupling reactions of a variety of substituted or unsubstituted aminoindoles with different alkanoic acids. All synthesized compounds were tested for QS inhibition using a P. aeruginosa QS reporter strain by measuring the amount of green fluorescent protein (GFP) production. Docking studies were performed to examine their potential to bind and therefore inhibit the target QS receptor protein. The most potent compounds 11a, 11d and 16a showed 44 to 65% inhibition of QS activity at 250 μM concentration, and represent promising drug leads for the further development of anti-QS antimicrobial compounds.

EVA-1 functions as an UNC-40 Co-receptor to enhance attraction to the MADD-4 guidance cue in Caenorhabditis elegans.

PubMed

Chan, Kevin Ka Ming; Seetharaman, Ashwin; Bagg, Rachel; Selman, Guillermo; Zhang, Yuqian; Kim, Joowan; Roy, Peter J

2014-08-01

We recently discovered a secreted and diffusible midline cue called MADD-4 (an ADAMTSL) that guides migrations along the dorsoventral axis of the nematode Caenorhabditis elegans. We showed that the transmembrane receptor, UNC-40 (DCC), whose canonical ligand is the UNC-6 (netrin) guidance cue, is required for extension towards MADD-4. Here, we demonstrate that MADD-4 interacts with an EVA-1/UNC-40 co-receptor complex to attract cell extensions. EVA-1 is a conserved transmembrane protein with predicted galactose-binding lectin domains. EVA-1 functions in the same pathway as MADD-4, physically interacts with both MADD-4 and UNC-40, and enhances UNC-40's sensitivity to the MADD-4 cue. This enhancement is especially important in the presence of UNC-6. In EVA-1's absence, UNC-6 interferes with UNC-40's responsiveness to MADD-4; in UNC-6's absence, UNC-40's responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue.

EVA-1 Functions as an UNC-40 Co-receptor to Enhance Attraction to the MADD-4 Guidance Cue in Caenorhabditis elegans

PubMed Central

Bagg, Rachel; Selman, Guillermo; Zhang, Yuqian; Kim, Joowan; Roy, Peter J.

2014-01-01

We recently discovered a secreted and diffusible midline cue called MADD-4 (an ADAMTSL) that guides migrations along the dorsoventral axis of the nematode Caenorhabditis elegans. We showed that the transmembrane receptor, UNC-40 (DCC), whose canonical ligand is the UNC-6 (netrin) guidance cue, is required for extension towards MADD-4. Here, we demonstrate that MADD-4 interacts with an EVA-1/UNC-40 co-receptor complex to attract cell extensions. EVA-1 is a conserved transmembrane protein with predicted galactose-binding lectin domains. EVA-1 functions in the same pathway as MADD-4, physically interacts with both MADD-4 and UNC-40, and enhances UNC-40's sensitivity to the MADD-4 cue. This enhancement is especially important in the presence of UNC-6. In EVA-1's absence, UNC-6 interferes with UNC-40's responsiveness to MADD-4; in UNC-6's absence, UNC-40's responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue. PMID:25122090

The Geometry of Selected U.S. Tidal Inlets.

DTIC Science & Technology

1980-05-01

wrong cluster. Table 6. Descriminant analysis results for three variables (DCC, EM2, and EM3). a. Coefficients for di i iminant functions based on three...47.95/ 3 07.72 0.975, 4,1 0 .310. 1 C1297 0,)1r, 55,94 o, D, C 24.07: 1. C5, 75 Iable-9. Descriminant analysis results for six variables (DMX, DMA, W

An Application of Singularity Analysis to a Heavy Precipitation Event

DTIC Science & Technology

1993-01-01

difference in this plot. 61 NORMAN RADAR ELEVATION: 3.094 DATE 28 MAY 87 TIM 005342 GUT Cumin a 10 Tpam c CD low am am Io CID e0UC 100 "CC C d~Cc 100...element of fluid shaped like a sphere. Assuming the fluid is friction- less, no tangential stresses or forces are applied to its surface. The pressure

5 CFR 9701.521 - Grievance procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... negotiated grievance procedure is subject to binding arbitration, which may be invoked by either the... for binding arbitration in accordance with paragraph (b)(1)(iii) of this section must, if or to the... appeal such action to the same extent and in the same manner as if the Department had taken the...

Adhesion and Early Colonization of S. Mutans on Lithium Disilicate Reinforced Glass-Ceramics, Monolithic Zirconia and Dual Cure Resin Cement.

PubMed

Viitaniemi, L; Abdulmajeed, A; Sulaiman, T; Söderling, E; Närhi, T

2017-12-01

Monolithic zirconia and glass ceramics are increasingly used in implant crowns. Limited data is available on bacterial adhesion and early biofilm formation on these materials. Four different materials were investigated: (1) Lithium disilicate glass-ceramics (LDS), (2) Fully stabilized zirconia (FSZ), (3) Partially stabilized zirconia (PSZ), and (4) Dual curing cement (DCC). The materials' surfaces were characterized with spinning disc confocal microscopy and by water contact angle and surface free energy (SFE) measurements. For the adhesion tests the materials were rolled in suspensions of Streptococcus mutans. Early biofilm formation was studied on the materials and allowing the biofilms to form for 24 h. S. mutans cell counts were determined by plate culturing. ANOVA and post-hoc Tukey's tests (p⟨0.05) were used for statistical evaluation. The LDS surfaces were clearly hydrophilic with the highest SFE value (p⟨0.001). For S. mutans adhesion, the ranking of the materials from lowest to highest was: LDS = FSZ ⟨ DCC ⟨ PSZ (p⟨0.05). No significant differences among the materials were noticed in biofilm formation. LDS has lower S.mutans adhesion than other materials examined in this study, but the difference was not reflected in early biofilm formation. Copyright© 2017 Dennis Barber Ltd.

Cartilage extracellular matrix as a biomaterial for cartilage regeneration.

PubMed

Kiyotake, Emi A; Beck, Emily C; Detamore, Michael S

2016-11-01

The extracellular matrix (ECM) of various tissues possesses the model characteristics that biomaterials for tissue engineering strive to mimic; however, owing to the intricate hierarchical nature of the ECM, it has yet to be fully characterized and synthetically fabricated. Cartilage repair remains a challenge because the intrinsic properties that enable its durability and long-lasting function also impede regeneration. In the last decade, cartilage ECM has emerged as a promising biomaterial for regenerating cartilage, partly because of its potentially chondroinductive nature. As this research area of cartilage matrix-based biomaterials emerged, investigators facing similar challenges consequently developed convergent solutions in constructing robust and bioactive scaffolds. This review discusses the challenges, emerging trends, and future directions of cartilage ECM scaffolds, including a comparison between two different forms of cartilage matrix: decellularized cartilage (DCC) and devitalized cartilage (DVC). To overcome the low permeability of cartilage matrix, physical fragmentation greatly enhances decellularization, although the process itself may reduce the chondroinductivity of fabricated scaffolds. The less complex processing of a scaffold composed of DVC, which has not been decellularized, appears to have translational advantages and potential chondroinductive and mechanical advantages over DCC, without detrimental immunogenicity, to ultimately enhance cartilage repair in a clinically relevant way. © 2016 New York Academy of Sciences.

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

Poenkae, A.

The weekly changes in ambient sulfur dioxide, nitrogen dioxide, and temperature were compared with the figures for respiratory infection in children and adults and for absenteeism from day-care centers (DCC), schools, and workplaces during a 1-year period in Helsinki. The annual average level of sulfur dioxide was 21 micrograms/m3 and of nitrogen dioxide 47 micrograms/m3; the average temperature was +3.1 degrees C. The levels of these pollutants and the temperature were significantly correlated with the number of upper respiratory infections reported from health centers. Low temperature also correlated with increased frequency of acute tonsillitis, of lower respiratory tract infection amongmore » DCC children, and of absenteeism from day-care centers, schools and workplaces. Furthermore, a significant association was found between levels of sulfur dioxide and absenteeism. After statistical standardization for temperature, no other correlations were observed apart from that between high levels of sulfur dioxide and numbers of upper respiratory tract infections diagnosed at health centers (P = 0.04). When the concentrations of sulfur dioxide were above the mean, the frequency of the upper respiratory tract infections was 15% higher than that during the periods of low concentration. The relative importance of the effects of low-level air pollution and low temperature on health is difficult to assess.« less

Characterizing Response Versus Scan-Angle for MODIS Reflective Solar Bands Using Deep Convective Clouds

NASA Technical Reports Server (NTRS)

Bhatt, Rajendra; Doelling, David R.; Angal, Amit; Xiong, Xiaoxiong; Scarino, Benjamin; Gopalan, Arun; Haney, Conor; Wu, Aisheng

2017-01-01

MODIS consists of a cross-track, two-sided scan mirror, whose reflectance is not uniform but is a function of angle of incidence (AOI). This feature, known as response versusscan-angle (RVS), was characterized for all reflective solar bands of both MODIS instruments prior to launch. The RVS characteristic has changed on orbit, which must be tracked precisely over time to ensure the quality of MODIS products. The MODIS characterization support team utilizes the onboard calibrators and the earth view responses from multiple pseudo invariant desert sites to track the RVS changes at different AOIs. The drawback of using deserts is the assumption that these sites are radiometrically stable during the monitoring period. In addition, the 16-day orbit repeat cycle of MODIS allows for only a limited set of AOIs over a given desert. We propose a novel and robust approach of characterizing the MODIS RVS using tropical deep convective clouds (DCC). The method tracks the monthly DCC response at specified sets of AOIs to compute the temporal RVS changes. Initial results have shown that the Aqua-MODIS collection 6 band 1 level 1B radiances show considerable residual RVS dependencies, with long-term drifts up to 2.3 at certain AOIs.

Initial Stability Assessment of S-NPP VIIRS Reflective Solar Band Calibration Using Invariant Desert and Deep Convective Cloud Targets

NASA Technical Reports Server (NTRS)

Bhatt, Rajendra; Doelling, David R.; Wu, Aisheng; Xiong, Xiaoxiong (Jack); Scarino, Benjamin R.; Haney, Conor O.; Gopalan, Arun

2014-01-01

The latest CERES FM-5 instrument launched onboard the S-NPP spacecraft will use the VIIRS visible radiances from the NASA Land Product Evaluation and Analysis Tool Elements (PEATE) product for retrieving the cloud properties associated with its TOA flux measurement. In order for CERES to provide climate quality TOA flux datasets, the retrieved cloud properties must be consistent throughout the record, which is dependent on the calibration stability of the VIIRS imager. This paper assesses the NASA calibration stability of the VIIRS reflective solar bands using the Libya-4 desert and deep convective clouds (DCC). The invariant targets are first evaluated for temporal natural variability. It is found for visible (VIS) bands that DCC targets have half of the variability of Libya-4. For the shortwave infrared (SWIR) bands, the desert has less variability. The brief VIIRS record and target variability inhibits high confidence in identifying any trends that are less than 0.6yr for most VIS bands, and 2.5yr for SWIR bands. None of the observed invariant target reflective solar band trends exceeded these trend thresholds. Initial assessment results show that the VIIRS data have been consistently calibrated and that the VIIRS instrument stability is similar to or better than the MODIS instrument.

Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior–Posterior Neuroblast Migration with Left–Right Functional Asymmetry in Caenorhabditis elegans

PubMed Central

Sundararajan, Lakshmi; Lundquist, Erik A.

2012-01-01

Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left–right axis. Initial migration is independent of a Wnt signal that controls later anterior–posterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other’s role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left–right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration. PMID:23051647

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer and optimal selection of traditional Chinese medicine target.

PubMed

Tian, Tongde; Chen, Chuanliang; Yang, Feng; Tang, Jingwen; Pei, Junwen; Shi, Bian; Zhang, Ning; Zhang, Jianhua

2017-03-01

The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. KEGG analysis was employed to establish apoptotic regulatory network model based on screened genetic markers, and optimization was conducted on TCM targets. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, P53, APC, DCC and PTEN, among which DCC has the highest diagnostic efficiency. Apoptotic regulatory network was built by KEGG analysis. Currently, it was reported that TCM has regulatory function on gene locus in apoptotic regulatory network. The apoptotic regulatory model of colorectal cancer established in this study provides theoretical evidence for early diagnosis and TCM targeted therapy of colorectal cancer in clinic.

Occurrence of triclosan, triclocarban, and its lesser chlorinated congeners in Minnesota freshwater sediments collected near wastewater treatment plants

USGS Publications Warehouse

Venkatesan, Arjun K.; Pycke, Benny F.G.; Barber, Larry B.; Lee, Kathy E.; Halden, Rolf U.

2012-01-01

The antimicrobial agents triclosan (TCS), triclocarban (TCC) and their associated transformation products are of increasing concern as environmental pollutants due to their potential adverse effects on humans and wildlife, including bioaccumulation and endocrine-disrupting activity. Analysis by tandem mass spectrometry of 24 paired freshwater bed sediment samples (top 10 cm) collected by the U.S. Geological Survey near 12 wastewater treatment plants (WWTPs) in Minnesota revealed TCS and TCC concentrations of up to 85 and 822 ng/g dry weight (dw), respectively. Concentrations of TCS and TCC in bed sediments collected downstream of WWTPs were significantly greater than upstream concentrations in 58% and 42% of the sites, respectively. Dichloro- and non-chlorinated carbanilides (DCC and NCC) were detected in sediments collected at all sites at concentrations of up to 160 and 1.1 ng/g dw, respectively. Overall, antimicrobial concentrations were significantly higher in lakes than in rivers and creeks, with relative abundances decreasing from TCC > TCS > DCC > NCC. This is the first statewide report on the occurrence of TCS, TCC and TCC transformation products in freshwater sediments. Moreover, the results suggest biological or chemical TCC dechlorination products to be ubiquitous in freshwater environments of Minnesota, but whether this transformation occurs in the WWTP or bed sediment remains to be determined.

Characterizing response versus scan-angle for MODIS reflective solar bands using deep convective clouds

NASA Astrophysics Data System (ADS)

Bhatt, Rajendra; Doelling, David R.; Angal, Amit; Xiong, Xiaoxiong; Scarino, Benjamin; Gopalan, Arun; Haney, Conor; Wu, Aisheng

2017-01-01

MODIS consists of a cross-track, two-sided scan mirror, whose reflectance is not uniform but is a function of angle of incidence (AOI). This feature, known as response versus scan-angle (RVS), was characterized for all reflective solar bands of both MODIS instruments prior to launch. The RVS characteristic has changed on orbit, which must be tracked precisely over time to ensure the quality of MODIS products. The MODIS characterization support team utilizes the onboard calibrators and the earth view responses from multiple pseudoinvariant desert sites to track the RVS changes at different AOIs. The drawback of using deserts is the assumption that these sites are radiometrically stable during the monitoring period. In addition, the 16-day orbit repeat cycle of MODIS allows for only a limited set of AOIs over a given desert. We propose a novel and robust approach of characterizing the MODIS RVS using tropical deep convective clouds (DCC). The method tracks the monthly DCC response at specified sets of AOIs to compute the temporal RVS changes. Initial results have shown that the Aqua-MODIS collection 6 band 1 level 1B radiances show considerable residual RVS dependencies, with long-term drifts up to 2.3% at certain AOIs.

Evaluating Dynamic Bivariate Correlations in Resting-state fMRI: A comparison study and a new approach

PubMed Central

Lindquist, Martin A.; Xu, Yuting; Nebel, Mary Beth; Caffo, Brain S.

2014-01-01

To date, most functional Magnetic Resonance Imaging (fMRI) studies have assumed that the functional connectivity (FC) between time series from distinct brain regions is constant across time. However, recently, there has been increased interest in quantifying possible dynamic changes in FC during fMRI experiments, as it is thought this may provide insight into the fundamental workings of brain networks. In this work we focus on the specific problem of estimating the dynamic behavior of pair-wise correlations between time courses extracted from two different regions of the brain. We critique the commonly used sliding-windows technique, and discuss some alternative methods used to model volatility in the finance literature that could also prove useful in the neuroimaging setting. In particular, we focus on the Dynamic Conditional Correlation (DCC) model, which provides a model-based approach towards estimating dynamic correlations. We investigate the properties of several techniques in a series of simulation studies and find that DCC achieves the best overall balance between sensitivity and specificity in detecting dynamic changes in correlations. We also investigate its scalability beyond the bivariate case to demonstrate its utility for studying dynamic correlations between more than two brain regions. Finally, we illustrate its performance in an application to test-retest resting state fMRI data. PMID:24993894

Rapid Biodegradation of the Herbicide 2,4-Dichlorophenoxyacetic Acid by Cupriavidus gilardii T-1.

PubMed

Wu, Xiangwei; Wang, Wenbo; Liu, Junwei; Pan, Dandan; Tu, Xiaohui; Lv, Pei; Wang, Yi; Cao, Haiqun; Wang, Yawen; Hua, Rimao

2017-05-10

Phytotoxicity and environmental pollution of residual herbicides have caused much public concern during the past several decades. An indigenous bacterial strain capable of degrading 2,4-dichlorophenoxyacetic acid (2,4-D), designated T-1, was isolated from soybean field soil and identified as Cupriavidus gilardii. Strain T-1 degraded 2,4-D 3.39 times more rapidly than the model strain Cupriavidus necator JMP134. T-1 could also efficiently degrade 2-methyl-4-chlorophenoxyacetic acid (MCPA), MCPA isooctyl ester, and 2-(2,4-dichlorophenoxy)propionic acid (2,4-DP). Suitable conditions for 2,4-D degradation were pH 7.0-9.0, 37-42 °C, and 4.0 mL of inoculums. Degradation of 2,4-D was concentration-dependent. 2,4-D was degraded to 2,4-dichlorophenol (2,4-DCP) by cleavage of the ether bond and then to 3,5-dichlorocatechol (3,5-DCC) via hydroxylation, followed by ortho-cleavage to cis-2-dichlorodiene lactone (CDL). The metabolites 2,4-DCP or 3,5-DCC at 10 mg L -1 were completely degraded within 16 h. Fast degradation of 2,4-D and its analogues highlights the potential for use of C. gilardii T-1 in bioremediation of phenoxyalkanoic acid herbicides.

Library Binding Manual. Revised Edition.

ERIC Educational Resources Information Center

Lakhanpal, S. K.

This procedural manual is designed to be used in bindery sections in public, university and special libraries. It briefly discusses these general matters: administrative control; selection of a binder; when and what to bind; conventional binding; routines; missing issues; schedule for shipments; temporary binding; rare books, maps and newspapers;…

Coupled thermal-fluid analysis with flowpath-cavity interaction in a gas turbine engine

NASA Astrophysics Data System (ADS)

Fitzpatrick, John Nathan

This study seeks to improve the understanding of inlet conditions of a large rotor-stator cavity in a turbofan engine, often referred to as the drive cone cavity (DCC). The inlet flow is better understood through a higher fidelity computational fluid dynamics (CFD) modeling of the inlet to the cavity, and a coupled finite element (FE) thermal to CFD fluid analysis of the cavity in order to accurately predict engine component temperatures. Accurately predicting temperature distribution in the cavity is important because temperatures directly affect the material properties including Young's modulus, yield strength, fatigue strength, creep properties. All of these properties directly affect the life of critical engine components. In addition, temperatures cause thermal expansion which changes clearances and in turn affects engine efficiency. The DCC is fed from the last stage of the high pressure compressor. One of its primary functions is to purge the air over the rotor wall to prevent it from overheating. Aero-thermal conditions within the DCC cavity are particularly challenging to predict due to the complex air flow and high heat transfer in the rotating component. Thus, in order to accurately predict metal temperatures a two-way coupled CFD-FE analysis is needed. Historically, when the cavity airflow is modeled for engine design purposes, the inlet condition has been over-simplified for the CFD analysis which impacts the results, particularly in the region around the compressor disc rim. The inlet is typically simplified by circumferentially averaging the velocity field at the inlet to the cavity which removes the effect of pressure wakes from the upstream rotor blades. The way in which these non-axisymmetric flow characteristics affect metal temperatures is not well understood. In addition, a constant air temperature scaled from a previous analysis is used as the simplified cavity inlet air temperature. Therefore, the objectives of this study are: (a) model the DCC cavity with a more physically representative inlet condition while coupling the solid thermal analysis and compressible air flow analysis that includes the fluid velocity, pressure, and temperature fields; (b) run a coupled analysis whose boundary conditions come from computational models, rather than thermocouple data; (c) validate the model using available experimental data; and (d) based on the validation, determine if the model can be used to predict air inlet and metal temperatures for new engine geometries. Verification with experimental results showed that the coupled analysis with the 3D no-bolt CFD model with predictive boundary conditions, over-predicted the HP6 offtake temperature by 16k. The maximum error was an over-prediction of 50k while the average error was 17k. The predictive model with 3D bolts also predicted cavity temperatures with an average error of 17k. For the two CFD models with predicted boundary conditions, the case without bolts performed better than the case with bolts. This is due to the flow errors caused by placing stationary bolts in a rotating reference frame. Therefore it is recommended that this type of analysis only be attempted for drive cone cavities with no bolts or shielded bolts.

Noncovalent Interactions of Tiopronin-Protected Gold Nanoparticles with DNA: Two Methods to Quantify Free Energy of Binding

PubMed Central

Prado-Gotor, R.; Grueso, E.

2014-01-01

The binding of gold nanoparticles capped with N-(2-mercaptopropionyl)glycine (Au@tiopronin) with double-stranded DNA has been investigated and quantified in terms of free energies by using two different approaches. The first approach follows the DNA conformational changes induced by gold nanoparticles using the CD technique. The second methodology consists in the use of pyrene-1-carboxaldehyde as a fluorescent probe. This second procedure implies the determination of the “true” free energy of binding of the probe with DNA, after corrections through solubility measurements. Working at different salt concentrations, the nonelectrostatic and electrostatic components of the binding free energy have been separated. The results obtained revealed that the binding is of nonelectrostatic character, fundamentally. The procedure used in this work could be extended to quantify the binding affinity of other AuNPs/DNA systems. PMID:24587710

PET Radiotracers for Imaging the Proliferation Status of Breast Tumors

DTIC Science & Technology

2004-12-01

390 627 ±244 12,900±111 8.2± 1.415 58.8± 13.7 2.1 ±0.4 809±66 75.0±4.1 75-85% yield. Reduction with either lithium aluminum 16 107.0± 19.0 10.2±5.3 751... hexafluorophosphate (BOP) or 1,3- dicyclohexylcarbodiimide (DCC) and 2.5 equivalents of triethylamine were added, and the solution was allowed to warm

A dye-binding assay for measurement of the binding of Cu(II) to proteins.

PubMed

Wilkinson-White, Lorna E; Easterbrook-Smith, Simon B

2008-10-01

We analysed the theory of the coupled equilibria between a metal ion, a metal ion-binding dye and a metal ion-binding protein in order to develop a procedure for estimating the apparent affinity constant of a metal ion:protein complex. This can be done by analysing from measurements of the change in the concentration of the metal ion:dye complex with variation in the concentration of either the metal ion or the protein. Using experimentally determined values for the affinity constant of Cu(II) for the dye, 2-(5-bromo-2-pyridylaxo)-5-(N-propyl-N-sulfopropylamino) aniline (5-Br-PSAA), this procedure was used to estimate the apparent affinity constants for formation of Cu(II):transthyretin, yielding values which were in agreement with literature values. An apparent affinity constant for Cu(II) binding to alpha-synuclein of approximately 1 x 10(9)M(-1) was obtained from measurements of tyrosine fluorescence quenching by Cu(II). This value was in good agreement with that obtained using 5-Br-PSAA. Our analysis and data therefore show that measurement of changes in the equilibria between Cu(II) and 5-Br-PSAA by Cu(II)-binding proteins provides a general procedure for estimating the affinities of proteins for Cu(II).

On the Use of Deep Convective Clouds to Characterize Response versus Scan-angle for MODIS Reflective Solar Bands

NASA Astrophysics Data System (ADS)

Bhatt, R.; Doelling, D. R.; Scarino, B. R.; Gopalan, A.; Haney, C.

2016-12-01

MODIS is a cross-track scanning radiometer with a two-sided scan mirror that images the Earth with an angular field of view of 55° on either side of the nadir. The reflectance of the scan mirror is not uniform and is a function of angle of incidence (AOI), as well as wavelength. This feature of the scan mirror is described by response versus scan-angle (RVS), and was characterized for all reflective solar bands (RSBs), for both MODIS instruments prior to launch. The RVS characteristic of the two MODIS instruments has changed on orbit and, therefore, must be tracked precisely over time to ensure high-quality data in the MODIS products. The MODIS Characterization Support Team (MCST) utilizes the onboard solar diffuser (SD) and lunar measurements to track the RVS changes at two fixed AOIs. The RVS at the remaining AOIs is characterized using the earth view (EV) responses from multiple pseudo-invariant desert sites located in Northern Africa. The drawback of this approach is the assumption that all of the desert sites imaged by the MODIS sensors at different AOIs are radiometrically stable during the same period of time. In addition, the desert samples do not always have continuous AOI coverage as they are limited by the 16-day repeat cycle of the satellite orbit, and by clear-sky conditions over the deserts. This paper proposes a novel and robust approach of characterizing the MODIS RVS using tropical deep convective clouds (DCCs) as an invariant calibration target. The method tracks the monthly DCC response at specified sets of AOIs to compute the temporal RVS changes. Because DCCs are distributed across the entirety of the tropics, they provide a continuum of AOI measurements. Initial results have shown that the Aqua-MODIS Collection 6 band 1 level 1b radiances show considerable residual, or artifact, RVS dependencies, especially on the left side of the cross-track scan. Long-term drifts, up to 2.3%, have been observed at certain AOIs. Temporal correction factors are computed using the DCC trends from 12 scan intervals encompassing all AOIs, and their effectiveness in correcting the observed RVS artifact is evaluated using the Libya-1 pseudo-invariant desert site. The desert and DCC temporal scan dependent trends are reduced to less than 1 standard error after the RVS correction.

Olefin Metathesis in Peptidomimetics, Dynamic Combinatorial Chemistry, and Molecular Imprinting

DTIC Science & Technology

2006-08-01

aryl iodide to the Grignard reagent . Treatment of the magnesium compound with allyl bromide and CuCN·2LiCl afforded benzoate 4-11, which was then...cyclization of a linear peptide by conventional coupling agents to form a new amide bond (Scheme 1-12)36,44 Some common reagents are...dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), and expensive reagents such as HATU or PyBroP, which are more efficient.44 Racemization of the chiral

Commercial Jet Transport Crashworthiness

DTIC Science & Technology

1982-04-01

airports is another area for improved safety. The avoidance of collisions between aircraft and with ground vehicles should be attainable. Reduction of...hazards such as drainage ditches, poles, trees, columns, outbuildings, and birds from airports is a matter of concern. In addition the short/overrun areas...071191 DCC DENVER X 122 17 0 LOG FIRE YES 011961 DC8 JFK X 106 4 ? TO FIRE PAR 061561 707 LISBON 103 0 2 LDG FIRE YES 122161 CMT ANKARA X 34 27 6 CLI

Development of the Ovarian Cancer Cohort Consortium: Risk Factor Associations by Heterogeneity of Disease

DTIC Science & Technology

2013-10-01

10 cohorts have collected pathology reports – we currently are working with these cohorts to have personnel from the DCC either train on- site staff...for abstraction or to travel to the site and conduct the abstraction directly. Due to the difficulties in obtaining the appropriate permissions to...REPRODUCTIVE HISTORY PREG Number of pregnancies lasting > 6 months Twins count as a single birth; 999=unknown AGEFIRST Age at first birth

Immunological Prevention of Spontaneous Mammary Carcinoma in Transgenic Mice

DTIC Science & Technology

1999-08-01

and their multiplication. The period between the 22nd and the 28th week appears to be of critical importance, as the ൤-week-old" protocol confers a...sustain their relatively low rate of proliferation. By contrast, blood supply is a critical factor for most fast-growing transplantable tumors, even...Piffanelli A, Fumero S, Pelizzola D, Berruto GP, Ricci L, and Science 244:707-712. Giovannini G (1982). Protocollo del metodo con Charcoal-destrano (DCC) per

A generalized conditional heteroscedastic model for temperature downscaling

NASA Astrophysics Data System (ADS)

Modarres, R.; Ouarda, T. B. M. J.

2014-11-01

This study describes a method for deriving the time varying second order moment, or heteroscedasticity, of local daily temperature and its association to large Coupled Canadian General Circulation Models predictors. This is carried out by applying a multivariate generalized autoregressive conditional heteroscedasticity (MGARCH) approach to construct the conditional variance-covariance structure between General Circulation Models (GCMs) predictors and maximum and minimum temperature time series during 1980-2000. Two MGARCH specifications namely diagonal VECH and dynamic conditional correlation (DCC) are applied and 25 GCM predictors were selected for a bivariate temperature heteroscedastic modeling. It is observed that the conditional covariance between predictors and temperature is not very strong and mostly depends on the interaction between the random process governing temporal variation of predictors and predictants. The DCC model reveals a time varying conditional correlation between GCM predictors and temperature time series. No remarkable increasing or decreasing change is observed for correlation coefficients between GCM predictors and observed temperature during 1980-2000 while weak winter-summer seasonality is clear for both conditional covariance and correlation. Furthermore, the stationarity and nonlinearity Kwiatkowski-Phillips-Schmidt-Shin (KPSS) and Brock-Dechert-Scheinkman (BDS) tests showed that GCM predictors, temperature and their conditional correlation time series are nonlinear but stationary during 1980-2000 according to BDS and KPSS test results. However, the degree of nonlinearity of temperature time series is higher than most of the GCM predictors.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

PubMed

Hao, Yibin; Shan, Guoyong; Nan, Kejun

2017-03-01

Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

Placental transfusion in preterm neonates of 30-33 weeks' gestation: a randomized controlled trial.

PubMed

Das, Bikramjit; Sundaram, Venkataseshan; Tarnow-Mordi, William; Ghadge, Alpana; Dhaliwal, Lakhbir Kaur; Kumar, Praveen

2018-02-06

To compare effect of placental transfusion by delayed cord clamping (DCC) or cord milking (CM) with early cord clamping (ECC) on a composite of mortality or abnormal neurological status at 40 weeks' post-menstrual age (PMA) and 24-30 months' chronological age in neonates of 30-33 weeks' gestation. Randomized, controlled trial. A composite of mortality or abnormal neurological status at 40 weeks PMA and survival free of neurodevelopmental abnormalities at 24-30 months' chronological age. A total of 461 neonates were randomized to placental transfusion (n = 233) or to ECC (n = 228). Among those assigned to placental transfusion group, 173 underwent DCC while in the remaining 60, CM was done. Incidence of mortality or abnormal neurological status at 40 weeks PMA (43 (18%) vs 35 (15%), RR (95% CI) 1.2 (0.8, 1.8), p = 0.4) and survival free of neurodevelopmental impairment at 24-30 months of chronological age (99 (47%) vs. 100 (50%); RR (95% CI): 0.9 (0.8, 1.2); P = 0.9) was similar between the study groups. The placental transfusion group showed a trend towards lower incidence of necrotizing enterocolitis. In 30-33 weeks' gestation preterm neonates, placental transfusion as compared to early cord clamping resulted in similar mortality or abnormal neurological status at 40 weeks PMA and at 24-30 months of chronological age.

The National NeuroAIDS Tissue Consortium (NNTC) Database: an integrated database for HIV-related studies

PubMed Central

Cserhati, Matyas F.; Pandey, Sanjit; Beaudoin, James J.; Baccaglini, Lorena; Guda, Chittibabu; Fox, Howard S.

2015-01-01

We herein present the National NeuroAIDS Tissue Consortium-Data Coordinating Center (NNTC-DCC) database, which is the only available database for neuroAIDS studies that contains data in an integrated, standardized form. This database has been created in conjunction with the NNTC, which provides human tissue and biofluid samples to individual researchers to conduct studies focused on neuroAIDS. The database contains experimental datasets from 1206 subjects for the following categories (which are further broken down into subcategories): gene expression, genotype, proteins, endo-exo-chemicals, morphometrics and other (miscellaneous) data. The database also contains a wide variety of downloadable data and metadata for 95 HIV-related studies covering 170 assays from 61 principal investigators. The data represent 76 tissue types, 25 measurement types, and 38 technology types, and reaches a total of 33 017 407 data points. We used the ISA platform to create the database and develop a searchable web interface for querying the data. A gene search tool is also available, which searches for NCBI GEO datasets associated with selected genes. The database is manually curated with many user-friendly features, and is cross-linked to the NCBI, HUGO and PubMed databases. A free registration is required for qualified users to access the database. Database URL: http://nntc-dcc.unmc.edu PMID:26228431

Effects of delayed cord clamping on the third stage of labour, maternal haematological parameters and acid-base status in fetuses at term.

PubMed

De Paco, Catalina; Herrera, Javier; Garcia, Carolina; Corbalán, Shiana; Arteaga, Alicia; Pertegal, Miriam; Checa, Rosario; Prieto, María Teresa; Nieto, Aníbal; Delgado, Juan Luis

2016-12-01

To compare the time in the third stage of labour, differences in maternal hematologic parameters 48h after birth and acid-base status in the umbilical cord between the early cord clamping (ECC) and delayed cord clamping (DCC). 97 healthy pregnancies at term and a spontaneous vertex delivery at Clinic University Hospital "Virgen de la Arrixaca" (Murcia, Spain), were randomized to ECC group (<10s post-delivery) or to DCC group (2min post-delivery). Duration of the third stage of labour was measured. Samples for acid-base status were taken both from the umbilical artery and vein. Blood samples were taken from the mothers 48h after birth. No statistical differences were found in the time of the third stage of labour (p=0.35). No statiscally significant differences were found between the number of red cells (p=0.25), hemoglobin (p=0.08) or hematocrit (p=0.15) in mothers. Umbilical acid-base status or gas analysis did not show any differences between the two groups CONCLUSIONS: Delayed cord clamping does not affect significantly the time of the third stage of labour. It does not show either any effect on the hematological parameters in the mother 48h after birth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An Assessment of the Shipboard Training Effectiveness of the Integrated Damage Control Training Technology (IDCTT) Version 3.0

DTIC Science & Technology

1998-03-01

damage control actions in an assigned area of the ship. Reports are received from the On Scene Leader ( OSL ) and Investigators. Simultaneously, the RPL...control location. A phone talker and plotter will perform in unison with their counterparts in DCC. Key members of the repair party, the OSL and...the obligation of the On Scene Leader ( OSL ). This experienced petty officer is tasked with directing the ATL’s actions and informing the RPL of repair

Chemiluminescence of Organic Peroxides: Intramolecular Electron-Exchange Luminescence from a Secondary Perester.

DTIC Science & Technology

1986-09-14

variety of conditions that would preserve the amino-coumarin functional group. Despite the commercial availability of 1 , Its synthesis has not been... synthesis of peresters and diacylperoxides12 . It was hoped that DCC would activate acid 1 in the presence of a secondary hydroperoxide and thereby...were used as received. 8-Methoxyjulolidine.14 3-Methoxyaniline (0.10 mol, 11 mL, 12.3 g), 1 -bromo-3- chloropropane (160 mL, 1.5 mol, 235 g) and

Security Police Officer Utilization Field, AFSCs 8111, 8116, 8121, and 8124.

DTIC Science & Technology

1981-06-01

STATEMENT A M C Approved for public release 82 0 4 26Distribution Unlimited C=DCC=D= APS 8 1 X CECI I CODING INSTRUCTIONS -- -- -" Print the booklet copy...m == NAME (Last, First, Middle Initial) DATE OF BIRTH SEX YR NO DAY (MALE -"(11-34) (3s-5- rayo (41) PRESENT GRADE: SOCIAL SECURITY ACCOUNT NUMBER...Branch - 11. OIC Missile Support Branch - __m 12. OIC Weapons Systems Security , 4 8 CODE 99 X ~.t ! AFS 81XX -mmm -C - . .’ .9 - =, BACKGROUND

Interaction of Cesium Ions with Calix[4]arene-bis(t-octylbenzo-18-crown-6): NMR and Theoretical Study

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

Kriz, Jaroslav; Dybal, Jiri; Vanura, Petr

2011-01-01

Using 1H, 13C, and 133Cs NMR spectra, it is shown that calix[4]arene-bis (t-octylbenzo-18-crown-6) (L) forms complexes with one (L 3 Cs ) and two (L 3 2Cs ) Cs ions offered by cesium bis(1,2-dicarbollide) cobaltate (CsDCC) in nitrobenzene-d5. The ions interact with all six oxygen atoms in the crown-ether ring and the electrons of the calixarene aromatic moieties. According to extraction technique, the stability constant of the first complex is log nb(L 3 Cs ) = 8.8 ( 0.1. According to 133Cs NMR spectra, the value of the equilibrium constant of the second complex is log Knb (2)(L 3 2Csmore » ) = 6.3(0.2, i.e., its stabilization constant is log nb(L 3 2Cs ) = 15.1 ( 0.3. Self-diffusion measurements by 1H pulsed-field gradient (PFG) NMRcombined with density functional theory (DFT) calculations suggest that one DCC ion is tightly associated with L 3 Cs , decreasing its positive charge and consequently stabilizing the second complex, L 3 2Cs . Using a saturation-transfer 133Cs NMR technique, the correlation times ex of chemical exchange between L 3 Cs and L 3 2Cs as well as between L 3 2Cs and free Cs ions were determined as 33.6 and 29.2 ms, respectively.« less

Microphysical effects determine macrophysical response for aerosol impacts on deep convective clouds

NASA Astrophysics Data System (ADS)

Fan, Jiwen; Leung, L. Ruby; Rosenfeld, Daniel; Chen, Qian; Li, Zhanqing; Zhang, Jinqiang; Yan, Hongru

2013-11-01

Deep convective clouds (DCCs) play a crucial role in the general circulation, energy, and hydrological cycle of our climate system. Aerosol particles can influence DCCs by altering cloud properties, precipitation regimes, and radiation balance. Previous studies reported both invigoration and suppression of DCCs by aerosols, but few were concerned with the whole life cycle of DCC. By conducting multiple monthlong cloud-resolving simulations with spectral-bin cloud microphysics that capture the observed macrophysical and microphysical properties of summer convective clouds and precipitation in the tropics and midlatitudes, this study provides a comprehensive view of how aerosols affect cloud cover, cloud top height, and radiative forcing. We found that although the widely accepted theory of DCC invigoration due to aerosol's thermodynamic effect (additional latent heat release from freezing of greater amount of cloud water) may work during the growing stage, it is microphysical effect influenced by aerosols that drives the dramatic increase in cloud cover, cloud top height, and cloud thickness at the mature and dissipation stages by inducing larger amounts of smaller but longer-lasting ice particles in the stratiform/anvils of DCCs, even when thermodynamic invigoration of convection is absent. The thermodynamic invigoration effect contributes up to ∼27% of total increase in cloud cover. The overall aerosol indirect effect is an atmospheric radiative warming (3-5 Wṡm-2) and a surface cooling (-5 to -8 Wṡm-2). The modeling findings are confirmed by the analyses of ample measurements made at three sites of distinctly different environments.

An organ-based approach to dose calculation in the assessment of dose-dependent biological effects of ionising radiation in Arabidopsis thaliana.

PubMed

Biermans, Geert; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Saenen, Eline; Van Hees, May; Wannijn, Jean; Vives i Batlle, Jordi; Cuypers, Ann

2014-07-01

There is a need for a better understanding of biological effects of radiation exposure in non-human biota. Correct description of these effects requires a more detailed model of dosimetry than that available in current risk assessment tools, particularly for plants. In this paper, we propose a simple model for dose calculations in roots and shoots of Arabidopsis thaliana seedlings exposed to radionuclides in a hydroponic exposure setup. This model is used to compare absorbed doses for three radionuclides, (241)Am (α-radiation), (90)Sr (β-radiation) and (133)Ba (γ radiation). Using established dosimetric calculation methods, dose conversion coefficient values were determined for each organ separately based on uptake data from the different plant organs. These calculations were then compared to the DCC values obtained with the ERICA tool under equivalent geometry assumptions. When comparing with our new method, the ERICA tool appears to overestimate internal doses and underestimate external doses in the roots for all three radionuclides, though each to a different extent. These observations might help to refine dose-response relationships. The DCC values for (90)Sr in roots are shown to deviate the most. A dose-effect curve for (90)Sr β-radiation has been established on biomass and photosynthesis endpoints, but no significant dose-dependent effects are observed. This indicates the need for use of endpoints at the molecular and physiological scale. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma

PubMed Central

Alabsi, Aied M.; Lim, Kai Li; Paterson, Ian C.; Ali-Saeed, Rola; Muharram, Bushra A.

2016-01-01

Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent. PMID:27123447

Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma.

PubMed

Alabsi, Aied M; Lim, Kai Li; Paterson, Ian C; Ali-Saeed, Rola; Muharram, Bushra A

2016-01-01

Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.

Microphysical effects determine macrophysical response for aerosol impacts on deep convective clouds.

