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Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate.
Mizuno, Naomi; Takahashi, Tsuyoshi; Iwase, Yumiko; Kusuhara, Hiroyuki; Niwa, Takuro; Sugiyama, Yuichi
3-Methyl-1-phenyl-2-pyrazolin-5-one (MCI-186; edaravone), a novel free radical scavenger, is used for the treatment of acute cerebral infarction. After marketing, a few cases of acute renal failure were reported in patients following treatment with this drug. Because edaravone is mainly excreted into the urine following conjugation to glucuronide or sulfate, the renal excretion mechanisms of edaravone should help provide important information when considering the clinical cases. We examined the transport of edaravone and its sulfate and glucuronide conjugates via human organic anion transporter 1 (hOAT1) and 3 (hOAT3), expressed on the basolateral membranes of proximal tubules. The hOAT1- and hOAT3-transfected human embryonic kidney (HEK)-293 cells exhibited a markedly higher uptake of edaravone sulfate and a slightly higher uptake of edaravone than vector-transfected cells. The K(m) values of edaravone sulfate uptake by hOAT1 and hOAT3 were 11 and 15 microM, respectively. Estimation of the relative contribution of hOAT1 and hOAT3 using reference compounds suggested that hOAT1 and hOAT3 might contribute to the renal uptake of edaravone sulfate to the same extent. However, edaravone and its sulfate showed no cytotoxicity toward both hOAT1-HEK and control cells, suggesting that higher uptake in hOAT1-HEK did not associate with cytotoxicity of these compounds. In conclusion, our results suggest that both hOAT1 and hOAT3 are responsible for the basolateral uptake of edaravone sulfate in the kidney.
Determination of the external loops and the cellular orientation of the N- and the C-termini of the human organic anion transporter hOAT1
Hong, Mei; Tanaka, Kunihiko; Pan, Zui; Ma, Jianjie; You, Guofeng
The OAT (organic anion transporter) family mediates the absorption, distribution and excretion of a diverse array of environmental toxins and clinically important drugs. OAT dysfunction significantly contributes to renal, hepatic, neurological and fetal toxicity and disease. As a first step to establish the topological model of hOAT1 (human OAT1), we investigated the external loops and the cellular orientation of the N- and the C-termini of this transporter. Combined approaches of immunofluorescence studies and site-directed chemical labelling were used for such purpose. Immunofluorescence microscopy of Myc-tagged hOAT1 expressed in cultured cells identified that both the N- and the C-termini of the transporter were located in the cytoplasm. Replacement of Lys59 in the predicted extracellular loop I with arginine resulted in a mutant (K59R), which was largely inaccessible for labelling by membrane-impermeable NHS (N-hydroxysuccinimido)-SS (dithio)-biotin present in the extracellular medium. This result suggests that loop I faces outside of the cell membrane. A single lysine residue introduced into putative extracellular loops III, V and VI of mutant K59R, which is devoid of extracellular lysine, reacted readily with membrane-impermeable NHS-SS-biotin, suggesting that these putative extracellular loops are in the extracellular domains of the protein. These studies provided the first experimental evidence on the extracellular loops and the cellular orientation of the N- and the C-termini of hOAT1. PMID:17014423
The oldest flora of the South China Block, and the stratigraphic bearings of the plant remains from the Ngoc Vung Series, northern Vietnam
NASA Astrophysics Data System (ADS)
Gonez, Paul; Nguyên Huu, Hung; Ta Hoa, Phuong; Clément, Gaël; Janvier, Philippe
Several outcrops of the Late Silurian and Devonian of the Ngoc Vung Series, northern Vietnam, yielded plant remains. The Late Silurian localities delivered the earliest known flora of the South China block. Although the fossils are fragmentary, they complement our knowledge about the global composition of the flora. The major components of the flora are plants with dichotomous habit and terminal bivalvate sporangia, which are close relatives to zosterophylls, and zosterophylls. Plants with possible euphyllophyte affinities and bryophytes are occasionally present. This floral composition is similar to that of the rich, younger South China block assemblages from the Posongchong and Xujiachong Formations of China, considered Pragian in age. The South China block flora is therefore likely to have been dominated by zosterophylls and pre-zosterophylls at least from the Late Silurian to the Pragian (i.e. a 20 million years long period). It also strengthens the hypothesis that more derived plants were present on eastern Gondwana earlier that elsewhere, in the first steps of tracheophyte evolution. The Devonian localities of the Ngoc Vung Series delivered a thick fibrous stem fragment and a basal euphyllophyte. These latter plant remains provide some stratigraphic data. The large stem fragment is consistent with an Eifelian age for the Duong Dong Formation (part of the Ngoc Vung Series), as suggested by the brachiopod fauna. The accompanying basal euphyllophyte displays a combination of characters (axes 3-4 mm wide and lateral branchings) that is also consistent with an Eifelian age, but possibly more characteristic of the Emsian flora. It is therefore suggested that the stratigraphic range of the Duong Dong Formation might be extended down to the Emsian.