PubMed

Fan, Jiwen; Leung, L Ruby; Rosenfeld, Daniel; Chen, Qian; Li, Zhanqing; Zhang, Jinqiang; Yan, Hongru

2013-11-26

Deep convective clouds (DCCs) play a crucial role in the general circulation, energy, and hydrological cycle of our climate system. Aerosol particles can influence DCCs by altering cloud properties, precipitation regimes, and radiation balance. Previous studies reported both invigoration and suppression of DCCs by aerosols, but few were concerned with the whole life cycle of DCC. By conducting multiple monthlong cloud-resolving simulations with spectral-bin cloud microphysics that capture the observed macrophysical and microphysical properties of summer convective clouds and precipitation in the tropics and midlatitudes, this study provides a comprehensive view of how aerosols affect cloud cover, cloud top height, and radiative forcing. We found that although the widely accepted theory of DCC invigoration due to aerosol's thermodynamic effect (additional latent heat release from freezing of greater amount of cloud water) may work during the growing stage, it is microphysical effect influenced by aerosols that drives the dramatic increase in cloud cover, cloud top height, and cloud thickness at the mature and dissipation stages by inducing larger amounts of smaller but longer-lasting ice particles in the stratiform/anvils of DCCs, even when thermodynamic invigoration of convection is absent. The thermodynamic invigoration effect contributes up to ~27% of total increase in cloud cover. The overall aerosol indirect effect is an atmospheric radiative warming (3-5 W m(-2)) and a surface cooling (-5 to -8 W m(-2)). The modeling findings are confirmed by the analyses of ample measurements made at three sites of distinctly different environments.

Lectin-binding histochemistry of non-decalcified growth plate cartilage: a postembedment method for light microscopy of epon-embedded tissue.

PubMed

Farnum, C E; Wilsman, N J

1984-06-01

A postembedment method for the localization of lectin-binding glycoconjugates was developed using Epon-embedded growth plate cartilage from Yucatan miniature swine. By testing a variety of etching, blocking, and incubation procedures, a standard protocol was developed for 1 micron thick sections that allowed visualization of both intracellular and extracellular glycoconjugates with affinity for wheat germ agglutinin and concanavalin A. Both fluorescent and peroxidase techniques were used, and comparisons were made between direct methods and indirect methods using the biotin-avidin bridging system. Differential extracellular lectin binding allowed visualization of interterritorial , territorial, and pericellular matrices. Double labeling experiments showed the precision with which intracellular binding could be localized to specific cytoplasmic compartments, with resolution of binding to the Golgi apparatus, endoplasmic reticulum, and nuclear membrane at the light microscopic level. This method allows the localization of both intracellular and extracellular lectin-binding glycoconjugates using fixation and embedment procedures that are compatible with simultaneous ultrastructural analysis. As such it should have applicability both to the morphological analysis of growth plate organization during normal endochondral ossification, as well as to the diagnostic pathology of matrix abnormalities in disease states of growing cartilage.

Evaluation of galectin binding by frontal affinity chromatography (FAC).

PubMed

Iwaki, Jun; Hirabayashi, Jun

2015-01-01

Frontal affinity chromatography (FAC) is a simple and versatile procedure enabling quantitative determination of diverse biological interactions in terms of dissociation constants (K d), even though these interactions are relatively weak. The method is best applied to glycans and their binding proteins, with the analytical system operating on the basis of highly reproducible isocratic elution by liquid chromatography. Its application to galectins has been successfully developed to characterize their binding specificities in detail. As a result, their minimal requirements for recognition of disaccharides, i.e., β-galactosides, as well as characteristic features of individual galectins, have been elucidated. In this chapter, we describe standard procedures to determine the K d's for interactions between a series of standard glycans and various galectins.

Development of Technology for Assessment of Electromagnetic Coupling - Automation and Extension of MIL-STD-1377

DTIC Science & Technology

1975-02-28

g g * * u a s ~ - .41 4 ^’ " 3UV L - M O O A S f4 o ~ j V q C P W P ~ l r w MDCE12 ELECTROMAGNETIC COUPLING 3 FEBRUARY1975 ’g Ir + 4-4- 3. IT 0 Ul...E ( U - - --------------------------- L1 TD N Ea 3n) IfVA VSSIOSOV DtJIMOfX3 H31i~d a3AIJ303 JO A1IISV9OHd 69 #DCC12 ELECTROMAGNETIC COUPLING n

[Determination of ochratoxin A by ELISA I. Study on the preparation of ochratoxin a antigen].

PubMed

Chen, Xuelan; Xu, Yang; Wu, Chenggang

2002-02-01

Ochratoxin A (OTA) antigen was prepared by activated ester method. Factors influencing OTA antigen were discussed and the optimum conditions was found by L9(3(4)) orthogonal design. The results showed that when the mole ratio was OTA:BSA = 20:1, OTA:NHS(N-hydroxy-succinamide):DCC(dicyclohexylcarbodiimide) = 1:2:4, the activate time was 120 min and the conjugation time was 90 min, the utilization of OTA could reach 48.2% and the best conjugation ratio of OTA and BSA was 9.64.

Study of Three Dimensional Transonic Flow Separations.

DTIC Science & Technology

1988-04-01

22222222222222222222222222222222222222 CD22 2 NN 22 0 2 2 C 22 .2 2 .2 .2 .2 .’ 22 . . . cD( C) DC)C DC D CC 222 2 22 2 2- C 2 22 22 22 - 22 02 N NT NL z...In1.0 INco (N -.- L’ c3 107 :-I--cnr -! - - N N 1 f;CC-7 cD c, 222 c222 cN -) H22 o cc -- -4 0,2222222" (D2 C22 22 D2 220 CD22 CD 2 CD CD N22 22D2

Does asymmetric correlation affect portfolio optimization?

NASA Astrophysics Data System (ADS)

Fryd, Lukas

2017-07-01

The classical portfolio optimization problem does not assume asymmetric behavior of relationship among asset returns. The existence of asymmetric response in correlation on the bad news could be important information in portfolio optimization. The paper applies Dynamic conditional correlation model (DCC) and his asymmetric version (ADCC) to propose asymmetric behavior of conditional correlation. We analyse asymmetric correlation among S&P index, bonds index and spot gold price before mortgage crisis in 2008. We evaluate forecast ability of the models during and after mortgage crisis and demonstrate the impact of asymmetric correlation on the reduction of portfolio variance.

Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens

EPA Pesticide Factsheets

This Supplemental Guidance does not establish any substantive “rules” under the Administrative Procedure Act or any other law and has no binding effect on EPA or any regulated entity, but instead represents a non-binding statement of policy.

The Sweetness of Aspartame: A Biochemistry Lab for Health Science Chemistry Courses.

ERIC Educational Resources Information Center

Stein, Paul J.

1997-01-01

Explains the procedures used in an experiment that reinforces the universality of the concepts of saturation using the binding of the ligand aspartame to the protein receptor that determines taste. Illustrates the hyperbolic nature of protein binding. (DDR)

Building blocks for the solution phase synthesis of oligonucleotides: regioselective hydrolysis of 3',5'-Di-O-levulinylnucleosides using an enzymatic approach.

PubMed

García, Javier; Fernández, Susana; Ferrero, Miguel; Sanghvi, Yogesh S; Gotor, Vicente

2002-06-28

A short and convenient synthesis of 3'- and 5'-O-levulinyl-2'-deoxynucleosides has been developed from the corresponding 3',5'-di-O-levulinyl derivatives by regioselective enzymatic hydrolysis, avoiding several tedious chemical protection/deprotection steps. Thus, Candida antartica lipase B (CAL-B) was found to selectively hydrolyze the 5'-levulinate esters, furnishing 3'-O-levulinyl-2'-deoxynucleosides 3 in >80% isolated yields. On the other hand, immobilized Pseudomonas cepacia lipase (PSL-C) and Candida antarctica lipase A (CAL-A) exhibit the opposite selectivity toward the hydrolysis at the 3'-position, affording 5'-O-levulinyl derivatives 4 in >70% yields. A similar hydrolysis procedure was successfully extended to the synthesis of 3'- and 5'-O-levulinyl-protected 2'-O-alkylribonucleosides 7 and 8. This work demonstrates for the first time application of commercial CAL-B and PSL-C toward regioselective hydrolysis of levulinyl esters with excellent selectivity and yields. It is noteworthy that protected cytidine and adenosine base derivatives were not adequate substrates for the enzymatic hydrolysis with CAL-B, whereas PSL-C was able to accommodate protected bases during selective hydrolysis. In addition, we report an improved synthesis of dilevulinyl esters using a polymer-bound carbodiimide as a replacement for dicyclohexylcarbodiimide (DCC), thus considerably simplifying the workup for esterification reactions.

Microphysical effects determine macrophysical response for aerosol impacts on deep convective clouds

PubMed Central

Fan, Jiwen; Leung, L. Ruby; Rosenfeld, Daniel; Chen, Qian; Li, Zhanqing; Zhang, Jinqiang; Yan, Hongru

2013-01-01

Deep convective clouds (DCCs) play a crucial role in the general circulation, energy, and hydrological cycle of our climate system. Aerosol particles can influence DCCs by altering cloud properties, precipitation regimes, and radiation balance. Previous studies reported both invigoration and suppression of DCCs by aerosols, but few were concerned with the whole life cycle of DCC. By conducting multiple monthlong cloud-resolving simulations with spectral-bin cloud microphysics that capture the observed macrophysical and microphysical properties of summer convective clouds and precipitation in the tropics and midlatitudes, this study provides a comprehensive view of how aerosols affect cloud cover, cloud top height, and radiative forcing. We found that although the widely accepted theory of DCC invigoration due to aerosol’s thermodynamic effect (additional latent heat release from freezing of greater amount of cloud water) may work during the growing stage, it is microphysical effect influenced by aerosols that drives the dramatic increase in cloud cover, cloud top height, and cloud thickness at the mature and dissipation stages by inducing larger amounts of smaller but longer-lasting ice particles in the stratiform/anvils of DCCs, even when thermodynamic invigoration of convection is absent. The thermodynamic invigoration effect contributes up to ∼27% of total increase in cloud cover. The overall aerosol indirect effect is an atmospheric radiative warming (3–5 W⋅m−2) and a surface cooling (−5 to −8 W⋅m−2). The modeling findings are confirmed by the analyses of ample measurements made at three sites of distinctly different environments. PMID:24218569

Healthy Living Partnerships to Prevent Diabetes (HELP PD): Design and Methods

PubMed Central

Katula, Jeffrey A.; Vitolins, Mara Z.; Rosenberger, Erica L.; Blackwell, Caroline; Espeland, Mark A.; Lawlor, Michael S.; Rejeski, W. Jack; Goff, David C.

2009-01-01

Although the Diabetes Prevention Program (DPP) developed a lifestyle weight loss intervention that has been demonstrated to prevent type 2 diabetes in high-risk individuals, it has yet to be widely adopted at the community level. The Healthy Living Partnership to Prevent Diabetes study (HELP PD) was designed to translate the DPP approach for use in community settings as a cost-effective intervention led by Community Health Workers (CHW's) and administered through a Diabetes Care Center (DCC). Approximately 300 overweight and obese (BMI 25-40 kg/m2) individuals with prediabetes (fasting blood glucose 95-124 mg/dl) were randomly assigned to either a lifestyle weight loss intervention (LW) or an enhanced usual care comparison condition (UC). The goal of LW is ≥7% weight loss achieved through increases in physical activity (180 min/wk) and decreases in caloric intake (approximately 1500 kcal/day). The intervention consists of CHW-led group-mediated cognitive behavioral meetings that occur weekly for 6 months and monthly thereafter for 18 months. UC consists of 2 individual meetings with a registered dietitian and a monthly newsletter. The primary outcome is change in fasting blood glucose. Secondary outcomes include cardiovascular risk factors, health-related quality of life, and social cognitive variables. Outcomes are masked and are collected every 6 months. The cost-effectiveness of the program will also be assessed. A community-based program that is administered through local DCC's and that harnesses the experience of community members (CHW's) may be a promising strategy for the widespread dissemination of interventions effective at preventing type 2 diabetes in high risk individuals. PMID:19758580

Spatial Segregation of γ-Secretase and Substrates in Distinct Membrane Domains*

PubMed Central

Vetrivel, Kulandaivelu S.; Cheng, Haipeng; Kim, Seong-Hun; Chen, Ying; Barnes, Natalie Y.; Parent, Ange‘le T.; Sisodia, Sangram S.; Thinakaran, Gopal

2005-01-01

γ-Secretase facilitates the regulated intramembrane proteolysis of select type I membrane proteins that play diverse physiological roles in multiple cell types and tissue. In this study, we used biochemical approaches to examine the distribution of amyloid precursor protein (APP) and several additional γ-secretase substrates in membrane microdomains. We report that APP C-terminal fragments (CTFs) and γ-secretase reside in Lubrol WX detergent-insoluble membranes (DIM) of cultured cells and adult mouse brain. APP CTFs that accumulate in cells lacking γ-secretase activity preferentially associate with DIM. Cholesterol depletion and magnetic im-munoisolation studies indicate recruitment of APP CTFs into cholesterol- and sphingolipid-rich lipid rafts, and co-residence of APP CTFs, PS1, and syntaxin 6 in DIM patches derived from the trans-Golgi network. Photoaffinity cross-linking studies provided evidence for the preponderance of active γ-secretase in lipid rafts of cultured cells and adult brain. Remarkably, unlike the case of APP, CTFs derived from Notch1, Jagged2, deleted in colorectal cancer (DCC), and N-cadherin remain largely detergent-soluble, indicative of their spatial segregation in non-raft domains. In embryonic brain, the majority of PS1 and nicastrin is present in Lubrol WX-soluble membranes, wherein the CTFs derived from APP, Notch1, DCC, and N-cadherin also reside. We suggest that γ-secretase residence in non-raft membranes facilitates proteolysis of diverse substrates during embryonic development but that the translocation of γ-secretase to lipid rafts in adults ensures processing of certain substrates, including APP CTFs, while limiting processing of other potential substrates. PMID:15886206

Spatial segregation of gamma-secretase and substrates in distinct membrane domains.

PubMed

Vetrivel, Kulandaivelu S; Cheng, Haipeng; Kim, Seong-Hun; Chen, Ying; Barnes, Natalie Y; Parent, Angèle T; Sisodia, Sangram S; Thinakaran, Gopal

2005-07-08

Gamma-secretase facilitates the regulated intramembrane proteolysis of select type I membrane proteins that play diverse physiological roles in multiple cell types and tissue. In this study, we used biochemical approaches to examine the distribution of amyloid precursor protein (APP) and several additional gamma-secretase substrates in membrane microdomains. We report that APP C-terminal fragments (CTFs) and gamma-secretase reside in Lubrol WX detergent-insoluble membranes (DIM) of cultured cells and adult mouse brain. APP CTFs that accumulate in cells lacking gamma-secretase activity preferentially associate with DIM. Cholesterol depletion and magnetic immunoisolation studies indicate recruitment of APP CTFs into cholesterol- and sphingolipid-rich lipid rafts, and co-residence of APP CTFs, PS1, and syntaxin 6 in DIM patches derived from the trans-Golgi network. Photoaffinity cross-linking studies provided evidence for the preponderance of active gamma-secretase in lipid rafts of cultured cells and adult brain. Remarkably, unlike the case of APP, CTFs derived from Notch1, Jagged2, deleted in colorectal cancer (DCC), and N-cadherin remain largely detergent-soluble, indicative of their spatial segregation in non-raft domains. In embryonic brain, the majority of PS1 and nicastrin is present in Lubrol WX-soluble membranes, wherein the CTFs derived from APP, Notch1, DCC, and N-cadherin also reside. We suggest that gamma-secretase residence in non-raft membranes facilitates proteolysis of diverse substrates during embryonic development but that the translocation of gamma-secretase to lipid rafts in adults ensures processing of certain substrates, including APP CTFs, while limiting processing of other potential substrates.

Analysis of Expression Pattern and Genetic Deletion of Netrin5 in the Developing Mouse

PubMed Central

Garrett, Andrew M.; Jucius, Thomas J.; Sigaud, Liam P. R.; Tang, Fu-Lei; Xiong, Wen-Cheng; Ackerman, Susan L.; Burgess, Robert W.

2016-01-01

Boundary cap cells (BCC) are a transient, neural-crest-derived population found at the motor exit point (MEP) and dorsal root entry zone (DREZ) of the embryonic spinal cord. These cells contribute to the central/peripheral nervous system (CNS/PNS) boundary, and in their absence neurons and glia from the CNS migrate into the PNS. We found Netrin5 (Ntn5), a previously unstudied member of the netrin gene family, to be robustly expressed in BCC. We generated Ntn5 knockout mice and examined neurodevelopmental and BCC-related phenotypes. No abnormalities in cranial nerve guidance, dorsal root organization, or sensory projections were found. However, Ntn5 mutant embryos did have ectopic motor neurons (MNs) that migrated out of the ventral horn and into the motor roots. Previous studies have implicated semaphorin6A (Sema6A) in BCC signaling to plexinA2 (PlxnA2)/neuropilin2 (Nrp2) in MNs in restricting MN cell bodies to the ventral horn, particularly in the caudal spinal cord. In Ntn5 mutants, ectopic MNs are likely to be a different population, as more ectopias were found rostrally. Furthermore, ectopic MNs in Ntn5 mutants were not immunoreactive for NRP2. The netrin receptor deleted in colorectal cancer (DCC) is a potential receptor for NTN5 in MNs, as similar ectopic neurons were found in Dcc mutant mice, but not in mice deficient for other netrin receptors. Thus, Ntn5 is a novel netrin family member that is expressed in BCC, functioning to prevent MN migration out of the CNS. PMID:26858598

Data consistency-driven scatter kernel optimization for x-ray cone-beam CT

NASA Astrophysics Data System (ADS)

Kim, Changhwan; Park, Miran; Sung, Younghun; Lee, Jaehak; Choi, Jiyoung; Cho, Seungryong

2015-08-01

Accurate and efficient scatter correction is essential for acquisition of high-quality x-ray cone-beam CT (CBCT) images for various applications. This study was conducted to demonstrate the feasibility of using the data consistency condition (DCC) as a criterion for scatter kernel optimization in scatter deconvolution methods in CBCT. As in CBCT, data consistency in the mid-plane is primarily challenged by scatter, we utilized data consistency to confirm the degree of scatter correction and to steer the update in iterative kernel optimization. By means of the parallel-beam DCC via fan-parallel rebinning, we iteratively optimized the scatter kernel parameters, using a particle swarm optimization algorithm for its computational efficiency and excellent convergence. The proposed method was validated by a simulation study using the XCAT numerical phantom and also by experimental studies using the ACS head phantom and the pelvic part of the Rando phantom. The results showed that the proposed method can effectively improve the accuracy of deconvolution-based scatter correction. Quantitative assessments of image quality parameters such as contrast and structure similarity (SSIM) revealed that the optimally selected scatter kernel improves the contrast of scatter-free images by up to 99.5%, 94.4%, and 84.4%, and of the SSIM in an XCAT study, an ACS head phantom study, and a pelvis phantom study by up to 96.7%, 90.5%, and 87.8%, respectively. The proposed method can achieve accurate and efficient scatter correction from a single cone-beam scan without need of any auxiliary hardware or additional experimentation.

Assessment of MODIS RSB Detector Uniformity Using Deep Convective Clouds

NASA Technical Reports Server (NTRS)

Chang, Tiejun; Xiong, Xiaoxiong (Jack); Angal, Amit; Mu, Qiaozhen

2016-01-01

For satellite sensor, the striping observed in images is typically associated with the relative multiple detector gain difference derived from the calibration. A method using deep convective cloud (DCC) measurements to assess the difference among detectors after calibration is proposed and demonstrated for select reflective solar bands (RSBs) of the Moderate Resolution Imaging Spectroradiometer (MODIS). Each detector of MODIS RSB is calibrated independently using a solar diffuser (SD). Although the SD is expected to accurately characterize detector response, the uncertainties associated with the SD degradation and characterization result in inadequacies in the estimation of each detector's gain. This work takes advantage of the DCC technique to assess detector uniformity and scan mirror side difference for RSB. The detector differences for Terra MODIS Collection 6 are less than 1% for bands 1, 3-5, and 18 and up to 2% for bands 6, 19, and 26. The largest difference is up to 4% for band 7. Most Aqua bands have detector differences less than 0.5% except bands 19 and 26 with up to 1.5%. Normally, large differences occur for edge detectors. The long-term trending shows seasonal oscillations in detector differences for some bands, which are correlated with the instrument temperature. The detector uniformities were evaluated for both unaggregated and aggregated detectors for MODIS band 1 and bands 3-7, and their consistencies are verified. The assessment results were validated by applying a direct correction to reflectance images. These assessments can lead to improvements to the calibration algorithm and therefore a reduction in striping observed in the calibrated imagery.

Effects of the proposed California WaterFix North Delta Diversion on flow reversals and entrainment of juvenile Chinook salmon (Oncorhynchus tshawytscha) into Georgiana Slough and the Delta Cross Channel, northern California

USGS Publications Warehouse

Perry, Russell W.; Romine, Jason G.; Pope, Adam C.; Evans, Scott D.

2018-02-27

The California Department of Water Resources and Bureau of Reclamation propose new water intake facilities on the Sacramento River in northern California that would convey some of the water for export to areas south of the Sacramento-San Joaquin River Delta (hereinafter referred to as the Delta) through tunnels rather than through the Delta. The collection of water intakes, tunnels, pumping facilities, associated structures, and proposed operations are collectively referred to as California WaterFix. The water intake facilities, hereinafter referred to as the North Delta Diversion (NDD), are proposed to be located on the Sacramento River downstream of the city of Sacramento and upstream of the first major river junction where Sutter Slough branches from the Sacramento River. The NDD can divert a maximum discharge of 9,000 cubic feet per second (ft3/s) from the Sacramento River, which reduces the amount of Sacramento River inflow into the Delta.In this report, we conducted three analyses to investigate the effect of the NDD and its proposed operation on entrainment of juvenile Chinook salmon (Oncorhynchus tshawytscha) into Georgiana Slough and the Delta Cross Channel (DCC). Fish that enter the interior Delta (the network of channels to the south of the Sacramento River) through Georgiana Slough and the DCC survive at lower rates than fish that use other migration routes (Sacramento River, Sutter Slough, and Steamboat Slough). Therefore, fisheries managers were concerned about the extent to which operation of the NDD would increase the proportion of the population entering the interior Delta, which, all else being equal, would lower overall survival through the Delta by increasing the fraction of the population subject to lower survival rates. Operation of the NDD would reduce flow in the Sacramento River, which has the potential to increase the magnitude and duration of reverse flows of the Sacramento River downstream of Georgiana Slough.In the first analysis, we evaluate the effect of the NDD bypass rules on flow reversals of the Sacramento River downstream of Georgiana Slough. The NDD bypass rules are a set of operational criteria designed to minimize upstream transport of fish into Georgiana Slough and the DCC, and were developed based on previous studies showing that the magnitude and duration of flow reversals increase the proportion of fish entering Georgiana Slough and the DCC. We estimated the frequency and duration of reverse-flow conditions of the Sacramento River downstream of Georgiana Slough under each of the prescribed minimum bypass flows described in the NDD bypass rules. To accommodate adaptive levels of protection during different times of year when juvenile salmon are migrating through the Delta, the NDD bypass rules prescribe a series of minimum allowable bypass flows that vary depending on (1) month of the year, and (2) progressively decreasing levels of protection following a pulse flow event.We determined that the NDD bypass rules increased the frequency and duration of reverse flows of the Sacramento River downstream of Georgiana Slough, with the magnitude of increase varying among scenarios. Constant low-level pumping, the most protective bypass rule that limits diversion to 10 percent of the maximum diversion and is implemented following a pulse-flow event, led to the smallest increase in frequency and duration of flow reversals. In contrast, we found that some scenarios led to sizeable increases in the fraction of the day with reverse flow. The conditions under which the proportion of the day with reverse flow can increase by greater than or equal to 10 percentage points between October and June, when juvenile salmon are present in the Delta, include October–November bypass rules and level-3 post-pulse operations during December–June. These conditions would be expected to increase the proportion of juvenile salmon entering the interior Delta through Georgiana Slough.In the second analysis, we assessed bias in Delta Simulation Model 2 (DSM2) flow predictions at the junction of the Sacramento River, DCC, and Georgiana Slough. Because DSM2 was being used to simulate California WaterFix operations, understanding the extent of bias relative to USGS streamgages was important since fish routing models were based on flow data at streamgages. We determined that river flow predicted by DSM2 was biased for Georgiana Slough and the Sacramento River. Therefore, for subsequent analysis, we bias-corrected the DSM2 flow predictions using measured stream flows as predictor variables.In the third analysis, we evaluated the effect of the NDD on the daily probability of fish entering Georgiana Slough and the DCC. We applied an existing model to predict entrainment from 15-minute flow simulations for an 82-year time series of flows simulated by DSM2 under the Proposed Action (PA), where the North Delta Diversion is implemented under California WaterFix, and the No Action Alternative (NAA), where the diversion is not implemented. To estimate the daily fraction of fish entering each river channel, entrainment probabilities were averaged over each day. To evaluate the two scenarios, we then compared mean annual entrainment probabilities by month, water year classification, and three different assumed run timings. Overall, the probability of remaining in the Sacramento River was lower under the PA scenario, but the magnitude of the difference was small (3/s. At flows greater than 41,000 ft3/s, we hypothesize that entrainment into the interior Delta is relatively constant, which would have caused little difference between scenarios at higher flows.

Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules.

PubMed

Holm, J; Hillenbrand, R; Steuber, V; Bartsch, U; Moos, M; Lübbert, H; Montag, D; Schachner, M

1996-08-01

We have identified a close homologue of L1 (CHL1) in the mouse. CHL1 comprises an N-terminal signal sequence, six immunoglobulin (Ig)-like domains, 4.5 fibronectin type III (FN)-like repeats, a transmembrane domain and a C-terminal, most likely intracellular domain of approximately 100 amino acids. CHL1 is most similar in its extracellular domain to chicken Ng-CAM (approximately 40% amino acid identity), followed by mouse L1, chicken neurofascin, chicken Nr-CAM, Drosophila neuroglian and zebrafish L1.1 (37-28% amino acid identity), and mouse F3, rat TAG-1 and rat BIG-1 (approximately 27% amino acid identity). The similarity with other members of the Ig superfamily [e.g. neural cell adhesion molecule (N-CAM), DCC, HLAR, rse] is 16-11%. The intracellular domain is most similar to mouse and chicken Nr-CAM, mouse and rat neurofascin (approximately 60% amino acid identity) followed by chicken neurofascin and Ng-CAM, Drosophila neuroglian and zebrafish L1.1 and L1.2 (approximately 40% amino acid identity). Besides the high overall homology and conserved modular structure among previously recognized members of the L1 family (mouse/human L1/rat NILE; chicken Ng-CAM; chicken/mouse Nr-CAM; Drosophila neuroglian; zebrafish L1.1 and L1.2; chicken/mouse neurofascin/rat ankyrin-binding glycoprotein), criteria characteristic of L1 were identified with regard to the number of amino acids between positions of conserved amino acid residues defining distances within and between two adjacent Ig-like domains and FN-like repeats. These show a collinearity in the six Ig-like domains and four adjacent FN-like repeats that is remarkably conserved between L1 and molecules containing these modules (designated the L1 family cassette), including the GPI-linked forms of the F3 subgroup (mouse F3/chicken F11/human CNTN1; rat BIG-1/mouse PANG; rat TAG-1/mouse TAX-1/chicken axonin-1). The colorectal cancer molecule (DCC), previously introduced as an N-CAM-like molecule, conforms to the L1 family cassette. Other structural features of CHL 1 shared between members of the L1 family are a high degree of N-glycosidically linked carbohydrates (approximately 20% of its molecular mass), which include the HNK-1 carbohydrate structure, and a pattern of protein fragments comprising a major 185 kDa band and smaller fragments of 165 and 125 kDa. As for the other L1 family members, predominant expression of CHL1 is observed in the nervous system and at later developmental stages. In the central nervous system CHL1 is expressed by neurons, but, in contrast to L1, also by glial cells. Our findings suggest a common ancestral L1-like molecule which evolved via gene duplication to generate a diversity of structurally and functionally distinct yet similar molecules.

Designing Recycled Hot Mix Asphalt Mixtures Using Superpave Technology

DOT National Transportation Integrated Search

1997-01-01

Mix design procedures for recycled asphalt pavements require the selection of : virgin asphalt binder or recycling agent. This research project was undertaken : to develop a procedure for selecting the performance grade (PG) of virgin : asphalt binde...

Effects of autoshaping procedures on 3H-8-OH-DPAT-labeled 5-HT1a binding and 125I-LSD-labeled 5-HT2a binding in rat brain.

PubMed

Tomie, Arthur; Di Poce, Jason; Aguado, Allison; Janes, Amy; Benjamin, Daniel; Pohorecky, Larissa

2003-06-13

Effects of experience with Pavlovian autoshaping procedures on lever-press autoshaping conditioned response (CR) performance and 3H-8-OH-DPAT-labeled binding of 5-HT(1a) receptors as well as 125I-LSD-labeled binding of 5-HT(2a) receptors were evaluated in four groups of male Long-Evans hooded rats. Two groups of rats (Group Paired High CR and Group Paired Low CR) received Pavlovian autoshaping procedures wherein the presentation of a lever (conditioned stimulus, CS) was followed by the response-independent presentation of food (unconditioned stimulus, US). Rats in Group Paired High CR (n=12) showed more rapid CR acquisition and higher asymptotic levels of lever-press autoshaping CR performance relative to rats in Group Low CR (n=12). Group Omission (n=9) received autoshaping with an omission contingency, such that performing the lever-press autoshaping CR resulted in the cancellation the food US, while Group Random (n=9) received presentations of lever CS and food US randomly with respect to one another. Though Groups Omission and Random did not differ in lever-press autoshaping CR performance, Group Omission showed significantly lower levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in post-synaptic areas (frontal cortex, septum, caudate putamen), as well as significantly higher plasma corticosterone levels than Group Random. In addition, Group Random showed higher levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in pre-synaptic somatodendritic autoreceptors on dorsal raphe nucleus relative to each of the other three groups. Autoradiographic analysis of 125I-LSD-labeled 5-HT(2a) receptor binding revealed no significant differences between Groups Paired High CR and Paired Low CR or between Groups Omission and Random in any brain regions.

Recent advances in colony stimulating factor-1 receptor/c-FMS as an emerging target for various therapeutic implications.

PubMed

Kumari, Archana; Silakari, Om; Singh, Rajesh K

2018-07-01

Colony stimulating factor-1 (CSF-1) is one of the most common proinflammatory cytokine responsible for various inflammatory disorders. It has a remarkable role in the development and progression of osteoarthritis, cancer and other autoimmune disease conditions. The CSF-1 acts by binding to the receptor, called colony stimulating factor-1 receptor (CSF-1R) also known as c-FMS resulting in the cascade of signalling pathway causing cell proliferation and differentiation. Interleukin-34 (IL-34), recently identified as another ligand for CSF-IR, is a cytokine protein. Both, CSF-1 and IL-34, although two distinct cytokines, follow the similar signalling pathway on binding to the same receptor, CSF-1R. Like CSF-1, IL-34 promotes the differentiation and survival of monocyte, macrophages and osteoclasts. This CSF-1R/c-FMS is over expressed in many cancers and on tumour associated macrophages, consequently, have been exploited as a drug target for promising treatment for cancer and inflammatory diseases. Some CSF-1R/c-FMS inhibitors such as ABT-869, Imatinib, AG013736, JNJ-40346527, PLX3397, DCC-3014 and Ki20227 have been successfully used in these disease conditions. Many c-FMS inhibitors have been the candidates of clinical trials, but suffer from some side effects like cardiotoxicity, vomiting, swollen eyes, diarrhoea, etc. If selectivity of cFMS inhibition is achieved successfully, side effects can be overruled and this approach may become a novel therapy for treatment of various therapeutic interventions. Thus, successful targeting of c-FMS may result in multifunctional therapy. With this background of information, the present review focuses on the recent developments in the area of CSF-1R/c-FMS inhibitors with emphasis on crystal structure, mechanism of action and various therapeutic implications in which c-FMS plays a pivotal role. The review on structure activity relationship of various compounds acting as the inhibitors of c-FMS which gives the selection criteria for the development of novel molecules is also being presented. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

47 CFR 90.699 - Transition of the upper 200 channels in the 800 MHz band to EA licensing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... over the amount of reimbursement required, will be encouraged to use expedited ADR procedures. ADR procedures provide several alternative methods such as binding arbitration, mediation, or other ADR...

20 CFR 667.600 - What local area, State and direct recipient grievance procedures must be established?

Code of Federal Regulations, 2010 CFR

2010-04-01

... INVESTMENT ACT Grievance Procedures, Complaints, and State Appeals Processes § 667.600 What local area, State... awards Title I funds must provide the information referred to in paragraph (b)(1) of this section to... violation to submit the grievance to a binding arbitration procedure, if a collective bargaining agreement...

20 CFR 667.600 - What local area, State and direct recipient grievance procedures must be established?

Code of Federal Regulations, 2011 CFR

2011-04-01

... INVESTMENT ACT Grievance Procedures, Complaints, and State Appeals Processes § 667.600 What local area, State... awards Title I funds must provide the information referred to in paragraph (b)(1) of this section to... violation to submit the grievance to a binding arbitration procedure, if a collective bargaining agreement...

Fibrinogen release and deposition on urinary catheters placed during urologic procedures

PubMed Central

Potretzke, Aaron M.; Schreiber, Henry L.; Park, Alyssa M.; Pinkner, Jerome S.; Caparon, Michael G.; Hultgren, Scott J.; Desai, Alana

2016-01-01

Purpose Catheter-associated urinary tract infections (CAUTI) account for ~40% of all hospital-acquired infections worldwide, with more than one million cases diagnosed annually. Recent data from a CAUTI animal model has shown that inflammation induced by catheterization releases host fibrinogen that accumulates on the catheter. Further, Enterococcus faecalis catheter colonization was found to be dependent on EbpA, a fibrinogen binding adhesin. We sought to evaluate this mechanism in a human model. Materials and methods Urinary catheters were collected from human subjects hospitalized for surgical or non-surgical urologic procedures. Catheters were subjected to immunofluorescence analyses by incubating them with anti-fibrinogen antibody and then stained for fluorescence. The fluorescence intensity was compared to standard catheters. Catheters were incubated with strains of Enterococcus faecalis, Staphylococcus aureus, or Candida to assess their binding to fibrinogen-laden catheters. Results Fifty catheters were collected after various surgical and urological procedures. In vivo dwell time ranged from 1 hour to 59 days. All catheters had fibrinogen deposition and its accumulation was dependent on dwell time but not on surgical procedure or catheter material. Catheters were probed ex vivo with E. faecalis, S. aureus, and Candida albicans, which bound to catheters only in those regions where fibrinogen was deposited. Conclusions Taken together, these data show that urinary catheters act as a binding surface for accumulation of fibrinogen, which is released due to inflammation resulting from a urological procedure or from catheter placement, creating a niche that can be exploited by uropathogens to cause CAUTI. PMID:26827873

Gas-phase binding energies for non-covalent Aβ-40 peptide/small molecule complexes from CID mass spectrometry and RRKM theory.

PubMed

Mayer, Paul M; Martineau, Eric

2011-03-21

The gas-phase binding of small molecules to the Amyloid β-40 peptide generated by electrospray ionization has been explored with collision-induced dissociation mass spectrometry and kinetic rate theory. This study discusses a simple procedure used to theoretically model the experimental breakdown diagrams for the Aβ-40 peptide complexed with a series of aminosulfonate small molecules, namely homotaurine, 3-cyclohexylamino-2-hydroxy-1-propanesulfonic acid (CAPSO), 3-(1,3,4,9-tetrahydro-2H-β-carbolin-2-yl)propane-1-sulfonic acid, 3-(1,3,4,9-tetrahydro-2H-β-carbolin-2-yl)butane-1-sulfonic acid, and 3-(cyclohexylamino)propane-1-sulfonic acid. An alternative procedure employing an extrapolation procedure for k(E) is also discussed.

Proceedings of Damping 󈨟, 13-15 February 1991, San Diego, California; Volume 1 (Pages AAC-1 through DCC-19)

DTIC Science & Technology

1991-08-01

typical flight conditions for which high load factor maneuver data was gathered. The range of dynamic pressure, 350 psf to 500 psf, for the 12...because PED systems do not outgas and are stable with respect to environmental temperature variations. In addition PED system performance is easily...0 (15) Equation (15) is rearranged to give: X2H2i + X3H21 + XAHAl + XsH5l + + + Xl+X2 + X3+X< + Xs X2 Y + X3(H2 + ^)+ XA(H2 + H3 + ^-) + XS (H2

Polynucleotides. XXXII. Further studies on the synthesis of oligonucleotides containing 8,2'-S-cycloadenosine.

PubMed Central

Ikehara, M; Tezuka, T

1975-01-01

A dinucleoside monophosphate, 8,2'-anhydro-8-mercapto-9-beta-D-arabinofuranosyladenine phosphoryl-(3'-5')-inosine (AspI) was synthesized by the condensation of protected 8-mercapto-adenosine 2',3'-cyclic phosphate and 2',3'-isopropylideneinosine with diphenylphosphorochloridate. 8-Mercaptoadenosine 2',3'-cyclic phosphate was polymerized by using tetraphenyl pyrophosphate as the condensing reagent. As oligonucleotides, thus obtained, contained some uncyclized 8-mercaptoadenosine residues and were cleaved at these sites with 0.3N KOH. As 5'-phosphate was synthesized and polymerized with DCC to give oligonucleotides with chain lengths 2 to 9. PMID:170595

Alkylating Derivatives of Vitamin D Hormone for Prostate Cancer

DTIC Science & Technology

2006-10-01

Acetic Anhydride / Pyridine/ 40C 1. UV / Toluene 2. EtOH - Reflux TBDMSCl / Imidazole /DMF BrCH2COOH / DCC / DMAP / CH2Cl2 1,25(OH)2D3-3-BE Figure 1...BE OH SO2 OTBDMS OH OTBDMS 1. Liq. SO2 / Reflux 2. TBDMSCl / Imidazole /DMF NaHCO3 / EtOH / Reflux NMO / SeO2 / CH2Cl2 / Reflux OH OTBDMSHO OTHP...containing 200 mg of 25-hydroxyvitamin D3 in a flask fitted with a trap that was cooled with dry ice-acetone (-780C). The yellow solution was refluxed

Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets.

PubMed

Feinstein, Wei P; Brylinski, Michal

2015-01-01

Computational approaches have emerged as an instrumental methodology in modern research. For example, virtual screening by molecular docking is routinely used in computer-aided drug discovery. One of the critical parameters for ligand docking is the size of a search space used to identify low-energy binding poses of drug candidates. Currently available docking packages often come with a default protocol for calculating the box size, however, many of these procedures have not been systematically evaluated. In this study, we investigate how the docking accuracy of AutoDock Vina is affected by the selection of a search space. We propose a new procedure for calculating the optimal docking box size that maximizes the accuracy of binding pose prediction against a non-redundant and representative dataset of 3,659 protein-ligand complexes selected from the Protein Data Bank. Subsequently, we use the Directory of Useful Decoys, Enhanced to demonstrate that the optimized docking box size also yields an improved ranking in virtual screening. Binding pockets in both datasets are derived from the experimental complex structures and, additionally, predicted by eFindSite. A systematic analysis of ligand binding poses generated by AutoDock Vina shows that the highest accuracy is achieved when the dimensions of the search space are 2.9 times larger than the radius of gyration of a docking compound. Subsequent virtual screening benchmarks demonstrate that this optimized docking box size also improves compound ranking. For instance, using predicted ligand binding sites, the average enrichment factor calculated for the top 1 % (10 %) of the screening library is 8.20 (3.28) for the optimized protocol, compared to 7.67 (3.19) for the default procedure. Depending on the evaluation metric, the optimal docking box size gives better ranking in virtual screening for about two-thirds of target proteins. This fully automated procedure can be used to optimize docking protocols in order to improve the ranking accuracy in production virtual screening simulations. Importantly, the optimized search space systematically yields better results than the default method not only for experimental pockets, but also for those predicted from protein structures. A script for calculating the optimal docking box size is freely available at www.brylinski.org/content/docking-box-size. Graphical AbstractWe developed a procedure to optimize the box size in molecular docking calculations. Left panel shows the predicted binding pose of NADP (green sticks) compared to the experimental complex structure of human aldose reductase (blue sticks) using a default protocol. Right panel shows the docking accuracy using an optimized box size.

Influence of binding pH and protein solubility on the dynamic binding capacity in hydrophobic interaction chromatography.

PubMed

Baumann, Pascal; Baumgartner, Kai; Hubbuch, Jürgen

2015-05-29

Hydrophobic interaction chromatography (HIC) is one of the most frequently used purification methods in biopharmaceutical industry. A major drawback of HIC, however, is the rather low dynamic binding capacity (DBC) obtained when compared to e.g. ion exchange chromatography (IEX). The typical purification procedure for HIC includes binding at neutral pH, independently of the proteins nature and isoelectric point. Most approaches to process intensification are based on resin and salt screenings. In this paper a combination of protein solubility data and varying binding pH leads to a clear enhancement of dynamic binding capacity. This is shown for three proteins of acidic, neutral, and alkaline isoelectric points. High-throughput solubility screenings as well as miniaturized and parallelized breakthrough curves on Media Scout RoboColumns (Atoll, Germany) were conducted at pH 3-10 on a fully automated robotic workstation. The screening results show a correlation between the DBC and the operational pH, the protein's isoelectric point and the overall solubility. Also, an inverse relationship of DBC in HIC and the binding kinetics was observed. By changing the operational pH, the DBC could be increased up to 30% compared to the standard purification procedure performed at neutral pH. As structural changes of the protein are reported during HIC processes, the applied samples and the elution fractions were proven not to be irreversibly unfolded. Copyright © 2015 Elsevier B.V. All rights reserved.