Serum- and glucocorticoid-inducible kinase sgk2 stimulates the transport activity of human organic anion transporters 1 by enhancing the stability of the transporter.
Xu, Da; Huang, Haozhe; Toh, May Fern; You, Guofeng
Human organic anion transporter 1 (hOAT1) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs, including anti-viral therapeutics, anti-cancer drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT1 is abundantly expressed in the kidney and brain. In the current study, we examined the regulation of hOAT1 by serum- and glucocorticoid-inducible kinase 2 (sgk2) in the kidney COS-7 cells. We showed that sgk2 stimulated hOAT1 transport activity. Such stimulation mainly resulted from an increased cell surface expression of the transporter, kinetically revealed as an increased maximal transport velocity V max without significant change in substrate-binding affinity K m. We further showed that stimulation of hOAT1 activity by sgk2 was achieved by preventing hOAT1 degradation. Our co-immunoprecipitation experiment revealed that the effect of sgk2 on hOAT1 was through a direct interaction between these two proteins. In conclusion, our study demonstrated that sgk2 stimulates hOAT1 transport activity by enhancing the stability of the transporter. This study provides the insights into sgk2 regulation of hOAT1-mediated transport in normal physiology and disease. PMID:27335683
Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats.
Feng, Yuan; Wang, Changyuan; Liu, Qi; Meng, Qiang; Huo, Xiaokui; Liu, Zhihao; Sun, Pengyuan; Yang, Xiaobo; Sun, Huijun; Qin, Jianhua; Liu, Kexin
A patient with rheumatoid arthritis developed rhabdomyolysis while undergoing treatment with mizoribine concomitantly with bezafibrate. The symptoms rapidly disappeared and laboratory test results normalized when she discontinued the two drugs. The purpose of the present study was to elucidate the transporter-mediated molecular pharmacokinetic mechanisms of drug-drug interactions between bezafibrate and mizoribine. Comparing bezafibrate-mizoribine group with bezafibrate group, the Tmax and Cmax of bezafibrate were essentially unchanged in rats. The AUC of bezafibrate was significantly increased and t1/2β was prolonged markedly with an obviously reduction in plasma clearance and cumulative urinary excretion. The changes were similar to oral studies following intravenous co-administration. In rat kidney slices, the uptake of bezafibrate was markedly inhibited by p-aminohippurate, benzylpenicillin and probenecid but not by tetraethyl ammonium. Mizoribine not only decreased the uptake of bezafibrate, but also inhibited the uptake of p-aminohippurate and benzylpenicillin. The uptakes of bezafibrate and mizoribine were significantly higher compared to vector-HEK293 cells. The uptakes of bezafibrate and mizoribine in highest concentration were increased 1.63 and 1.46 folds in hOAT1-transfected cells, 1.43 and 1.24 folds in hOAT3-transfected cells, respectively. The Km values of bezafibrate uptake by hOAT1/3hOAT1-/hOAT3-HEK293 K293 cells were increased 1.68 fold in hOAT1-HEK293 cell and 2.12 fold in hOAT3-HEK293 cell in the presence of mizoribine with no change of Vmax. It indicated that mizoribine could inhibit the uptake of bezafibrate by hOAT1/3-HEK293 cells in a competitive way. In conclusion, OAT1 and OAT3 are the target transporters of drug-drug interactions between bezafibrate and mizoribine in pharmacokinetic aspects. PMID:26474691
Coordination of Gaze and Speech in Communication between Children with Hearing Impairment and Normal-Hearing Peers
ERIC Educational Resources Information Center
Sandgren, Olof; Andersson, Richard; van de Weijer, Joost; Hansson, Kristina; Sahlén, Birgitta
Purpose: To investigate gaze behavior during communication between children with hearing impairment (HI) and normal-hearing (NH) peers. Method: Ten HI-NH and 10 NH-NH dyads performed a referential communication task requiring description of faces. During task performance, eye movements and speech were tracked. Using verbal event (questions,…
A three-dimensional model of human organic anion transporter 1: aromatic amino acids required for substrate transport.
Perry, Jennifer L; Dembla-Rajpal, Neetu; Hall, Laura A; Pritchard, John B
Organic anion transporters (OATs) play a critical role in the handling of endogenous and exogenous organic anions by excretory and barrier tissues. Little is known about the OAT three-dimensional structure or substrate/protein interactions involved in transport. In this investigation, a theoretical three-dimensional model was generated for human OAT1 (hOAT1) based on fold recognition to the crystal structure of the glycerol 3-phosphate transporter (GlpT) from Escherichia coli. GlpT and hOAT1 share several sequence motifs as major facilitator superfamily members. The structural hOAT1 model shows that helices 5, 7, 8, 10, and 11 surround an electronegative putative active site ( approximately 830A(3)). The site opens to the cytoplasm and is surrounded by three residues not previously examined for function (Tyr(230) (domain 5) and Lys(431) and Phe(438) (domain 10)). Effects of these residues on p-aminohippurate (PAH) and cidofovir transport were assessed by point mutations in a Xenopus oocyte expression system. Membrane protein expression was severely limited for the Y230A mutant. For the K431A and F438A mutants, [(3)H]PAH uptake was less than 30% of wild-type hOAT1 uptake after protein expression correction. Reduced V(max) values for the F438A mutant confirmed lower protein expression. In addition, the F438A mutant exhibited an increased affinity for cidofovir but was not significantly different for PAH. Differences in handling of PAH and cidofovir were also observed for the Y230F mutant. Little uptake was determined for cidofovir, whereas PAH uptake was similar to wild-type hOAT1. Therefore, the hOAT1 structural model has identified two new residues, Tyr(230) and Phe(438), which are important for substrate/protein interactions. PMID:17038320
Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3.
Ikemura, Kenji; Hamada, Yugo; Kaya, Chinatsu; Enokiya, Tomoyuki; Muraki, Yuichi; Nakahara, Hiroki; Fujimoto, Hajime; Kobayashi, Tetsu; Iwamoto, Takuya; Okuda, Masahiro
Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015. We established that pemetrexed was transported via hOAT3 (Km = 68.3 ± 11.1 µM). Lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan inhibited hOAT3-mediated uptake of pemetrexed in a concentration-dependent manner. The inhibitory effect of lansoprazole was much greater than those of other PPIs and the apparent IC50 value of lansoprazole against pemetrexed transport via hOAT3 was 0.57 ± 0.17 µM. The inhibitory type of lansoprazole was competitive. In a retrospective study, multivariate analysis revealed that coadministration of lansoprazole, but not other PPIs, with pemetrexed and carboplatin was an independent risk factor significantly contributing to the development of hematologic toxicity (odds ratio: 10.004, P = 0.005). These findings demonstrated that coadministration of lansoprazole could exacerbate the hematologic toxicity associated with pemetrexed, at least in part, by competitive inhibition of hOAT3. Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interaction-induced side effects for achievement of safe and appropriate chemotherapy with pemetrexed. PMID:27465369
Catalytic Ester–Amide Exchange Using Group (IV) Metal Alkoxide–Activator Complexes
Han, Chong; Lee, Jonathan P.; Lobkovsky, Emil; Porco, John A.
A process for preparation of amides from unactivated esters and amines has been developed using a catalytic system comprised of group (IV) metal alkoxides in conjunction with additives including 1-hydroxy-7-azabenzotriazole (HOAt). In general, ester–amide exchange proceeds using a variety of structurally diverse esters and amines without azeotropic reflux to remove the alcohol byproduct. Initial mechanistic studies on the Zr(Ot-Bu)4–HOAt system revealed that the active catalyst is a novel, dimeric zirconium complex as determined by X-ray crystallography. PMID:16011366
Controlled rotation mechanism of DNA strand exchange by the Hin serine recombinase
Xiao, Botao; McLean, Meghan M.; Lei, Xianbin; Marko, John F.; Johnson, Reid C.