An eye tracking investigation of color-location binding in infants' visual short-term memory.

PubMed

Oakes, Lisa M; Baumgartner, Heidi A; Kanjlia, Shipra; Luck, Steven J

2017-01-01

Two experiments examined 8- and 10-month-old infants' ( N = 71) binding of object identity (color) and location information in visual short-term memory (VSTM) using a one-shot change detection task . Building on previous work using the simultaneous streams change detection task, we confirmed that 8- and 10-month-old infants are sensitive to changes in binding between identity and location in VSTM. Further, we demonstrated that infants recognize specifically what changed in these events. Thus, infants' VSTM for binding is robust and can be observed in different procedures and with different stimuli.

Novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies.

PubMed

Wright, Michael; Miller, Andrew D

2006-02-15

Tandem synthetic-biosynthetic procedures were used to prepare two novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies. These compounds (dial-mant-Ap4A and azido-mant-Ap4A) are shown to clearly distinguish known Ap4A-binding proteins from Escherichia coli (LysU and GroEL) and a variety of other control proteins. Successful labelling of chaperonin GroEL appears to be allosteric with respect to the well-characterized adenosine 5'-triphosphate (ATP)-binding site, suggesting that GroEL possesses a distinct Ap4A-binding site.

Fast Modeling of Binding Affinities by Means of Superposing Significant Interaction Rules (SSIR) Method

PubMed Central

Besalú, Emili

2016-01-01

The Superposing Significant Interaction Rules (SSIR) method is described. It is a general combinatorial and symbolic procedure able to rank compounds belonging to combinatorial analogue series. The procedure generates structure-activity relationship (SAR) models and also serves as an inverse SAR tool. The method is fast and can deal with large databases. SSIR operates from statistical significances calculated from the available library of compounds and according to the previously attached molecular labels of interest or non-interest. The required symbolic codification allows dealing with almost any combinatorial data set, even in a confidential manner, if desired. The application example categorizes molecules as binding or non-binding, and consensus ranking SAR models are generated from training and two distinct cross-validation methods: leave-one-out and balanced leave-two-out (BL2O), the latter being suited for the treatment of binary properties. PMID:27240346

Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE.

PubMed

Trinh, Quang M; Jen, Fei-Yang Arthur; Zhou, Ziru; Chu, Kar Ming; Perry, Marc D; Kephart, Ellen T; Contrino, Sergio; Ruzanov, Peter; Stein, Lincoln D

2013-07-22

Funded by the National Institutes of Health (NIH), the aim of the Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the biological research community with a comprehensive encyclopedia of functional genomic elements for both model organisms C. elegans (worm) and D. melanogaster (fly). With a total size of just under 10 terabytes of data collected and released to the public, one of the challenges faced by researchers is to extract biologically meaningful knowledge from this large data set. While the basic quality control, pre-processing, and analysis of the data has already been performed by members of the modENCODE consortium, many researchers will wish to reinterpret the data set using modifications and enhancements of the original protocols, or combine modENCODE data with other data sets. Unfortunately this can be a time consuming and logistically challenging proposition. In recognition of this challenge, the modENCODE DCC has released uniform computing resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE-DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In particular, we have released Galaxy workflows for interpreting ChIP-seq data which use the same quality control (QC) and peak calling standards adopted by the modENCODE and ENCODE communities. For convenience of use, we have created Amazon and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE data, software and other dependencies. Using these resources provides a framework for running consistent and reproducible analyses on modENCODE data, ultimately allowing researchers to use more of their time using modENCODE data, and less time moving it around.

Copper removal using electrosterically stabilized nanocrystalline cellulose.

PubMed

Sheikhi, Amir; Safari, Salman; Yang, Han; van de Ven, Theo G M

2015-06-03

Removal of heavy metal ions such as copper using an efficient and low-cost method with low ecological footprint is a critical process in wastewater treatment, which can be achieved in a liquid phase using nanoadsorbents such as inorganic nanoparticles. Recently, attention has turned toward developing sustainable and environmentally friendly nanoadsorbents to remove heavy metal ions from aqueous media. Electrosterically stabilized nanocrystalline cellulose (ENCC), which can be prepared from wood fibers through periodate/chlorite oxidation, has been shown to have a high charge content and colloidal stability. Here, we show that ENCC scavenges copper ions by different mechanisms depending on the ion concentration. When the Cu(II) concentration is low (C0≲200 ppm), agglomerates of starlike ENCC particles appear, which are broken into individual starlike entities by shear and Brownian motion, as evidenced by photometric dispersion analysis, dynamic light scattering, and transmission electron microscopy. On the other hand, at higher copper concentrations, the aggregate morphology changes from starlike to raftlike, which is probably due to the collapse of protruding dicarboxylic cellulose (DCC) chains and ENCC charge neutralization by copper adsorption. Such raftlike structures result from head-to-head and lateral aggregation of neutralized ENCCs as confirmed by transmission electron microscopy. As opposed to starlike aggregates, the raftlike structures grow gradually and are prone to sedimentation at copper concentrations C0≳500 ppm, which eliminates a costly separation step in wastewater treatment processes. Moreover, a copper removal capacity of ∼185 mg g(-1) was achieved thanks to the highly charged DCC polyanions protruding from ENCC. These properties along with the biorenewability make ENCC a promising candidate for wastewater treatment, in which fast, facile, and low-cost removal of heavy metal ions is desired most.

MONTE CARLO STUDY OF THE CARDIAC ABSORBED DOSE DURING X-RAY EXAMINATION OF AN ADULT PATIENT.

PubMed

Kadri, O; Manai, K; Alfuraih, A

2016-12-01

The computational voxel phantom 'High-Definition Reference Korean-Man (HDRK-Man)' was implemented into the Monte Carlo transport toolkit Geant4. The voxel model, adjusted to the Reference Korean Man, is 171 cm in height and 68 kg in weight and composed of ∼30 million voxels whose size is 1.981 × 1.981 × 2.0854 mm 3 The Geant4 code is then utilised to compute the dose conversion coefficients (DCCs) expressed in absorbed dose per air kerma free in air for >30 tissues and organs, including almost all organs required in the new recommendation of the ICRP 103, due to a broad parallel beam of monoenergetic photons impinging in antero-postero direction with energy ranging from 10 to 150 keV. The computed DCCs of different organs are found to be in good agreement with data published using other simulation codes. Also, the influence of patient size on DCC values was investigated for a representative body size of the adult Korean patient population. The study was performed using five different sizes covering the range of 0.8-1.2 magnification order of the original HDRK-Man. It focussed on the computation of DCC for the human heart. Moreover, the provided DCCs were used to present an analytical parameterisation for the calculation of the cardiac absorbed dose for any arbitrary X-ray spectrum and for those patient sizes. Thus, the present work can be considered as an enhancement of the continuous studies performed by medical physicist as part of quality control tests and radiation protection dosimetry. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Monitoring and mass balance analysis of endocrine disrupting compounds and their transformation products in an anaerobic-anoxic-oxic wastewater treatment system in Xiamen, China.

PubMed

Ashfaq, Muhammad; Li, Yan; Wang, Yuwen; Qin, Dan; Rehman, Muhammad Saif Ur; Rashid, Azhar; Yu, Chang-Ping; Sun, Qian

2018-08-01

We investigated the occurrence, removal and mass balance of 8 endocrine disrupting compounds (EDCs), including estrone (E1), estradiol (E2), estriol (E3), ethinylestradiol (EE2), triclosan (TCS), triclocarbon (TCC), 4-n-nonyl phenol (NP) and 4-n-octyl phenol (OP), along with 5 of their transformation products (TPs), including 4-hydroxy estrone (4-OH E1), 4-hydroxy estradiol (4-OH E2), methyl triclosan (MeTCS), carbanilide (NCC), dichlorocarbanilide (DCC) in a wastewater treatment plant. Generally, E3 showed the highest concentrations in wastewater with median value of 514 ng/L in influent, while TCS and TCC showed highest level in sludge and suspended solids (SS) with median value of 960 and 724 μg/kg, respectively. Spatial variations were observed along each unit of the wastewater treatment processes for dissolved analytes in wastewater and adsorbed analytes in suspended solids and sludge. Special emphasis was placed to understand the mass load of EDCs and their TPs to the wastewater treatment unit and mass loss during the wastewater treatment processes. Mass loss based on both aqueous and suspended phase concentration revealed that majority of these chemicals were significantly removed during the treatment process except for TCS, TCC, and three of their TPs (MeTCS, NCC, DCC), which were released or generated during the treatment process. Mass load results showed that 42.4 g of these EDCs and their TPs entered this wastewater treatment system daily via influent, whereas 6.15 g and 7.60 g were discharged through effluent and sludge. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transformation products and human metabolites of triclocarban and tricllosan in sewage sludge across the United States

USGS Publications Warehouse

Pycke, Benny F.G.; Roll, Isaac B.; Brownawell, Bruce J.; Kinney, Chad A.; Furlong, Edward T.; Kolpin, Dana W.; Halden, Rolf U.

2014-01-01

Removal of triclocarban (TCC) and triclosan (TCS) from wastewater is a function of adsorption, abiotic degradation, and microbial mineralization or transformation, reactions that are not currently controlled or optimized in the pollution control infrastructure of standard wastewater treatment. Here, we report on the levels of eight transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in raw and treated sewage sludge. Two sample sets were studied: samples collected once from 14 wastewater treatment plants (WWTPs) representing nine states, and multiple samples collected from one WWTP monitored for 12 months. Time-course analysis of significant mass fluxes (α = 0.01) indicate that transformation of TCC (dechlorination) and TCS (methylation) occurred during sewage conveyance and treatment. Strong linear correlations were found between TCC and the human metabolite 2′-hydroxy-TCC (r = 0.84), and between the TCC-dechlorination products dichlorocarbanilide (DCC) and monochlorocarbanilide (r = 0.99). Mass ratios of DCC-to-TCC and of methyl-triclosan (MeTCS)-to-TCS, serving as indicators of transformation activity, revealed that transformation was widespread under different treatment regimes across the WWTPs sampled, though the degree of transformation varied significantly among study sites (α = 0.01). The analysis of sludge sampled before and after different unit operation steps (i.e., anaerobic digestion, sludge heat treatment, and sludge drying) yielded insights into the extent and location of TCC and TCS transformation. Results showed anaerobic digestion to be important for MeTCS transformation (37–74%), whereas its contribution to partial TCC dechlorination was limited (0.4–2.1%). This longitudinal and nationwide survey is the first to report the occurrence of transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in sewage sludge.

A Consistent EPIC Visible Channel Calibration Using VIIRS and MODIS as a Reference.

NASA Astrophysics Data System (ADS)

Haney, C.; Doelling, D. R.; Minnis, P.; Bhatt, R.; Scarino, B. R.; Gopalan, A.

2017-12-01

The Earth Polychromatic Imaging Camera (EPIC) aboard the Deep Space Climate Observatory (DSCOVR) satellite constantly images the sunlit disk of Earth from the Lagrange-1 (L1) point in 10 spectral channels spanning the UV, VIS, and NIR spectrums. Recently, the DSCOVR EPIC team has publicly released version 2 dataset, which has implemented improved navigation, stray-light correction, and flat-fielding of the CCD array. The EPIC 2-year data record must be well-calibrated for consistent cloud, aerosol, trace gas, land use and other retrievals. Because EPIC lacks onboard calibrators, the observations made by EPIC channels must be calibrated vicariously using the coincident measurements from radiometrically stable instruments that have onboard calibration systems. MODIS and VIIRS are best-suited instruments for this task as they contain similar spectral bands that are well-calibrated onboard using solar diffusers and lunar tracking. We have previously calibrated the EPIC version 1 dataset by using EPIC and VIIRS angularly matched radiance pairs over both all-sky ocean and deep convective clouds (DCC). We noted that the EPIC image required navigations adjustments, and that the EPIC stray-light correction provided an offset term closer to zero based on the linear regression of the EPIC and VIIRS ray-matched radiance pairs. We will evaluate the EPIC version 2 navigation and stray-light improvements using the same techniques. In addition, we will monitor the EPIC channel calibration over the two years for any temporal degradation or anomalous behavior. These two calibration methods will be further validated using desert and DCC invariant Earth targets. The radiometric characterization of the selected invariant targets is performed using multiple years of MODIS and VIIRS measurements. Results of these studies will be shown at the conference.

Transformation products and human metabolites of triclocarban and triclosan in sewage sludge across the United States.

PubMed

Pycke, Benny F G; Roll, Isaac B; Brownawell, Bruce J; Kinney, Chad A; Furlong, Edward T; Kolpin, Dana W; Halden, Rolf U

2014-07-15

Removal of triclocarban (TCC) and triclosan (TCS) from wastewater is a function of adsorption, abiotic degradation, and microbial mineralization or transformation, reactions that are not currently controlled or optimized in the pollution control infrastructure of standard wastewater treatment. Here, we report on the levels of eight transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in raw and treated sewage sludge. Two sample sets were studied: samples collected once from 14 wastewater treatment plants (WWTPs) representing nine states, and multiple samples collected from one WWTP monitored for 12 months. Time-course analysis of significant mass fluxes (α=0.01) indicate that transformation of TCC (dechlorination) and TCS (methylation) occurred during sewage conveyance and treatment. Strong linear correlations were found between TCC and the human metabolite 2'-hydroxy-TCC (r=0.84), and between the TCC-dechlorination products dichlorocarbanilide (DCC) and monochlorocarbanilide (r=0.99). Mass ratios of DCC-to-TCC and of methyl-triclosan (MeTCS)-to-TCS, serving as indicators of transformation activity, revealed that transformation was widespread under different treatment regimes across the WWTPs sampled, though the degree of transformation varied significantly among study sites (α=0.01). The analysis of sludge sampled before and after different unit operation steps (i.e., anaerobic digestion, sludge heat treatment, and sludge drying) yielded insights into the extent and location of TCC and TCS transformation. Results showed anaerobic digestion to be important for MeTCS transformation (37-74%), whereas its contribution to partial TCC dechlorination was limited (0.4-2.1%). This longitudinal and nationwide survey is the first to report the occurrence of transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in sewage sludge.

Transformation Products and Human Metabolites of Triclocarban and Triclosan in Sewage Sludge Across the United States

PubMed Central

2015-01-01

Removal of triclocarban (TCC) and triclosan (TCS) from wastewater is a function of adsorption, abiotic degradation, and microbial mineralization or transformation, reactions that are not currently controlled or optimized in the pollution control infrastructure of standard wastewater treatment. Here, we report on the levels of eight transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in raw and treated sewage sludge. Two sample sets were studied: samples collected once from 14 wastewater treatment plants (WWTPs) representing nine states, and multiple samples collected from one WWTP monitored for 12 months. Time-course analysis of significant mass fluxes (α = 0.01) indicate that transformation of TCC (dechlorination) and TCS (methylation) occurred during sewage conveyance and treatment. Strong linear correlations were found between TCC and the human metabolite 2′-hydroxy-TCC (r = 0.84), and between the TCC-dechlorination products dichlorocarbanilide (DCC) and monochlorocarbanilide (r = 0.99). Mass ratios of DCC-to-TCC and of methyl-triclosan (MeTCS)-to-TCS, serving as indicators of transformation activity, revealed that transformation was widespread under different treatment regimes across the WWTPs sampled, though the degree of transformation varied significantly among study sites (α = 0.01). The analysis of sludge sampled before and after different unit operation steps (i.e., anaerobic digestion, sludge heat treatment, and sludge drying) yielded insights into the extent and location of TCC and TCS transformation. Results showed anaerobic digestion to be important for MeTCS transformation (37–74%), whereas its contribution to partial TCC dechlorination was limited (0.4–2.1%). This longitudinal and nationwide survey is the first to report the occurrence of transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in sewage sludge. PMID:24932693

Evaluation of the antimicrobial efficacy and skin safety of a novel color additive in combination with chlorine disinfectants.

PubMed

Tyan, Kevin; Kang, Jason; Jin, Katherine; Kyle, Aaron M

2018-05-23

A novel color additive colorizes chlorine disinfectants blue to improve visibility and enhance spray surface coverage, and it fades to colorless to indicate elapsed contact time. We investigated its interactions with 3 chlorine disinfectants to determine if the additive would adversely affect the disinfectants' antimicrobial efficacy or skin safety. We tested 0.5% sodium hypochlorite, 0.2% calcium hypochlorite, and 0.5% sodium dichloroisocyanurate (NaDCC) alone versus with color additive. An independent laboratory tested efficacy against Staphylococcus aureus, Pseudomonas aeruginosa, Vibrio cholerae, and human coronavirus 229E. An independent laboratory also tested direct skin irritation. Chlorine disinfectants with and without color additive achieved equal levels of efficacy against the tested pathogens. Against S. aureus, 0.5% sodium hypochlorite with and without color additive met Environmental Protection Agency criteria for disinfection success. Against human coronavirus 229E, 0.5% sodium hypochlorite alone failed disinfection success criteria, whereas 0.5% sodium hypochlorite with color additive achieved full viral inactivation (≥4.50 log 10 reduction). Against V. cholerae, 0.2% calcium hypochlorite alone and with color additive achieved 5.99 log 10 and >6.03 log 10 reductions, respectively. Against S. aureus and P. aeruginosa, 0.5% NaDCC with and without color additive achieved >4.9 log 10 and >3.54 log 10 reductions, respectively. All 3 chlorine disinfectants with color additive tested as negligible skin irritants. This color additive can be combined with chlorine disinfectants without adversely affecting antimicrobial efficacy or skin safety. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE

PubMed Central

2013-01-01

Background Funded by the National Institutes of Health (NIH), the aim of the Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the biological research community with a comprehensive encyclopedia of functional genomic elements for both model organisms C. elegans (worm) and D. melanogaster (fly). With a total size of just under 10 terabytes of data collected and released to the public, one of the challenges faced by researchers is to extract biologically meaningful knowledge from this large data set. While the basic quality control, pre-processing, and analysis of the data has already been performed by members of the modENCODE consortium, many researchers will wish to reinterpret the data set using modifications and enhancements of the original protocols, or combine modENCODE data with other data sets. Unfortunately this can be a time consuming and logistically challenging proposition. Results In recognition of this challenge, the modENCODE DCC has released uniform computing resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE-DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In particular, we have released Galaxy workflows for interpreting ChIP-seq data which use the same quality control (QC) and peak calling standards adopted by the modENCODE and ENCODE communities. For convenience of use, we have created Amazon and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE data, software and other dependencies. Conclusions Using these resources provides a framework for running consistent and reproducible analyses on modENCODE data, ultimately allowing researchers to use more of their time using modENCODE data, and less time moving it around. PMID:23875683

A Consistent EPIC Visible Channel Calibration using VIIRS and MODIS as a Reference

NASA Technical Reports Server (NTRS)

Haney, C. O.; Doelling, D. R.; Minnis, P.; Bhatt, R.; Scarino, B. R.; Gopalan, A.

2017-01-01

The Earth Polychromatic Imaging Camera (EPIC) aboard the Deep Space Climate Observatory (DSCOVR) satellite constantly images the sunlit disk of Earth from the Lagrange-1 (L1) point in 10 spectral channels spanning the UV, VIS, and NIR spectrums. Recently, the DSCOVR EPIC team has publicly released version 2 dataset, which has implemented improved navigation, stray-light correction, and flat-fielding of the CCD array. The EPIC 2-year data record must be well-calibrated for consistent cloud, aerosol, trace gas, land use and other retrievals. Because EPIC lacks onboard calibrators, the observations made by EPIC channels must be calibrated vicariously using the coincident measurements from radiometrically stable instruments that have onboard calibration systems. MODIS and VIIRS are best-suited instruments for this task as they contain similar spectral bands that are well-calibrated onboard using solar diffusers and lunar tracking. We have previously calibrated the EPIC version 1 dataset by using EPIC and VIIRS angularly matched radiance pairs over both all-sky ocean and deep convective clouds (DCC). We noted that the EPIC image required navigations adjustments, and that the EPIC stray-light correction provided an offset term closer to zero based on the linear regression of the EPIC and VIIRS ray-matched radiance pairs. We will evaluate the EPIC version 2 navigation and stray-light improvements using the same techniques. In addition, we will monitor the EPIC channel calibration over the two years for any temporal degradation or anomalous behavior. These two calibration methods will be further validated using desert and DCC invariant Earth targets. The radiometric characterization of the selected invariant targets is performed using multiple years of MODIS and VIIRS measurements. Results of these studies will be shown at the conference.

Response Versus Scan-Angle Corrections for MODIS Reflective Solar Bands Using Deep Convective Clouds

NASA Technical Reports Server (NTRS)

Bhatt, Rajendra; Angal, Amit; Doelling, David R.; Xiong, Xiaoxiong; Wu, Aisheng; Haney, Conor O.; Scarino, Benjamin R.; Gopalan, Arun

2016-01-01

The absolute radiometric calibration of the reflective solar bands (RSBs) of Aqua- and Terra-MODIS is performed using on-board calibrators. A solar diffuser (SD) panel along with a solar diffuser stability monitor (SDSM) system, which tracks the performance of the SD over time, provides the absolute reference for calibrating the MODIS sensors. MODIS also views the moon and deep space through its space view (SV) port for lunar-based calibration and computing the zero input radiance, respectively. The MODIS instrument views the Earths surface through a two-sided scan mirror, whose reflectance is a function of angle of incidence (AOI) and is described by response versus scan-angle (RVS). The RVS for both MODIS instruments was characterized prior to launch. MODIS also views the SD and the moon at two different assigned RVS positions. There is sufficient evidence that the RVS is changing on orbit over time and as a function of wavelength. The SD and lunar observation scans can only track the RVS variation at two RVS positions. Consequently, the MODIS Characterization Support Team (MCST) developed enhanced approaches that supplement the onboard calibrator measurements with responses from pseudo-invariant desert sites. This approach has been implemented in Level 1B (L1B) Collection 6 (C6) for selected short-wavelength bands. This paper presents an alternative approach of characterizing the mirror RVS to derive the time-dependent RVS correction factors for MODIS RSBs using tropical deep convective cloud (DCC) targets. An initial assessment of the DCC response from Aqua-MODIS band 1 C6 data indicates evidence of RVS artifacts, which are not uniform across the scans and are more prevalent in the left side Earth-view scans.

Response Versus Scan-Angle Corrections for MODIS Reflective Solar Bands Using Deep Convective Clouds

NASA Technical Reports Server (NTRS)

Bhatt, Rajendra; Angal, Amit; Doelling, David R.; Xiong, Xiaoxiong; Wu, Aisheng; Haney, Conor O.; Scarino, Benjamin R.; Gopalan, Arun

2016-01-01

The absolute radiometric calibration of the reflective solar bands (RSBs) of Aqua- and Terra-MODIS is performed using on-board calibrators. A solar diffuser (SD) panel along with a solar diffuser stability monitor (SDSM) system, which tracks the performance of the SD over time, provides the absolute reference for calibrating the MODIS sensors. MODIS also views the moon and deep space through its space view (SV) port for lunar-based calibration and computing the zero input radiance, respectively. The MODIS instrument views the Earth's surface through a two-sided scan mirror, whose reflectance is a function of angle of incidence (AOI) and is described by response versus scan-angle (RVS). The RVS for both MODIS instruments was characterized prior to launch. MODIS also views the SD and the moon at two different assigned RVS positions. There is sufficient evidence that the RVS is changing on orbit over time and as a function of wavelength. The SD and lunar observation scans can only track the RVS variation at two RVS positions. Consequently, the MODIS Characterization Support Team (MCST) developed enhanced approaches that supplement the onboard calibrator measurements with responses from pseudo-invariant desert sites. This approach has been implemented in Level 1B (L1B) Collection 6 (C6) for selected short-wavelength bands. This paper presents an alternative approach of characterizing the mirror RVS to derive the time-dependent RVS correction factors for MODIS RSBs using tropical deep convective cloud (DCC) targets. An initial assessment of the DCC response from Aqua-MODIS band 1 C6 data indicates evidence of RVS artifacts, which are not uniform across the scans and are more prevalent in the left side Earth-view scans.

VIIRS Reflective Solar Band Radiometric and Stability Evaluation Using Deep Convective Clouds

NASA Technical Reports Server (NTRS)

Chang, Tiejun; Xiong, Xiaoxiong; Mu, Qiaozhen

2016-01-01

This work takes advantage of the stable distribution of deep convective cloud (DCC) reflectance measurements to assess the calibration stability and detector difference in Visible Infrared Imaging Radiometer Suite (VIIRS) reflective bands. VIIRS Sensor Data Records (SDRs) from February 2012 to June 2015 are utilized to analyze the long-term trending, detector difference, and half angle mirror (HAM) side difference. VIIRS has two thermal emissive bands with coverage crossing 11 microns for DCC pixel identification. The comparison of the results of these two processing bands is one of the indicators of analysis reliability. The long-term stability analysis shows downward trends (up to approximately 0.4 per year) for the visible and near-infrared bands and upward trends (up to 0.5per year) for the short- and mid-wave infrared bands. The detector difference for each band is calculated as the difference relative to the average reflectance overall detectors. Except for the slightly greater than 1 difference in the two bands at 1610 nm, the detector difference is less than1 for other solar reflective bands. The detector differences show increasing trends for some short-wave bands with center wavelengths from 400 to 600 nm and remain unchanged for the bands with longer center wavelengths. The HAM side difference is insignificant and stable. Those short-wave bands from 400 to 600 nm also have relatively larger HAM side difference, up to 0.25.Comparing the striped images from SDR and the smooth images after the correction validates the analyses of detector difference and HAM side difference. These analyses are very helpful for VIIRS calibration improvement and thus enhance product quality

Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation.

PubMed

Macabenta, Frank D; Jensen, Amber G; Cheng, Yi-Shan; Kramer, Joseph J; Kramer, Sunita G

2013-08-15

Drosophila embryonic dorsal vessel (DV) morphogenesis is a highly stereotyped process that involves the migration and morphogenesis of 52 pairs of cardioblasts (CBs) in order to form a linear tube. This process requires spatiotemporally-regulated localization of signaling and adhesive proteins in order to coordinate the formation of a central lumen while maintaining simultaneous adhesion between CBs. Previous studies have shown that the Slit/Roundabout and Netrin/Unc5 repulsive signaling pathways facilitate site-specific loss of adhesion between contralateral CBs in order to form a luminal space. However, the concomitant mechanism by which attraction initiates CB outgrowth and discrete localization of adhesive proteins remains poorly understood. Here we provide genetic evidence that Netrin signals through DCC (Deleted in Colorectal Carcinoma)/UNC-40/Frazzled (Fra) to mediate CB outgrowth and attachment and that this function occurs prior to and independently of Netrin/UNC-5 signaling. fra mRNA is expressed in the CBs prior to and during DV morphogenesis. Loss-of-fra-function results in significant defects in cell shape and alignment between contralateral CB rows. In addition, CB outgrowth and attachment is impaired in both fra loss- and gain-of-function mutants. Deletion of both Netrin genes (NetA and NetB) results in CB attachment phenotypes similar to fra mutants. Similar defects are also seen when both fra and unc5 are deleted. Finally we show that Fra accumulates at dorsal and ventral leading edges of paired CBs, and this localization is dependent upon Netrin. We propose that while repulsive guidance mechanisms contribute to lumen formation by preventing luminal domains from coming together, site-specific Netrin/Frazzled signaling mediates CB attachment. Copyright © 2013 Elsevier Inc. All rights reserved.

Response versus scan-angle corrections for MODIS reflective solar bands using deep convective clouds

NASA Astrophysics Data System (ADS)

Bhatt, Rajendra; Angal, Amit; Doelling, David R.; Xiong, Xiaoxiong; Wu, Aisheng; Haney, Conor O.; Scarino, Benjamin R.; Gopalan, Arun

2016-05-01

The absolute radiometric calibration of the reflective solar bands (RSBs) of Aqua- and Terra-MODIS is performed using on-board calibrators. A solar diffuser (SD) panel along with a solar diffuser stability monitor (SDSM) system, which tracks the degradation of the SD over time, provides the baseline for calibrating the MODIS sensors. MODIS also views the moon and deep space through its space view (SV) port for lunar-based calibration and computing the background, respectively. The MODIS instrument views the Earth's surface using a two-sided scan mirror, whose reflectance is a function of the angle of incidence (AOI) and is described by response versus scan-angle (RVS). The RVS for both MODIS instruments was characterized prior to launch. MODIS also views the SD and the moon at two different AOIs. There is sufficient evidence that the RVS is changing on orbit over time and as a function of wavelength. The SD and lunar observation scans can only track the RVS variation at two AOIs. Consequently, the MODIS Characterization Support Team (MCST) developed enhanced approaches that supplement the onboard calibrator measurements with responses from the pseudo-invariant desert sites. This approach has been implemented in Level 1B (L1B) Collection 6 (C6) for select short-wavelength bands. This paper presents an alternative approach of characterizing the mirror RVS to derive the time-dependent RVS correction factors for MODIS RSBs using tropical deep convective cloud (DCC) targets. An initial assessment of the DCC response from Aqua-MODIS band 1 C6 data indicates evidence of RVS artifacts, which are not uniform across the scans and are more prevalent at the beginning of the earth-view scan.

Cardio-supportive devices (VRD & DCC device) and patches for advanced heart failure: A review, summary of state of the art and future directions.

PubMed

Naveed, Muhammad; Han, Lei; Khan, Ghulam Jilany; Yasmeen, Sufia; Mikrani, Reyaj; Abbas, Muhammad; Cunyu, Li; Xiaohui, Zhou

2018-06-01

Congestive heart failure (CHF) is a complicated pathophysiological syndrome, leading cause of hospitalization as well as mortalities in developed countries wherein an irregular function of the heart leads to the insufficient blood supply to the body organs. It is an accumulative slackening of various complications including myocardial infarction (MI), coronary heart disease (CAD), hypertension, valvular heart disease (VHD) and cardiomyopathy; its hallmarks include hypertrophy, increased interstitial fibrosis and loss of myocytes. The etiology of CHF is very complex and despite the rapid advancement in pharmacological and device-based interventional therapies still, a single therapy may not be sufficient to meet the demand for coping with the diseases. Total artificial hearts (TAH) and ventricular assist devices (VADs) have been widely used clinically to assist patients with severe HF. Unfortunately, direct contact between the patient's blood and device leads to thromboembolic events, and then coagulatory factors, as well as, infection contribute significantly to complicate the situation. There is no effective treatment of HF except cardiac transplantation, however, genetic variations, tissue mismatch; differences in certain immune response and socioeconomic crisis are an important concern with cardiac transplantation suggesting an alternate bridge to transplant (BTT) or destination therapies (DT). For these reasons, researchers have turned to mechanically driven compression devices, ventricular restraint devices (VRD) and heart patches. The ASD is a combination of all operational patches and cardiac support devices (CSD) by delivering biological agents and can restrain or compress the heart. Present study summarizes the accessible peer-reviewed literature focusing on the mechanism of Direct Cardiac Compression (DCC) devices, VRD and patches and their acquaintance to optimize the therapeutic efficacy in a synergistic way. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration.

PubMed

Shahin, Mohamed H; Gong, Yan; McDonough, Caitrin W; Rotroff, Daniel M; Beitelshees, Amber L; Garrett, Timothy J; Gums, John G; Motsinger-Reif, Alison; Chapman, Arlene B; Turner, Stephen T; Boerwinkle, Eric; Frye, Reginald F; Fiehn, Oliver; Cooper-DeHoff, Rhonda M; Kaddurah-Daouk, Rima; Johnson, Julie A

2016-09-01

Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide-treated patients to identify novel genetic markers associated with hydrochlorothiazide BP response. The primary analysis included 228 white hypertensives treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Genome-wide analysis was conducted using Illumina Omni 1 mol/L-Quad Chip, and untargeted metabolomics was performed on baseline fasting plasma samples using a gas chromatography-time-of-flight mass spectrometry platform. We found 13 metabolites significantly associated with hydrochlorothiazide systolic BP (SBP) and diastolic BP (DBP) responses (false discovery rate, <0.05). In addition, integrating genomic and metabolomic data revealed 3 polymorphisms (rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2) along with arachidonic acid, converging in the netrin signaling pathway (P=1×10(-5)), as potential markers, significantly influencing hydrochlorothiazide BP response. We successfully replicated the 3 genetic signals in 212 white hypertensives treated with hydrochlorothiazide and created a response score by summing their BP-lowering alleles. We found patients carrying 1 response allele had a significantly lower response than carriers of 6 alleles (∆SBP/∆DBP: -1.5/1.2 versus -16.3/-10.4 mm Hg, respectively, SBP score, P=1×10(-8) and DBP score, P=3×10(-9)). This score explained 11.3% and 11.9% of the variability in hydrochlorothiazide SBP and DBP responses, respectively, and was further validated in another independent study of 196 whites treated with hydrochlorothiazide (DBP score, P=0.03; SBP score, P=0.07). This study suggests that PRKAG2, DCC, and EPHX2 might be important determinants of hydrochlorothiazide BP response. © 2016 American Heart Association, Inc.

Dynamic Control of Chromosome Topology and Gene Expression by a Chromatin Modification.

PubMed

Bian, Qian; Anderson, Erika C; Brejc, Katjuša; Meyer, Barbara J

2018-02-22

The function of chromatin modification in establishing higher-order chromosome structure during gene regulation has been elusive. We dissected the machinery and mechanism underlying the enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during Caenorhabditis elegans dosage compensation and discovered a key role for H4K20me1 in regulating X-chromosome topology and chromosome-wide gene expression. Structural and functional analysis of the dosage compensation complex (DCC) subunit DPY-21 revealed a novel Jumonji C demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals. Inactivation of demethylase activity in vivo by genome editing eliminated H4K20me1 enrichment on X chromosomes of somatic cells, increased X-linked gene expression, reduced X-chromosome compaction, and disrupted X-chromosome conformation by diminishing the formation of topologically associated domains. H4K20me1 is also enriched on the inactive X of female mice, making our studies directly relevant to mammalian development. Unexpectedly, DPY-21 also associates specifically with autosomes of nematode germ cells in a DCC-independent manner to enrich H4K20me1 and trigger chromosome compaction. Thus, DPY-21 is an adaptable chromatin regulator. Its H4K20me2 demethylase activity can be harnessed during development for distinct biological functions by targeting it to diverse genomic locations through different mechanisms. In both somatic cells and germ cells, H4K20me1 enrichment modulates three-dimensional chromosome architecture, demonstrating the direct link between chromatin modification and higher-order chromosome structure. © 2017 Bian et al.; Published by Cold Spring Harbor Laboratory Press.

A Gap Analysis Needs Assessment Tool to Drive a Care Delivery and Research Agenda for Integration of Care and Sharing of Best Practices Across a Health System.

PubMed

Golden, Sherita Hill; Hager, Daniel; Gould, Lois J; Mathioudakis, Nestoras; Pronovost, Peter J

2017-01-01

In a complex health system, it is important to establish a systematic and data-driven approach to identifying needs. The Diabetes Clinical Community (DCC) of Johns Hopkins Medicine's Armstrong Institute for Patient Safety and Quality developed a gap analysis tool and process to establish the system's current state of inpatient diabetes care. The collectively developed tool assessed the following areas: program infrastructure; protocols, policies, and order sets; patient and health care professional education; and automated data access. For the purposes of this analysis, gaps were defined as those instances in which local resources, infrastructure, or processes demonstrated a variance against the current national evidence base or institutionally defined best practices. Following the gap analysis, members of the DCC, in collaboration with health system leadership, met to identify priority areas in order to integrate and synergize diabetes care resources and efforts to enhance quality and reduce disparities in care across the system. Key gaps in care identified included lack of standardized glucose management policies, lack of standardized training of health care professionals in inpatient diabetes management, and lack of access to automated data collection and analysis. These results were used to gain resources to support collaborative diabetes health system initiatives and to successfully obtain federal research funding to develop and pilot a pragmatic diabetes educational intervention. At a health system level, the summary format of this gap analysis tool is an effective method to clearly identify disparities in care to focus efforts and resources to improve care delivery. Copyright © 2016 The Joint Commission. Published by Elsevier Inc. All rights reserved.

Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Aβ42 and the Ratios of Aβ Isoforms Using Low Protein Binding Tubes.

PubMed

Vanderstichele, Hugo Marcel Johan; Janelidze, Shorena; Demeyer, Leentje; Coart, Els; Stoops, Erik; Herbst, Victor; Mauroo, Kimberley; Brix, Britta; Hansson, Oskar

2016-05-31

Reduced cerebrospinal fluid (CSF) concentration of amyloid-β1-42 (Aβ1-42) reflects the presence of amyloidopathy in brains of subjects with Alzheimer's disease (AD). To qualify the use of Aβ1-42/Aβ1-40 for improvement of standard operating procedures (SOP) for measurement of CSF Aβ with a focus on CSF collection, storage, and analysis. Euroimmun ELISAs for CSF Aβ isoforms were used to set up a SOP with respect to recipient properties (low binding, polypropylene), volume of tubes, freeze/thaw cycles, addition of detergents (Triton X-100, Tween-20) in collection or storage tubes or during CSF analysis. Data were analyzed with linear repeated measures and mixed effects models. Optimization of CSF analysis included a pre-wash of recipients (e.g., tubes, 96-well plates) before sample analysis. Using the Aβ1-42/Aβ1-40 ratio, in contrast to Aβ1-42, eliminated effects of tube type, additional freeze/thaw cycles, or effect of CSF volumes for polypropylene storage tubes. 'Low binding' tubes reduced the loss of Aβ when aliquoting CSF or in function of additional freeze/thaw cycles. Addition of detergent in CSF collection tubes resulted in an almost complete absence of variation in function of collection procedures, but affected the concentration of Aβ isoforms in the immunoassay. The ratio of Aβ1-42/Aβ1-40 is a more robust biomarker than Aβ1-42 toward (pre-) analytical interfering factors. Further, 'low binding' recipients and addition of detergent in collection tubes are able to remove effects of SOP-related confounding factors. Integration of the Aβ1-42/Aβ1-40 ratio and 'low-binding tubes' into guidance criteria may speed up worldwide standardization of CSF biomarker analysis.

Procedure for pressure contact on high-power semiconductor devices free of thermal fatigue

NASA Technical Reports Server (NTRS)

Knobloch, J.

1979-01-01

To eliminate thermal fatigue, a procedure for manufacturing semiconductor power devices with pure pressure contact without solid binding was developed. Pressure contact without the use of a solid binding to avoid a limitation of the maximum surface in the contact was examined. A silicon wafer covered with a relatively thick metal layer is imbedded with the aid of a soft silver foil between two identically sized hard contact discs (molybdenum or tungsten) which are rotationally symmetrical. The advantages of this concept are shown for large diameters. The pressure contact was tested successfully in many devices in a large variety of applications.

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

Caberoy, Nora B.; Zhou, Yixiong; Alvarado, Gabriela

To efficiently elucidate the biological roles of phosphatidylserine (PS), we developed open-reading-frame (ORF) phage display to identify PS-binding proteins. The procedure of phage panning was optimized with a phage clone expressing MFG-E8, a well-known PS-binding protein. Three rounds of phage panning with ORF phage display cDNA library resulted in {approx}300-fold enrichment in PS-binding activity. A total of 17 PS-binding phage clones were identified. Unlike phage display with conventional cDNA libraries, all 17 PS-binding clones were ORFs encoding 13 real proteins. Sequence analysis revealed that all identified PS-specific phage clones had dimeric basic amino acid residues. GST fusion proteins were expressedmore » for 3 PS-binding proteins and verified for their binding activity to PS liposomes, but not phosphatidylcholine liposomes. These results elucidated previously unknown PS-binding proteins and demonstrated that ORF phage display is a versatile technology capable of efficiently identifying binding proteins for non-protein molecules like PS.« less

An RNA motif that binds ATP

NASA Technical Reports Server (NTRS)

Sassanfar, M.; Szostak, J. W.

1993-01-01

RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.

A Superintendent's Perspective of the Grievance Process.

ERIC Educational Resources Information Center

Salmon, Hanford A.

Grievance procedures must be fast and fair to satisfy everyone and to disrupt the normal workflow as little as possible. The following factors help make for effective procedures: (1) binding arbitration, because it is orderly and unbiased; (2) contributions to contract language by the contract administrators; (3) absolute honesty about contract…

31 CFR 203.8 - Application of part and procedural instructions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... binding on financial institutions that process Federal tax payments or maintain a TT&L account, TIP main... (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE PAYMENT OF FEDERAL TAXES... originating Federal tax payments, the financial institution agrees to be bound by this part and by procedural...

31 CFR 203.8 - Application of part and procedural instructions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... binding on financial institutions that process Federal tax payments or maintain a TT&L account, TIP main... (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE PAYMENT OF FEDERAL TAXES... originating Federal tax payments, the financial institution agrees to be bound by this part and by procedural...