DNA strand exchange by serine recombinases has been proposed to occur by a large-scale rotation of halves of the recombinase tetramer. Here we provide the first direct physical evidence for the subunit rotation mechanism for the Hin serine invertase. Single-DNA looping assays using an activated mutant (Hin-H107Y) reveal specific synapses between two hix sites. Two-DNA "braiding" experiments, where separate DNA molecules carrying a single hix are interwound, show that Hin-H107Y cleaves both hix sites and mediates multi-step rotational relaxation of the interwinding. The variable numbers of rotations in the DNA braid experiments are in accord with data from bulk experiments that follow DNA topological changes accompanying recombination by the hyperactive enzyme. The relatively slow Hin rotation rates, combined with pauses, indicate considerable rotary friction between synapsed subunit pairs. A rotational pausing mechanism intrinsic to serine recombinases is likely to be crucial for DNA ligation and for preventing deleterious DNA rearrangements. PMID:27032966
Emergency department use among patients from residential aged care facilities under a Hospital in the Nursing Home scheme in public hospitals in Queensland Australia
Lukin, Bill; Fan, Li-jun; Zhao, Jing-zhou; Sun, Jian-dong; Dingle, Kaeleen; Purtill, Rhonda; Tapp, Sam; Hou, Xiang-yu
BACKGROUND: Hospital emergency department (ED) use by patients from residential aged care facilities (RACFs) is not always appropriate, and this calls for interventions to avoid some unnecessary uses. This study aims to compare patterns of ED use by RACF patients with and without a Hospital in the Nursing Home (HiNH) program. METHODS: RACF patients presenting to EDs of a hospital with and a hospital without this program during pre- and post-intervention periods were included. Data on patient demographics and ED presentation characteristics were obtained from the Emergency Department Information System database, and were analysed by descriptive and comparative statistics. RESULTS: In both hospitals, most RACF residents presenting to EDs were aged between 75–94 years, female, triaged at scale 3 to 5, and transferred on weekdays and during working hours. Almost half of them were subsequently admitted to hospitals. In accordance with the ICD-10-AM diagnostic coding system, diagnoses that consistently ranked among the top three reasons for visiting the two hospitals before and after intervention included Chapter XIX: injury and poisoning and Chapter X: respiratory diseases. Associated with the intervention, significant decreases in the numbers of presentations per 1 000 RACF beds were identified among patients diagnosed with Chapter XI: digestive diseases [rate ratio (95%CI): 0.09 (0.04, 0.22); P<0.0001] and Chapter XXI: factors influencing health status and contact with health services [rate ratio (95%CI): 0.22 (0.07, 0.66); P=0.007]. CONCLUSION: The HiNH program may reduce the incidence of RACF residents visiting EDs for diagnoses of Chapter XI and Chapter XXI. PMID:27547277
War time experiences of triage and resuscitation: Australian Army nurses in the Vietnam War, 1967-1971.
Biedermann, N E; Harvey, N R
The experiences of nurses in war is prolifically described in the North American scholarly literature, and in the Australian nursing literature to a lesser extent. The literature describes the plights and achievements of nurses caring for soldiers and civilians often under the most undesirable of circumstances. A central focus of war time nursing is the resuscitation of critically wounded soldiers. This paper addresses the experiences of the Australian Army nurses who were involved in the triage and resuscitation of critically wounded allied and enemy soldiers in the Vietnam War between 1967 and 1971. As part of a research study to explore and analyse the nature of nursing work in the Vietnam War, seventeen Vietnam veteran nurses were interviewed about their experiences. This paper explores the progression of the triage department in the Australian military hospital in Vung Tau, and it highlights that the majority of the nurses who took part in this study were clinically unprepared, particularly as emergency nurses.
Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.
Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin
This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp
Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.
Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin
This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp
Concerted Amidation of Activated Esters: Reaction Path and Origins of Selectivity in the Kinetic Resolution of Cyclic Amines via N-Heterocyclic Carbenes and Hydroxamic Acid Cocatalyzed Acyl Transfer
The N-heterocyclic carbene and hydroxamic acid cocatalyzed kinetic resolution of cyclic amines generates enantioenriched amines and amides with selectivity factors up to 127. In this report, a quantum mechanical study of the reaction mechanism indicates that the selectivity-determining aminolysis step occurs via a novel concerted pathway in which the hydroxamic acid plays a key role in directing proton transfer from the incoming amine. This modality was found to be general in amide bond formation from a number of activated esters including those generated from HOBt and HOAt, reagents that are broadly used in peptide coupling. For the kinetic resolution, the proposed model accurately predicts the faster reacting enantiomer. A breakdown of the steric and electronic control elements shows that a gearing effect in the transition state is responsible for the observed selectivity. PMID:25050843
Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries.
Li, Yizhou; Gabriele, Elena; Samain, Florent; Favalli, Nicholas; Sladojevich, Filippo; Scheuermann, Jörg; Neri, Dario
DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins of biological or pharmaceutical interest. In the majority of cases, synthetic procedures for the formation of DNA-encoded combinatorial libraries incorporate at least one step of amide bond formation between amino-modified DNA and a carboxylic acid. We investigated reaction conditions and established a methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole and N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% for 423/543 (78%) of the carboxylic acids tested. These reaction conditions were efficient with a variety of primary and secondary amines, as well as with various types of amino-modified oligonucleotides. The reaction conditions, which also worked efficiently over a broad range of DNA concentrations and reaction scales, should facilitate the synthesis of novel DNA-encoded combinatorial libraries.
PEPT1- and OAT1/3-mediated drug-drug interactions between bestatin and cefixime in vivo and in vitro in rats, and in vitro in human.
Wang, Li; Wang, Changyuan; Liu, Qi; Meng, Qiang; Huo, Xiaokui; Sun, Pengyuan; Yang, Xiaobo; Sun, Huijun; Zhen, Yuhong; Peng, Jinyong; Ma, Xiaochi; Liu, Kexin
The purpose of the present study was to elucidate the transporter-mediated pharmacokinetics mechanism of drug-drug interactions (DDIs) between bestatin and cefixime. The plasma concentrations and bioavailabilities of bestatin and cefixime were decreased after oral co-administration in rats. The uptake in rat everted intestinal sacs of bestatin and cefixime were dramatically declined after co-administration of the two drugs. Bestatin and cefixime can mutually competitively inhibit the uptake by hPEPT1-HeLa cells. The plasma concentrations of bestatin and cefixime were increased; however, the cumulative biliary excretion had no significant change, and the cumulative urinary excretion and renal clearance of the two drugs in rats decreased after intravenous coadministration. Moreover, decreased uptake of the two drugs was observed in human kidney slices, rat kidney slices and hOAT1/hOAT3-transfected HEK293 cells when bestatin and cefixime were coadministered. The accumulation of bestatin and cefixime in kidney slices can be inhibited by p-aminohippurate, benzylpenicillin and probenecid, but not by tetraethyl ammonium. The results suggest that intestinal absorption and renal excretion of bestatin and cefixime can be inhibited when the two drugs were co-administered in rats. The pharmacokinetic mechanism indicates that the DDIs between bestatin and cefixime are mainly mediated by Pept1 and Oat1/3 in rats. PEPT1 and OAT1/3 are the target transporters of DDIs between bestatin and cefixime in human kidney slices and human transfected cells, proposing possible drug-drug interaction in humans.
Altered Glycine Decarboxylation Inhibition in Isonicotinic Acid Hydrazide-Resistant Mutant Callus Lines and in Regenerated Plants and Seed Progeny
Zelitch, Israel; Berlyn, Mary B.