31 CFR 203.8 - Application of part and procedural instructions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... binding on financial institutions that process Federal tax payments or maintain a TT&L account, TIP main... (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE PAYMENT OF FEDERAL TAXES... originating Federal tax payments, the financial institution agrees to be bound by this part and by procedural...

[The UV-Vis spectra and substituent effect of organoimido derivatives of polyoxometalates].

PubMed

Li, Qiang; Wei, Yong-ge; Wang, Yuan; Guo, Hong-you

2005-06-01

In the presence of a carbodiimine, i.e. DCC, a series of organoimido derivatives of polyoxometalates have been synthesized via the reaction of [alpha-Mo8O26]4- with aromatic amines and its hydrochloride salt. Elemental analysis, IR, 1H-NMR and UV-Vis spectra were used to characterize those hybrids, in particular their UV-Vis spectra have been studied. The results show that typical metal-ligand charge transfer (MLCT) transitions occur in the organic-inorganic hybrid molecules. There is a good linear relationship between the shift of UV-Vis absorptions (delta lamda max) and conjugation effect of the p-substituted group (sigmaR).

An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

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

Pauly, J.R.; Marks, M.J.; Gross, S.D.

1991-09-01

Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-(3H)nicotine or alpha-(125I)bungarotoxin; (3H)quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the numbermore » of sites labeled by (3H)nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-(125I)bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment.« less

Structural changes in calcium-binding allergens: use of circular dichroism to study binding characteristics.

PubMed

Hebenstreit, D; Ferreira, F

2005-09-01

Several studies showed that calcium-binding proteins have a fixed place in the spectrum of allergenic substances. Often the binding of a calcium ion induces conformational changes and affects immunoglobulin E-binding to the allergen. Hence, the quantitative characterization of the binding to calcium is of importance to understand both the biologic and allergenic activity of these proteins. In the present study we describe a procedure for determining the stoichiometry and dissociation constant (K(D)) of calcium-binding allergens using circular dichroism (CD) techniques. For the experiments, we used recombinant Bet v 4, a two EF-hand allergen from birch pollen. Solutions of Bet v 4 were titrated with calcium and the change in molar ellipticity at 222 nm was monitored with a CD spectropolarimeter. The determination of the binding stoichiometry as well as of the K(D) for one EF-hand (4 microM) demonstrated the applicability of the method. CD-monitored calcium-titration of protein solutions represents a fast and easy method for determining the binding characteristics of calcium-binding allergens.

Body mass index is not associated with sperm-zona pellucida binding ability in subfertile males.

PubMed

Sermondade, Nathalie; Dupont, Charlotte; Faure, Céline; Boubaya, Marouane; Cédrin-Durnerin, Isabelle; Chavatte-Palmer, Pascale; Sifer, Christophe; Lévy, Rachel

2013-09-01

Lifestyle factors, such as weight and nutritional status may affect male fertility, including sperm fertilization ability. The objective of this retrospective study was to evaluate the association between body mass index (BMI) and sperm-zona pellucida binding ability assessed according to the zona binding (ZB) test, which has been described to be a relevant diagnostic tool for the prediction of in vitro fertilization (IVF) ability. Three hundred and six male patients from couples diagnosed with primary idiopathic or mild male factor infertility were included. Correlations between BMI and semen parameters according to ZB test indices were assessed, together with frequencies of positive and negative tests across the BMI categories. In this selected population, BMI was not related to conventional semen parameters or sperm quality assessed according to the ability of spermatozoa to bind to the zona pellucida. The previously described poor outcomes of IVF procedures in cases of male obesity could be due to other sperm defects, such as alterations of sperm capacitation or acrosome reaction. The link between male BMI and biological outcomes during IVF procedures, such as fertilization rates, should be further evaluated.

Domain wise docking analyses of the modular chitin binding protein CBP50 from Bacillus thuringiensis serovar konkukian S4.

PubMed

Sehar, Ujala; Mehmood, Muhammad Aamer; Hussain, Khadim; Nawaz, Salman; Nadeem, Shahid; Siddique, Muhammad Hussnain; Nadeem, Habibullah; Gull, Munazza; Ahmad, Niaz; Sohail, Iqra; Gill, Saba Shahid; Majeed, Summera

2013-01-01

This paper presents an in silico characterization of the chitin binding protein CBP50 from B. thuringiensis serovar konkukian S4 through homology modeling and molecular docking. The CBP50 has shown a modular structure containing an N-terminal CBM33 domain, two consecutive fibronectin-III (Fn-III) like domains and a C-terminal CBM5 domain. The protein presented a unique modular structure which could not be modeled using ordinary procedures. So, domain wise modeling using MODELLER and docking analyses using Autodock Vina were performed. The best conformation for each domain was selected using standard procedure. It was revealed that four amino acid residues Glu-71, Ser-74, Glu-76 and Gln-90 from N-terminal domain are involved in protein-substrate interaction. Similarly, amino acid residues Trp-20, Asn-21, Ser-23 and Val-30 of Fn-III like domains and Glu-15, Ala-17, Ser-18 and Leu-35 of C-terminal domain were involved in substrate binding. Site-directed mutagenesis of these proposed amino acid residues in future will elucidate the key amino acids involved in chitin binding activity of CBP50 protein.

Legal Consequences of Employer Discharge Procedures

ERIC Educational Resources Information Center

Joseph, Stephanie

2008-01-01

The employment contract is sometimes misunderstood by both employees and employers. Drafters of employee manuals, policies, and procedures should be aware that the nature of the at-will employment relationship can be transformed into a binding employment contract by the words and phrases chosen. In this article, the author uses the case of Eric,…

BindML/BindML+: Detecting Protein-Protein Interaction Interface Propensity from Amino Acid Substitution Patterns.

PubMed

Wei, Qing; La, David; Kihara, Daisuke

2017-01-01

Prediction of protein-protein interaction sites in a protein structure provides important information for elucidating the mechanism of protein function and can also be useful in guiding a modeling or design procedures of protein complex structures. Since prediction methods essentially assess the propensity of amino acids that are likely to be part of a protein docking interface, they can help in designing protein-protein interactions. Here, we introduce BindML and BindML+ protein-protein interaction sites prediction methods. BindML predicts protein-protein interaction sites by identifying mutation patterns found in known protein-protein complexes using phylogenetic substitution models. BindML+ is an extension of BindML for distinguishing permanent and transient types of protein-protein interaction sites. We developed an interactive web-server that provides a convenient interface to assist in structural visualization of protein-protein interactions site predictions. The input data for the web-server are a tertiary structure of interest. BindML and BindML+ are available at http://kiharalab.org/bindml/ and http://kiharalab.org/bindml/plus/ .

Contingency blindness: location-identity binding mismatches obscure awareness of spatial contingencies and produce profound interference in visual working memory.

PubMed

Fiacconi, Chris M; Milliken, Bruce

2012-08-01

The purpose of the present study was to highlight the role of location-identity binding mismatches in obscuring explicit awareness of a strong contingency. In a spatial-priming procedure, we introduced a high likelihood of location-repeat trials. Experiments 1, 2a, and 2b demonstrated that participants' explicit awareness of this contingency was heavily influenced by the local match in location-identity bindings. In Experiment 3, we sought to determine why location-identity binding mismatches produce such low levels of contingency awareness. Our results suggest that binding mismatches can interfere substantially with visual-memory performance. We attribute the low levels of contingency awareness to participants' inability to remember the critical location-identity binding in the prime on a trial-to-trial basis. These results imply a close interplay between object files and visual working memory.

Intravenous iron-dextran: studies on unsaturated iron-binding capacity

PubMed Central

Cox, J. S. G.; Moss, G. F.; Bremner, I.; Reason, Janet

1968-01-01

A method is described for measuring the plasma unsaturated iron-binding capacity in the presence of very high concentrations of iron as iron-dextran. The procedure utilizes 59Fe to label the apotransferrin with subsequent separation of ionic iron from transferrin-bound iron on an ion exchange or Sephadex G.25 column. The unsaturated iron-binding capacity has been measured in rabbits and dogs after intravenous injection of iron-dextran and in human subjects after total dose infusion of iron-dextran. No evidence of saturation of the unsaturated iron-binding capacity was found even when the plasma iron values were greater than 40,000 μg Fe/100 ml. PMID:5697365

Molecular dynamics and principal components of potassium binding with human telomeric intra-molecular G-quadruplex.

PubMed

Wang, Zhiguo; Chen, Ruping; Hou, Ling; Li, Jianfeng; Liu, Jun-Ping

2015-06-01

Telomere assumes intra-molecular G-quadruplex that is a significant drug target for inhibiting telomerase maintenance of telomeres in cancer. Metal cations have been recognized as playing important roles in stabilizing G-quadruplex, but their binding processes to human telomeric G-quadruplex remain uncharacterized. To investigate the detailed binding procedures, molecular dynamics simulations were conducted on the hybrid [3 + 1] form-one human telomeric intra-molecular G-quadruplex. We show here that the binding of a potassium ion to a G-tetrad core is mediated by two alternative pathways. Principal component analysis illustrated the dominant concerted motions of G-quadruplex occurred at the loop domains. MM-PBSA calculations revealed that binding was energetically favorable and driven by the electrostatic interactions. The lower binding site was found more constructive favorable for binding. Our data provide useful information on a potassium-mediated stable structure of human telomeric intra-molecular G-quadruplex, implicating in ion disorder associated conformational changes and targeted drug design.

Simultaneous effects of temperature and pressure on the donor binding energy in a V-groove quantum wire

NASA Astrophysics Data System (ADS)

Khordad, R.

2010-03-01

The influence of temperature and pressure, simultaneously, on the binding energy of a hydrogenic donor impurity in a ridge GaAs/Ga 1- xAl xAs quantum wire is studied using a variational procedure within the effective mass approximation. The subband energy and the binding energy of the donor impurity in its ground state as a function of the wire bend width and impurity location at different temperatures and pressures are calculated. The results show that, when the temperature increases, the donor binding energy decreases for a constant applied pressure for all wire bend widths. Also, the binding energy increases by increasing the pressure for a constant temperature for all wire bend widths. In addition, when the temperature and pressure are applied simultaneously the binding energy decreases as the quantum wire bend width increases. On the whole, it is deduced that the temperature and pressure have important effects on the donor binding energy in a V-groove quantum wire.

Studies on fatty acid-binding proteins. The detection and quantification of the protein from rat liver by using a fluorescent fatty acid analogue.

PubMed Central

Wilkinson, T C; Wilton, D C

1986-01-01

Fatty acid-binding protein from rat liver is shown to bind the fluorescent fatty acid probe dansyl undecanoic acid. Binding is accompanied by a shift in the fluorescence emission maximum from 550 nm to 500 nm and a 60-fold fluorescence enhancement at 500 nm. These spectral properties have allowed the use of this probe to detect and quantify microgram amounts of liver fatty acid-binding protein during purification procedures. In conjunction with h.p.l.c. the method allows the rapid estimation of liver fatty acid-binding protein in biological samples. The validity of the method is demonstrated by measuring the concentration of fatty acid-binding protein in livers from control and hypolipidaemic-drug-treated rats. The dramatic diurnal rhythm previously reported for this protein [Dempsey (1984) Curr. Top. Cell. Regul. 24, 63-86] was not observed with this method. Images Fig. 1. PMID:3800946

An immunoassay for the study of DNA-binding activities of herpes simplex virus protein ICP8.

PubMed

Lee, C K; Knipe, D M

1985-06-01

An immunoassay was used to examine the interaction between a herpes simplex virus protein, ICP8, and various types of DNA. The advantage of this assay is that the protein is not subjected to harsh purification procedures. We characterized the binding of ICP8 to both single-stranded (ss) and double-stranded (ds) DNA. ICP8 bound ss DNA fivefold more efficiently than ds DNA, and both binding activities were most efficient in 150 mM NaCl. Two lines of evidence indicate that the binding activities were not identical: (i) ds DNA failed to complete with ss DNA binding even with a large excess of ds DNA; (ii) Scatchard plots of DNA binding with various amounts of DNA were fundamentally different for ss DNA and ds DNA. However, the two activities were related in that ss DNA efficiently competed with the binding of ds DNA. We conclude that the ds DNA-binding activity of ICP8 is probably distinct from the ss DNA-binding activity. No evidence for sequence-specific ds DNA binding was obtained for either the entire herpes simplex virus genome or cloned viral sequences.

26 CFR 301.6224(c)-2 - Pass-thru partner binds indirect partners.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the following example: Example. Partnership J is a partner in partnership P. C is a partner in J but... C holds in P is through J. The tax matters partner of J enters into a settlement agreement with the... (CONTINUED) PROCEDURE AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6224(c)-2...

Evaluation of variability and quality control procedures for a receptor-binding assay for paralytic shellfish poisoning toxins.

PubMed

Ruberu, S R; Langlois, G W; Masuda, M; Perera, S Kusum

2012-01-01

The receptor-binding assay (RBA) method for determining saxatoxin (STX) and its numerous analogues, which cause paralytic shellfish poisoning (PSP) in humans, was evaluated in a single laboratory study. Each step of the assay preparation procedure including the performance of the multi-detector TopCount® instrument was evaluated for its contribution to method variability. The overall inherent RBA variability was determined to be 17%. Variability within the 12 detectors was observed; however, there was no reproducible pattern in detector performance. This observed variability among detectors could be attributed to other factors, such as pipetting errors. In an attempt to reduce the number of plates rejected due to excessive variability in the method's quality control parameters, a statistical approach was evaluated using either Grubbs' test or the Student's t-test for rejecting outliers in the measurement of triplicate wells. This approach improved the ratio of accepted versus rejected plates, saving cost and time for rerunning the assay. However, the potential reduction in accuracy and the lack of improvement in precision suggests caution when using this approach. The current study has recommended an alternate quality control procedure for accepting or rejecting plates in place of the criteria currently used in the published assay, or the alternative of outlier testing. The recommended procedure involves the development of control charts to monitor the critical parameters identified in the published method (QC sample, EC₅₀, slope of calibration curve), with the addition of a fourth critical parameter which is the top value (100% binding) of the calibration curve.

Generation of Dynamic Combinatorial Libraries Using Hydrazone‐Functionalized Surface Mimetics

PubMed Central

Hewitt, Sarah H.

2018-01-01

Dynamic combinatorial chemistry (DCC) represents an approach, whereby traditional supramolecular scaffolds used for protein surface recognition might be exploited to achieve selective high affinity target recognition. Synthesis, in situ screening and amplification under selection pressure allows the generation of ligands, which bear different moieties capable of making multivalent non‐covalent interactions with target proteins. Generic tetracarboxyphenyl porphyrin scaffolds bearing four hydrazide moieties have been used to form dynamic combinatorial libraries (DCLs) using aniline‐catalyzed reversible hydrazone exchange reactions, in 10 % DMSO, 5 mm NH4OAc, at pH 6.75. High resolution mass spectrometry (HRMS) was used to monitor library composition and establish conditions under which equilibria were established.

Novel Hybrid Molecules on the Basis of Steroids and (5Z,9Z)-Tetradeca-5,9-dienoic Acid: Synthesis, Anti-Cancer Studies and Human Topoisomerase I Inhibitory Activity.

PubMed

D'yakonov, Vladimir A; Dzhemileva, Lilya U; Tuktarova, Regina A; Ishmukhametova, Svetlana R; Yunusbaeva, Milyausha M; Ramazanova, Ilfir R; Dzhemilev, Usein M

2017-01-01

Novel steroid derivatives of 5Z,9Z-dienoic acids were prepared by the DCC/DMAP-catalyzed esterification of (5Z,9Z)-tetradeca-5,9-dienoic acid with hydroxy steroids. High cytotoxicity towards the HEK293, Jurkat, K562 cancer cell lines and human topoisomerase I (hTop1) inhibitory activity in vitro were found for the synthesized acids. A probable mechanism of topoisomerase I inhibition was hypothesized on the basis of in silico studies resorting to docking. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Data Curation: Improving Environmental Health Data Quality.

PubMed

Yang, Lin; Li, Jiao; Hou, Li; Qian, Qing

2015-01-01

With the growing recognition of the influence of climate change on human health, scientists' attention to analyzing the relationship between meteorological factors and adverse health effects. However, the paucity of high quality integrated data is one of the great challenges, especially when scientific studies rely on data-intensive computing. This paper aims to design an appropriate curation process to address this problem. We present a data curation workflow that: (i) follows the guidance of DCC Curation Lifecycle Model; (ii) combines manual curation with automatic curation; (iii) and solves environmental health data curation problem. The workflow was applied to a medical knowledge service system and showed that it was capable of improving work efficiency and data quality.

Construction Norms Straightened. Part II. Section G, Chapter 12, Gas Supply, Gas-Distributing Stations, Cylinder and Reservoir Settings up of the Liquefied Gas of the Norm of Design, SNIP II-G.12-65.

DTIC Science & Technology

1980-05-19

Maze20 30OA lCeI SeM- ,aO50 BK.O~K~jlbo10 0 75 indust--iaj. ant-~rpr-,s!s, baicu ria vr the total1 vc lum-i of raservcirs -4t is more than 500 Mn3, or...liquefied gas shcula Le deterrfined in depending cr accepted fcr this indutria1 entezirisp rora fcr stcrage of standby fuel / vr ooellant. DcC = 30CL42901 34...degree cf refractoriness (fcr example, theaters, cinemas , clubs, touses cf culture, therapeutic and childrengs institutions, educational institutions

A new procedure for fast soft staining of BN-PAGEs on photosynthetic complexes.

PubMed

Farci, Domenica; Kirkpatrick, Joanna; Piano, Dario

2017-02-01

We report a fast and sensitive procedure for blue native PAGE staining, in which the conventional staining step with CBB is avoided. After running, a short exposure to a mix of polar protic solvents (ethanol and acetic acid) leads to a fast and selective removal of the dye from the migration front and a specific binding to the protein bands, while the rest undergo a selective and complete background removal, leading to an intense contrast. This single-step staining-destaining technique is useful in protein samples that bind colored cofactors such as photosystems, which can be selectively discerned by their characteristic green color. After the staining of such samples, the green color persists, while the other unpigmented protein complexes and the molecular standard remain CBB stained, creating a useful reference system for the assignment of the bands. The advantages and chemical basis of this staining procedure are discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

One-step selection of Vaccinia virus-binding DNA aptamers by MonoLEX

PubMed Central

Nitsche, Andreas; Kurth, Andreas; Dunkhorst, Anna; Pänke, Oliver; Sielaff, Hendrik; Junge, Wolfgang; Muth, Doreen; Scheller, Frieder; Stöcklein, Walter; Dahmen, Claudia; Pauli, Georg; Kage, Andreas

2007-01-01

Background As a new class of therapeutic and diagnostic reagents, more than fifteen years ago RNA and DNA aptamers were identified as binding molecules to numerous small compounds, proteins and rarely even to complete pathogen particles. Most aptamers were isolated from complex libraries of synthetic nucleic acids by a process termed SELEX based on several selection and amplification steps. Here we report the application of a new one-step selection method (MonoLEX) to acquire high-affinity DNA aptamers binding Vaccinia virus used as a model organism for complex target structures. Results The selection against complete Vaccinia virus particles resulted in a 64-base DNA aptamer specifically binding to orthopoxviruses as validated by dot blot analysis, Surface Plasmon Resonance, Fluorescence Correlation Spectroscopy and real-time PCR, following an aptamer blotting assay. The same oligonucleotide showed the ability to inhibit in vitro infection of Vaccinia virus and other orthopoxviruses in a concentration-dependent manner. Conclusion The MonoLEX method is a straightforward procedure as demonstrated here for the identification of a high-affinity DNA aptamer binding Vaccinia virus. MonoLEX comprises a single affinity chromatography step, followed by subsequent physical segmentation of the affinity resin and a single final PCR amplification step of bound aptamers. Therefore, this procedure improves the selection of high affinity aptamers by reducing the competition between aptamers of different affinities during the PCR step, indicating an advantage for the single-round MonoLEX method. PMID:17697378

Development of a lectin binding assay to differentiate between recombinant and endogenous proteins in pharmacokinetic studies of protein-biopharmaceuticals.

PubMed

Weber, Alfred; Minibeck, Eva; Scheiflinger, Friedrich; Turecek, Peter L

2015-04-10

Human glycoproteins, expressed in hamster cell lines, show similar glycosylation patterns to naturally occurring human molecules except for a minute difference in the linkage of terminal sialic acid: both cell types lack α2,6-galactosyl-sialyltransferase, abundantly expressed in human hepatocytes and responsible for the α2,6-sialylation of circulating glycoproteins. This minute difference, which is currently not known to have any physiological relevance, was the basis for the selective measurement of recombinant glycoproteins in the presence of their endogenous counterparts. The assay is based on using the lectin Sambucus nigra agglutinin (SNA), selectively binding to α2,6-sialylated N-glycans. Using von Willebrand factor (VWF), factor IX (FIX), and factor VIIa (FVIIa), it was demonstrated that (i) the plasma-derived proteins, but not the corresponding recombinant proteins, specifically bind to SNA and (ii) this binding can be used to deplete the plasma-derived proteins. The feasibility of this approach was confirmed in spike-recovery studies for all three recombinant coagulation proteins in human plasma and for recombinant VWF (rVWF) in macaque plasma. Analysis of plasma samples from macaques after administration of recombinant and a plasma-derived VWF demonstrated the suitability and robustness of this approach. Data showed that rVWF could be selectively measured without changing the ELISAs and furthermore revealed the limitations of baseline adjustment using a single measurement of the predose concentration only. The SNA gel-based depletion procedure can easily be integrated in existing procedures as a specific sample pre-treatment step. While ELISA-based methods were used to measure the recombinant coagulation proteins in the supernatants obtained by depletion, this procedure is applicable for all biochemical analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

Yeast enolase: mechanism of activation by metal ions.

PubMed

Brewer, J M

1981-01-01

Yeast enolase as prepared by current procedures is inherently chemically homogeneous, though deamidation and partial denaturation can produce electrophoretically distinct forms. A true isozyme of the enzyme exists but does not survive the purification procedure. The chemical sequence for both has been established. The enzyme behaves in solution like a compact, nearly spherical molecule of moderate hydration. Strong intramolecular forces maintain the structure of the individual subunits. The enzyme as isolated is dimeric. If dissociated in the presence of magnesium ions and substrate, then the subunits are active, but if the dissociation occurs in the absence of metal ions, they are inactive until they have reassociated and undergone a first order "annealing" process. Magnesium (II) enhances association. The interaction between the subunits is hydrophobic in character. The enzyme can bind up to 2 mol of most metal ions in "conformational" sites which then allows up to 2 mol of substrate or some substrate analogue to bind. This is not sufficient for catalysis, but conformational metal ions do more than just allow substrate binding. A change in the environment of the metal ions occurs on substrate or substrate analogue binding. There is an absolute correlation between the occurrence of a structural change undergone by the 3-amino analogue of phosphoenolpyruvate and whether the metal ions produce any level of enzymatic activity. For catalysis, two more moles of metal ions, called "catalytic", must bind. There is evidence that the enzymatic reaction involves a carbanion mechanism. It is likely that two more moles of metal ion can bind which inhibit the reaction. The requirement for 2 mol of metal ion per subunit which contribute in different ways to catalysis is exhibited by a number of other enzymes.

Experimental study of water desorption isotherms and thin-layer convective drying kinetics of bay laurel leaves

NASA Astrophysics Data System (ADS)

Ghnimi, Thouraya; Hassini, Lamine; Bagane, Mohamed

2016-12-01

The aim of this work is to determine the desorption isotherms and the drying kinetics of bay laurel leaves ( Laurus Nobilis L.). The desorption isotherms were performed at three temperature levels: 50, 60 and 70 °C and at water activity ranging from 0.057 to 0.88 using the statistic gravimetric method. Five sorption models were used to fit desorption experimental isotherm data. It was found that Kuhn model offers the best fitting of experimental moisture isotherms in the mentioned investigated ranges of temperature and water activity. The Net isosteric heat of water desorption was evaluated using The Clausius-Clapeyron equation and was then best correlated to equilibrium moisture content by the empirical Tsami's equation. Thin layer convective drying curves of bay laurel leaves were obtained for temperatures of 45, 50, 60 and 70 °C, relative humidity of 5, 15, 30 and 45 % and air velocities of 1, 1.5 and 2 m/s. A non linear regression procedure of Levenberg-Marquardt was used to fit drying curves with five semi empirical mathematical models available in the literature, The R2 and χ2 were used to evaluate the goodness of fit of models to data. Based on the experimental drying curves the drying characteristic curve (DCC) has been established and fitted with a third degree polynomial function. It was found that the Midilli Kucuk model was the best semi-empirical model describing thin layer drying kinetics of bay laurel leaves. The bay laurel leaves effective moisture diffusivity and activation energy were also identified.

Accurate determinations of one-bond 13C-13C couplings in 13C-labeled carbohydrates

NASA Astrophysics Data System (ADS)

Azurmendi, Hugo F.; Freedberg, Darón I.

2013-03-01

Carbon plays a central role in the molecular architecture of carbohydrates, yet the availability of accurate methods for 1DCC determination has not been sufficiently explored, despite the importance that such data could play in structural studies of oligo- and polysaccharides. Existing methods require fitting intensity ratios of cross- to diagonal-peaks as a function of the constant-time (CT) in CT-COSY experiments, while other methods utilize measurement of peak separation. The former strategies suffer from complications due to peak overlap, primarily in regions close to the diagonal, while the latter strategies are negatively impacted by the common occurrence of strong coupling in sugars, which requires a reliable assessment of their influence in the context of RDC determination. We detail a 13C-13C CT-COSY method that combines a variation in the CT processed with diagonal filtering to yield 1JCC and RDCs. The strategy, which relies solely on cross-peak intensity modulation, is inspired in the cross-peak nulling method used for JHH determinations, but adapted and extended to applications where, like in sugars, large one-bond 13C-13C couplings coexist with relatively small long-range couplings. Because diagonal peaks are not utilized, overlap problems are greatly alleviated. Thus, one-bond couplings can be determined from different cross-peaks as either active or passive coupling. This results in increased accuracy when more than one determination is available, and in more opportunities to measure a specific coupling in the presence of severe overlap. In addition, we evaluate the influence of strong couplings on the determination of RDCs by computer simulations. We show that individual scalar couplings are notably affected by the presence of strong couplings but, at least for the simple cases studied, the obtained RDC values for use in structural calculations were not, because the errors introduced by strong couplings for the isotropic and oriented phases are very similar and therefore cancel when calculating the difference to determine 1DCC values.

Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia.

PubMed

Ward, Joey; Strawbridge, Rona J; Bailey, Mark E S; Graham, Nicholas; Ferguson, Amy; Lyall, Donald M; Cullen, Breda; Pidgeon, Laura M; Cavanagh, Jonathan; Mackay, Daniel F; Pell, Jill P; O'Donovan, Michael; Escott-Price, Valentina; Smith, Daniel J

2017-11-30

Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14 and 18), and a common single-nucleotide polymorphism (SNP)-based heritability estimate of ~8%. We found a strong genetic correlation between mood instability and MDD (r g  = 0.60, SE = 0.07, p = 8.95 × 10 -17 ) and a small but significant genetic correlation with both schizophrenia (r g  = 0.11, SE = 0.04, p = 0.01) and anxiety disorders (r g  = 0.28, SE = 0.14, p = 0.04), although no genetic correlation with BD, ADHD or PTSD was observed. Several genes at the associated loci may have a role in mood instability, including the DCC netrin 1 receptor (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2), placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation.

Field study on evaluation of the efficacy and usability of two disinfectants for drinking water treatment at small cattle breeders and dairy cattle farms.

PubMed

Mohammed, Asmaa N

2016-03-01

The hygienic quality of drinking water for cattle originated from different sources together with the efficacy and usability of two types of disinfectants against waterborne pathogens were assessed for small cattle breeders and dairy cattle farms. A total of 120 drinking water samples were collected from water troughs representing three different water sources commonly used for cattle drinking (tap, underground and surface water; n = 65, 25, and 30, respectively). Collected samples were cultured for isolation and identification of pathogenic bacteria using serological techniques and PCR. The bactericidal efficacy of the disinfectants, sodium dichloroisocyanurate (NaDCC) and hydrogen peroxide (H2O2) 50%, at different concentrations were evaluated by the determination of total viable and coliform counts of water prior and postwater treatment. In small cattle breeders, Escherichia coli was the most prevalent bacterial isolates from surface water (56.7%) followed by Staphylococcus aureus (36.7%), Salmonella spp. (26.7%), Streptococcus faecalis (23.3%), Shigella flexneri (16.7%), Proteus spp. (16.7%), and Klebsiella pneumonae (10.0 %) at X(2) = 9, P ≤ 0.01. Prior to the use of disinfectants, the averages of total bacterial and coliform counts were the highest in surface water (3.56 × 10(7), 240.0, and 38.0 CFU/100 ml, respectively). It has been found that hydrogen peroxide 50% at a concentration of 35 mg/l had a lethal effect (100 %) on indicator microorganisms compared with NaDCC at concentration of 2 mg/l. In conclusion, the higher bacterial contaminants in drinking water were found in surface water followed by tap water, particularly for small cattle breeders. Therefore, the usage of more hygienic water troughs with their regular treatment by hydrogen peroxide 50% at concentration of 35 mg/l is highly recommended to control waterborne bacteria and consequently improve and maintain the animal health.

Effect of Groundwater Iron on Residual Chlorine in Water Treated with Sodium Dichloroisocyanurate Tablets in Rural Bangladesh

PubMed Central

Naser, Abu Mohd.; Higgins, Eilidh M.; Arman, Shaila; Ercumen, Ayse; Ashraf, Sania; Das, Kishor K.; Rahman, Mahbubur; Luby, Stephen P.; Unicomb, Leanne

2018-01-01

Abstract. We assessed the ability of sodium dichloroisocyanurate (NaDCC) to provide adequate chlorine residual when used to treat groundwater with variable iron concentration. We randomly selected 654 tube wells from nine subdistricts in central Bangladesh to measure groundwater iron concentration and corresponding residual-free chlorine after treating 10 L of groundwater with a 33-mg-NaDCC tablet. We assessed geographical variations of iron concentration using the Kruskal–Wallis test and examined the relationships between the iron concentrations and chlorine residual by quantile regression. We also assessed whether user-reported iron taste in water and staining of storage vessels can capture the presence of iron greater than 3 mg/L (the World Health Organization threshold). The median iron concentration among measured wells was 0.91 (interquartile range [IQR]: 0.36–2.01) mg/L and free residual chlorine was 1.3 (IQR: 0.6–1.7) mg/L. The groundwater iron content varied even within small geographical regions. The median free residual chlorine decreased by 0.29 mg/L (95% confidence interval: 0.27, 0.33, P < 0.001) for every 1 mg/L increase in iron concentration. Owner-reported iron staining of the storage vessel had a sensitivity of 92%, specificity of 75%, positive predictive value of 41%, and negative predictive value of 98% for detecting > 3 mg/L iron in water. Similar findings were observed for user-reported iron taste in water. Our findings reconfirm that chlorination of groundwater that contains iron may result in low-level or no residual. User reports of no iron taste or no staining of storage containers can be used to identify low-iron tube wells suitable for chlorination. Furthermore, research is needed to develop a color-graded visual scale for iron staining that corresponds to different iron concentrations in water. PMID:29436334

The metabolic signature associated with the Western dietary pattern: a cross-sectional study.

PubMed

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-12-11

Metabolic profiles have been shown to be associated to obesity status and insulin sensitivity. Dietary intakes influence metabolic pathways and therefore, different dietary patterns may relate to modifications in metabolic signatures. The objective was to verify associations between dietary patterns and metabolic profiles composed of amino acids (AAs) and acylcarnitines (ACs). 210 participants were recruited in the greater Quebec City area between September 2009 and December 2011. Dietary patterns had been previously derived using principal component analysis (PCA). The Prudent dietary pattern was characterised by higher intakes of vegetables, fruits, whole grain products, non-hydrogenated fat and lower intakes of refined grain products, whereas the Western dietary pattern was associated with higher intakes of refined grain products, desserts, sweets and processed meats. Targeted metabolites were quantified in 37 participants with the Biocrates Absolute IDQ p150 (Biocrates Life Sciences AG, Austria) mass spectrometry method (including 14 amino acids and 41 acylcarnitines). PCA analysis with metabolites including AAs and ACs revealed two main components explaining the most variance in overall data (13.8%). PC1 was composed mostly of medium- to long-chain ACs (C16:2, C14:2, C14:2-OH, C16, C14:1-OH, C14:1, C10:2, C5-DC/C6-OH, C12, C18:2, C10, C4:1-DC/C6, C8:1 and C2) whereas PC2 included certain AAs and short-chain ACs (xLeu, Met, Arg, Phe, Pro, Orn, His, C0, C3, C4 and C5). The Western dietary pattern correlated negatively with PC1 and positively with PC2 (r = -0.34, p = 0.05 and r = 0.38, p = 0.03, respectively), independently of age, sex and BMI. These findings suggest that the Western dietary pattern is associated with a specific metabolite signature characterized by increased levels of AAs including branched-chain AAs (BCAAs) and short-chain ACs.

Onset of η-nuclear binding in a pionless EFT approach

NASA Astrophysics Data System (ADS)

Barnea, N.; Bazak, B.; Friedman, E.; Gal, A.

2017-08-01

ηNNN and ηNNNN bound states are explored in stochastic variational method (SVM) calculations within a pionless effective field theory (EFT) approach at leading order. The theoretical input consists of regulated NN and NNN contact terms, and a regulated energy dependent ηN contact term derived from coupled-channel models of the N* (1535) nucleon resonance. A self consistency procedure is applied to deal with the energy dependence of the ηN subthreshold input, resulting in a weak dependence of the calculated η-nuclear binding energies on the EFT regulator. It is found, in terms of the ηN scattering length aηN, that the onset of binding η 3He requires a minimal value of ReaηN close to 1 fm, yielding then a few MeV η binding in η 4He. The onset of binding η 4He requires a lower value of ReaηN, but exceeding 0.7 fm.

Clathrin and synaptic vesicle endocytosis: studies at the squid giant synapse

PubMed Central

Augustine, G.J.; Morgan, J.R.; Villalba-Galea, C.A.; Jin, S.; Prasad, K.; Lafer, E.M.

2015-01-01

The role of clathrin-mediated endocytosis in SV (synaptic vesicle) recycling has been studied by combining molecular biology, physiology and electron microscopy at the squid giant synapse. Procedures that prevent clathrin from assembling into membrane coats, such as impairment of binding of the AP180 and AP-2 adaptor proteins, completely prevent membrane budding during endocytosis. These procedures also reduce exocytosis, presumably an indirect effect of a reduction in the number of SVs following block of endocytosis. Disrupting the binding of auxilin to Hsc70 (heat-shock cognate 70) prevents clathrin-coated vesicles from uncoating and also disrupts SV recycling. Taken together, these results indicate that a clathrin-dependent pathway is the primary means of SV recycling at this synapse under physiological conditions. PMID:16417485

Label-Free, LC-MS-Based Assays to Quantitate Small-Molecule Antagonist Binding to the Mammalian BLT1 Receptor.

PubMed

Chen, Xun; Stout, Steven; Mueller, Uwe; Boykow, George; Visconti, Richard; Siliphaivanh, Phieng; Spencer, Kerrie; Presland, Jeremy; Kavana, Michael; Basso, Andrea D; McLaren, David G; Myers, Robert W

2017-08-01

We have developed and validated label-free, liquid chromatography-mass spectrometry (LC-MS)-based equilibrium direct and competition binding assays to quantitate small-molecule antagonist binding to recombinant human and mouse BLT1 receptors expressed in HEK 293 cell membranes. Procedurally, these binding assays involve (1) equilibration of the BLT1 receptor and probe ligand, with or without a competitor; (2) vacuum filtration through cationic glass fiber filters to separate receptor-bound from free probe ligand; and (3) LC-MS analysis in selected reaction monitoring mode for bound probe ligand quantitation. Two novel, optimized probe ligands, compounds 1 and 2, were identified by screening 20 unlabeled BLT1 antagonists for direct binding. Saturation direct binding studies confirmed the high affinity, and dissociation studies established the rapid binding kinetics of probe ligands 1 and 2. Competition binding assays were established using both probe ligands, and the affinities of structurally diverse BLT1 antagonists were measured. Both binding assay formats can be executed with high specificity and sensitivity and moderate throughput (96-well plate format) using these approaches. This highly versatile, label-free method for studying ligand binding to membrane-associated receptors should find broad application as an alternative to traditional methods using labeled ligands.

A statistical model for investigating binding probabilities of DNA nucleotide sequences using microarrays.

PubMed

Lee, Mei-Ling Ting; Bulyk, Martha L; Whitmore, G A; Church, George M

2002-12-01

There is considerable scientific interest in knowing the probability that a site-specific transcription factor will bind to a given DNA sequence. Microarray methods provide an effective means for assessing the binding affinities of a large number of DNA sequences as demonstrated by Bulyk et al. (2001, Proceedings of the National Academy of Sciences, USA 98, 7158-7163) in their study of the DNA-binding specificities of Zif268 zinc fingers using microarray technology. In a follow-up investigation, Bulyk, Johnson, and Church (2002, Nucleic Acid Research 30, 1255-1261) studied the interdependence of nucleotides on the binding affinities of transcription proteins. Our article is motivated by this pair of studies. We present a general statistical methodology for analyzing microarray intensity measurements reflecting DNA-protein interactions. The log probability of a protein binding to a DNA sequence on an array is modeled using a linear ANOVA model. This model is convenient because it employs familiar statistical concepts and procedures and also because it is effective for investigating the probability structure of the binding mechanism.

Autoradiographic demonstration of oxytocin-binding sites in the macula densa

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

Stoeckel, M.E.; Freund-Mercier, M.J.

1989-08-01

Specific oxytocin (OT)-binding sites were localized in the rat kidney with use of a selective {sup 125}I-labeled OT antagonist ({sup 125}I-OTA). High concentrations of OT binding sites were detected on the juxtaglomerular apparatus with use of the conventional film autoradiographic technique. No labeling occurred on other renal structures. The cellular localization of the OT binding sites within the juxtaglomerular apparatus was studied in light microscope autoradiography, on semithin sections from paraformaldehyde-fixed kidney slices incubated in the presence of {sup 125}I-OTA. These preparations revealed selective labeling of the macula densa, mainly concentrated at the basal pole of the cells. Control experimentsmore » showed first that {sup 125}I-OTA binding characteristics were not noticeably altered by prior paraformaldehyde fixation of the kidneys and second that autoradiographic detection of the binding sites was not impaired by histological treatments following binding procedures. In view of the role of the macula densa in the tubuloglomerular feedback, the putative OT receptors of this structure might mediate the stimulatory effect of OT on glomerular filtration.« less

A 115 kDa calmodulin-binding protein is located in rat liver endosome fractions.

PubMed Central

Enrich, C; Bachs, O; Evans, W H

1988-01-01

The distribution of calmodulin-binding polypeptides in various rat liver subcellular fractions was investigated. Plasma-membrane, endosome, Golgi and lysosome fractions were prepared by established procedures. The calmodulin-binding polypeptides present in the subcellular fractions were identified by using an overlay technique after transfer from gels to nitrocellulose sheets. Distinctive populations of calmodulin-binding polypeptides were present in all the fractions examined except lysosomes. A major 115 kDa calmodulin-binding polypeptide of pI 4.3 was located to the endosome subfractions, and it emerges as a candidate endosome-specific protein. Partitioning of endosome fractions between aqueous and Triton X-114 phases indicated that the calmodulin-binding polypeptide was hydrophobic. Major calmodulin-binding polypeptides of 140 and 240 kDa and minor polypeptides of 40-60 kDa were present in plasma membranes. The distribution of calmodulin in the various endosome and plasma-membrane fractions was also analysed, and the results indicated that the amounts were high compared with those in the cytosol. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:3214436

Comparison of convective clouds observed by spaceborne W-band radar and simulated by cloud-resolving atmospheric models

NASA Astrophysics Data System (ADS)

Dodson, Jason B.