Isonicotinic acid hydrazide (INH), an inhibitor of the photorespiratory pathway blocking the conversion of glycine to serine and CO2, has been used as a selective agent to obtain INH-resistant tobacco (Nicotiana tabacum) callus cells. Of 22 cell lines that were INH-resistant, none were different from wild-type cells in their ability to take up [3H]INH or to oxidize INH to isonicotinic acid. In 7 of the 22 cell lines, INH resistance was associated with decreased inhibition of NAD-dependent glycine decarboxylation activity in isolated mitochondrial preparations. In the cell line that was most extensively investigated (I 24), this biochemical phenotype (exhibiting a 3-fold higher Ki with INH) was observed in leaf mitochondria of regenerated plants and of plants produced from them by self-fertilization. After crosses between resistant and sensitive plants, the decreased inhibition of glycine decarboxylation was observed among F2 and backcross progeny only in those plants previously identified as INH-resistant by callus growth tests. In contrast, in siblings identified as INH-sensitive, glycine decarboxylation was inhibited by INH at the wild-type level. This demonstration of the transfer of an altered enzyme property from callus to regenerated plants and through seed progeny fulfills an important requirement for the use of somatic cell genetics to produce biochemical mutants of higher plants. PMID:16662158
Scenario-based tsunami hazard assessment for the coast of Vietnam from the Manila Trench source
NASA Astrophysics Data System (ADS)
Hong Nguyen, Phuong; Cong Bui, Que; Ha Vu, Phuong; The Pham, Truyen
This paper assesses the impact of tsunamis in the East Vietnam Sea potentially originated from a giant rupture along the Manila Trench to the Vietnamese coast. Tsunami heights and arrival times to the major forecast points along the Vietnamese coast are computed using COMCOT model. The results of the worst case scenario (Mw = 9.3) and two extreme scenarios were used to assess the tsunami hazards. The simulation results show that Vietnamese coast can be divided into three parts with different levels of tsunami hazard. The highest threat exists along the coasts of Central and North-Central Vietnam, from Quang Binh to Ba Ria - Vung Tau provinces, with maximum wave height of 18 m observed near Quang Ngai coast, and a tsunami would reach this coastline in two hours at the earliest. The northern coastal zone of Vietnam has lower tsunami hazard. In the worst case scenario, maximum amplitudes of tsunami waves at Hai Phong sea port and Nam Dinh city, North Vietnam, are 3.5 m and 3.7 m, respectively, while the travel times to these sites are much longer, over 8 h. The southern coastal zone of Vietnam has very low tsunami hazard. In the worst case scenario, the maximum amplitude at Ca Mau is 0.12 m, while the travel time is over 10 h.
Larval morphology and complex vocal repertoire of Rhacophorus helenae (Anura: Rhacophoridae), a rare flying frog from Vietnam.
Vassilieva, Anna B; Gogoleva, Svetlana S; Poyarkov, Nikolay A Jr
We present new data on the distribution, reproduction, larval morphology and vocalization of Rhacophorus helenae (Rhacophoridae), a narrowly distributed frog from southern Vietnam. Two new populations of R. helenae were discovered during field surveys in the lowland monsoon forests in Dong Nai and Ba Ria-Vung Tau provinces in 2010-2013. Spawning was observed in May 2013. Egg clutches containing small (2.3±0.1 mm) unpigmented eggs were embedded in a foam nest and suspended high on trees above temporary ponds. The tadpoles of R. helenae have a morphology typical of pond-dwelling Rhacophorus larvae with a moderate tail length and a labial tooth row formula of 5(2-5)/3. Postmetamorphic juveniles differed from adult frogs in the features of their coloration and less developed webbing. The complex vocal repertoire of R. helenae included five types of tonal, wideband and pulsed calls and several transitional signal types differentiated by frequency and amplitude parameters. Calls were uttered as singular signals (pulsed calls) or within non-stereotyped series of variable duration (other call types). The complex structure of the advertisement call markedly distinguishes R. helenae from other members of the Rhacophorus reinwardtii species complex. PMID:27395638
Larval morphology and complex vocal repertoire of Rhacophorus helenae (Anura: Rhacophoridae), a rare flying frog from Vietnam.
Vassilieva, Anna B; Gogoleva, Svetlana S; Poyarkov, Nikolay A Jr
We present new data on the distribution, reproduction, larval morphology and vocalization of Rhacophorus helenae (Rhacophoridae), a narrowly distributed frog from southern Vietnam. Two new populations of R. helenae were discovered during field surveys in the lowland monsoon forests in Dong Nai and Ba Ria-Vung Tau provinces in 2010-2013. Spawning was observed in May 2013. Egg clutches containing small (2.3±0.1 mm) unpigmented eggs were embedded in a foam nest and suspended high on trees above temporary ponds. The tadpoles of R. helenae have a morphology typical of pond-dwelling Rhacophorus larvae with a moderate tail length and a labial tooth row formula of 5(2-5)/3. Postmetamorphic juveniles differed from adult frogs in the features of their coloration and less developed webbing. The complex vocal repertoire of R. helenae included five types of tonal, wideband and pulsed calls and several transitional signal types differentiated by frequency and amplitude parameters. Calls were uttered as singular signals (pulsed calls) or within non-stereotyped series of variable duration (other call types). The complex structure of the advertisement call markedly distinguishes R. helenae from other members of the Rhacophorus reinwardtii species complex.
Identification of human metabolites of (-)-N-{2-[(R)-3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758), a novel If channel inhibitor, and investigation of the transporter-mediated renal and hepatic excretion of these metabolites.
Umehara, Ken-ichi; Shirai, Nobuaki; Iwatsubo, Takafumi; Noguchi, Kiyoshi; Usui, Takashi; Kamimura, Hidetaka
(-)-N-{2-[(R)-3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758) is a novel inhibitor of the "funny" If current channel (If channel) that is expressed in the sinus node of heart and is being developed as a treatment for stable angina and atrial fibrillation. Its metabolites were identified in human urine, plasma, and feces by radio-high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analyses after oral administration of [(14)C]YM758. 6,7-Dimethoxy-2-[(3R)-piperidin-3-ylcarbonyl]-1,2,3,4-tetrahydroisoquinoline (YM-252124), (5R)-5-[(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]piperidin-2-one (YM-385459), 2-{[(3R)-1-{2-[(4-fluorobenzoyl)amino]ethyl}piperidin-3-yl]carbonyl}-7-methoxy-1,2,3,4-tetrahydroisonolin-6-yl beta-D-glucopyranosiduronic acid (AS2036329), and the unchanged drug were detected as major constituents in both urine and plasma, whereas N-(4-fluorobenzoyl)glycine (YM-385461) was detected in plasma, but not in urine. The renal and hepatic uptake transporters for these metabolites were investigated by assessing their inhibitory effect on uptake activity in human (h) organic cation transporter (OCT) 1-3/rat (r) Oct1-3, human organic anion transporter (OAT) 1/rOat1, hOAT3/rOat3, and organic anion-transporting protein 1B1/1B3-expressing HEK293 cells. IC(50) values of YM-252124 for 1-methyl-4-phenylpyridinium uptake via hOCT2 and rOct2 were 93.9 and 1700 microM, respectively, suggesting that this metabolite is secreted into urine via hOCT2/rOct2 and that the large difference in the inhibitory potentials between hOCT2 and rOct2 explains the species difference in the urinary excretion ratio of the radioactivity. The renal secretion of YM-385461, one derivative of p-aminohippuric acid, via hOAT1/rOat1, and hepatic uptake of YM-252124 via hOCT1/rOct1 was also expected. This kind of study was useful in investigating the relationship between the urinary
Thermal properties and physicochemical behavior in aqueous solution of pyrene-labeled poly(ethylene glycol)-polylactide conjugate
Chen, Wei-Lin; Peng, Yun-Fen; Chiang, Sheng-Kuo; Huang, Ming-Hsi
A fluorescence-labeled bioresorbable polymer was prepared by a coupling reaction of poly(ethylene glycol)-polylactide (PEG-PLA) with carboxyl pyrene, using N,N'-diisopropylcarbodiimide/1-hydroxy-7-azabenzotriazole (DIC/HOAt) as a coupling agent and 4-dimethylaminopyridine (DMAP) as a catalyst. The obtained copolymer, termed PEG-PLA-pyrene, was characterized using various analytical techniques, such as gel permeation chromatography (GPC), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), proton nuclear magnetic resonance (1H-NMR), infrared spectroscopy (IR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), to identify the molecular structure and to monitor the thermal property changes before and after the reaction. The presence of a pyrene moiety at the end of polylactide (PLA) did not alter the crystallization ability of the poly(ethylene glycol) (PEG) blocks, indicating that the conjugate preserved the inherent thermal properties of PEG-PLA. However, the presence of PEG-PLA blocks strongly reduced the melting of pyrene, indicating that the thermal characteristics were sensitive to PEG-PLA incorporation. Regarding the physicochemical behavior in aqueous solution, a higher concentration of PEG-PLA-pyrene resulted in a higher ultraviolet-visible (UV-vis) absorbance and fluorescence emission intensity. This is of great interest for the use of this conjugate as a fluorescence probe to study the in vivo distribution as well as the internalization and intracellular localization of polymeric micelles. PMID:25914532
Functional expression of pig renal organic anion transporter 3 (pOAT3).