Deep convective clouds (DCCs) play an important role in regulating global climate through vertical mass flux, vertical water transport, and radiation. For general circulation models (GCMs) to simulate the global climate realistically, they must simulate DCCs realistically. GCMs have traditionally used cumulus parameterizations (CPs). Much recent research has shown that multiple persistent unrealistic behaviors in GCMs are related to limitations of CPs. Two alternatives to CPs exist: the global cloud-resolving model (GCRM), and the multiscale modeling framework (MMF). Both can directly simulate the coarser features of DCCs because of their multi-kilometer horizontal resolutions, and can simulate large-scale meteorological processes more realistically than GCMs. However, the question of realistic behavior of simulated DCCs remains. How closely do simulated DCCs resemble observed DCCs? In this study I examine the behavior of DCCs in the Nonhydrostatic Icosahedral Atmospheric Model (NICAM) and Superparameterized Community Atmospheric Model (SP-CAM), the latter with both single-moment and double-moment microphysics. I place particular emphasis on the relationship between cloud vertical structure and convective environment. I also emphasize the transition between shallow clouds and mature DCCs. The spatial domains used are the tropical oceans and the contiguous United States (CONUS), the latter of which produces frequent vigorous convection during the summer. CloudSat is used to observe DCCs, and A-Train and reanalysis data are used to represent the large-scale environment in which the clouds form. The CloudSat cloud mask and radar reflectivity profiles for CONUS cumuliform clouds (defined as clouds with a base within the planetary boundary layer) during boreal summer are first averaged and compared. Both NICAM and SP-CAM greatly underestimate the vertical growth of cumuliform clouds. Then they are sorted by three large-scale environmental variables: total preciptable water (TPW), surface air temperature (SAT), and 500hPa vertical velocity (W500), representing the dynamical and thermodynamical environment in which the clouds form. The sorted CloudSat profiles are then compared with NICAM and SP-CAM profiles simulated with the Quickbeam CloudSat simulator. Both models have considerable difficulty representing the relationship of SAT and clouds over CONUS. For TPW and W500, shallow clouds transition to DCCs at higher values than observed. This may be an indication of the models' inability to represent the formation of DCCs in marginal convective environments. NICAM develops tall DCCs in highly favorable environments, but SP-CAM appears to be incapable of developing tall DCCs in almost any environment. The use of double moment microphysics in SP-CAM improves the frequency of deep clouds and their relationship with TPW, but not SAT. Both models underpredict radar reflectivity in the upper cloud of mature DCCs. SP-CAM with single moment microphysics has a particularly unrealistic DCC reflectivity profile, but with double moment microphysics it improves substantially. SP-CAM with double-moment microphysics unexpectedly appears to weaken DCC updraft strength as TPW increases, but otherwise both NICAM and SP-CAM represent the environment-versus-DCC relationships fairly realistically.

Quartz crystal microbalance for the cardiac markers/antibodies binding kinetic measurements in the plasma samples

NASA Astrophysics Data System (ADS)

Agafonova, L. E.; Shumyantseva, V. V.; Archakov, A. I.

2014-06-01

The quartz crystal microbalance (QCM) was exploited for cardiac markers detection and kinetic studies of immunochemical reaction of cardiac troponin I (cTnI) and human heart fatty acid binding protein (H-FABP) with the corresponding monoclonal antibodies in undiluted plasma (serum) and standard solutions. The QCM technique allowed to dynamically monitor the kinetic differences in specific interactions and nonspecific sorption, without multiple labeling procedures and separation steps. The affinity binding process was characterized by the association (ka) and the dissociation (kd) kinetic constants and the equilibrium association (K) constant, all of which were obtained from experimental data.

Application of hollow fiber-supported liquid-phase microextraction coupled with HPLC for the determination of guaifenesin enantiomer-protein binding.

PubMed

Hatami, Mehdi; Farhadi, Khalil

2012-07-01

A hollow fiber liquid-phase microextraction technique coupled with high-performance liquid chromatography with fluorescence detection was employed for determination and evaluation of the binding characteristics of drugs to bovine serum albumin (BSA). Enantiomers of guaifenesin (an expectorant drug) were investigated as a model system. After optimization of some influencing parameters on microextraction, the proposed method was used for calculation of the target drug distribution coefficient between n-octanol and the buffer solution as well as study of drug-BSA binding in physiological conditions. The developed method shows a new, improved and simple procedure for determination of free drug concentration in biological fluids and the extent of drug-protein binding. Copyright © 2011 John Wiley & Sons, Ltd.

Statistical Aspects of Ice Gouging on the Alaskan Shelf of the Beaufort Sea,

DTIC Science & Technology

1983-09-01

ici 1)N I’ao’ ofciv i1111 da t Cl t it:c) dcc iiiiik i onIII ol l % I IIouI ile as~ d a 1c’ iiici of ,ic dcli al\\2 Not1. I % .. ol I lOt ii title...Ccii hilial dclisl to fileicll of a p-ii peline lot a IX1 (X)-. Miid 10-\\Cat McUMr 1crOd .31 .... v STATISTICAL ASPECTS OF ICE GOUGING ON THE ALASKAN...dlata obtained hetceni 19-2 and -l aw etcnatr’’ib (I-). I Ilti, v, ’Icletriiutted 1 9,9 (ele cl iug 1 974) \\ -ere CL Ird in the pr~ mI. a~ctag ing tile

The dynamic correlation between policy uncertainty and stock market returns in China

NASA Astrophysics Data System (ADS)

Yang, Miao; Jiang, Zhi-Qiang

2016-11-01

The dynamic correlation is examined between government's policy uncertainty and Chinese stock market returns in the period from January 1995 to December 2014. We find that the stock market is significantly correlated to policy uncertainty based on the results of the Vector Auto Regression (VAR) and Structural Vector Auto Regression (SVAR) models. In contrast, the results of the Dynamic Conditional Correlation Generalized Multivariate Autoregressive Conditional Heteroscedasticity (DCC-MGARCH) model surprisingly show a low dynamic correlation coefficient between policy uncertainty and market returns, suggesting that the fluctuations of each variable are greatly influenced by their values in the preceding period. Our analysis highlights the understanding of the dynamical relationship between stock market and fiscal and monetary policy.

The dynamic conditional relationship between stock market returns and implied volatility

NASA Astrophysics Data System (ADS)

Park, Sung Y.; Ryu, Doojin; Song, Jeongseok

2017-09-01

Using the dynamic conditional correlation multivariate generalized autoregressive conditional heteroskedasticity (DCC-MGARCH) model, we empirically examine the dynamic relationship between stock market returns (KOSPI200 returns) and implied volatility (VKOSPI), as well as their statistical mechanics, in the Korean market, a representative and leading emerging market. We consider four macroeconomic variables (exchange rates, risk-free rates, term spreads, and credit spreads) as potential determinants of the dynamic conditional correlation between returns and volatility. Of these macroeconomic variables, the change in exchange rates has a significant impact on the dynamic correlation between KOSPI200 returns and the VKOSPI, especially during the recent financial crisis. We also find that the risk-free rate has a marginal effect on this dynamic conditional relationship.

Optimization of Time-Resolved Fluorescence Assay for Detection of Eu-DOTA-labeled Ligand-Receptor Interactions

PubMed Central

De Silva, Channa R.; Vagner, Josef; Lynch, Ronald; Gillies, Robert J.; Hruby, Victor J.

2010-01-01

Lanthanide-based luminescent ligand binding assays are superior to traditional radiolabel assays due to improved sensitivity and affordability in high throughput screening while eliminating the use of radioactivity. Despite significant progress using lanthanide(III)-coordinated chelators such as DTPA derivatives, dissociation-enhanced lanthanide fluoroimmunoassays (DELFIA) have not yet been successfully used with more stable chelators, e.g. DOTA derivatives, due to the incomplete release of lanthanide(III) ions from the complex. Here, a modified and an optimized DELFIA procedure incorporating an acid treatment protocol is introduced for use with Eu(III)-DOTA labeled peptides. Complete release of Eu(III) ions from DOTA labeled ligands was observed using hydrochloric acid (2.0 M) prior to the luminescent enhancement step. NDP-α-MSH labeled with Eu(III)-DOTA was synthesized and the binding affinity to cells overexpressing the human melanocortin-4 receptors (hMC4R) was evaluated using the modified protocol. Binding data indicate that the Eu(III)-DOTA linked peptide bound to these cells with an affinity similar to its DTPA analogue. The modified DELFIA procedure was further used to monitor the binding of an Eu(III)-DOTA labeled heterobivalent peptide to the cells expressing both hMC4R and CCK-2 (Cholecystokinin) receptors. The modified assay provides superior results and is appropriate for high-throughput screening of ligand libraries. PMID:19852924

Improved Tandem Affinity Purification Tag and Methods for Isolation of Proteins and Protein Complexes from Schizosaccharomyces pombe.

PubMed

Zilio, Nicola; Boddy, Michael N

2017-03-01

The tandem affinity purification (TAP) method uses an epitope that contains two different affinity purification tags separated by a site-specific protease site to isolate a protein rapidly and easily. Proteins purified via the TAP tag are eluted under mild conditions, allowing them to be used for structural and biochemical analyses. The original TAP tag contains a calmodulin-binding peptide and the IgG-binding domain from protein A separated by a tobacco etch virus (TEV) protease cleavage site. After capturing the Protein A epitope on an IgG resin, bound proteins are released by incubation with the TEV protease and then isolated on a calmodulin matrix in the presence of calcium; elution from this resin is achieved by chelating calcium with EGTA. However, because the robustness of the calmodulin-binding step in this procedure is highly variable, we replaced the calmodulin-binding peptide with three copies of the FLAG epitope, (3× FLAG)-TEV-Protein A, which can be isolated using an anti-FLAG resin. Elution from this matrix is achieved in the presence of an excess of a 3× FLAG peptide. In addition to allowing proteins to be released under mild conditions, elution by the 3× FLAG peptide adds an extra layer of specificity to the TAP procedure, because it liberates only FLAG-tagged proteins. © 2017 Cold Spring Harbor Laboratory Press.

Reaction of the isosteric methylenephosphonate analog of alpha-D-glucose 1-phosphate with phosphoglucomutase. Induced-fit specificity revisited.

PubMed

Ray, W J; Post, C B; Puvathingal, J M

1993-01-12

The phospho form of phosphoglucomutase reacts with the isosteric methylenephosphonate analog of alpha-D-glucose 1-phosphate to produce the corresponding analog of alpha-D-glucose 1,6-bisphosphate plus the dephosphoenzyme. In a coupled reaction, kcat/Km = 1.7 x 10(3) M-1 s-1, which is about 2 x 10(-5) times that for the corresponding reaction with alpha-D-glucose 1-phosphate. The decrease in kcat/Km is divided more or less evenly between less efficient PO3- transfer and decreased binding, although smaller phosphates and phosphonates bind approximately equally. There is a much smaller difference in the binding of glucose 1-methylenephosphonate 6-phosphate and glucose 1,6-bisphosphate to the dephosphoenzyme: the binding ratio is < 1:35 when the glucose ring is oriented similarly. Preferred binding patterns for a number of substrates/inhibitors, studied by 31P NMR and UV-difference spectroscopy, suggest that in the ground state the phosphonate group is tolerated to a much greater extent at the catalytic subsite than at the phosphate-binding subsite, where binding specificity appears to be directed toward a tetrahedral-PO3(2-) group attached to a bridging atom that can act as a hydrogen-bond acceptor. Binding specificity at the catalytic subsite apparently is directed toward a different array, possibly (-O...PO3...O-)2-. Some of these results are considered in terms of a modified version of the "induced fit" concept of enzymic specificity, which is reexamined in view of implied thermodynamic restrictions. The internal rearrangement whereby the positions of the anionic groups of the phosphate/phosphonate are exchanged is compared with the analogous rearrangements involving glucose 1,6-bisphosphate and 1,4-butanediol bisphosphate. The supplementary material describes a three-step synthesis of 1-deoxy-alpha-D-glucose 1-methylenephosphonate together with a procedure for phosphorylating the phosphonate to produce an analog of alpha-D-glucose 1,6-bisphosphate and also describes a facile procedure for the qualitative conversion of organic phosphonates to inorganic phosphate.

A semi-grand canonical Monte Carlo simulation model for ion binding to ionizable surfaces: proton binding of carboxylated latex particles as a case study.

PubMed

Madurga, Sergio; Rey-Castro, Carlos; Pastor, Isabel; Vilaseca, Eudald; David, Calin; Garcés, Josep Lluís; Puy, Jaume; Mas, Francesc

2011-11-14

In this paper, we present a computer simulation study of the ion binding process at an ionizable surface using a semi-grand canonical Monte Carlo method that models the surface as a discrete distribution of charged and neutral functional groups in equilibrium with explicit ions modelled in the context of the primitive model. The parameters of the simulation model were tuned and checked by comparison with experimental titrations of carboxylated latex particles in the presence of different ionic strengths of monovalent ions. The titration of these particles was analysed by calculating the degree of dissociation of the latex functional groups vs. pH curves at different background salt concentrations. As the charge of the titrated surface changes during the simulation, a procedure to keep the electroneutrality of the system is required. Here, two approaches are used with the choice depending on the ion selected to maintain electroneutrality: counterion or coion procedures. We compare and discuss the difference between the procedures. The simulations also provided a microscopic description of the electrostatic double layer (EDL) structure as a function of pH and ionic strength. The results allow us to quantify the effect of the size of the background salt ions and of the surface functional groups on the degree of dissociation. The non-homogeneous structure of the EDL was revealed by plotting the counterion density profiles around charged and neutral surface functional groups. © 2011 American Institute of Physics

Capture-SELEX: Selection of DNA Aptamers for Aminoglycoside Antibiotics

PubMed Central

2012-01-01

Small organic molecules are challenging targets for an aptamer selection using the SELEX technology (SELEX—Systematic Evolution of Ligans by EXponential enrichment). Often they are not suitable for immobilization on solid surfaces, which is a common procedure in known aptamer selection methods. The Capture-SELEX procedure allows the selection of DNA aptamers for solute targets. A special SELEX library was constructed with the aim to immobilize this library on magnetic beads or other surfaces. For this purpose a docking sequence was incorporated into the random region of the library enabling hybridization to a complementary oligo fixed on magnetic beads. Oligonucleotides of the library which exhibit high affinity to the target and a secondary structure fitting to the target are released from the beads for binding to the target during the aptamer selection process. The oligonucleotides of these binding complexes were amplified, purified, and immobilized via the docking sequence to the magnetic beads as the starting point of the following selection round. Based on this Capture-SELEX procedure, the successful DNA aptamer selection for the aminoglycoside antibiotic kanamycin A as a small molecule target is described. PMID:23326761

Quantitative cytochemistry of nuclear and cytoplasmic proteins using the Naphthol Yellow S and dinitrofluorobenzene staining methods.

PubMed

Tas, J; James, J

1981-09-01

The 'total protein staining' of biological specimens with the electrostatically binding Naphthol Yellow S or the covalently binding dinitrofluorobenzene must be interpreted as methods which yield data on the specific amino acid pool of the proteins concerned. Both dyes bind to certain free amino-acid side-chains, giving different dye--protein ratios for various proteins. In the presence of DNA, dinitrofluorobenzene stains all proteins present in cell nuclei, whereas Naphthol Yellow S only stains the majority of the non-histone proteins. When protein staining methods are combined with the Feulgen--Pararosanile (SO2) procedure for DNA, decreased Feulgen--DNA contents were measured in dinitrofluorobenzene-stained isolated nuclei and lymphocytes.

Development of [3H]2-Carboxy-4,6-dichloro-1H-indole-3-propionic Acid ([3H]PSB-12150): A Useful Tool for Studying GPR17

PubMed Central

2014-01-01

The recently described synthetic GPR17 agonist 2-carboxy-4,6-dichloro-1H-indole-3-propionic acid (1) was prepared in tritium-labeled form by catalytic hydrogenation of the corresponding propenoic acid derivative 8 with tritium gas. The radioligand [3H]PSB-12150 (9) was obtained with a specific activity of 17 Ci/mmol (629 GBq/mmol). It showed specific and saturable binding to a single binding site in membrane preparations from Chinese hamster ovary cells recombinantly expressing the human GPR17. A competition assay procedure was established, which allows the determination of ligand binding affinities. PMID:24900835

Development of [(3)H]2-Carboxy-4,6-dichloro-1H-indole-3-propionic Acid ([(3)H]PSB-12150): A Useful Tool for Studying GPR17.

PubMed

Köse, Meryem; Ritter, Kirsten; Thiemke, Katharina; Gillard, Michel; Kostenis, Evi; Müller, Christa E

2014-04-10

The recently described synthetic GPR17 agonist 2-carboxy-4,6-dichloro-1H-indole-3-propionic acid (1) was prepared in tritium-labeled form by catalytic hydrogenation of the corresponding propenoic acid derivative 8 with tritium gas. The radioligand [(3)H]PSB-12150 (9) was obtained with a specific activity of 17 Ci/mmol (629 GBq/mmol). It showed specific and saturable binding to a single binding site in membrane preparations from Chinese hamster ovary cells recombinantly expressing the human GPR17. A competition assay procedure was established, which allows the determination of ligand binding affinities.

Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

PubMed

Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

1980-04-01

Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency.

Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

PubMed Central

Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

1980-01-01

Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency. PMID:6246537

DNA-aptamers binding aminoglycoside antibiotics.

PubMed

Nikolaus, Nadia; Strehlitz, Beate

2014-02-21

Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

The Dot Blot ELISA.

ERIC Educational Resources Information Center

Gerbig, Donald G., Jr.; Fenk, Christopher J.; Goodhart, Amy S.

2000-01-01

Uses two laboratory techniques, Enzyme Linked Immunosorbent Assay (ELISA) and Western Blot, to demonstrate antibody-antigen binding concepts. Includes a list of required materials and directions for the procedure, and makes suggestions for classroom applications. (Contains 13 references.) (YDS)

Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2′-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells

PubMed Central

Lee, Kyue Yim; Kang, Hyungu; Ryu, Sung Ho; Lee, Dong Soo; Lee, Jung Hwan; Kim, Soonhag

2010-01-01

Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2′-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures. PMID:20204158

Mechanistic and conformational studies on the interaction of food dye amaranth with human serum albumin by multispectroscopic methods.

PubMed

Zhang, Guowen; Ma, Yadi

2013-01-15

The mechanism of interaction between food dye amaranth and human serum albumin (HSA) in physiological buffer (pH 7.4) was investigated by fluorescence, UV-vis absorption, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy. Results obtained from analysis of fluorescence spectra indicated that amaranth had a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The negative value of enthalpy change and positive value of entropy change elucidated that the binding of amaranth to HSA was driven mainly by hydrophobic and hydrogen bonding interactions. The surface hydrophobicity of HSA increased after binding with amaranth. The binding distance between HSA and amaranth was estimated to be 3.03 nm and subdomain IIA (Sudlow site I) was the primary binding site for amaranth on HSA. The results of CD and FT-IR spectra showed that binding of amaranth to HSA induced conformational changes of HSA. Copyright © 2012 Elsevier Ltd. All rights reserved.

Acceleration of Binding Site Comparisons by Graph Partitioning.

PubMed

Krotzky, Timo; Klebe, Gerhard

2015-08-01

The comparison of protein binding sites is a prominent task in computational chemistry and has been studied in many different ways. For the automatic detection and comparison of putative binding cavities the Cavbase system has been developed which uses a coarse-grained set of pseudocenters to represent the physicochemical properties of a binding site and employs a graph-based procedure to calculate similarities between two binding sites. However, the comparison of two graphs is computationally quite demanding which makes large-scale studies such as the rapid screening of entire databases hardly feasible. In a recent work, we proposed the method Local Cliques (LC) for the efficient comparison of Cavbase binding sites. It employs a clique heuristic to detect the maximum common subgraph of two binding sites and an extended graph model to additionally compare the shape of individual surface patches. In this study, we present an alternative to further accelerate the LC method by partitioning the binding-site graphs into disjoint components prior to their comparisons. The pseudocenter sets are split with regard to their assigned phyiscochemical type, which leads to seven much smaller graphs than the original one. Applying this approach on the same test scenarios as in the former comprehensive way results in a significant speed-up without sacrificing accuracy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selectivity mapping of the binding sites of (E)-resveratrol imprinted polymers using structurally diverse polyphenolic compounds present in Pinot noir grape skins.

PubMed

Hashim, Shima N N S; Schwarz, Lachlan J; Danylec, Basil; Potdar, Mahesh K; Boysen, Reinhard I; Hearn, Milton T W

2016-12-01

This investigation describes a general procedure for the selectivity mapping of molecularly imprinted polymers, using (E)-resveratrol-imprinted polymers as the exemplar, and polyphenolic compounds present in Pinot noir grape skin extracts as the test compounds. The procedure is based on the analysis of samples generated before and after solid-phase extraction of (E)-resveratrol and other polyphenols contained within the Pinot noir grape skins using (E)-resveratrol-imprinted polymers. Capillary reversed-phase high-performance liquid chromatography (RP-HPLC) and electrospray ionisation tandem mass spectrometry (ESI MS/MS) was then employed for compound analysis and identification. Under optimised solid-phase extraction conditions, the (E)-resveratrol-imprinted polymer showed high binding affinity and selectivity towards (E)-resveratrol, whilst no resveratrol was bound by the corresponding non-imprinted polymer. In addition, quercetin-3-O-glucuronide and a dimer of catechin-methyl-5-furfuraldehyde, which share some structural features with (E)-resveratrol, were also bound by the (E)-resveratrol-imprinted polymer. Polyphenols that were non-specifically retained by both the imprinted and non-imprinted polymer were (+)-catechin, a B-type procyanidin and (-)-epicatechin. The compounds that did not bind to the (E)-resveratrol molecularly imprinted polymer had at least one of the following molecular characteristics in comparison to the (E)-resveratrol template: (i) different spatial arrangements of their phenolic hydroxyl groups, (ii) less than three or more than four phenolic hydroxyl groups, or (iii) contained a bulky substituent moiety. The results show that capillary RP-HPLC in conjunction with ESI MS/MS represent very useful techniques for mapping the selectivity of the binding sites of imprinted polymer. Moreover, this procedure permits performance monitoring of the characteristics of molecularly imprinted polymers intended for solid-phase extraction of bioactive and nutraceutical molecules from diverse agricultural waste sources. Copyright © 2016 Elsevier B.V. All rights reserved.

Prediction of enzyme binding: human thrombin inhibition study by quantum chemical and artificial intelligence methods based on X-ray structures.

PubMed

Mlinsek, G; Novic, M; Hodoscek, M; Solmajer, T

2001-01-01

Thrombin is a serine protease which plays important roles in the human body, the key one being the control of thrombus formation. The inhibition of thrombin has become a target for new antithrombotics. The aim of our work was to (i) construct a model which would enable us to predict Ki values for the binding of an inhibitor into the active site of thrombin based on a database of known X-ray structures of inhibitor-enzyme complexes and (ii) to identify the structural and electrostatic characteristics of inhibitor molecules crucially important to their effective binding. To retain as much of the 3D structural information of the bound inhibitor as possible, we implemented the quantum mechanical/molecular mechanical (QM/MM) procedure for calculating the molecular electrostatic potential (MEP) at the van der Waals surfaces of atoms in the protein's active site. The inhibitor was treated quantum mechanically, while the rest of the complex was treated by classical means. The obtained MEP values served as inputs into the counter-propagation artificial neural network (CP-ANN), and a genetic algorithm was subsequently used to search for the combination of atoms that predominantly influences the binding. The constructed CP-ANN model yielded Ki values predictions with a correlation coefficient of 0.96, with Ki values extended over 7 orders of magnitude. Our approach also shows the relative importance of the various amino acid residues present in the active site of the enzyme for inhibitor binding. The list of residues selected by our automatic procedure is in good correlation with the current consensus regarding the importance of certain crucial residues in thrombin's active site.

De novo design and engineering of functional metal and porphyrin-binding protein domains

NASA Astrophysics Data System (ADS)

Everson, Bernard H.

In this work, I describe an approach to the rational, iterative design and characterization of two functional cofactor-binding protein domains. First, a hybrid computational/experimental method was developed with the aim of algorithmically generating a suite of porphyrin-binding protein sequences with minimal mutual sequence information. This method was explored by generating libraries of sequences, which were then expressed and evaluated for function. One successful sequence is shown to bind a variety of porphyrin-like cofactors, and exhibits light- activated electron transfer in mixed hemin:chlorin e6 and hemin:Zn(II)-protoporphyrin IX complexes. These results imply that many sophisticated functions such as cofactor binding and electron transfer require only a very small number of residue positions in a protein sequence to be fixed. Net charge and hydrophobic content are important in determining protein solubility and stability. Accordingly, rational modifications were made to the aforementioned design procedure in order to improve its overall success rate. The effects of these modifications are explored using two `next-generation' sequence libraries, which were separately expressed and evaluated. Particular modifications to these design parameters are demonstrated to effectively double the purification success rate of the procedure. Finally, I describe the redesign of the artificial di-iron protein DF2 into CDM13, a single chain di-Manganese four-helix bundle. CDM13 acts as a functional model of natural manganese catalase, exhibiting a kcat of 0.08s-1 under steady-state conditions. The bound manganese cofactors have a reduction potential of +805 mV vs NHE, which is too high for efficient dismutation of hydrogen peroxide. These results indicate that as a high-potential manganese complex, CDM13 may represent a promising first step toward a polypeptide model of the Oxygen Evolving Complex of the photosynthetic enzyme Photosystem II.

47 CFR 90.699 - Transition of the upper 200 channels in the 800 MHz band to EA licensing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... activities necessary for implementing the replacement facilities, including engineering and cost analysis of... procedures provide several alternative methods such as binding arbitration, mediation, or other ADR...

Subsite mapping of enzymes. Depolymerase computer modelling.

PubMed Central

Allen, J D; Thoma, J A

1976-01-01

We have developed a depolymerase computer model that uses a minimization routine. The model is designed so that, given experimental bond-cleavage frequencies for oligomeric substrates and experimental Michaelis parameters as a function of substrate chain length, the optimum subsite map is generated. The minimized sum of the weighted-squared residuals of the experimental and calculated data is used as a criterion of the goodness-of-fit for the optimized subsite map. The application of the minimization procedure to subsite mapping is explored through the use of simulated data. A procedure is developed whereby the minimization model can be used to determine the number of subsites in the enzymic binding region and to locate the position of the catalytic amino acids among these subsites. The degree of propagation of experimental variance into the subsite-binding energies is estimated. The question of whether hydrolytic rate coefficients are constant or a function of the number of filled subsites is examined. PMID:999629

Highly Stable, Functional Hairy Nanoparticles and Biopolymers from Wood Fibers: Towards Sustainable Nanotechnology.

PubMed

Sheikhi, Amir; Yang, Han; Alam, Md Nur; van de Ven, Theo G M

2016-07-20

Nanoparticles, as one of the key materials in nanotechnology and nanomedicine, have gained significant importance during the past decade. While metal-based nanoparticles are associated with synthetic and environmental hassles, cellulose introduces a green, sustainable alternative for nanoparticle synthesis. Here, we present the chemical synthesis and separation procedures to produce new classes of hairy nanoparticles (bearing both amorphous and crystalline regions) and biopolymers based on wood fibers. Through periodate oxidation of soft wood pulp, the glucose ring of cellulose is opened at the C2-C3 bond to form 2,3-dialdehyde groups. Further heating of the partially oxidized fibers (e.g., T = 80 °C) results in three products, namely fibrous oxidized cellulose, sterically stabilized nanocrystalline cellulose (SNCC), and dissolved dialdehyde modified cellulose (DAMC), which are well separated by intermittent centrifugation and co-solvent addition. The partially oxidized fibers (without heating) were used as a highly reactive intermediate to react with chlorite for converting almost all aldehyde to carboxyl groups. Co-solvent precipitation and centrifugation resulted in electrosterically stabilized nanocrystalline cellulose (ENCC) and dicarboxylated cellulose (DCC). The aldehyde content of SNCC and consequently surface charge of ENCC (carboxyl content) were precisely controlled by controlling the periodate oxidation reaction time, resulting in highly stable nanoparticles bearing more than 7 mmol functional groups per gram of nanoparticles (e.g., as compared to conventional NCC bearing < 1 mmol functional group/g). Atomic force microscopy (AFM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) attested to the rod-like morphology. Conductometric titration, Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), electrokinetic-sonic-amplitude (ESA) and acoustic attenuation spectroscopy shed light on the superior properties of these nanomaterials.

On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein.

PubMed

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Roitberg, Adrian E; Fernandez-Alberti, Sebastian

2015-06-28

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

NASA Astrophysics Data System (ADS)

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Roitberg, Adrian E.; Fernandez-Alberti, Sebastian

2015-06-01

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

Insights into the selective binding and toxic mechanism of microcystin to catalase

NASA Astrophysics Data System (ADS)

Hu, Yuandong; Da, Liangjun

2014-03-01

Microcystin is a sort of cyclic nonribosomal peptides produced by cyanobacteria. It is cyanotoxin, which can be very toxic for plants and animals including humans. The present study evaluated the interaction of microcystin and catalase, under physiological conditions by means of fluorescence, three-dimensional (3D) fluorescence, circular dichroism (CD), Fourier Transform infrared (FT-IR) spectroscopy, and enzymatic reactionkinetic techniques. The fluorescence data showed that microcystin could bind to catalase to form a complex. The binding process was a spontaneous molecular interaction procedure, in which electrostatic interactions played a major role. Energy transfer and fluorescence studies proved the existence of a static binding process. Additionally, as shown by the three-dimensional fluorescence, CD and FT-IR results, microcystin could lead to conformational and microenvironmental changes of the protein, which may affect the physiological functions of catalase. The work provides important insights into the toxicity mechanism of microcystin in vivo.

Programmable calculator software for computation of the plasma binding of ligands.

PubMed

Conner, D P; Rocci, M L; Larijani, G E

1986-01-01

The computation of the extent of plasma binding of a ligand to plasma constituents using radiolabeled ligand and equilibrium dialysis is complex and tedious. A computer program for the HP-41C Handheld Computer Series (Hewlett-Packard) was developed to perform these calculations. The first segment of the program constructs a standard curve for quench correction of post-dialysis plasma and buffer samples, using either external standard ratio (ESR) or sample channels ratio (SCR) techniques. The remainder of the program uses the counts per minute, SCR or ESR, and post-dialysis volume of paired plasma and buffer samples generated from the dialysis procedure to compute the extent of binding after correction for background radiation, counting efficiency, and intradialytic shifts of fluid between plasma and buffer compartments during dialysis. This program greatly simplifies the analysis of equilibrium dialysis data and has been employed in the analysis of dexamethasone binding in normal and uremic sera.

Serial interactome capture of the human cell nucleus.

PubMed

Conrad, Thomas; Albrecht, Anne-Susann; de Melo Costa, Veronica Rodrigues; Sauer, Sascha; Meierhofer, David; Ørom, Ulf Andersson

2016-04-04

Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present 'serial RNA interactome capture' (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)-RNA-protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA-RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.

Binding modes of dihydroquinoxalinones in a homology model of bradykinin receptor 1.

PubMed

Ha, Sookhee N; Hey, Pat J; Ransom, Rick W; Harrell, C Meacham; Murphy, Kathryn L; Chang, Ray; Chen, Tsing-Bau; Su, Dai-Shi; Markowitz, M Kristine; Bock, Mark G; Freidinger, Roger M; Hess, Fred J

2005-05-27

We report the first homology model of human bradykinin receptor B1 generated from the crystal structure of bovine rhodopsin as a template. Using an automated docking procedure, two B1 receptor antagonists of the dihydroquinoxalinone structural class were docked into the receptor model. Site-directed mutagenesis data of the amino acid residues in TM1, TM3, TM6, and TM7 were incorporated to place the compounds in the binding site of the homology model of the human B1 bradykinin receptor. The best pose in agreement with the mutation data was selected for detailed study of the receptor-antagonist interaction. To test the model, the calculated antagonist-receptor binding energy was correlated with the experimentally measured binding affinity (K(i)) for nine dihydroquinoxalinone analogs. The model was used to gain insight into the molecular mechanism for receptor function and to optimize the dihydroquinoxalinone analogs.

Binding energies and modelling of nuclei in semiclassical simulations

NASA Astrophysics Data System (ADS)

Pérez-García, M. Ángeles; Tsushima, K.; Valcarce, A.

2008-03-01

We study the binding energies of spin isospin saturated nuclei with nucleon number 8⩽A⩽100 in semiclassical Monte Carlo many-body simulations. The model Hamiltonian consists of (i) nucleon kinetic energy, (ii) a nucleon nucleon interaction potential, and (iii) an effective Pauli potential which depends on density. The basic ingredients of the nucleon nucleon potential are a short-range repulsion, and a medium-range attraction. Our results demonstrate that one can always expect to obtain the empirical binding energies for a set of nuclei by introducing a proper density dependent Pauli potential in terms of a single variable, the nucleon number, A. The present work shows that in the suggested procedure there is a delicate counterbalance of kinetic and potential energetic contributions allowing a good reproduction of the experimental nuclear binding energies. This type of calculations may be of interest in further reproduction of other properties of nuclei such as radii and also exotic nuclei.

Lubricant Performance and Evaluation.

DTIC Science & Technology

1987-06-01

Robert E. Kauffman * University of Day..on Research InstituteI Dayton, Ohio 4546; Jun 1987 S U- 4BD Interim Technical Report For Period17 June 1985...InI 133 43-.-l 311 u0.C ) 4- ta 0 0)0 m~tO tD r-ww D Chm4- -4 CD ") I-MW--- L)Ci 00 LnCD 0000004.4.(AJC cctO 0~ CO 4 LAU, CL 4) 4i M0 m 0 cmi CA...L)E- CP L) C,1-4 P)1- lz 1 0 "’ dccE-4 C") LA tD wx I (𔃻 :D W wI 363 0 -4 0) %0 0** *A ONV 9) kn k )4) 12LnA 4-4 0 0m - O .Dt-C%0 ~ 0 -0 *-LA .h %D

The Space and Earth Science Data Compression Workshop

NASA Technical Reports Server (NTRS)

Tilton, James C. (Editor)

1993-01-01

This document is the proceedings from a Space and Earth Science Data Compression Workshop, which was held on March 27, 1992, at the Snowbird Conference Center in Snowbird, Utah. This workshop was held in conjunction with the 1992 Data Compression Conference (DCC '92), which was held at the same location, March 24-26, 1992. The workshop explored opportunities for data compression to enhance the collection and analysis of space and Earth science data. The workshop consisted of eleven papers presented in four sessions. These papers describe research that is integrated into, or has the potential of being integrated into, a particular space and/or Earth science data information system. Presenters were encouraged to take into account the scientists's data requirements, and the constraints imposed by the data collection, transmission, distribution, and archival system.

Epidermal dysplasia and abnormal hair follicles in transgenic mice overexpressing homeobox gene MSX-2.

PubMed

Jiang, T X; Liu, Y H; Widelitz, R B; Kundu, R K; Maxson, R E; Chuong, C M

1999-08-01

The homeobox gene Msx-2 is expressed specifically in sites of skin appendage formation. To explore its part in skin morphogenesis, we produced transgenic mice expressing Msx-2 under the control of the cytomegalovirus promoter. The skin of these transgenic mice was flaky, exhibiting desquamation and shorter hairs. Histologic analysis showed thickened epidermis with hyperproliferation, which was restricted to the basal layer. Hyperkeratosis was also evident. A wide zone of suprabasal cells were misaligned and coexpressed keratins 14 and 10. There was reduced expression of integrin beta 1 and DCC in the basal layer. Hair follicles were misaligned with a shrunken matrix region. The dermis showed increased cellularity and empty vacuoles. We suggest that Msx-2 is involved in the growth control of skin and skin appendages.

Mission Control Center (MCC) System Specification for the Shuttle Orbital Flight Test (OFT) Timeframe

NASA Technical Reports Server (NTRS)

1976-01-01

System specifications to be used by the mission control center (MCC) for the shuttle orbital flight test (OFT) time frame were described. The three support systems discussed are the communication interface system (CIS), the data computation complex (DCC), and the display and control system (DCS), all of which may interfere with, and share processing facilities with other applications processing supporting current MCC programs. The MCC shall provide centralized control of the space shuttle OFT from launch through orbital flight, entry, and landing until the Orbiter comes to a stop on the runway. This control shall include the functions of vehicle management in the area of hardware configuration (verification), flight planning, communication and instrumentation configuration management, trajectory, software and consumables, payloads management, flight safety, and verification of test conditions/environment.

The DIRC front-end electronics chain for BaBar

NASA Astrophysics Data System (ADS)

Bailly, P.; Chauveau, J.; Del Buono, L.; Genat, J. F.; Lebbolo, H.; Roos, L.; Zhang, B.; Beigbeder, C.; Bernier, R.; Breton, D.; Caceres, T.; Chase, R.; Ducorps, A.; Hrisoho, A.; Imbert, P.; Sen, S.; Tocut, V.; Truong, K.; Wormser, G.; Zomer, F.; Bonneaud, G.; Dohou, F.; Gastaldi, F.; Matricon, P.; Renard, C.; Thiebaux, C.; Vasileiadis, G.; Verderi, M.; Oxoby, G.; Va'Vra, J.; Warner, D.; Wilson, R. J.

1999-08-01

The detector of Internally Reflected Cherenkov light (DIRC) of the BaBar detector (SLAC Stanford, USA) measures better than 1 ns the arrival time of Cherenkov photoelectrons, detected in a 11 000 phototubes array and their amplitude spectra. It mainly comprises of 64-channel DIRC Front-End Boards (DFB) equipped with eight full-custom Analog chips performing zero-cross discrimination with 2 mV threshold and pulse shaping, four full-custom Digital TDC chips for timing measurements with 500 ps binning and a readout logic selecting hits in the trigger window, and DIRC Crate Controller cards (DCC) serializing the data collected from up to 16 DFBs onto a 1.2 Gb/s optical link. Extensive test of the pre-production chips have been performed as well as system tests.

Detergent enhances binding of a secreted HLA-A2 molecule to solid phase peptides.

PubMed

Tussey, L G; Frelinger, J A

1991-11-01

We have constructed a secreted analogue (sA2) of the human class I molecule HLA-A2. sA2 was affinity purified both in the presence and absence of detergent and the effects of detergent on the magnitude and specificity of A2 binding to solid phase peptides tested. sA2 purified in the presence of detergent and detergent-solubilized A2 are shown to function comparably in the binding of the synthetic peptide M.Y + 57-68, a known T-cell epitope derived from the influenza A matrix protein. The molecules binding to M.Y + 57-68 typically represent 8% to 10% of the added protein. In contrast, less than 1% of sA2 protein purified in the absence of detergent binds M.Y + 57-68. This reduced binding is not due to a change in the affinity of sA2 for M.Y + 57-68. Addition of detergent at various stages of the purification and iodination procedures indicates that the longer the sA2 molecules are exposed to detergent the better they bind. However, the concentration of detergent during the actual binding assay does not appear to be critical. We also find that while the sA2-detergent and the sA2-no detergent molecules differ in the extent to which they bind various peptides, they do not differ in their patterns of binding. We conclude that detergent probably does not influence the specificity of class I/peptide binding but does increase the number of sA2 molecules that can participate in the binding of peptide either by generating and stabilizing "empty" sA2 molecules or by stabilizing a structure that is more amenable to binding peptide.

Cloud computing approaches for prediction of ligand binding poses and pathways.

PubMed

Lawrenz, Morgan; Shukla, Diwakar; Pande, Vijay S

2015-01-22

We describe an innovative protocol for ab initio prediction of ligand crystallographic binding poses and highly effective analysis of large datasets generated for protein-ligand dynamics. We include a procedure for setup and performance of distributed molecular dynamics simulations on cloud computing architectures, a model for efficient analysis of simulation data, and a metric for evaluation of model convergence. We give accurate binding pose predictions for five ligands ranging in affinity from 7 nM to > 200 μM for the immunophilin protein FKBP12, for expedited results in cases where experimental structures are difficult to produce. Our approach goes beyond single, low energy ligand poses to give quantitative kinetic information that can inform protein engineering and ligand design.

Characterization of the swine adipocyte A1 adenosine receptor using an optimized assay system.

PubMed

Dong, Q; Schuchman, J; Carey, G B

1994-07-01

The radioligand binding assay of A1 adenosine receptors in adipocyte crude plasma membrane from Yucatan miniature swine was optimized by evaluating 17 factors involved in the assay. Significant effects of CHAPS, adenosine deaminase, EDTA, pre-rinsing glass fiber filters and pH were found for the binding measurements. Using the optimized procedure, [3H]8-cyclopentyl-1,3-dipropylxanthine, ([3H]-DPCPX) binding to A1 adenosine receptors in swine subcutaneous adipocyte crude plasma membrane was measured; Bmax and Kd values were 479 +/- 77 fmol/mg protein and 0.87 +/- 0.10 nM, respectively. Values for mesenteric adipose tissue from sedentary swine and subcutaneous adipose tissue from exercise-trained swine were also measured.

Studies with an immobilized metal affinity chromatography cassette system involving binuclear triazacyclononane-derived ligands: automation of batch adsorption measurements with tagged recombinant proteins.

PubMed

Petzold, Martin; Coghlan, Campbell J; Hearn, Milton T W

2014-07-18

This study describes the determination of the adsorption isotherms and binding kinetics of tagged recombinant proteins using a recently developed IMAC cassette system and employing automated robotic liquid handling procedures for IMAC resin screening. These results confirm that these new IMAC resins, generated from a variety of different metal-charged binuclear 1,4,7-triaza-cyclononane (tacn) ligands, interact with recombinant proteins containing a novel N-terminal metal binding tag, NT1A, with static binding capacities similar to those obtained with conventional hexa-His tagged proteins, but with significantly increased association constants. In addition, higher kinetic binding rates were observed with these new IMAC systems, an attribute that can be positively exploited to increase process productivity. The results from this investigation demonstrate that enhancements in binding capacities and affinities were achieved with these new IMAC resins and chosen NT1A tagged protein. Further, differences in the binding performances of the bis(tacn) xylenyl-bridged ligands were consistent with the distance between the metal binding centres of the two tacn moieties, the flexibility of the ligand and the potential contribution from the aromatic ring of the xylenyl group to undergo π/π stacking interactions with the tagged proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of ageing on recollection: the role of the binding updating process.

PubMed

Boujut, Arnaud; Clarys, David

2016-10-01

The aim of this study was to highlight the underlying process responsible for the age-related deficit in recollection. Through two experiments using the Remember-Know-Guess procedure (Gardiner, J. M., & Richardson-Klavehn, A. [2000]. Remembering and knowing. In The Oxford handbook of memory (pp. 229-244). New York, NY: Oxford University Press) in recognition, we manipulated the opportunity to update bindings between target items and their encoding context, in young and older adults. In the first experiment we impaired the binding updating process during the encoding of items, while in the second we supported this process. The results indicated that the "Remember" responses in the younger group were specifically reduced by the impairment of the binding updating process (Exp. 1), suggesting that this ability is useful for them to encode a specific episode. Conversely, only the "Remember" responses in the older group were improved in accuracy by supporting the binding updating process (Exp. 2), suggesting that their weakness in this ability is the source of their failure to improve the accuracy of their memories. The overall results support the hypothesis that the age-related decline in episodic memory is partly due to a greater vulnerability to interference on bindings, impairing the ability to update content-context bindings as and when events occur.

PolyaPeak: Detecting Transcription Factor Binding Sites from ChIP-seq Using Peak Shape Information

PubMed Central

Wu, Hao; Ji, Hongkai

2014-01-01

ChIP-seq is a powerful technology for detecting genomic regions where a protein of interest interacts with DNA. ChIP-seq data for mapping transcription factor binding sites (TFBSs) have a characteristic pattern: around each binding site, sequence reads aligned to the forward and reverse strands of the reference genome form two separate peaks shifted away from each other, and the true binding site is located in between these two peaks. While it has been shown previously that the accuracy and resolution of binding site detection can be improved by modeling the pattern, efficient methods are unavailable to fully utilize that information in TFBS detection procedure. We present PolyaPeak, a new method to improve TFBS detection by incorporating the peak shape information. PolyaPeak describes peak shapes using a flexible Pólya model. The shapes are automatically learnt from the data using Minorization-Maximization (MM) algorithm, then integrated with the read count information via a hierarchical model to distinguish true binding sites from background noises. Extensive real data analyses show that PolyaPeak is capable of robustly improving TFBS detection compared with existing methods. An R package is freely available. PMID:24608116

Misuse of thermodynamics in the interpretation of isothermal titration calorimetry data for ligand binding to proteins.

PubMed

Pethica, Brian A

2015-03-01

Isothermal titration calorimetry (ITC) has given a mass of data on the binding of small molecules to proteins and other biopolymers, with particular interest in drug binding to proteins chosen as therapeutic indicators. Interpretation of the enthalpy data usually follows an unsound protocol that uses thermodynamic relations in circumstances where they do not apply. Errors of interpretation include incomplete definitions of ligand binding and equilibrium constants and neglect of the non-ideality of the solutions under study, leading to unreliable estimates of standard free energies and entropies of binding. The mass of reported thermodynamic functions for ligand binding to proteins estimated from ITC enthalpies alone is consequently of uncertain thermodynamic significance and utility. ITC and related experiments to test the protocol assumptions are indicated. A thermodynamic procedure avoiding equilibrium constants or other reaction models and not requiring protein activities is given. The discussion draws attention to the fundamental but neglected relation between the thermodynamic activity and bioactivity of drugs and to the generally unknown thermodynamic status of ligand solutions, which for drugs relates directly to effective therapeutic dosimetry. Copyright © 2014 Elsevier Inc. All rights reserved.

Rational Design of Peptide-Functionalized Surface Plasmon Resonance Sensor for Specific Detection of TNT Explosive.

PubMed

Wang, Jin; Muto, Masaki; Yatabe, Rui; Onodera, Takeshi; Tanaka, Masayoshi; Okochi, Mina; Toko, Kiyoshi

2017-09-30

In this study, a rationally-designed 2,4,6-trinitrotoluene (TNT) binding peptide derived from an amino acid sequence of the complementarity-determining region (CDR) of an anti-TNT monoclonal antibody was used for TNT detection based on a maleimide-functionalized surface plasmon resonance (SPR) sensor. By antigen-docking simulation and screening, the TNT binding candidate peptides were obtained as TNTHCDR1 derived from the heavy chain of CDR1, TNTHCDR2 derived from CDR2, and TNTHCDR3 from CDR3 of an anti-TNT antibody. The binding events between candidate peptides and TNT were evaluated using the SPR sensor by direct determination based on the 3-aminopropyltriethoxysilane (APTES) surface. The TNT binding peptide was directly immobilized on the maleimide-functionalized sensor chip surface from N-γ-maleimidobutyryl-oxysuccinimide ester (GMBS). The results demonstrated that peptide TNTHCDR3 was identified and selected as a TNT binding peptide among the other two candidate peptides. Five kinds of TNT analogues were also investigated to testify the selectivity of TNT binding peptide TNTHCDR3. Furthermore, the results indicated that the APTES-GMBS-based SPR sensor chip procedure featured a great potential application for the direct detection of TNT.

Rational Design of Peptide-Functionalized Surface Plasmon Resonance Sensor for Specific Detection of TNT Explosive

PubMed Central

Wang, Jin; Muto, Masaki; Yatabe, Rui; Onodera, Takeshi; Okochi, Mina; Toko, Kiyoshi

2017-01-01

In this study, a rationally-designed 2,4,6-trinitrotoluene (TNT) binding peptide derived from an amino acid sequence of the complementarity-determining region (CDR) of an anti-TNT monoclonal antibody was used for TNT detection based on a maleimide-functionalized surface plasmon resonance (SPR) sensor. By antigen-docking simulation and screening, the TNT binding candidate peptides were obtained as TNTHCDR1 derived from the heavy chain of CDR1, TNTHCDR2 derived from CDR2, and TNTHCDR3 from CDR3 of an anti-TNT antibody. The binding events between candidate peptides and TNT were evaluated using the SPR sensor by direct determination based on the 3-aminopropyltriethoxysilane (APTES) surface. The TNT binding peptide was directly immobilized on the maleimide-functionalized sensor chip surface from N-γ-maleimidobutyryl-oxysuccinimide ester (GMBS). The results demonstrated that peptide TNTHCDR3 was identified and selected as a TNT binding peptide among the other two candidate peptides. Five kinds of TNT analogues were also investigated to testify the selectivity of TNT binding peptide TNTHCDR3. Furthermore, the results indicated that the APTES-GMBS-based SPR sensor chip procedure featured a great potential application for the direct detection of TNT. PMID:28973962

36 CFR 51.57 - How does a concessioner request arbitration of the construction cost of a capital improvement?

Code of Federal Regulations, 2010 CFR

2010-07-01

... of the Director's determination of construction cost under § 51.56. The arbitration procedures are... improvement will be binding on the concessioner and the Director. [66 FR 35083, July 3, 2001] ...

36 CFR 51.57 - How does a concessioner request arbitration of the construction cost of a capital improvement?

Code of Federal Regulations, 2011 CFR

2011-07-01

... of the Director's determination of construction cost under § 51.56. The arbitration procedures are... improvement will be binding on the concessioner and the Director. [66 FR 35083, July 3, 2001] ...

Seeking Clearer Recommendations for Hand Hygiene in Communities Facing Ebola: A Randomized Trial Investigating the Impact of Six Handwashing Methods on Skin Irritation and Dermatitis.

PubMed

Wolfe, Marlene K; Wells, Emma; Mitro, Brittany; Desmarais, Anne Marie; Scheinman, Pamela; Lantagne, Daniele

2016-01-01

To prevent disease transmission, 0.05% chlorine solution is commonly recommended for handwashing in Ebola Treatment Units. In the 2014 West Africa outbreak this recommendation was widely extended to community settings, although many organizations recommend soap and hand sanitizer over chlorine. To evaluate skin irritation caused by frequent handwashing that may increase transmission risk in Ebola-affected communities, we conducted a randomized trial with 91 subjects who washed their hands 10 times a day for 28 days. Subjects used soap and water, sanitizer, or one of four chlorine solutions used by Ebola responders (calcium hypochlorite (HTH), sodium dichloroisocyanurate (NaDCC), and generated or pH-stabilized sodium hypochlorite (NaOCl)). Outcomes were self-reported hand feel, irritation as measured by the Hand Eczema Score Index (HECSI) (range 0-360), signs of transmission risk (e.g., cracking), and dermatitis diagnosis. All groups experienced statistically significant increases in HECSI score. Subjects using sanitizer had the smallest increases, followed by higher pH chlorine solutions (HTH and stabilized NaOCl), and soap and water. The greatest increases were among neutral pH chlorine solutions (NaDCC and generated NaOCl). Signs of irritation related to higher transmission risk were observed most frequently in subjects using soap and least frequently by those using sanitizer or HTH. Despite these irritation increases, all methods represented minor changes in HECSI score. Average HECSI score was only 9.10 at endline (range 1-33) and 4% (4/91) of subjects were diagnosed with dermatitis, one each in four groups. Each handwashing method has benefits and drawbacks: soap is widely available and inexpensive, but requires water and does not inactivate the virus; sanitizer is easy-to use and effective but expensive and unacceptable to many communities, and chlorine is easy-to-use but difficult to produce properly and distribute. Overall, we recommend Ebola responders and communities use whichever handwashing method(s) are most acceptable, available, and sustainable for community handwashing. International Standard Randomized Controlled Trial Registry ISRCTN89815514.

Cohort profile: the TrueNTH Global Registry - an international registry to monitor and improve localised prostate cancer health outcomes.

PubMed

Evans, Sue M; Millar, Jeremy L; Moore, Caroline M; Lewis, John D; Huland, Hartwig; Sampurno, Fanny; Connor, Sarah E; Villanti, Paul; Litwin, Mark S

2017-11-28

Globally, prostate cancer treatment and outcomes for men vary according to where they live, their race and the care they receive. The TrueNTH Global Registry project was established as an international registry monitoring care provided to men with localised prostate cancer (CaP). Sites with existing CaP databases in Movember fundraising countries were invited to participate in the international registry. In total, 25 Local Data Centres (LDCs) representing 113 participating sites across 13 countries have nominated to contribute to the project. It will collect a dataset based on the International Consortium for Health Outcome Measures (ICHOM) standardised dataset for localised CaP. A governance strategy has been developed to oversee registry operation, including transmission of reversibly anonymised data. LDCs are represented on the Project Steering Committee, reporting to an Executive Committee. A Project Coordination Centre and Data Coordination Centre (DCC) have been established. A project was undertaken to compare existing datasets, understand capacity at project commencement (baseline) to collect the ICHOM dataset and assist in determining the final data dictionary. 21/25 LDCs provided data dictionaries for review. Some ICHOM data fields were well collected (diagnosis, treatment start dates) and others poorly collected (complications, comorbidities). 17/94 (18%) ICHOM data fields were relegated to non-mandatory fields due to poor capture by most existing registries. Participating sites will transmit data through a web interface biannually to the DCC. Recruitment to the TrueNTH Global Registry-PCOR project will commence in late 2017 with sites progressively contributing reversibly anonymised data following ethical review in local regions. Researchers will have capacity to source deidentified data after the establishment phase. Quality indicators are to be established through a modified Delphi approach in later 2017, and it is anticipated that reports on performance against quality indicators will be provided to LDCs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

ESBL/AmpC-producing Enterobacteriaceae in households with children of preschool age: prevalence, risk factors and co-carriage.

PubMed

van den Bunt, G; Liakopoulos, A; Mevius, D J; Geurts, Y; Fluit, A C; Bonten, M J M; Mughini-Gras, L; van Pelt, W

2017-02-01

ESBL/AmpC-producing Enterobacteriaceae are an emerging public health concern. As households with preschool children may substantially contribute to the community burden of antimicrobial resistance, we determined the prevalence, risk factors and co-carriage of ESBL/AmpC-producing bacteria in preschool children and their parents. From April 2013 to January 2015, each month 2000 preschool children were randomly selected from Dutch population registries. The parents were invited to complete an epidemiological questionnaire and to obtain and send a faecal sample from the selected child and from one parent. Samples were tested for ESBL/AmpC-producing bacteria. Logistic regression was used to identify risk factors for ESBL/AmpC carriage in children and parents, and findings were internally validated by bootstrapping. In total, 1016 families were included and ESBL/AmpC prevalence was 4.0% (95% CI 3.2%-5.0%); 3.5% (95% CI 2.5%-4.8%) in children and 4.5% (95% CI 3.4%-6.0%) in parents. Attending a daycare centre (DCC) was the only significant risk factor for children (OR 2.1, 95% CI 1.0-4.3). For parents, the only significant risk factor was having one or more children attending DCCs (OR 2.2, 95% CI 1.2-4.8). For parents of ESBL/AmpC-positive children the OR for ESBL/AmpC carriage was 19.7 (95% CI 9.2-42.4). Co-carriage of specific ESBL/AmpC genotypes in child and parent occurred more often than expected by chance (14.6% versus 1.1%, P < 0.001). In this study, intestinal carriage with ESBL/AmpCs was detected in ∼4% of households with preschool children. DCC attendance was a risk factor in both children and parents and co-carriage of specific genotypes frequently occurred in child-parent pairs. These findings suggest household transmission or/and family-specific exposure to common sources of ESBL/AmpC-producing bacteria. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

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

Yu, V; Nguyen, D; Pajonk, F

Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to exploremore » the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work is supported by the NSF Graduate Research Fellowship (DGE-1144087)« less

Accuracy, Precision, Ease-Of-Use, and Cost of Methods to Test Ebola-Relevant Chlorine Solutions

PubMed Central

Wells, Emma; Wolfe, Marlene K.; Murray, Anna; Lantagne, Daniele

2016-01-01

To prevent transmission in Ebola Virus Disease (EVD) outbreaks, it is recommended to disinfect living things (hands and people) with 0.05% chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% chlorine solution. In the current West African EVD outbreak, these solutions (manufactured from calcium hypochlorite (HTH), sodium dichloroisocyanurate (NaDCC), and sodium hypochlorite (NaOCl)) have been widely used in both Ebola Treatment Unit and community settings. To ensure solution quality, testing is necessary, however test method appropriateness for these Ebola-relevant concentrations has not previously been evaluated. We identified fourteen commercially-available methods to test Ebola-relevant chlorine solution concentrations, including two titration methods, four DPD dilution methods, and six test strips. We assessed these methods by: 1) determining accuracy and precision by measuring in quintuplicate five different 0.05% and 0.5% chlorine solutions manufactured from NaDCC, HTH, and NaOCl; 2) conducting volunteer testing to assess ease-of-use; and, 3) determining costs. Accuracy was greatest in titration methods (reference-12.4% error compared to reference method), then DPD dilution methods (2.4–19% error), then test strips (5.2–48% error); precision followed this same trend. Two methods had an accuracy of <10% error across all five chlorine solutions with good precision: Hach digital titration for 0.05% and 0.5% solutions (recommended for contexts with trained personnel and financial resources), and Serim test strips for 0.05% solutions (recommended for contexts where rapid, inexpensive, and low-training burden testing is needed). Measurement error from test methods not including pH adjustment varied significantly across the five chlorine solutions, which had pH values 5–11. Volunteers found test strip easiest and titration hardest; costs per 100 tests were $14–37 for test strips and $33–609 for titration. Given the ease-of-use and cost benefits of test strips, we recommend further development of test strips robust to pH variation and appropriate for Ebola-relevant chlorine solution concentrations. PMID:27243817

Human granulocyte/pollen-binding protein. Recognition and identification as transferrin.

PubMed Central

Sass-Kuhn, S P; Moqbel, R; Mackay, J A; Cromwell, O; Kay, A B

1984-01-01

Normal human serum was found to contain a heat-stable protein which promoted the binding of granulocytes to timothy grass pollen (granulocyte/pollen-binding protein [GPBP]). GPBP was purified by gel filtration, anion exchange, and affinity chromatography. Virtually all of the granulocyte/pollen-binding activity was associated with a beta-1-protein having a molecular mass of approximately 77,000 D and an isoelectric point of between 5.5 and 6.1. By immunoelectrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein was identified as transferrin. Monospecific antisera raised against either GPBP or transferrin removed biological activity from GPBP preparations, and GPBP and transferrin gave lines of identity with these two antisera. The apparent heterogeneity in the molecular size and charge of GPBP observed during progressive purification was minimal when GPBP was saturated with ferric ions before the separation procedures. These experiments indicate that granulocyte/pollen binding is a hitherto unrecognized property of transferrin which appears to be unrelated to iron transport and raises the possibility that transferrin might have a physiological role in the removal of certain organic matter. Images PMID:6690479

Interaction of SR 33557 with skeletal muscle calcium channel blocker receptors in the baboon: characterization of its binding sites

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

Sol-Rolland, J.; Joseph, M.; Rinaldi-Carmona, M.

1991-05-01

A procedure for the isolation of primate skeletal microsomal membranes was initiated. Membranes exhibited specific enzymatic markers such as 5'-nucleotidase, Ca{sup 2}{sup +},Mg({sup 2}{sup +})-adenosine triphosphatase and an ATP-dependent calcium uptake. Baboon skeletal microsomes bound specifically with high-affinity potent Ca{sup 2}{sup +} channel blockers such as dihydropyridine, phenylalkylamine and benzothiazepine derivatives. Scatchard analysis of equilibrium binding assays with ({sup 3}H)(+)-PN 200-110, ({sup 3}H)(-)-desmethoxyverapamil (( {sup 3}H)(-)-D888) and ({sup 3}H)-d-cis-dilitiazem were consistent with a single class of binding sites for the three radioligands. The pharmacological profile of SR 33557, an original compound with calcium antagonist properties, was investigated using radioligand bindingmore » studies. SR 33557 totally inhibited the specific binding of the three main classes of Ca{sup 2}{sup +} channel effectors and interacted allosterically with them. In addition, SR 33557 bound with high affinity to a homogeneous population of binding sites in baboon skeletal muscle.« less

Step-By-Step In Vitro Mutagenesis: Lessons From Fucose-Binding Lectin PA-IIL.

PubMed

Mrázková, Jana; Malinovská, Lenka; Wimmerová, Michaela

2017-01-01

Site-directed mutagenesis is a powerful technique which is used to understand the basis of interactions between proteins and their binding partners, as well as to modify these interactions. Methods of rational design that are based on detailed knowledge of the structure of a protein of interest are often used for preliminary investigations of the possible outcomes which can result from the practical application of site-directed mutagenesis. Also, random mutagenesis can be used in tandem with site-directed mutagenesis for an examination of amino acid "hotspots."Lectins are sugar-binding proteins which, among other functions, mediate the recognition of host cells by a pathogen and its adhesion to the host cell surface. Hence, lectins and their binding properties are studied and engineered using site-directed mutagenesis.In this chapter, we describe a site-directed mutagenesis method used for investigating the sugar binding pattern of the PA-IIL lectin from the pathogenic bacterium Pseudomonas aeruginosa. Moreover, procedures for the production and purification of PA-IIL mutants are described, and several basic methods for characterizing the mutants are discussed.

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

Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptormore » density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.« less

Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography

NASA Technical Reports Server (NTRS)

Hu, S.; Brady, S. R.; Kovar, D. R.; Staiger, C. J.; Clark, G. B.; Roux, S. J.; Muday, G. K.

2000-01-01

Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.

Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography.

PubMed

Hu, S; Brady, S R; Kovar, D R; Staiger, C J; Clark, G B; Roux, S J; Muday, G K

2000-10-01

Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.

A Bioanalytical Chemistry Experiment for Undergraduate Students: Biosensors Based on Metal Nanoparticles

ERIC Educational Resources Information Center

Niagi, John; Warner, John; Andreesco, Silvana

2007-01-01

The study describes the development of new biosensors based on metal nanoparticles because of its high surface area and large binding ability. The adopted procedure is extremely simple and versatile and can be used in various applications of electrochemistry.

Asphalt binder grade selection and ignition oven calibration factors for HMAC with recycled asphalt products.

DOT National Transportation Integrated Search

2013-02-01

This study investigated several characteristics of laboratory-fabricated and plant-produced hot-mix asphalt mixtures containing : various proportions of RAP and RAS with the principal objectives of developing a procedure for selecting the virgin bind...

Validation of dye-binding/high-resolution thermal denaturation for the identification of mutations in the SLC22A5 gene.

PubMed

Dobrowolski, Steven F; McKinney, Jason T; Amat di San Filippo, Cristina; Giak Sim, Keow; Wilcken, Bridget; Longo, Nicola

2005-03-01

Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation resulting from defective carnitine transport. This disease is caused by mutations in the OCTN2 carnitine transporter encoded by the SLC22A5 gene. Here we validate dye-binding/high-resolution thermal denaturation as a screening procedure to identify novel mutations in this gene. This procedure is based on the amplification of DNA by PCR in capillaries with the dsDNA binding dye LCGreen I. The PCR reaction is then analyzed in the same capillary by high-resolution thermal denaturation. Samples with abnormal melting profiles are sequenced. This technique correctly identified all known patients who were compound heterozygotes for different mutations in the carnitine transporter gene and about 30% of homozygous patients. The remaining 70% of homozygous patients were identified by a second amplification, in which the patient's DNA was mixed with the DNA of a normal control. This screening system correctly identified eight novel mutations and both abnormal alleles in six new families with primary carnitine deficiency. The causative role of the missense mutations identified (c.3G>T/p.M1I, c.695C>T/p.T232M, and c.1403 C>G/p.T468R) was confirmed by expression in Chinese hamster ovary (CHO) cells. These results expand the mutational spectrum in primary carnitine deficiency and indicate dye-binding/high-resolution thermal denaturation as an ideal system to screen for mutations in diseases with no prevalent molecular alteration. (c) 2005 Wiley-Liss, Inc.

A computational approach for predicting off-target toxicity of antiviral ribonucleoside analogues to mitochondrial RNA polymerase.

PubMed

Freedman, Holly; Winter, Philip; Tuszynski, Jack; Tyrrell, D Lorne; Houghton, Michael

2018-06-22

In the development of antiviral drugs that target viral RNA-dependent RNA polymerases, off-target toxicity caused by the inhibition of the human mitochondrial RNA polymerase (POLRMT) is a major liability. Therefore, it is essential that all new ribonucleoside analogue drugs be accurately screened for POLRMT inhibition. A computational tool that can accurately predict NTP binding to POLRMT could assist in evaluating any potential toxicity and in designing possible salvaging strategies. Using the available crystal structure of POLRMT bound to an RNA transcript, here we created a model of POLRMT with an NTP molecule bound in the active site. Furthermore, we implemented a computational screening procedure that determines the relative binding free energy of an NTP analogue to POLRMT by free energy perturbation (FEP), i.e. a simulation in which the natural NTP molecule is slowly transformed into the analogue and back. In each direction, the transformation was performed over 40 ns of simulation on our IBM Blue Gene Q supercomputer. This procedure was validated across a panel of drugs for which experimental dissociation constants were available, showing that NTP relative binding free energies could be predicted to within 0.97 kcal/mol of the experimental values on average. These results demonstrate for the first time that free-energy simulation can be a useful tool for predicting binding affinities of NTP analogues to a polymerase. We expect that our model, together with similar models of viral polymerases, will be very useful in the screening and future design of NTP inhibitors of viral polymerases that have no mitochondrial toxicity. © 2018 Freedman et al.

Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

NASA Astrophysics Data System (ADS)

Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

2003-03-01

Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

Binding properties and colour of Bologna sausage made with varying fat levels, protein levels and cooking temperatures.

PubMed

Carballo, J; Mota, N; Barreto, G; Colmenero, F J

1995-01-01

A little-studied procedure for adjusting the properties of low-fat products is to use the influence that both composition and certain processing factors exert on these properties. The object of the present work was to assess the effects of protein level (P, ranging from 10% to 16%), fat level (F, ranging from 10.1% to 22%) and cooking temperature (HT, ranging from 77 °C to 105 °C) on the binding properties and colour of meat emulsions. Protein content was the variable that most influenced total expressible fluid (TEF) and purge loss. Heating rate had scarcely any effect on the binding properties of Bologna sausages. Analysis of variance indicated that the regression models for parameters L, a and b were not significant.

The Ebola contagion and forecasting virus: evidence from four African countries.

PubMed

Nadhem, Selmi; Nejib, Hachicha D

2015-12-01

This paper is focused on examining the number of deaths' increases participation in the propagating the Ebola virus during the period ranging from March to October 2014. An application of the MGARCH-DCC model regressions on four countries has led to discover that the finding that human contact play a significant role in transmitting the Ebola virus. Our findings also reveal that Guinea has already suffered from a spread-like virus originating from Sierra Lione and Liberia. Noteworthy also, other countries are now liable to such a risk; for instance, Nigeria is a country vulnerable to the propagation of this virus. Consequently, we undertake to conduct our forecasts for EGARCH model estimates implements; which has estimated a decrease in the Ebola virus incurred number of deadly Ebola virus over the two months following the November and December.

Cryochemistry: freezing effect on peptide coupling in different organic solutions.

PubMed

Vajda, T; Szókán, G; Hollósi, M

1998-06-01

The freezing effect on peptide coupling in organic solutions of different polarity has been investigated and compared with the results obtained in liquid phase. The model reaction of DCC-activated coupling of Boc-Ala-Phe-OH with H-Ala-OBu(t) has been carried out in dioxane, dimethylsulfoxide and formamide, as well as in mixtures (90%/10%, v/v) of dioxane with acetonitrile, dimethylformamide, dimethylsulfoxide and formamide. The reactions have been traced and evaluated by RP-HPLC analysis. Freezing the reaction mixture resulted in all cases in a significant suppression of the N-dipeptidylurea side-product formation together with a slight decrease of tripeptide epimerization. The coupling yields and the side effects depended on the solvent, with the dioxane and dioxane/acetonitrile mixture produced the best results. The role of freezing and solvent in the improved results is discussed.

Synthesis and characterization of a novel inorganic-organic hybrid material based on polyoxometalates and dicyclohexylcarbodiimide

NASA Astrophysics Data System (ADS)

Huang, Bo; Hu, Xiaokang; Hu, Xunliang; Wang, Nan; Yang, Kang; Xiao, Zicheng; Wu, Pingfan

2017-12-01

Towards design and synthesis of bulky molecules and molecular machines, we reported a new inorganic-organic hybrid material based on polyoxometalates and 1, 3-dicyclohexylcarbodiimide (DCC): (Bu4N)2[V6O13{(OCH2)3CCH2OOCCH2CH2CON(C6H11)CONHC6H11}2]. The hybrid was characterized by FT-IR, 1H NMR, UV-Vis, ESI-MS, and the structure of the compound was determined through single-crystal X-ray diffraction. There was an interesting supramolecular assembly in the hybrid material through intermolecular hydrogen bonding, and each cyclohexyl in the polymer looks like one of blades in the propeller. Furthermore, the thermal stability of the hybrid was tested by TGA analyses, and the electrochemical property has also been studied by cyclic voltammogram.

Background-Oriented Schlieren (BOS) for Scramjet Inlet-isolator Investigation

NASA Astrophysics Data System (ADS)

Che Idris, Azam; Rashdan Saad, Mohd; Hing Lo, Kin; Kontis, Konstantinos

2018-05-01

Background-oriented Schlieren (BOS) technique is a recently invented non-intrusive flow diagnostic method which has yet to be fully explored in its capabilities. In this paper, BOS technique has been applied for investigating the general flow field characteristics inside a generic scramjet inlet-isolator with Mach 5 flow. The difficulty in finding the delicate balance between measurement sensitivity and measurement area image focusing has been demonstrated. The differences between direct cross-correlation (DCC) and Fast Fourier Transform (FFT) raw data processing algorithm have also been demonstrated. As an exploratory study of BOS capability, this paper found that BOS is simple yet robust enough to be used to visualize complex flow in a scramjet inlet in hypersonic flow. However, in this case its quantitative data can be strongly affected by 3-dimensionality thus obscuring the density value with significant errors.

Solid-phase receptor binding assay for /sup 125/I-hCG

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

Bortolussi, M.; Selmin, O.; Colombatti, A.

1987-01-01

A solid-phase radioligand-receptor assay (RRA) to measure the binding of /sup 125/I-labelled human chorionic gonadotropin (/sup 125/I-hCG) to target cell membranes has been developed. The binding of /sup 125/I-hCG to membranes immobilized on the wells of microtitration plates reached a maximum at about 3 hours at 37 degrees C, was saturable, displayed a high affinity (Ka = 2.4 X 10(9) M-1) and was specifically inhibited by unlabelled hCG. In comparison with RRAs carried out with membranes in suspension, the solid-phase RRA is significantly simpler and much faster to perform as it avoids centrifugation or filtration procedures. The solid-phase RRA wasmore » adapted profitably to process large numbers of samples at the same time. It proved particularly useful as a screening assay to detect anti-hCG monoclonal antibodies with high inhibitory activity for binding of /sup 125/I-hCG to its receptors.« less

X-RAY MICROSCOPY AND SPECTROSCOPY STUDIES ON METAL BINDING IN BIOSOLIDS

EPA Science Inventory

Sorption/desorption data from intact and different fractions of biosolids and biosolids-amended soils indicated the importance of Fe and Mn fractions on both sorption and desorption of metals in biosolids and biosolids-amended soils. Extraction procedures used to separate organi...

X-RAY MICROSCOPY AND SPECTROSCOPY STUDIES ON METAL BINDING IN BIOSOLIDS (ABSTRACT)

EPA Science Inventory

Sorption/desorption data from intact and different fractions of biosolids and biosolids-amended soils indicated the importance of Fe and Mn fractions on both sorption and desorption of metals in biosolids and biosolids-amended soils. Extraction procedures used to separate organi...

76 FR 60503 - Guidance for Industry on Target Animal Safety and Effectiveness Protocol Development and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... regarding how and when data collection forms and standard operating procedures should be included with the... topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or...

Book Repair Manual.

ERIC Educational Resources Information Center

Milevski, Robert J.

1995-01-01

This book repair manual developed for the Illinois Cooperative Conservation Program includes book structure and book problems, book repair procedures for 4 specific problems, a description of adhesive bindings, a glossary, an annotated list of 11 additional readings, book repair supplies and suppliers, and specifications for book repair kits. (LRW)

Untangling the Diverse Interior and Multiple Exterior Guest Interactions of a Supramolecular Host by the Simultaneous Analysis of Complementary Observables.

PubMed

Sgarlata, Carmelo; Raymond, Kenneth N

2016-07-05

The entropic and enthalpic driving forces for encapsulation versus sequential exterior guest binding to the [Ga4L6](12-) supramolecular host in solution are very different, which significantly complicates the determination of these thermodynamic parameters. The simultaneous use of complementary techniques, such as NMR, UV-vis, and isothermal titration calorimetry, enables the disentanglement of such multiple host-guest interactions. Indeed, data collected by each technique measure different components of the host-guest equilibria and together provide a complete picture of the solution thermodynamics. Unfortunately, commercially available programs do not allow for global analysis of different physical observables. We thus resorted to a novel procedure for the simultaneous refinement of multiple parameters (ΔG°, ΔH°, and ΔS°) by treating different observables through a weighted nonlinear least-squares analysis of a constrained model. The refinement procedure is discussed for the multiple binding of the Et4N(+) guest, but it is broadly applicable to the deconvolution of other intricate host-guest equilibria.

Attention to Attributes and Objects in Working Memory

PubMed Central

Cowan, Nelson; Blume, Christopher L.; Saults, J. Scott

2013-01-01

It has been debated on the basis of change-detection procedures whether visual working memory is limited by the number of objects, task-relevant attributes within those objects, or bindings between attributes. This debate, however, has been hampered by several limitations, including the use of conditions that vary between studies and the absence of appropriate mathematical models to estimate the number of items in working memory in different stimulus conditions. We re-examined working memory limits in two experiments with a wide array of conditions involving color and shape attributes, relying on a set of new models to fit various stimulus situations. In Experiment 2, a new procedure allowed identical retrieval conditions across different conditions of attention at encoding. The results show that multiple attributes compete for attention, but that retaining the binding between attributes is accomplished only by retaining the attributes themselves. We propose a theoretical account in which a fixed object capacity limit contains within it the possibility of the incomplete retention of object attributes, depending on the direction of attention. PMID:22905929

A new graphic plot analysis for determination of neuroreceptor binding in positron emission tomography studies.

PubMed

Ito, Hiroshi; Yokoi, Takashi; Ikoma, Yoko; Shidahara, Miho; Seki, Chie; Naganawa, Mika; Takahashi, Hidehiko; Takano, Harumasa; Kimura, Yuichi; Ichise, Masanori; Suhara, Tetsuya

2010-01-01

In positron emission tomography (PET) studies with radioligands for neuroreceptors, tracer kinetics have been described by the standard two-tissue compartment model that includes the compartments of nondisplaceable binding and specific binding to receptors. In the present study, we have developed a new graphic plot analysis to determine the total distribution volume (V(T)) and nondisplaceable distribution volume (V(ND)) independently, and therefore the binding potential (BP(ND)). In this plot, Y(t) is the ratio of brain tissue activity to time-integrated arterial input function, and X(t) is the ratio of time-integrated brain tissue activity to time-integrated arterial input function. The x-intercept of linear regression of the plots for early phase represents V(ND), and the x-intercept of linear regression of the plots for delayed phase after the equilibrium time represents V(T). BP(ND) can be calculated by BP(ND)=V(T)/V(ND)-1. Dynamic PET scanning with measurement of arterial input function was performed on six healthy men after intravenous rapid bolus injection of [(11)C]FLB457. The plot yielded a curve in regions with specific binding while it yielded a straight line through all plot data in regions with no specific binding. V(ND), V(T), and BP(ND) values calculated by the present method were in good agreement with those by conventional non-linear least-squares fitting procedure. This method can be used to distinguish graphically whether the radioligand binding includes specific binding or not.

Effects of flow changes on radiotracer binding: Simultaneous measurement of neuroreceptor binding and cerebral blood flow modulation.

PubMed

Sander, Christin Y; Mandeville, Joseph B; Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M; Rosen, Bruce R

2017-01-01

The potential effects of changes in blood flow on the delivery and washout of radiotracers has been an ongoing question in PET bolus injection studies. This study provides practical insight into this topic by experimentally measuring cerebral blood flow (CBF) and neuroreceptor binding using simultaneous PET/MRI. Hypercapnic challenges (7% CO 2 ) were administered to non-human primates in order to induce controlled increases in CBF, measured with pseudo-continuous arterial spin labeling. Simultaneously, dopamine D 2 /D 3 receptor binding of [ 11 C]raclopride or [ 18 F]fallypride was monitored with dynamic PET. Experiments showed that neither time activity curves nor quantification of binding through binding potentials ( BP ND ) were measurably affected by CBF increases, which were larger than two-fold. Simulations of experimental procedures showed that even large changes in CBF should have little effect on the time activity curves of radiotracers, given a set of realistic assumptions. The proposed method can be applied to experimentally assess the flow sensitivity of other radiotracers. Results demonstrate that CBF changes, which often occur due to behavioral tasks or pharmacological challenges, do not affect PET [ 11 C]raclopride or [ 18 F]fallypride binding studies and their quantification. The results from this study suggest flow effects may have limited impact on many PET neuroreceptor tracers with similar properties.

Prediction of small molecule binding property of protein domains with Bayesian classifiers based on Markov chains.

PubMed

Bulashevska, Alla; Stein, Martin; Jackson, David; Eils, Roland

2009-12-01

Accurate computational methods that can help to predict biological function of a protein from its sequence are of great interest to research biologists and pharmaceutical companies. One approach to assume the function of proteins is to predict the interactions between proteins and other molecules. In this work, we propose a machine learning method that uses a primary sequence of a domain to predict its propensity for interaction with small molecules. By curating the Pfam database with respect to the small molecule binding ability of its component domains, we have constructed a dataset of small molecule binding and non-binding domains. This dataset was then used as training set to learn a Bayesian classifier, which should distinguish members of each class. The domain sequences of both classes are modelled with Markov chains. In a Jack-knife test, our classification procedure achieved the predictive accuracies of 77.2% and 66.7% for binding and non-binding classes respectively. We demonstrate the applicability of our classifier by using it to identify previously unknown small molecule binding domains. Our predictions are available as supplementary material and can provide very useful information to drug discovery specialists. Given the ubiquitous and essential role small molecules play in biological processes, our method is important for identifying pharmaceutically relevant components of complete proteomes. The software is available from the author upon request.

Volatile anesthetic binding to proteins is influenced by solvent and aliphatic residues.

PubMed

Streiff, John H; Jones, Keith A

2008-10-01

The main objective of this work was to characterize VA binding sites in multiple anesthetic target proteins. A computational algorithm was used to quantify the solvent exclusion and aliphatic character of amphiphilic pockets in the structures of VA binding proteins. VA binding sites in the protein structures were defined as the pockets with solvent exclusion and aliphatic character that exceeded minimum values observed in the VA binding sites of serum albumin, firefly luciferase, and apoferritin. We found that the structures of VA binding proteins are enriched in these pockets and that the predicted binding sites were consistent with experimental determined binding locations in several proteins. Autodock3 was used to dock the simulated molecules of 1,1,1,2,2-pentafluoroethane, difluoromethyl 1,1,1,2-tetrafluoroethyl ether, and sevoflurane and the isomers of halothane and isoflurane into these potential binding sites. We found that the binding of the various VA molecules to the amphiphilic pockets is driven primarily by VDW interactions and to a lesser extent by weak hydrogen bonding and electrostatic interactions. In addition, the trend in Delta G binding values follows the Meyer-Overton rule. These results suggest that VA potencies are related to the VDW interactions between the VA ligand and protein target. It is likely that VA bind to sites with a high degree of solvent exclusion and aliphatic character because aliphatic residues provide favorable VDW contacts and weak hydrogen bond donors. Water molecules occupying these sites maintain pocket integrity, associate with the VA ligand, and diminish the unfavorable solvation enthalpy of the VA. Water molecules displaced into the bulk by the VA ligand may provide an additional favorable enthalpic contribution to VA binding. Anesthesia is a component of many health related procedures, the outcomes of which could be improved with a better understanding of the molecular targets and mechanisms of anesthetic action.

[3H]aniracetam binds to specific recognition sites in brain membranes.

PubMed

Fallarino, F; Genazzani, A A; Silla, S; L'Episcopo, M R; Camici, O; Corazzi, L; Nicoletti, F; Fioretti, M C

1995-08-01

[3H]Aniracetam bound to specific and saturable recognition sites in membranes prepared from discrete regions of rat brain. In crude membrane preparation from rat cerebral cortex, specific binding was Na+ independent, was still largely detectable at low temperature (4 degrees C), and underwent rapid dissociation. Scatchard analysis of [3H]aniracetam binding revealed a single population of sites with an apparent KD value of approximately 70 nM and a maximal density of 3.5 pmol/mg of protein. Specifically bound [3H]aniracetam was not displaced by various metabolites of aniracetam, nor by other pyrrolidinone-containing nootropic drugs such as piracetam or oxiracetam. Subcellular distribution studies showed that a high percentage of specific [3H]aniracetam binding was present in purified synaptosomes or mitochondria, whereas specific binding was low in the myelin fraction. The possibility that at least some [3H]aniracetam binding sites are associated with glutamate receptors is supported by the evidence that specific binding was abolished when membranes were preincubated at 37 degrees C under fast shaking (a procedure that substantially reduced the amount of glutamate trapped in the membranes) and could be restored after addition of either glutamate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) but not kainate. The action of AMPA was antagonized by DNQX, which also reduced specific [3H]aniracetam binding in unwashed membranes. High levels of [3H]aniracetam binding were detected in hippocampal, cortical, or cerebellar membranes, which contain a high density of excitatory amino acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Theoretical kinetic studies of models for binding myosin subfragment-1 to regulated actin: Hill model versus Geeves model.

PubMed Central

Chen , Y; Yan, B; Chalovich, J M; Brenner, B

2001-01-01

It was previously shown that a one-dimensional Ising model could successfully simulate the equilibrium binding of myosin S1 to regulated actin filaments (T. L. Hill, E. Eisenberg and L. Greene, Proc. Natl. Acad. Sci. U.S.A. 77:3186-3190, 1980). However, the time course of myosin S1 binding to regulated actin was thought to be incompatible with this model, and a three-state model was subsequently developed (D. F. McKillop and M. A. Geeves, Biophys. J. 65:693-701, 1993). A quantitative analysis of the predicted time course of myosin S1 binding to regulated actin, however, was never done for either model. Here we present the procedure for the theoretical evaluation of the time course of myosin S1 binding for both models and then show that 1) the Hill model can predict the "lag" in the binding of myosin S1 to regulated actin that is observed in the absence of Ca++ when S1 is in excess of actin, and 2) both models generate very similar families of binding curves when [S1]/[actin] is varied. This result shows that, just based on the equilibrium and pre-steady-state kinetic binding data alone, it is not possible to differentiate between the two models. Thus, the model of Hill et al. cannot be ruled out on the basis of existing pre-steady-state and equilibrium binding data. Physical mechanisms underlying the generation of the lag in the Hill model are discussed. PMID:11325734

Guiding plant virus particles to integrin-displaying cells

NASA Astrophysics Data System (ADS)

Hovlid, Marisa L.; Steinmetz, Nicole F.; Laufer, Burkhardt; Lau, Jolene L.; Kuzelka, Jane; Wang, Qian; Hyypiä, Timo; Nemerow, Glen R.; Kessler, Horst; Manchester, Marianne; Finn, M. G.

2012-05-01

Viral nanoparticles (VNPs) are structurally regular, highly stable, tunable nanomaterials that can be conveniently produced in high yields. Unmodified VNPs from plants and bacteria generally do not show tissue specificity or high selectivity in binding to or entry into mammalian cells. They are, however, malleable by both genetic and chemical means, making them useful scaffolds for the display of large numbers of cell- and tissue-targeting ligands, imaging moieties, and/or therapeutic agents in a well-defined manner. Capitalizing on this attribute, we modified the genetic sequence of the Cowpea mosaic virus (CPMV) coat protein to display an RGD oligopeptide sequence derived from human adenovirus type 2 (HAdV-2). Concurrently, wild-type CPMV was modified via NHS acylation and Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to attach an integrin-binding cyclic RGD peptide. Both types of particles showed strong and selective affinity for several different cancer cell lines that express RGD-binding integrin receptors.Viral nanoparticles (VNPs) are structurally regular, highly stable, tunable nanomaterials that can be conveniently produced in high yields. Unmodified VNPs from plants and bacteria generally do not show tissue specificity or high selectivity in binding to or entry into mammalian cells. They are, however, malleable by both genetic and chemical means, making them useful scaffolds for the display of large numbers of cell- and tissue-targeting ligands, imaging moieties, and/or therapeutic agents in a well-defined manner. Capitalizing on this attribute, we modified the genetic sequence of the Cowpea mosaic virus (CPMV) coat protein to display an RGD oligopeptide sequence derived from human adenovirus type 2 (HAdV-2). Concurrently, wild-type CPMV was modified via NHS acylation and Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to attach an integrin-binding cyclic RGD peptide. Both types of particles showed strong and selective affinity for several different cancer cell lines that express RGD-binding integrin receptors. Electronic supplementary information (ESI) available: Synthetic procedures and compound characterization data; assay procedures; additional confocal micrographs at different time points. See DOI: 10.1039/c2nr30571b

Determination of blood concentrations of main active compounds in Zi-Cao-Cheng-Qi decoction and their total plasma protein binding rates based on hollow fiber liquid phase microextraction coupled with high performance liquid chromatography.

PubMed

Li, Miaomiao; Chen, Xuan; Hu, Shuang; Wang, Runqin; Peng, Xiaoli; Bai, Xiaohong

2018-01-01

Oil-in-salt hollow fiber liquid phase microextraction coupled with high performance liquid chromatography ultraviolet detection (HPLC-UV) was developed for determination of the blood concentrations of the main active compounds, hesperidin, honokiol, shikonin, magnolol, emodin and β,β'-dimethylacrylshikonin, after oral administration of Zi-Cao-Cheng-Qi decoction (ZCCQD) and their total plasma protein binding rates. In the procedure, a hollow fiber segment was immersed in organic solvent to fill the solvent in the fiber lumen and wall pore, and then the fiber was immersed into sodium chloride solution to cover a thin salt membrane on the fiber wall pore filling organic solvent. Various factors affecting the procedure, such as extraction solvent, sample phase pH, stirring rate, extraction time, NaCl concentration and fiber immersion time in the NaCl solution, were optimized. Under the optimum conditions, good linearities (r 2 ≥0.9905), low limits of detection (0.7-2.5ng/mL) or quantitation (1.2-12ng/mL), satisfactory precision (2.6%-12.8%) and accuracy (81.0%-114.2%) of this method, were observed. The results showed that, after oral administration of a 25g/kg dose, (1) the blood concentrations (at 0.5h) of hesperidin, honokiol, shikonin, magnolol, emodin and β,β'-dimethylacrylshikonin were 0.45, 0.40, 0.48, 0.74, 0.11 and 1.11μg/mL, respectively; (2) the total plasma protein binding rates of the six active compounds were 42.0% (hesperidin), 71.8% (honokiol), 64.6% (shikonin), 77.7% (magnolol), 75.3% (emodin) and 75.7% (β,β'-dimethylacrylshikonin), respectively. The proposed procedure coupled with HPLC shows obvious advantages, such as low solvent consumption, simple operation, high sensitivity and strong purifying and can be used for the determination of both the blood concentrations and total plasma protein binding rates of active compounds in traditional Chinese medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Studies on the binding behavior of prodigiosin with bovine hemoglobin by multi-spectroscopic techniques

NASA Astrophysics Data System (ADS)

Tang, Jing; Yang, Chao; Zhou, Lin; Ma, Fei; Liu, Shuchao; Wei, Shaohua; Zhou, Jiahong; Zhou, Yanhuai

2012-10-01

In this article, the interaction mechanism of prodigiosin (PG) with bovine hemoglobin (BHb) is studied in detail using various spectroscopic technologies. UV-vis absorption and fluorescence spectra demonstrate the interaction process. The Stern-Volmer plot and the time-resolved fluorescence study suggest the quenching mechanism of fluorescence of BHb by PG is a static quenching procedure, and the hydrophobic interactions play a major role in binding of PG to BHb. Furthermore, synchronous fluorescence studies, Fourier transform infrared (FTIR) and circular dichroism (CD) spectra reveal that the conformation of BHb is changed after conjugation with PG.

Scattering matrix of arbitrary tight-binding Hamiltonians

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

Ramírez, C., E-mail: carlos@ciencias.unam.mx; Medina-Amayo, L.A.

2017-03-15

A novel efficient method to calculate the scattering matrix (SM) of arbitrary tight-binding Hamiltonians is proposed, including cases with multiterminal structures. In particular, the SM of two kinds of fundamental structures is given, which can be used to obtain the SM of bigger systems iteratively. Also, a procedure to obtain the SM of layer-composed periodic leads is described. This method allows renormalization approaches, which permits computations over macroscopic length systems without introducing additional approximations. Finally, the transmission coefficient of a ring-shaped multiterminal system and the transmission function of a square-lattice nanoribbon with a reduced width region are calculated.

Comparison of the interaction between lactoferrin and isomeric drugs

NASA Astrophysics Data System (ADS)

Guo, Ming; Lu, Xiaowang; Wang, Yan; Brodelius, Peter E.

2017-02-01

The binding properties of pentacyclic triterpenoid isomeric drugs, i.e. ursolic acid (UA) and oleanolic acid (OA), to bovine lactoferrin (BLF) have been studied by molecule modeling, fluorescence spectroscopy, UV-visible absorbance spectroscopy and infrared spectroscopy (IR). Molecular docking, performed to reveal the possible binding mode or mechanism, suggested that hydrophobic interaction and hydrogen bonding play important roles to stabilize the complex. The results of spectroscopic measurements showed that the two isomeric drugs both strongly quenched the intrinsic fluorescence of BLF through a static quenching procedure although some differences between UA and OA binding strength and non-radiation energy transfer occurred within the molecules. The number of binding sites was 3.44 and 3.10 for UA and OA, respectively, and the efficiency of Förster energy transfer provided a distance of 0.77 and 1.21 nm for UA and OA, respectively. The conformation transformation of BLF affected by the drugs conformed to the ;all-or-none; pattern. In addition, the changes of the ratios of α-helices, β-sheets and β-turns of BLF during the process of the interaction were obtained. The results of the experiments in combination with the calculations showed that there are two modes of pentacyclic triterpenoid binding to BLF instead of one binding mode only governed by the principle of the lowest bonding energy.

Transport capabilities of environmental Pseudomonads for sulfur compounds

DOE PAGES

Zerbs, Sarah; Korajczyk, Peter J.; Noirot, Philippe H.; ...

2017-01-27

Sulfur is an essential element in plant rhizospheres and microbial activity plays a key role in increasing the biological availability of sulfur in soil environments. To better understand the mechanisms facilitating the exchange of sulfur-containing molecules in soil, we profiled the binding specificities of eight previously uncharacterized ABC transporter solute-binding proteins from plant-associated Pseudomonads. A high-throughput screening procedure indicated eighteen significant organosulfur binding ligands, with at least one high-quality screening hit for each protein target. Calorimetric and spectroscopic methods were used to validate the best ligand assignments and catalog the thermodynamic properties of the protein-ligand interactions. Two novel high-affinity ligandmore » binding activities were identified and quantified in this set of solute binding proteins. Bacteria were cultured in minimal media with screening library components supplied as the sole sulfur sources, demonstrating that these organosulfur compounds can be metabolized and confirming the relevance of ligand assignments. These results expand the set of experimentally validated ligands amenable to transport by this ABC transporter family and demonstrate the complex range of protein-ligand interactions that can be accomplished by solute-binding proteins. As a result, characterizing new nutrient import pathways provides insight into Pseudomonad metabolic capabilities which can be used to further interrogate bacterial survival and participation in soil and rhizosphere communities.« less

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

Zerbs, Sarah; Korajczyk, Peter J.; Noirot, Philippe H.

Sulfur is an essential element in plant rhizospheres and microbial activity plays a key role in increasing the biological availability of sulfur in soil environments. To better understand the mechanisms facilitating the exchange of sulfur-containing molecules in soil, we profiled the binding specificities of eight previously uncharacterized ABC transporter solute-binding proteins from plant-associated Pseudomonads. A high-throughput screening procedure indicated eighteen significant organosulfur binding ligands, with at least one high-quality screening hit for each protein target. Calorimetric and spectroscopic methods were used to validate the best ligand assignments and catalog the thermodynamic properties of the protein-ligand interactions. Two novel high-affinity ligandmore » binding activities were identified and quantified in this set of solute binding proteins. Bacteria were cultured in minimal media with screening library components supplied as the sole sulfur sources, demonstrating that these organosulfur compounds can be metabolized and confirming the relevance of ligand assignments. These results expand the set of experimentally validated ligands amenable to transport by this ABC transporter family and demonstrate the complex range of protein-ligand interactions that can be accomplished by solute-binding proteins. As a result, characterizing new nutrient import pathways provides insight into Pseudomonad metabolic capabilities which can be used to further interrogate bacterial survival and participation in soil and rhizosphere communities.« less

Fast and reliable prediction of domain-peptide binding affinity using coarse-grained structure models.

PubMed

Tian, Feifei; Tan, Rui; Guo, Tailin; Zhou, Peng; Yang, Li

2013-07-01

Domain-peptide recognition and interaction are fundamentally important for eukaryotic signaling and regulatory networks. It is thus essential to quantitatively infer the binding stability and specificity of such interaction based upon large-scale but low-accurate complex structure models which could be readily obtained from sophisticated molecular modeling procedure. In the present study, a new method is described for the fast and reliable prediction of domain-peptide binding affinity with coarse-grained structure models. This method is designed to tolerate strong random noises involved in domain-peptide complex structures and uses statistical modeling approach to eliminate systematic bias associated with a group of investigated samples. As a paradigm, this method was employed to model and predict the binding behavior of various peptides to four evolutionarily unrelated peptide-recognition domains (PRDs), i.e. human amph SH3, human nherf PDZ, yeast syh GYF and yeast bmh 14-3-3, and moreover, we explored the molecular mechanism and biological implication underlying the binding of cognate and noncognate peptide ligands to their domain receptors. It is expected that the newly proposed method could be further used to perform genome-wide inference of domain-peptide binding at three-dimensional structure level. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A

PubMed Central

Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate

2015-01-01

A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5’-end including the 5’-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer. PMID:26221730

In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A.

PubMed

Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate

2015-01-01

A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5'-end including the 5'-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer.

New approaches for the reliable in vitro assessment of binding affinity based on high-resolution real-time data acquisition of radioligand-receptor binding kinetics.

PubMed

Zeilinger, Markus; Pichler, Florian; Nics, Lukas; Wadsak, Wolfgang; Spreitzer, Helmut; Hacker, Marcus; Mitterhauser, Markus

2017-12-01

Resolving the kinetic mechanisms of biomolecular interactions have become increasingly important in early-phase drug development. Since traditional in vitro methods belong to dose-dependent assessments, binding kinetics is usually overlooked. The present study aimed at the establishment of two novel experimental approaches for the assessment of binding affinity of both, radiolabelled and non-labelled compounds targeting the A 3 R, based on high-resolution real-time data acquisition of radioligand-receptor binding kinetics. A novel time-resolved competition assay was developed and applied to determine the K i of eight different A 3 R antagonists, using CHO-K1 cells stably expressing the hA 3 R. In addition, a new kinetic real-time cell-binding approach was established to quantify the rate constants k on and k off , as well as the dedicated K d of the A 3 R agonist [ 125 I]-AB-MECA. Furthermore, lipophilicity measurements were conducted to control influences due to physicochemical properties of the used compounds. Two novel real-time cell-binding approaches were successfully developed and established. Both experimental procedures were found to visualize the kinetic binding characteristics with high spatial and temporal resolution, resulting in reliable affinity values, which are in good agreement with values previously reported with traditional methods. Taking into account the lipophilicity of the A 3 R antagonists, no influences on the experimental performance and the resulting affinity were investigated. Both kinetic binding approaches comprise tracer administration and subsequent binding to living cells, expressing the dedicated target protein. Therefore, the experiments resemble better the true in vivo physiological conditions and provide important markers of cellular feedback and biological response.

High-affinity binding of (/sup 3/H)estradiol-17 beta by an estrogen receptor in the liver of the turtle

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

Ho, S.M.; Fehrer, S.; Yu, M.

1988-06-01

Specific (3H)estradiol-17 beta ((3H)E2) binding activity (EBA) with characteristics of an estrogen receptor (ER) was demonstrated in cytosols and nuclear extracts of the female turtle, Chrysemys picta. Three different receptor assays (dextran-coated charcoal assay, hydroxylapatite batch procedure, and DNA-cellulose chromatography) were evaluated in terms of their applicability in analyzing large numbers of samples. For the measurement of cytosolic EBA, the hydroxylapatite batch procedure was found to be the most reliable assay. On the other hand, the dextran-coated charcoal assay was found to be the most appropriate method for the measurement of nuclear EBA. Turtle hepatic EBA binds (3H)E2 with highmore » affinity (cytosolic, 17.4 +/- 2.8 X 10(9) M-1; nuclear, 17.7 +/- 1.9 X 10(9) M-1), limited capacity (cytosolic, 133.7 +/- 4.6 fmol/g tissue; nuclear, 81.1 +/- 9.0 fmol/g tissue), and strict steroid specificity. The EBA bound natural estrogens (E2, estrone, estriol) as well as the nonsteroidal estrogen, diethylstilbestrol, but exhibited little affinity for androgens, progesterone, or corticosterone. The turtle hepatic EBA resembled mammalian and avian ERs in terms of binding characteristics; however, unlike mammalian and avian ERs it was shown to be heat-labile. Incubation at 30 degrees caused rapid loss of (3H)E2 binding activity in both cytosolic and nuclear fractions. The exchange between (3H)E2 and the endogenously bound estrogen was slow at 4 and 15 degrees, but the exchange process was facilitated in the presence of the chaotropic salt, NaSCN. Establishment of quantitation methods for both cytosolic and nuclear forms of EBA will enable future investigation of the mechanism and regulation of estrogen action in the liver of this turtle species.« less

Structured programming: Principles, notation, procedure

NASA Technical Reports Server (NTRS)

JOST

1978-01-01

Structured programs are best represented using a notation which gives a clear representation of the block encapsulation. In this report, a set of symbols which can be used until binding directives are republished is suggested. Structured programming also allows a new method of procedure for design and testing. Programs can be designed top down, that is, they can start at the highest program plane and can penetrate to the lowest plane by step-wise refinements. The testing methodology also is adapted to this procedure. First, the highest program plane is tested, and the programs which are not yet finished in the next lower plane are represented by so-called dummies. They are gradually replaced by the real programs.

49 CFR 1108.9 - Decisions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... TRANSPORTATION RULES OF PRACTICE ARBITRATION OF CERTAIN DISPUTES SUBJECT TO THE STATUTORY JURISDICTION OF THE... procedures, each party agrees that the decision and award of the Arbitrator shall be binding and judicially enforceable in law and equity in any court of appropriate jurisdiction, subject to a limited right of appeal...

Mathematical simulations for bioanalytical assay development: the (un-)necessity and (im-)possibility of free drug quantification.

PubMed

Staack, Roland F; Jordan, Gregor; Heinrich, Julia

2012-02-01

For every drug development program it needs to be discussed whether discrimination between free and total drug concentrations is required to accurately describe its pharmacokinetic behavior. This perspective describes the application of mathematical simulation approaches to guide this initial decision based on available knowledge about target biology, binding kinetics and expected drug concentrations. We provide generic calculations that can be used to estimate the necessity of free drug quantification for different drug molecules. In addition, mathematical approaches are used to simulate various assay conditions in bioanalytical ligand-binding assays: it is demonstrated that due to the noncovalent interaction between the binding partners and typical assay-related interferences in the equilibrium, a correct quantification of the free drug concentration is highly challenging and requires careful design of different assay procedure steps.

Steady-state kinetics of substrate binding and iron release in tomato ACC oxidase.

PubMed

Thrower, J S; Blalock, R; Klinman, J P

2001-08-14

1-Aminocyclopropane-1-carboxylate oxidase (ACC oxidase) catalyzes the last step in the biosynthetic pathway of the plant hormone, ethylene. This unusual reaction results in the oxidative ring cleavage of 1-aminocyclopropane carboxylate (ACC) into ethylene, cyanide, and CO2 and requires ferrous ion, ascorbate, and molecular oxygen for catalysis. A new purification procedure and assay method have been developed for tomato ACC oxidase that result in greatly increased enzymatic activity. This method allowed us to determine the rate of iron release from the enzyme and the effect of the activator, CO2, on this rate. Initial velocity studies support an ordered kinetic mechanism where ACC binds first followed by O2; ascorbate can bind after O2 or possibly before ACC. This kinetic mechanism differs from one recently proposed for the ACC oxidase from avocado.

Comprehensive comparative analysis and identification of RNA-binding protein domains: multi-class classification and feature selection.

PubMed

Jahandideh, Samad; Srinivasasainagendra, Vinodh; Zhi, Degui

2012-11-07

RNA-protein interaction plays an important role in various cellular processes, such as protein synthesis, gene regulation, post-transcriptional gene regulation, alternative splicing, and infections by RNA viruses. In this study, using Gene Ontology Annotated (GOA) and Structural Classification of Proteins (SCOP) databases an automatic procedure was designed to capture structurally solved RNA-binding protein domains in different subclasses. Subsequently, we applied tuned multi-class SVM (TMCSVM), Random Forest (RF), and multi-class ℓ1/ℓq-regularized logistic regression (MCRLR) for analysis and classifying RNA-binding protein domains based on a comprehensive set of sequence and structural features. In this study, we compared prediction accuracy of three different state-of-the-art predictor methods. From our results, TMCSVM outperforms the other methods and suggests the potential of TMCSVM as a useful tool for facilitating the multi-class prediction of RNA-binding protein domains. On the other hand, MCRLR by elucidating importance of features for their contribution in predictive accuracy of RNA-binding protein domains subclasses, helps us to provide some biological insights into the roles of sequences and structures in protein-RNA interactions.

A six-year longitudinal PET study of (+)-[11C]DTBZ binding to the VMAT2 in monkey brain.

PubMed

Kilbourn, Michael R; Koeppe, Robert A

2017-12-01

The longitudinal reproducibility of in vivo binding potential measures for [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ) binding to the vesicular monoamine transporter 2 (VMAT2) site in primate brain was examined using a unique dataset of repeated control PET imaging studies. Forty-one dynamic [ 11 C]DTBZ PET studies were completed in a single rhesus monkey. Imaging equipment (microPET P4), personnel, radiotracer characteristics (injected mass amounts, molar activity) and image data analysis (BP ND-Logan ) were consistent throughout the entire sequence of PET studies. Same day reproducibility of BP ND-Logan estimates of specific binding was very good (-3% and -7% changes) for two control-control sessions. Over the full 74 months, the average BP ND-Logan value for [ 11 C]DTBZ-PET studies was 4.19±0.52, for a variance of 12%. No age-dependent change in binding potentials was observed over the six-year period. If the technical variables associated with PET scanner are consistently maintained, including PET scanner, imaging procedures and radiotracer preparation, in vivo biochemistry can be reproducibly measured in the primate brain over a multi-year period of time. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of new composite biosorbents from olive pomace wastes

NASA Astrophysics Data System (ADS)

Pagnanelli, Francesca; Viggi, Carolina Cruz; Toro, Luigi

2010-06-01

In this study olive pomace was used as a source of binding substances for the development of composite biosorbents to be used in heavy metal removal from aqueous solutions. The aim was to obtain biosorbent material with an increased concentration of binding sites. The effects of two different extraction procedures (one using only methanol and the other one hexane followed by methanol) on the binding properties of olive pomace were tested by potentiometric titrations and batch biosorption tests for copper and cadmium removal. Titration modelling evidenced that both kinds of extractions generated a solid with a reduced amount of protonatable sites. Biosorption tests were organized according to full factorial designs. Analysis of variance denoted that both kinds of extractions determined a statistically significant negative effect on metal biosorption. In the case of cadmium extractions also determined a significant decrease of selectivity with respect to olive pomace. When the acid-base and binding properties of the substances extracted were determined, they were adsorbed onto a synthetic resin (octadecylsilane) and calcium alginate beads. In this way two kinds of composite biosorbents have been obtained both having an increased concentration of binding substances with respect to native olive pomace, also working more efficiently in metal removal.

SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity.

PubMed

Kumar, Sunil; Ambrosini, Giovanna; Bucher, Philipp

2017-01-04

SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Peroxisome proliferator-binding protein: identification and partial characterization of nafenopin-, clofibric acid-, and ciprofibrate-binding proteins from rat liver.

PubMed Central

Lalwani, N D; Alvares, K; Reddy, M K; Reddy, M N; Parikh, I; Reddy, J K

1987-01-01

Peroxisome proliferators (PP) induce a highly predictable pleiotropic response in rat and mouse liver that is characterized by hepatomegaly, increase in peroxisome number in hepatocytes, and induction of certain peroxisomal enzymes. The PP-binding protein (PPbP) was purified from rat liver cytosol by a two-step procedure involving affinity chromatography and ion-exchange chromatography. Three PP, nafenopin and its structural analogs clofibric acid and ciprofibrate, were used as affinity ligands and eluting agents. This procedure yields a major protein with an apparent Mr of 70,000 on NaDodSO4/PAGE in the presence of reducing agent and Mr 140,000 (Mr 140,000-160,000) on gel filtration and polyacrylamide gradient gel electrophoresis under nondenaturing conditions, indicating that the active protein is a dimer. This protein has an acidic pI of 4.2 under nondenaturing conditions, which rises to 5.6 under denaturing conditions. The isolation of the same Mr 70,000 protein with three different, but structurally related, agents as affinity ligands and the immunological identity of the isolated proteins constitute strong evidence that this protein is the PPbP capable of recognizing PP that are structurally related to clofibrate. The PPbP probably plays an important role in the regulation of PP-induced pleiotropic response. Images PMID:3474650

Single molecule tracking of Ace1p in Saccharomyces cerevisiae defines a characteristic residence time for non-specific interactions of transcription factors with chromatin

PubMed Central

Ball, David A.; Mehta, Gunjan D.; Salomon-Kent, Ronit; Mazza, Davide; Morisaki, Tatsuya; Mueller, Florian; McNally, James G.; Karpova, Tatiana S.

2016-01-01

In vivo single molecule tracking has recently developed into a powerful technique for measuring and understanding the transient interactions of transcription factors (TF) with their chromatin response elements. However, this method still lacks a solid foundation for distinguishing between specific and non-specific interactions. To address this issue, we took advantage of the power of molecular genetics of yeast. Yeast TF Ace1p has only five specific sites in the genome and thus serves as a benchmark to distinguish specific from non-specific binding. Here, we show that the estimated residence time of the short-residence molecules is essentially the same for Hht1p, Ace1p and Hsf1p, equaling 0.12–0.32 s. These three DNA-binding proteins are very different in their structure, function and intracellular concentration. This suggests that (i) short-residence molecules are bound to DNA non-specifically, and (ii) that non-specific binding shares common characteristics between vastly different DNA-bound proteins and thus may have a common underlying mechanism. We develop new and robust procedure for evaluation of adverse effects of labeling, and new quantitative analysis procedures that significantly improve residence time measurements by accounting for fluorophore blinking. Our results provide a framework for the reliable performance and analysis of single molecule TF experiments in yeast. PMID:27566148

Effective Identification of Akt Interacting Proteins by Two-Step Chemical Crosslinking, Co-Immunoprecipitation and Mass Spectrometry

PubMed Central

Huang, Bill X.; Kim, Hee-Yong

2013-01-01

Akt is a critical protein for cell survival and known to interact with various proteins. However, Akt binding partners that modulate or regulate Akt activation have not been fully elucidated. Identification of Akt-interacting proteins has been customarily achieved by co-immunoprecipitation combined with western blot and/or MS analysis. An intrinsic problem of the method is loss of interacting proteins during procedures to remove non-specific proteins. Moreover, antibody contamination often interferes with the detection of less abundant proteins. Here, we developed a novel two-step chemical crosslinking strategy to overcome these problems which resulted in a dramatic improvement in identifying Akt interacting partners. Akt antibody was first immobilized on protein A/G beads using disuccinimidyl suberate and allowed to bind to cellular Akt along with its interacting proteins. Subsequently, dithiobis[succinimidylpropionate], a cleavable crosslinker, was introduced to produce stable complexes between Akt and binding partners prior to the SDS-PAGE and nanoLC-MS/MS analysis. This approach enabled identification of ten Akt partners from cell lysates containing as low as 1.5 mg proteins, including two new potential Akt interacting partners. None of these but one protein was detectable without crosslinking procedures. The present method provides a sensitive and effective tool to probe Akt-interacting proteins. This strategy should also prove useful for other protein interactions, particularly those involving less abundant or weakly associating partners. PMID:23613850

Characterization of a Cadmium-Binding Complex of Cabbage Leaves 1

PubMed Central

Wagner, George J.

1984-01-01

The chemical nature of a principal, inducible cadmium-binding complex which accumulates in cabbage leaves (Wagner and Trotter 1982 Plant Physiol 69: 804-809) was studied and compared with that of animal metallothionein and copper-binding proteins isolated from various organisms. The apparent molecular weight of native cabbage complex and carboxymethylated ligand of the complex under native conditions as determined by gel filtration was about 10,000 daltons. Under denaturing conditions their apparent molecular weights were about 2000 daltons. Ligand of native complex contained 37, 28, and 9 residue per cent of glutamic acid-glutamine, cysteine, and glycine, respectively, and low aromatic residue, serine and lysine content. The high acidic and low hydrophobic residue content explain the behavior of complex on electrophoresis in the presence and absence of sodium dodecyl sulfate. Its isoelectric point was below 4.0 and it bound 4 to 6 moles cadmium per mole ligand in what appear to be cadmium-mercaptide chromophores. The complex was found to be heat stable, relatively protease insensitive, and lacking in disulfide bonds. Attempts to determine the primary sequence of reduced native complex and carboxymethylated, cleaved ligand using the Edman degradation procedure were unsuccessful. An electrophoretic procedure is described for preparative isolation of purified complex and a method is described for monitoring ligand of complex as its fluorescent dibromobimane adduct. Images Fig. 1 Fig. 3 PMID:16663927

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

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use inmore » combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.« less

Fluorogenic Substrate Detection of Viable Intracellular and Extracellular Pathogenic Protozoa

NASA Astrophysics Data System (ADS)

Jackson, Peter R.; Pappas, Michael G.; Hansen, Brian D.

1985-01-01

Viable Leishmania promastigotes and amastigotes were detected by epifluorescence microscopy with fluorescein diacetate being used to mark living parasites and the nucleic acid-binding compound ethidium bromide to stain dead cells. This procedure is superior to other assays because it is faster and detects viable intracellular as well as extracellular Leishmania. Furthermore, destruction of intracellular pathogens by macrophages is more accurately determined with fluorescein diacetate than with other stains. The procedure may have applications in programs to develop drugs and vaccines against protozoa responsible for human and animal disease.

A generic HTS assay for kinase screening: Validation for the isolation of an engineered malate kinase

PubMed Central

Irague, Romain; Topham, Christopher M.; Martineau, Nelly; Baylac, Audrey; Auriol, Clément; Walther, Thomas; François, Jean-Marie; Remaud-Siméon, Magali

2018-01-01

An end-point ADP/NAD+ acid/alkali assay procedure, directly applicable to library screening of any type of ATP-utilising/ADP producing enzyme activity, was implemented. Typically, ADP production is coupled to NAD+ co-enzyme formation by the conventional addition of pyruvate kinase and lactate dehydrogenase. Transformation of enzymatically generated NAD+ into a photometrically active alkali derivative product is then achieved through the successive application of acidic/alkali treatment steps. The assay was successfully miniaturized to search for malate kinase activity in a structurally-guided library of LysC aspartate kinase variants comprising 6,700 clones. The screening procedure enabled the isolation of nine positive variants showing novel kinase activity on (L)-malate, the best mutant, LysC V115A:E119S:E434V exhibited strong substrate selectivity for (L)-malate compared to (L)-aspartate with a (kcat/Km)malate/(kcat/Km)aspartate ratio of 86. Double mutants V115A:E119S, V115A:E119C and E119S:E434V were constructed to further probe the origins of stabilising substrate binding energy gains for (L)-malate due to mutation. The introduction of less sterically hindering side-chains in engineered enzymes carrying E119S and V115A mutations increases the effective volume available for substrate binding in the catalytic pocket. Improved binding of the (L)-malate substrate may be assisted by less hindered movement of the Phe184 aromatic side-chain. Additional favourable long-range electostatic effects on binding arising from the E434V surface mutation are conditionally dependent upon the presence of the V115A mutation close to Phe184 in the active-site. PMID:29462203

An Automated Strategy for Binding-Pose Selection and Docking Assessment in Structure-Based Drug Design.

PubMed

Ballante, Flavio; Marshall, Garland R

2016-01-25

Molecular docking is a widely used technique in drug design to predict the binding pose of a candidate compound in a defined therapeutic target. Numerous docking protocols are available, each characterized by different search methods and scoring functions, thus providing variable predictive capability on a same ligand-protein system. To validate a docking protocol, it is necessary to determine a priori the ability to reproduce the experimental binding pose (i.e., by determining the docking accuracy (DA)) in order to select the most appropriate docking procedure and thus estimate the rate of success in docking novel compounds. As common docking programs use generally different root-mean-square deviation (RMSD) formulas, scoring functions, and format results, it is both difficult and time-consuming to consistently determine and compare their predictive capabilities in order to identify the best protocol to use for the target of interest and to extrapolate the binding poses (i.e., best-docked (BD), best-cluster (BC), and best-fit (BF) poses) when applying a given docking program over thousands/millions of molecules during virtual screening. To reduce this difficulty, two new procedures called Clusterizer and DockAccessor have been developed and implemented for use with some common and "free-for-academics" programs such as AutoDock4, AutoDock4(Zn), AutoDock Vina, DOCK, MpSDockZn, PLANTS, and Surflex-Dock to automatically extrapolate BD, BC, and BF poses as well as to perform consistent cluster and DA analyses. Clusterizer and DockAccessor (code available over the Internet) represent two novel tools to collect computationally determined poses and detect the most predictive docking approach. Herein an application to human lysine deacetylase (hKDAC) inhibitors is illustrated.

Improved Silica-Guanidiniumthiocyanate DNA Isolation Procedure Based on Selective Binding of Bovine Alpha-Casein to Silica Particles

PubMed Central

Boom, René; Sol, Cees; Beld, Marcel; Weel, Jan; Goudsmit, Jaap; Wertheim-van Dillen, Pauline

1999-01-01

DNA purified from clinical cerebrospinal fluid and urine specimens by a silica-guanidiniumthiocyanate procedure frequently contained an inhibitor(s) of DNA-processing enzymes which may have been introduced by the purification procedure itself. Inhibition could be relieved by the use of a novel lysis buffer containing alpha-casein. When the novel lysis buffer was used, alpha-casein was bound by the silica particles in the first step of the procedure and eluted together with DNA in the last step, after which it exerted its beneficial effects for DNA-processing enzymes. In the present study we have compared the novel lysis buffer with the previously described lysis buffer with respect to double-stranded DNA yield (which was nearly 100%) and the performance of DNA-processing enzymes. PMID:9986822

45 CFR 160.546 - ALJ's decision.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false ALJ's decision. 160.546 Section 160.546 Public... GENERAL ADMINISTRATIVE REQUIREMENTS Procedures for Hearings § 160.546 ALJ's decision. (a) The ALJ must... be final and binding on the parties 60 days from the date of service of the ALJ's decision. ...

SW-846 Test Method 4025: Screening for Polychlorinated Dibenzodioxins and Polychlorinated Dibenzofurans (PCDD/PCDFs) by Immunoassay

EPA Pesticide Factsheets

a procedure for the analysis of (PCDDs/PCDFs) in soil at 500 ppt (pg/g) using a simple onestep liquid phase oxidative cleanup or, at mid to low ppt levels, using a two step coupled column cleanup (oxidation and activated carbon binding)

Species Identity of Commercial Stocks of Paramecium in the U.S.

ERIC Educational Resources Information Center

Cole, Thomas A.; And Others

1992-01-01

Describes how paramecium can be identified through the use of DNA-binding fluorescent compounds. The authors used these techniques to test the paramecium stocks from 12 commercial sources. The details of the staining procedures and the results of the commercial tests are presented in this article. (PR)

[35S]-LABELING OF THE SALMONELLA TYPHIMURIUM GLUTATHIONE POOL TO ASSESS GLUTATHIONE-MEDIATED DNA BINDING BY 1,2-DIBROMOETHANE

EPA Science Inventory

Biotransformation of drugs and environmental chemicals to reactive intermediates is often studied with the use of radiolabeled compounds that are synthesized by expensive and technically difficult procedures. In general, glutathione (GSH) conjugation serves as a detoxification m...

The Preservation of Leather Bindings: Background, Organization of a Project, and Procedures.

ERIC Educational Resources Information Center

Brown, Meredith

This manual, intended primarily for use by preservation supervisors, includes a discussion of basic leather preservation techniques, and a description of the entire leather book preservation program at Olin Library, Cornell University. Discussions of work flow, materials, treatment steps, schedulinq, and recruiting student assistants are included.…

The involvement of the sodium-potassium pump in postjunctional supersensitivity of the guinea-pig vas deferens as assessed by [3H]ouabain binding.

PubMed

Wong, S K; Westfall, D P; Fedan, J S; Fleming, W W

1981-10-01

Previous evidence has suggested that postjunctional supersensitivity of the guinea-pig vas deferens results, in part, from partial depolarization of the cell membrane. The depolarization is believed to result from a reduction in the activity of the Na-K pump. Indeed, the Na, K+ -adenosine triphosphatase activity of subcellular fractions from supersensitive vas deferens is reduced. In order to determine whether the biochemical alteration seen in subcellular fractions correlate with Na-K pump sites in intact tissues, we have studied the binding of [3H] ouabain to intact vas deferens. [3H]ouabain binds to membrane sites which have the characteristics expected of Na+, K+ - adenosine triphosphatase. Specific binding was saturable and reversible. Scatchard analysis of ouabain-binding in control tissues yielded a single class of binding sites with a dissociation constant (KD) of 156 +/- 7 nM and a maximum number of binding sites (Bmax) of 558.7 +/- 15.6 fmol/mg wet wt. [3H]Ouabain binding was displaceable by several cardiac glycosides and aglycones, but not by steroid hormones or sodium vanadate. Alteration of concentrations of Na+ and K+ markedly affected ouabain binding. Denervation (with 6-hydroxydopamine), decentralization or reserpine treatment for 1 day, which do not produce supersensitivity, did not alter the Bmax, whereas 5 to 7 days after these procedures, when supersensitivity was present, the Bmax was significantly reduced by 20 to 40%. The KD was not changed by any of the treatments. These data provide additional support for the concept that a reduction in the NaK pump sites contributes to postjunctional supersensitivity.

Automated docking of ligands to an artificial active site: augmenting crystallographic analysis with computer modeling

NASA Astrophysics Data System (ADS)

Rosenfeld, Robin J.; Goodsell, David S.; Musah, Rabi A.; Morris, Garrett M.; Goodin, David B.; Olson, Arthur J.

2003-08-01

The W191G cavity of cytochrome c peroxidase is useful as a model system for introducing small molecule oxidation in an artificially created cavity. A set of small, cyclic, organic cations was previously shown to bind in the buried, solvent-filled pocket created by the W191G mutation. We docked these ligands and a set of non-binders in the W191G cavity using AutoDock 3.0. For the ligands, we compared docking predictions with experimentally determined binding energies and X-ray crystal structure complexes. For the ligands, predicted binding energies differed from measured values by ± 0.8 kcal/mol. For most ligands, the docking simulation clearly predicted a single binding mode that matched the crystallographic binding mode within 1.0 Å RMSD. For 2 ligands, where the docking procedure yielded an ambiguous result, solutions matching the crystallographic result could be obtained by including an additional crystallographically observed water molecule in the protein model. For the remaining 2 ligands, docking indicated multiple binding modes, consistent with the original electron density, suggesting disordered binding of these ligands. Visual inspection of the atomic affinity grid maps used in docking calculations revealed two patches of high affinity for hydrogen bond donating groups. Multiple solutions are predicted as these two sites compete for polar hydrogens in the ligand during the docking simulation. Ligands could be distinguished, to some extent, from non-binders using a combination of two trends: predicted binding energy and level of clustering. In summary, AutoDock 3.0 appears to be useful in predicting key structural and energetic features of ligand binding in the W191G cavity.

Seeking potential anticonvulsant agents that target GABAA receptors using experimental and theoretical procedures

NASA Astrophysics Data System (ADS)

Saavedra-Vélez, Margarita Virginia; Correa-Basurto, José; Matus, Myrna H.; Gasca-Pérez, Eloy; Bello, Martiniano; Cuevas-Hernández, Roberto; García-Rodríguez, Rosa Virginia; Trujillo-Ferrara, José; Ramos-Morales, Fernando Rafael

2014-12-01

The aim of this study was to identify compounds that possess anticonvulsant activity by using a pentylenetetrazol (PTZ)-induced seizure model. Theoretical studies of a set of ligands, explored the binding affinities of the ligands for the GABAA receptor (GABAAR), including some benzodiazepines. The ligands satisfy the Lipinski rules and contain a pharmacophore core that has been previously reported to be a GABAAR activator. To select the ligands with the best physicochemical properties, all of the compounds were analyzed by quantum mechanics and the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital were determined. Docking calculations between the ligands and the GABAAR were used to identify the complexes with the highest Gibbs binding energies. The identified compound D1 (dibenzo( b,f)(1,4)diazocine-6,11(5H,12H)-dione) was synthesized, experimentally tested, and the GABAAR-D1 complex was submitted to 12-ns-long molecular dynamics (MD) simulations to corroborate the binding conformation obtained by docking techniques. MD simulations were also used to analyze the decomposition of the Gibbs binding energy of the residues involved in the stabilization of the complex. To validate our theoretical results, molecular docking and MD simulations were also performed for three reference compounds that are currently in commercial use: clonazepam (CLZ), zolpidem and eszopiclone. The theoretical results show that the GABAAR-D1, and GABAAR-CLZ complexes bind to the benzodiazepine binding site, share a similar map of binding residues, and have similar Gibbs binding energies and entropic components. Experimental studies using a PTZ-induced seizure model showed that D1 possesses similar activity to CLZ, which corroborates the predicted binding free energy identified by theoretical calculations.

The feasibility of an efficient drug design method with high-performance computers.

PubMed

Yamashita, Takefumi; Ueda, Akihiko; Mitsui, Takashi; Tomonaga, Atsushi; Matsumoto, Shunji; Kodama, Tatsuhiko; Fujitani, Hideaki

2015-01-01

In this study, we propose a supercomputer-assisted drug design approach involving all-atom molecular dynamics (MD)-based binding free energy prediction after the traditional design/selection step. Because this prediction is more accurate than the empirical binding affinity scoring of the traditional approach, the compounds selected by the MD-based prediction should be better drug candidates. In this study, we discuss the applicability of the new approach using two examples. Although the MD-based binding free energy prediction has a huge computational cost, it is feasible with the latest 10 petaflop-scale computer. The supercomputer-assisted drug design approach also involves two important feedback procedures: The first feedback is generated from the MD-based binding free energy prediction step to the drug design step. While the experimental feedback usually provides binding affinities of tens of compounds at one time, the supercomputer allows us to simultaneously obtain the binding free energies of hundreds of compounds. Because the number of calculated binding free energies is sufficiently large, the compounds can be classified into different categories whose properties will aid in the design of the next generation of drug candidates. The second feedback, which occurs from the experiments to the MD simulations, is important to validate the simulation parameters. To demonstrate this, we compare the binding free energies calculated with various force fields to the experimental ones. The results indicate that the prediction will not be very successful, if we use an inaccurate force field. By improving/validating such simulation parameters, the next prediction can be made more accurate.

A fast-locking all-digital delay-locked loop for phase/delay generation in an FPGA

NASA Astrophysics Data System (ADS)

Zhujia, Chen; Haigang, Yang; Fei, Liu; Yu, Wang

2011-10-01

A fast-locking all-digital delay-locked loop (ADDLL) is proposed for the DDR SDRAM controller interface in a field programmable gate array (FPGA). The ADDLL performs a 90° phase-shift so that the data strobe (DQS) can enlarge the data valid window in order to minimize skew. In order to further reduce the locking time and to prevent the harmonic locking problem, a time-to-digital converter (TDC) is proposed. A duty cycle corrector (DCC) is also designed in the ADDLL to adjust the output duty cycle to 50%. The ADDLL, implemented in a commercial 0.13 μm CMOS process, occupies a total of 0.017 mm2 of active area. Measurement results show that the ADDLL has an operating frequency range of 75 to 350 MHz and a total delay resolution of 15 ps. The time interval error (TIE) of the proposed circuit is 60.7 ps.

Revisions to US EPA Superfund Risk and Dose Assessment Models and Guidance - 13403

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

Walker, Stuart A.

2013-07-01

The U.S. Environmental Protection Agency (EPA) Superfund program's six Preliminary Remediation Goal (PRG) and Dose Compliance Concentration (DCC) internet based calculators for risk and dose assessment at Superfund sites are being revised to reflect better science, revisions to existing exposure scenarios and new scenarios, and changes to match up more closely with the EPA chemical regional screening level calculator. A revised version of the 1999 guidance document that provides an overview for the Superfund risk assessment process at radioactively contaminated sites, 'Radiation Risk Assessment At CERCLA Sites: Q and A', is being completed that will reflect Superfund recommended guidance andmore » other technical documents issued over the past 13 years. EPA is also issuing a series of fact sheets in the document 'Superfund Radiation Risk Assessment: A Community Tool-kit'. This presentation would go over those changes that are expected to be finished by this spring. (authors)« less

Early dissemination seeds metastasis in breast cancer

PubMed Central

Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

2016-01-01

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

The time-varying correlation between policy uncertainty and stock returns: Evidence from China

NASA Astrophysics Data System (ADS)

Xiong, Xiong; Bian, Yuxiang; Shen, Dehua

2018-06-01

In this paper, we use a new policy uncertainty index to investigate the time-varying correlation between economic policy uncertainty (EPU) and Chinese stock market returns. The correlation is examined in the period from January 1995 to December 2016. We show that absolute changes in EPU have a significant impact on stock market returns. Specifically, empirical results based on the DCC-GARCH model reveal that the correlation between EPU and stock returns has large fluctuations, especially during a financial crisis; in addition, the impact of EPU on the Shanghai stock market is greater than on the Shenzhen stock market. Robustness results reveal that the impact of EPU on state-owned enterprises is larger than on non-state enterprises. All of these results highlight the important role of EPU in the Chinese stock market, and shed light on such issues for future research.

Repulsive Guidance Molecules (RGMs) and Neogenin in Bone Morphogenetic Protein (BMP) signaling

PubMed Central

Tian, Chenxi; Liu, Jun

2015-01-01

Summary Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGFβ) superfamily. BMPs mediate a highly conserved signal transduction cascade through the type I and type II serine/threonine kinase receptors and intracellular Smad proteins. The BMP pathway regulates multiple developmental and homeostatic processes. Mutations in this pathway can cause various diseases in humans, such as skeletal disorders, cardiovascular diseases and various cancers. Multiple levels of regulation, including extracellular regulation, help to ensure proper spatiotemporal control of BMP signaling in the right cellular context. The family of repulsive guidance molecules (RGMs) and the type I trans-membrane protein neogenin, a paralog of DCC (Deleted in Colorectal Cancer), have been implicated in modulating the BMP pathway. In this review, we discuss the properties and functions of RGM proteins and neogenin, focusing on their roles in the modulation of BMP signal transduction. PMID:23740870

Results of the Community Health Applied Research Network (CHARN) National Research Capacity Survey of Community Health Centers.

PubMed

Song, Hui; Li, Vivian; Gillespie, Suzanne; Laws, Reesa; Massimino, Stefan; Nelson, Christine; Singal, Robbie; Wagaw, Fikirte; Jester, Michelle; Weir, Rosy Chang

2015-01-01

The mission of the Community Health Applied Research Network (CHARN) is to build capacity to carry out Patient-Centered Outcomes Research at community health centers (CHCs), with the ultimate goal to improve health care for vulnerable populations. The CHARN Needs Assessment Staff Survey investigates CHCs' involvement in research, as well as their need for research training and resources. Results will be used to guide future training. The survey was developed and implemented in partnership with CHARN CHCs. Data were collected across CHARN CHCs. Data analysis and reports were conducted by the CHARN data coordinating center (DCC). Survey results highlighted gaps in staff research training, and these gaps varied by staff role. There is considerable variation in research involvement, partnerships, and focus both within and across CHCs. Development of training programs to increase research capacity should be tailored to address the specific needs and roles of staff involved in research.

Sensitivity curves for searches for gravitational-wave backgrounds

NASA Astrophysics Data System (ADS)

Thrane, Eric; Romano, Joseph D.

2013-12-01

We propose a graphical representation of detector sensitivity curves for stochastic gravitational-wave backgrounds that takes into account the increase in sensitivity that comes from integrating over frequency in addition to integrating over time. This method is valid for backgrounds that have a power-law spectrum in the analysis band. We call these graphs “power-law integrated curves.” For simplicity, we consider cross-correlation searches for unpolarized and isotropic stochastic backgrounds using two or more detectors. We apply our method to construct power-law integrated sensitivity curves for second-generation ground-based detectors such as Advanced LIGO, space-based detectors such as LISA and the Big Bang Observer, and timing residuals from a pulsar timing array. The code used to produce these plots is available at https://dcc.ligo.org/LIGO-P1300115/public for researchers interested in constructing similar sensitivity curves.

Preparation, Characterization, and Insecticidal Activity of Avermectin-Grafted-Carboxymethyl Chitosan

PubMed Central

Li, Yan; Qin, Yukun; Liu, Song; Xing, Ronge; Yu, Huahua; Li, Kecheng; Li, Pengcheng

2016-01-01

Avermectin-grafted-N,O-carboxymethyl chitosan (NOCC) derivative was obtained by esterification reaction using dicyclohexylcarbodiimide (DCC) as dehydrating agent and 4-methylaminopyridine as catalyst. The structures of the conjugate were confirmed by FT-IR, 1H NMR, and XRD. Insecticidal activities against armyworms, carmine spider mites, black bean aphids, and brown plant hoppers were investigated at concentrations ranging from 0.16 to 1000 mg/L. At the concentration of 1000 mg/L and 500 mg/L, the lethal rate was 100%. Good insecticidal activity at 4 mg/L was still shown, especially against the black bean aphids and brown plant hoppers. Moreover, the photostability of the conjugate was evaluated and showed an apparent improvement. At 300 mins, the residual rate of the conjugate was 11.22%, much higher than 0.2% of the avermectin technical material. The conjugate we developed showed potential for further study and application in crop protection. PMID:27213156

The DIRC front-end electronics chain for BaBar

NASA Astrophysics Data System (ADS)

Bailly, P.; Beigbeder, C.; Bernier, R.; Breton, D.; Bonneaud, G.; Caceres, T.; Chase, R.; Chauveau, J.; Del Buono, L.; Dohou, F.; Ducorps, A.; Gastaldi, F.; Genat, J. F.; Hrisoho, A.; Imbert, P.; Lebbolo, H.; Matricon, P.; Oxoby, G.; Renard, C.; Roos, L.; Sen, S.; Thiebaux, C.; Truong, K.; Tocut, V.; Vasileiadis, G.; Va'Vra, J.; Verderi, M.; Warner, D.; Wilson, R. J.; Wormser, G.; Zhang, B.; Zomer, F.

2000-12-01

Recent results from the Front-End electronics of the Detector of Internally Reflected Cerenkov light (DIRC) for the BaBar experiment at SLAC (Stanford, USA) are presented. It measures to better than 1 ns the arrival time of Cerenkov photoelectrons detected in a 11000 phototubes array and their amplitude spectra. It mainly comprises 64-channel DIRC Front-End Boards (DFB) equipped with eight full-custom analog chips performing zero-cross discrimination with 2 mV threshold and pulse shaping, four full-custom digital time to digital chips (TDC) for timing measurements with 500 ps binning and a readout logic selecting hits in the trigger window, and DIRC Crate Controller cards (DCC) serializing the data collected front up to 16 DFBs onto a 1.2 Gb/s optical link. Extensive test results of the pre-production chips are presented, as well as system tests.

Arctic Ice Dynamics Joint Experiment 1975-1976. Physical Oceanography Data Report, Salinity, Temperature and Depth Data, Camp Caribou. Volume I.

DTIC Science & Technology

1980-02-01

produced on casts from a rolling ship. De - lineation of small scale structures is limited almost entirely by instrument characteristics alone. The...1976 1E 1 14 1s isE 17 is 1B w1 a e3 eA g .K -Jv coU ,a 0 d" do ) 0) op ) 0 01 1 j j -i j j U a : o " ri i ft de daab ri 01 t ~ o mco a m al ’U 0’U0...8217 j. ij J J .J --j J -1 I -J - UP Li (i goi de I= dcC CAl CAi a) @ Lii Us ~ W. CA j 5ii I ’ S&L a NO MORE~ THAN ON’E PROFILE PER HALF DAY (AM/PM GMT3 IS

THE MECHANISM OF ACTION OF COLCHICINE

PubMed Central

Wilson, Leslie; Meza, Isaura

1973-01-01

The thermal depolymerization procedure of Stephens (1970. J. Mol. Biol. 47:353) has been employed for solubilization of Strongylocentrotus purpuratus sperm tail outer doublet microtubules with the use of a buffer during solubilization which is of optimal pH and ionic strength for the preservation of colchicine binding activity of chick embryo brain tubulin. Colchicine binding values were corrected for first-order decay during heat solubilization at 50°C (t½ = 5.4 min) and incubation with colchicine at 37°C in the presence of vinblastine sulfate (t½ = 485 min). The colchicine binding properties of heat-solubilized outer doublet tubulin were qualitatively identical with those of other soluble forms of tubulin. The solubilized tubulin (mol wt, 115,000) bound 0.9 ± 0.2 mol of colchicine per mol of tubulin, with a binding constant of 6.3 x 105 liters/mol at 37°C. The colchicine binding reaction was both time and temperature dependent, and the binding of colchicine was prevented in a competitive manner by podophyllotoxin (Ki = 1.3 x 10-6 M). The first-order decay of colchicine binding activity was substantially decreased by the addition of the vinca alkaloids, vinblastine sulfate or vincristine sulfate, thus demonstrating the presence of a vinca alkaloid binding site(s) on the outer doublet tubulin. Tubulin contained within the assembled microtubules did not decay. Intact outer doublet microtubules bound less than 0.001 mol of colchicine per mol of tubulin contained in the microtubules, under conditions where soluble tubulin would have bound 1 mol of colchicine per mol of tubulin (saturating concentration of colchicine, no decay of colchicine binding activity). The presence of colchicine had no effect on the rate of solubilization of outer doublet microtubules during incubation at 37°C. Therefore, the colchicine binding site on tubulin is blocked (not available to bind colchicine) when the tubulin is in the assembled outer doublet microtubules. PMID:4747924

Expression of Plant Receptor Kinases in Tobacco BY-2 Cells.

PubMed

Shinohara, Hidefumi; Matsubayashi, Yoshikatsu

2017-01-01

Although more than 600 single-transmembrane receptor kinase genes have been found in the Arabidopsis genome, only a few of them have known physiological functions, and even fewer plant receptor kinases have known specific ligands. Ligand-binding analysis must be operated using the functionally expressed receptor form. However, the relative abundance of native receptor kinase molecules in the plasma membrane is often quite low. Here, we present a method for stable and functional expression of plant receptor kinases in tobacco BY-2 cells that allows preparation of microsomal fractions containing the receptor. This procedure provides a sufficient amount of receptor proteins while maintaining its ligand-binding activities.

Basis sets for the calculation of core-electron binding energies

NASA Astrophysics Data System (ADS)

Hanson-Heine, Magnus W. D.; George, Michael W.; Besley, Nicholas A.

2018-05-01

Core-electron binding energies (CEBEs) computed within a Δ self-consistent field approach require large basis sets to achieve convergence with respect to the basis set limit. It is shown that supplementing a basis set with basis functions from the corresponding basis set for the element with the next highest nuclear charge (Z + 1) provides basis sets that give CEBEs close to the basis set limit. This simple procedure provides relatively small basis sets that are well suited for calculations where the description of a core-ionised state is important, such as time-dependent density functional theory calculations of X-ray emission spectroscopy.

[Mitomycin C in head and neck surgical procedures].

PubMed

Scheithauer, M O; Riechelmann, H

2007-05-01

Mitomycin C (MMC) is frequently used in combination chemotherapy. Its metabolites bind to DNA-molecules and causes DNA crosslinking, which interferes with the synthesis of DNA, RNA and proteins. MMC is thus able to reduce fibroblast proliferation. Moreover, MMC particularly inhibits the synthesis of extracellular matrix proteins including fibronectin and various collagens. These properties have been demonstrated in several experimental studies. Beside its merits in treatment of malignancies, MMC may thus be useful to prevent hypertrophic scars and keloids, adhesions and ostial restenosis following head and neck surgical procedures. Clinically, MMC has been applied to prevent scarring after ophthalmologic surgery. Recent experimental and clinical trials investigating the effects of MMC on wound healing following head and neck surgical procedures are reviewed.

Binding in agrammatic aphasia: Processing to comprehension

PubMed Central

Janet Choy, Jungwon; Thompson, Cynthia K.

2010-01-01

Background Theories of comprehension deficits in Broca’s aphasia have largely been based on the pattern of deficit found with movement constructions. However, some studies have found comprehension deficits with binding constructions, which do not involve movement. Aims This study investigates online processing and offline comprehension of binding constructions, such as reflexive (e.g., himself) and pronoun (e.g., him) constructions in unimpaired and aphasic individuals in an attempt to evaluate theories of agrammatic comprehension. Methods & Procedures Participants were eight individuals with agrammatic Broca’s aphasia and eight age-matched unimpaired individuals. We used eyetracking to examine online processing of binding constructions while participants listened to stories. Offline comprehension was also tested. Outcomes & Results The eye movement data showed that individuals with Broca’s aphasia were able to automatically process the correct antecedent of reflexives and pronouns. In addition, their syntactic processing of binding was not delayed compared to normal controls. Nevertheless, offline comprehension of both pronouns and reflexives was significantly impaired compared to the control participants. This comprehension failure was reflected in the aphasic participants’ eye movements at sentence end, where fixations to the competitor increased. Conclusions These data suggest that comprehension difficulties with binding constructions seen in agrammatic aphasic patients are not due to a deficit in automatic syntactic processing or delayed processing. Rather, they point to a possible deficit in lexical integration. PMID:20535243

The type III effector HsvG of the gall-forming Pantoea agglomerans mediates expression of the host gene HSVGT.

PubMed

Nissan, Gal; Manulis-Sasson, Shulamit; Chalupowicz, Laura; Teper, Doron; Yeheskel, Adva; Pasmanik-Chor, Metsada; Sessa, Guido; Barash, Isaac

2012-02-01

The type III effector HsvG of the gall-forming Pantoea agglomerans pv. gypsophilae is a DNA-binding protein that is imported to the host nucleus and involved in host specificity. The DNA-binding region of HsvG was delineated to 266 amino acids located within a secondary structure region near the N-terminus of the protein but did not display any homology to canonical DNA-binding motifs. A binding site selection procedure was used to isolate a target gene of HsvG, named HSVGT, in Gypsophila paniculata. HSVGT is a predicted acidic protein of the DnaJ family with 244 amino acids. It harbors characteristic conserved motifs of a eukaryotic transcription factor, including a bipartite nuclear localization signal, zinc finger, and leucine zipper DNA-binding motifs. Quantitative real-time polymerase chain reaction analysis demonstrated that HSVGT transcription is specifically induced in planta within 2 h after inoculation with the wild-type P. agglomerans pv. gypsophilae compared with the hsvG mutant. Induction of HSVGT reached a peak of sixfold at 4 h after inoculation and progressively declined thereafter. Gel-shift assay demonstrated that HsvG binds to the HSVGT promoter, indicating that HSVGT is a direct target of HsvG. Our results support the hypothesis that HsvG functions as a transcription factor in gypsophila.

Time-resolved analysis of DNA-protein interactions in living cells by UV laser pulses.

PubMed

Nebbioso, Angela; Benedetti, Rosaria; Conte, Mariarosaria; Carafa, Vincenzo; De Bellis, Floriana; Shaik, Jani; Matarese, Filomena; Della Ventura, Bartolomeo; Gesuele, Felice; Velotta, Raffaele; Martens, Joost H A; Stunnenberg, Hendrik G; Altucci, Carlo; Altucci, Lucia

2017-09-15

Interactions between DNA and proteins are mainly studied through chemical procedures involving bi-functional reagents, mostly formaldehyde. Chromatin immunoprecipitation is used to identify the binding between transcription factors (TFs) and chromatin, and to evaluate the occurrence and impact of histone/DNA modifications. The current bottleneck in probing DNA-protein interactions using these approaches is caused by the fact that chemical crosslinkers do not discriminate direct and indirect bindings or short-lived chromatin occupancy. Here, we describe a novel application of UV laser-induced (L-) crosslinking and demonstrate that a combination of chemical and L-crosslinking is able to distinguish between direct and indirect DNA-protein interactions in a small number of living cells. The spatial and temporal dynamics of TF bindings to chromatin and their role in gene expression regulation may thus be assessed. The combination of chemical and L-crosslinking offers an exciting and unprecedented tool for biomedical applications.

Calculations of antiproton-nucleus quasi-bound states using the Paris N bar N potential

NASA Astrophysics Data System (ADS)

Hrtánková, Jaroslava; Mareš, Jiří

2018-01-01

An optical potential constructed using the p bar N scattering amplitudes derived from the 2009 version of the Paris N bar N potential is applied in calculations of p bar quasi-bound states in selected nuclei across the periodic table. A proper self-consistent procedure for treating energy dependence of the amplitudes in a nucleus appears crucial for evaluating p bar binding energies and widths. Particular attention is paid to the role of P-wave amplitudes. While the P-wave potential nearly does not affect calculated p bar binding energies, it reduces considerably the corresponding widths. The Paris S-wave potential supplemented by a phenomenological P-wave term yields in dynamical calculations p bar binding energies Bpbar ≈ 200 MeV and widths Γpbar ∼ 200- 230 MeV, which is very close to the values obtained within the RMF model consistent with p bar -atom data.

Quantitative structure activity relationships from optimised ab initio bond lengths: steroid binding affinity and antibacterial activity of nitrofuran derivatives

NASA Astrophysics Data System (ADS)

Smith, P. J.; Popelier, P. L. A.

2004-02-01

The present day abundance of cheap computing power enables the use of quantum chemical ab initio data in Quantitative Structure-Activity Relationships (QSARs). Optimised bond lengths are a new such class of descriptors, which we have successfully used previously in representing electronic effects in medicinal and ecological QSARs (enzyme inhibitory activity, hydrolysis rate constants and pKas). Here we use AM1 and HF/3-21G* bond lengths in conjunction with Partial Least Squares (PLS) and a Genetic Algorithm (GA) to predict the Corticosteroid-Binding Globulin (CBG) binding activity of the classic steroid data set, and the antibacterial activity of nitrofuran derivatives. The current procedure, which does not require molecular alignment, produces good r2 and q2 values. Moreover, it highlights regions in the common steroid skeleton deemed relevant to the active regions of the steroids and nitrofuran derivatives.

Surface functionalization of magnetic nanoparticles formed by self-associating hydrophobized oxidized dextrans

NASA Astrophysics Data System (ADS)

Farber, Shimon; Ickowicz, Diana E.; Melnik, Kristie; Yudovin-Farber, Ira; Recko, Daniel; Rampersaud, Arfaan; Domb, Abraham J.

2014-06-01

Magnetic iron oxide nanoparticles surface covered with oleic acid layer followed by a second layer of hydrophobized oxidized dextran aldehyde were prepared and tested for physico-chemical properties and ligand- and cell-specific binding. It was demonstrated that oleic acid-iron oxide nanoparticles coated with an additional layer of hydrophobized oxidized dextran were dispersible in buffer solutions and possess surface aldehyde active groups available for further binding of ligands or markers via imine or amine bond formation. Hydrophobized dextrans were synthesized by periodate oxidation and conjugation of various alkanamines to oxidized dextran by imination. Physico-chemical properties, as separation using magnetic field, magnetite concentration, and particle diameter, of the prepared magnetic samples are reported. The biotin-binding protein, neutravidin, was coupled to the particle surface by a simple reductive amination procedure. The particles were used for specific cell separation with high specificity.

Rapid, High Affinity Binding by a Fluorescein Templated Copolymer Combining Covalent, Hydrophobic, and Acid–Base Noncovalent Crosslinks

PubMed Central

Timberman, Anthony; Yang, Rongfang; Papantones, Alex; Seitz, W. Rudolf

2018-01-01

A new type of biomimetic templated copolymer has been prepared by reverse addition fragmentation chain transfer polymerization (RAFT) in dioxane. The initial formulation includes the template fluorescein, N-isopropylacrylamide (NIPAM, 84 mol %), methacrylic acid (MAA, 5-mol %), 4-vinylpyridine (4-VP, 9 mmol %), and N,N′-methylenebis(acrylamide) (MBA, 2 mol %). PolyNIPAM is a thermosensitive polymer that comes out of aqueous solution above its lower critical solution temperature forming hydrophobic ‘crosslinks’. MAA and 4-VP interact in dioxane forming acid–base crosslinks. The excess 4-VP serves as a recognition monomer organizing around the template fluorescein to form a binding site that is held in place by the noncovalent and covalent crosslinks. The MBA is a covalent crosslinker. The RAFT agent in the resulting copolylmer was reduced to a thiol and attached to gold nanoparticles. The gold nanoparticle bound copolymer binds fluorescein completely in less than two seconds with an affinity constant greater than 108 M−1. A reference copolymer prepared with the same monomers by the same procedure binds fluorescein much more weakly. PMID:29693601

Attention to Attributes and Objects in Working Memory

ERIC Educational Resources Information Center

Cowan, Nelson; Blume, Christopher L.; Saults, J. Scott

2013-01-01

It has been debated on the basis of change-detection procedures whether visual working memory is limited by the number of objects, task-relevant attributes within those objects, or bindings between attributes. This debate, however, has been hampered by several limitations, including the use of conditions that vary between studies and the absence…

48 CFR 52.222-33 - Notice of Requirement for Project Labor Agreement.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Definitions. “Labor organization” and “project labor agreement,” as used in this provision, are defined in the... offeror shall negotiate a project labor agreement with one or more labor organizations for the term of the... disruptions; (4) Set forth effective, prompt, and mutually binding procedures for resolving labor disputes...

48 CFR 52.222-33 - Notice of Requirement for Project Labor Agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Definitions. “Labor organization” and “project labor agreement,” as used in this provision, are defined in the... offeror shall negotiate a project labor agreement with one or more labor organizations for the term of the... disruptions; (4) Set forth effective, prompt, and mutually binding procedures for resolving labor disputes...

9 CFR 147.14 - Procedures to determine status and effectiveness of sanitation monitored program.

Code of Federal Regulations, 2012 CFR

2012-01-01

... coliforms. Such eggs should also be cultured for the dependable recovery of salmonellae. Culturing for the dependable recovery of salmonellae should include the use of: (i) Preenrichment broths supplemented with 35 mg ferrous sulfate per 1,000 ml preenrichment to block iron-binding, Salmonella-inhibiting effects of...

9 CFR 147.14 - Procedures to determine status and effectiveness of sanitation monitored program.

Code of Federal Regulations, 2014 CFR

2014-01-01

... coliforms. Such eggs should also be cultured for the dependable recovery of salmonellae. Culturing for the dependable recovery of salmonellae should include the use of: (i) Preenrichment broths supplemented with 35 mg ferrous sulfate per 1,000 ml preenrichment to block iron-binding, Salmonella-inhibiting effects of...

9 CFR 147.14 - Procedures to determine status and effectiveness of sanitation monitored program.

Code of Federal Regulations, 2013 CFR

2013-01-01

... coliforms. Such eggs should also be cultured for the dependable recovery of salmonellae. Culturing for the dependable recovery of salmonellae should include the use of: (i) Preenrichment broths supplemented with 35 mg ferrous sulfate per 1,000 ml preenrichment to block iron-binding, Salmonella-inhibiting effects of...

9 CFR 147.14 - Procedures to determine status and effectiveness of sanitation monitored program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... coliforms. Such eggs should also be cultured for the dependable recovery of salmonellae. Culturing for the dependable recovery of salmonellae should include the use of: (i) Preenrichment broths supplemented with 35 mg ferrous sulfate per 1,000 ml preenrichment to block iron-binding, Salmonella-inhibiting effects of...

One-step purification of nisin A by immunoaffinity chromatography.

PubMed

Suárez, A M; Azcona, J I; Rodríguez, J M; Sanz, B; Hernández, P E

1997-12-01

The lantibiotic nisin A was purified to homogeneity by a single-step immunoaffinity chromatography method. An immunoadsorption matrix was developed by direct binding of anti-nisin A monoclonal antibodies to N-hydroxysuccinimide-activated Sepharose. The purification procedure was rapid and reproducible and rendered much higher final yields of nisin than any other described method.

28 CFR 80.11 - Effect of FCPA Opinion.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Effect of FCPA Opinion. 80.11 Section 80.11 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE § 80.11 Effect of FCPA Opinion. Except as specified in § 80.10, an FCPA Opinion will not bind or...

Assessment of the Visible Channel Calibrations of the TRMM VIRS and MODIS on Aqua and Terra

NASA Technical Reports Server (NTRS)

Minnis, Patrick; Doelling, David R.; Nguyen, Louis; Miller, Walter F.; Chakrapani, Venketesan

2007-01-01

Several recent research satellites carry self-calibrating multispectral imagers that can be used for calibrating operational imagers lacking complete self-calibrating capabilities. In particular, the visible (VIS, 0.65 m) channels on operational meteorological satellites are generally calibrated before launch, but require vicarious calibration techniques to monitor the gains and offsets once they are in orbit. To ensure that the self-calibrating instruments are performing as expected, this paper examines the consistencies between the VIS channel (channel 1) reflectances of the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on the Terra and Aqua satellites and the Version 5a and 6 reflectances of the Visible Infrared Scanner (VIRS) on the Tropical Rainfall Measuring Mission using a variety of techniques. These include comparisons of Terra and Aqua VIS radiances with coincident broadband shortwave radiances from the well-calibrated Clouds and the Earth s Radiant Energy System (CERES), time series of deep convective cloud (DCC) albedos, and ray-matching intercalibrations between each of the three satellites. Time series of matched Terra and VIRS data, Aqua and VIRS data, and DCC reflected fluxes reveal that an older version (Version 5a, ending in early 2004) of the VIRS calibration produced a highly stable record, while the latest version (Version 6) appears to overestimate the sensor gain change by approx.1%/y as the result of a manually induced gain adjustment. Comparisons with the CERES shortwave radiances unearthed a sudden change in the Terra MODIS calibration that caused a 1.17% decrease in the gain on 19 November 2003 that can be easily reversed. After correction for these manual adjustments, the trends in the VIRS and Terra channels are no greater than 0.1%/y. Although the results were more ambiguous, no statistically significant trends were found in the Aqua MODIS channel-1 gain. The Aqua radiances are 1% greater, on average, than their Terra counterparts, and after normalization are 4.6% greater than VIRS radiances, in agreement with theoretical calculations. The discrepancy between the two MODIS instruments should be taken into account to ensure consistency between parameters derived from them. With the adjustments, any of the three instruments can serve as references for calibrating other satellites. Monitoring of the calibrations continues in near-real-time and the results are available via the world wide web.

A conserved juxtacrine signal regulates synaptic partner recognition in Caenorhabditis elegans

PubMed Central

2011-01-01

Background An essential stage of neural development involves the assembly of neural circuits via formation of inter-neuronal connections. Early steps in neural circuit formation, including cell migration, axon guidance, and the localization of synaptic components, are well described. However, upon reaching their target region, most neurites still contact many potential partners. In order to assemble functional circuits, it is critical that within this group of cells, neurons identify and form connections only with their appropriate partners, a process we call synaptic partner recognition (SPR). To understand how SPR is mediated, we previously developed a genetically encoded fluorescent trans-synaptic marker called NLG-1 GRASP, which labels synaptic contacts between individual neurons of interest in dense cellular environments in the genetic model organism Caenorhabditis elegans. Results Here, we describe the first use of NLG-1 GRASP technology, to identify SPR genes that function in this critical process. The NLG-1 GRASP system allows us to assess synaptogenesis between PHB sensory neurons and AVA interneurons instantly in live animals, making genetic analysis feasible. Additionally, we employ a behavioral assay to specifically test PHB sensory circuit function. Utilizing this approach, we reveal a new role for the secreted UNC-6/Netrin ligand and its transmembrane receptor UNC-40/Deleted in colorectal cancer (DCC) in SPR. Synapses between PHB and AVA are severely reduced in unc-6 and unc-40 animals despite normal axon guidance and subcellular localization of synaptic components. Additionally, behavioral defects indicate a complete disruption of PHB circuit function in unc-40 mutants. Our data indicate that UNC-40 and UNC-6 function in PHB and AVA, respectively, to specify SPR. Strikingly, overexpression of UNC-6 in postsynaptic neurons is sufficient to promote increased PHB-AVA synaptogenesis and to potentiate the behavioral response beyond wild-type levels. Furthermore, an artificially membrane-tethered UNC-6 expressed in the postsynaptic neurons promotes SPR, consistent with a short-range signal between adjacent synaptic partners. Conclusions These results indicate that the conserved UNC-6/Netrin-UNC-40/DCC ligand-receptor pair has a previously unknown function, acting in a juxtacrine manner to specify recognition of individual postsynaptic neurons. Furthermore, they illustrate the potential of this new approach, combining NLG-1 GRASP and behavioral analysis, in gene discovery and characterization. PMID:21663630

``In silico'' study of the binding of two novel antagonists to the nociceptin receptor

NASA Astrophysics Data System (ADS)

Della Longa, Stefano; Arcovito, Alessandro

2018-02-01

Antagonists of the nociceptin receptor (NOP) are raising interest for their possible clinical use as antidepressant drugs. Recently, the structure of NOP in complex with some piperidine-based antagonists has been revealed by X-ray crystallography. In this study, a multi-flexible docking (MF-docking) procedure, i.e. docking to multiple receptor conformations extracted by preliminary molecular dynamics trajectories, together with hybrid quantum mechanics/molecular mechanics (QM/MM) simulations have been carried out to provide the binding mode of two novel NOP antagonists, one of them selective (BTRX-246040, formerly named LY-2940094) and one non selective (AT-076), i.e. able to inactivate NOP as well as the classical µ- k- and δ-opioid receptors (MOP KOP and DOP). According to our results, the pivotal role of residue D1303,32 (upper indexes are Ballesteros-Weinstein notations) is analogous to that enlighten by the already known X-ray structures of opioid receptors: binding of the molecules are predicted to require a slight readjustment of the hydrophobic pocket (residues Y1313,33, M1343,36, I2195,43, Q2806,52 and V2836,55) in the orthosteric site of NOP, accommodating either the pyridine-pyrazole (BTRX-246040) or the isoquinoline (AT-076) moiety of the ligand, in turn allowing the protonated piperidine nitrogen to maximize interaction (salt-bridge) with residue D1303,32 of the NOP, and the aromatic head to be sandwiched in optimal π-stacking between Y1313,33 and M1343,36. The QM/MM optimization after the MF-docking procedure has provided the more likely conformations for the binding to the NOP receptor of BTRX-246040 and AT-076, based on different pharmacophores and exhibiting different selectivity profiles. While the high selectivity for NOP of BTRX-246040 can be explained by interactions with NOP specific residues, the lack of selectivity of AT-076 could be associated to its ability to penetrate into the deep hydrophobic pocket of NOP, while retaining a conformation very similar to the one assumed by the antagonist JDTic into the K-opioid receptor. The proposed binding geometries fit better the binding pocket environment providing clues for experimental studies aimed to design selective or multifunctional opioid drugs.

Generalized Jastrow variational method for liquid3He-4He mixtures at T=0 K

NASA Astrophysics Data System (ADS)

Mirabbaszadeh, K.

1989-07-01

The ground state energy of a dilute solution of mass-3 fermions in liquid4He is analyzed by a variational procedure based on the Jastrow many body theory. The antisymmetry of the wave function for fermions is incorporated following the procedure given by Lado, Inguva, and Smith. A set of coupled integrodifferential equations is solved in the hypernetted chain approximation yielding expressions for the binding energy of3He-4He mixtures; the radial distribution function is given together with the total energy for various values of density and the interparticle separation r s.

Isolation of monomeric photosystem II that retains the subunit PsbS.

PubMed

Haniewicz, Patrycja; De Sanctis, Daniele; Büchel, Claudia; Schröder, Wolfgang P; Loi, Maria Cecilia; Kieselbach, Thomas; Bochtler, Matthias; Piano, Dario

2013-12-01

Photosystem II has been purified from a transplastomic strain of Nicotiana tabacum according to two different protocols. Using the procedure described in Piano et al. (Photosynth Res 106:221-226, 2010) it was possible to isolate highly active PSII composed of monomers and dimers but depleted in their PsbS protein content. A "milder" procedure than the protocol reported by Fey et al. (Biochim Biophys Acta 1777:1501-1509, 2008) led to almost exclusively monomeric PSII complexes which in part still bind the PsbS protein. This finding might support a role for PSII monomers in higher plants.

Image Restoration and Analysis of Influenza Virions Binding to Membrane Receptors Reveal Adhesion-Strengthening Kinetics

PubMed Central

Lee, Donald W.; Hsu, Hung-Lun; Bacon, Kaitlyn B.; Daniel, Susan

2016-01-01

With the development of single-particle tracking (SPT) microscopy and host membrane mimics called supported lipid bilayers (SLBs), stochastic virus-membrane binding interactions can be studied in depth while maintaining control over host receptor type and concentration. However, several experimental design challenges and quantitative image analysis limitations prevent the widespread use of this approach. One main challenge of SPT studies is the low signal-to-noise ratio of SPT videos, which is sometimes inevitable due to small particle sizes, low quantum yield of fluorescent dyes, and photobleaching. These situations could render current particle tracking software to yield biased binding kinetic data caused by intermittent tracking error. Hence, we developed an effective image restoration algorithm for SPT applications called STAWASP that reveals particles with a signal-to-noise ratio of 2.2 while preserving particle features. We tested our improvements to the SPT binding assay experiment and imaging procedures by monitoring X31 influenza virus binding to α2,3 sialic acid glycolipids. Our interests lie in how slight changes to the peripheral oligosaccharide structures can affect the binding rate and residence times of viruses. We were able to detect viruses binding weakly to a glycolipid called GM3, which was undetected via assays such as surface plasmon resonance. The binding rate was around 28 folds higher when the virus bound to a different glycolipid called GD1a, which has a sialic acid group extending further away from the bilayer surface than GM3. The improved imaging allowed us to obtain binding residence time distributions that reflect an adhesion-strengthening mechanism via multivalent bonds. We empirically fitted these distributions using a time-dependent unbinding rate parameter, koff, which diverges from standard treatment of koff as a constant. We further explain how to convert these models to fit ensemble-averaged binding data obtained by assays such as surface plasmon resonance. PMID:27695072

NetMHCIIpan-2.0 - Improved pan-specific HLA-DR predictions using a novel concurrent alignment and weight optimization training procedure.

PubMed

Nielsen, Morten; Justesen, Sune; Lund, Ole; Lundegaard, Claus; Buus, Søren

2010-11-13

Binding of peptides to Major Histocompatibility class II (MHC-II) molecules play a central role in governing responses of the adaptive immune system. MHC-II molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Predicting which peptides bind to an MHC-II molecule is therefore of pivotal importance for understanding the immune response and its effect on host-pathogen interactions. The experimental cost associated with characterizing the binding motif of an MHC-II molecule is significant and large efforts have therefore been placed in developing accurate computer methods capable of predicting this binding event. Prediction of peptide binding to MHC-II is complicated by the open binding cleft of the MHC-II molecule, allowing binding of peptides extending out of the binding groove. Moreover, the genes encoding the MHC molecules are immensely diverse leading to a large set of different MHC molecules each potentially binding a unique set of peptides. Characterizing each MHC-II molecule using peptide-screening binding assays is hence not a viable option. Here, we present an MHC-II binding prediction algorithm aiming at dealing with these challenges. The method is a pan-specific version of the earlier published allele-specific NN-align algorithm and does not require any pre-alignment of the input data. This allows the method to benefit also from information from alleles covered by limited binding data. The method is evaluated on a large and diverse set of benchmark data, and is shown to significantly out-perform state-of-the-art MHC-II prediction methods. In particular, the method is found to boost the performance for alleles characterized by limited binding data where conventional allele-specific methods tend to achieve poor prediction accuracy. The method thus shows great potential for efficient boosting the accuracy of MHC-II binding prediction, as accurate predictions can be obtained for novel alleles at highly reduced experimental costs. Pan-specific binding predictions can be obtained for all alleles with know protein sequence and the method can benefit by including data in the training from alleles even where only few binders are known. The method and benchmark data are available at http://www.cbs.dtu.dk/services/NetMHCIIpan-2.0.

Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation.

PubMed

Ordway, Gregory A; Jia, Weihong; Li, Jing; Zhu, Meng-Yang; Mandela, Prashant; Pan, Jun

2005-04-30

Previous research has shown that exposure of norepinephrine transporter (NET)-expressing cells to desipramine (DMI) downregulates the norepinephrine transporter, although changes in the several transporter parameters do not demonstrate the same time course. Exposures to desipramine for <1 day reduces only radioligand binding and uptake capacity while transporter-immunoreactivity is unaffected. Recent demonstration of persistent drug retention in cells following desipramine exposures raises the possibility that previous reported changes in the norepinephrine transporter may be partly accountable by residual drug. In this study, potential effects of residual desipramine on norepinephrine transporter binding and uptake were re-evaluated following exposures of PC12 cells to desipramine using different methods to remove residual drug. Using a method that minimizes residual drug, exposure of intact PC12 cells to desipramine for 4h had no effect on uptake capacity or [(3)H]nisoxetine binding to the norepinephrine transporter, while exposures for > or =16 h reduced uptake capacity. Desipramine-induced reductions in binding to the transporter required >24 h or greater periods of desipramine exposure. This study confirms that uptake capacity of the norepinephrine transporter is reduced earlier than changes in radioligand binding, but with a different time course than originally shown. Special pre-incubation procedures are required to abolish effects of residual transporter inhibitor when studying inhibitor-induced transporter regulation.

A Bromodomain-Containing Protein from Tomato Specifically Binds Potato Spindle Tuber Viroid RNA In Vitro and In Vivo

PubMed Central

Martínez de Alba, Angel Emilio; Sägesser, Rudolf; Tabler, Martin; Tsagris, Mina

2003-01-01

For the identification of RNA-binding proteins that specifically interact with potato spindle tuber viroid (PSTVd), we subjected a tomato cDNA expression library prepared from viroid-infected leaves to an RNA ligand screening procedure. We repeatedly identified cDNA clones that expressed a protein of 602 amino acids. The protein contains a bromodomain and was termed viroid RNA-binding protein 1 (VIRP1). The specificity of interaction of VIRP1 with viroid RNA was studied by different methodologies, which included Northwestern blotting, plaque lift, and electrophoretic mobility shift assays. VIRP1 interacted strongly and specifically with monomeric and oligomeric PSTVd positive-strand RNA transcripts. Other RNAs, for example, U1 RNA, did not bind to VIRP1. Further, we could immunoprecipitate complexes from infected tomato leaves that contained VIRP1 and viroid RNA in vivo. Analysis of the protein sequence revealed that VIRP1 is a member of a newly identified family of transcriptional regulators associated with chromatin remodeling. VIRP1 is the first member of this family of proteins, for which a specific RNA-binding activity is shown. A possible role of VIRP1 in viroid replication and in RNA mediated chromatin remodeling is discussed. PMID:12915580

Comparative studies of human and chicken retinol-binding proteins and prealbumins.

PubMed

Kopelman, M; Mokady, S; Cogan, U

1976-08-09

Microheterogeneity of retinol-binding proteins of human plasma and urine, and of chicken plasma was studied by polyacrylamide gel electrophoresis. All three protein systems were found microheterogenous. Incorporation of retinol into the protein preparations on the one hand, and depletion of these proteins from retinol on the other hand, enabled us to clarify the extent to which the presence or absence of the ligand affects the apparent heterogeneity. Upon electrophoresis, each of the native proteins displayed two pairs of protein zones. It appeared that within each pair the fast moving band corresponded to aporetinol-binding protein which upon binding of retinol was converted to a holoprotein with a slightly lower mobility. However, it did not seem that proteins of one pair were converted to proteins of the second pair upon binding of retinol, substantiating ghe microheterogenous character of this protein system. A rapid, two step procedure for isolation of prealbumins from plasma is described. The method which consists of DEAE-cellulose chromatography follwed by preparative electrophoresis was utilized to separate human and chicken prealbumins. Routine dodecyl sulphate electrophoresis resulted in partial dissociation of human prealbumin but in no dissociation of the chicken protein. More drastic treatments prior to electrophoresis were needed to effect complete disruption of both proteins into subunits.