Hagos, Yohannes; Braun, Isabella M; Krick, Wolfgang; Burckhardt, Gerhard; Bahn, Andrew
With the cloning of pig renal organic anion transporter 1 (pOAT1) (Biochimie 84 (2002) 1219) we set up a model system for comparative studies of cloned and natively isolated membrane located transport proteins. Meanwhile, another transport protein involved in p-aminohippurate (PAH) uptake on the basolateral side of the proximal tubule cells was identified, designated organic anion transporter 3 (OAT3). To explore the contribution of pOAT1 to the PAH clearance in comparison to OAT3, it was the aim of this study to extend our model by cloning of the pig ortholog of OAT3. Sequence comparisons of human organic anion transporter 3 (hOAT3) with the expressed sequence tag (EST) database revealed a clone and partial sequence of the pig renal organic anion transporter 3 (pOAT3) ortholog. Sequencing of the entire open reading frame resulted in a protein of 543 amino acid residues encoded by 1632 base pairs (EMBL Acc. No. AJ587003). It showed high homologies of 81%, 80%, 76%, and 77% to the human, rabbit, rat, and mouse OAT3, respectively. A functional characterization of pOAT3 in Xenopus laevis oocytes yielded an apparent Km (Kt) for [3H]estrone sulfate of 7.8 +/- 1.3 microM. Moreover, pOAT3 mediated [3H]estrone sulfate uptake was almost abolished by 0.5 mM of glutarate, dehydroepiandosterone sulfate, or probenecid consistent with the hallmarks of OAT3 function.
Weaver ant role in cashew orchards in Vietnam.
Peng, Renkang; Lan, La Pham; Christian, Keith
Cashew (Anacardium occidentale L.) is a very important source of income for more than 200,000 farmer households in Vietnam. The present cashew productivity in Vietnam is low and unstable, and pest damage is partly responsible for this. Cashew farmers rely on pesticides to minimize the damage, resulting in adverse impacts on farm environment and farmers' health. Weaver ants (Oecophylla spp) are effective biocontrol agents of a range of cashew insect pests in several cashew-growing countries, and these ants are widely distributed in Vietnam. The aim of this study is to evaluate the potential of weaver ants in cashew orchards in Vietnam. Field surveys and field experiment were conducted in five cashew orchards from July 2006 to January 2008 in Binh Phuoc, Dong Nai, and Ba Ria Vung Tau provinces, Vietnam. Based on the field surveys, the most important pests that damage flushing foliar and floral shoots and young cashew fruits and nuts were mosquito bugs, brown shoot borers, blue shoot borers, and fruit-nut borers. The damage caused by each of these pests was significantly lower on trees with weaver ants compared with trees without the ants, showing that the ants were able to keep these pest damages under the control threshold. Regular monitoring of the field experiment showed that weaver ants were similar to insecticides for controlling mosquito bugs, blue shoot borers, fruit-nut borers, leaf rollers, and leaf miners. Aphids did not become major pests in plot with weaver ants. To manage insect pest assemblage in cashew orchards, an integrated pest management using weaver ants as a major component is discussed.
Weaver ant role in cashew orchards in Vietnam.
Peng, Renkang; Lan, La Pham; Christian, Keith
Cashew (Anacardium occidentale L.) is a very important source of income for more than 200,000 farmer households in Vietnam. The present cashew productivity in Vietnam is low and unstable, and pest damage is partly responsible for this. Cashew farmers rely on pesticides to minimize the damage, resulting in adverse impacts on farm environment and farmers' health. Weaver ants (Oecophylla spp) are effective biocontrol agents of a range of cashew insect pests in several cashew-growing countries, and these ants are widely distributed in Vietnam. The aim of this study is to evaluate the potential of weaver ants in cashew orchards in Vietnam. Field surveys and field experiment were conducted in five cashew orchards from July 2006 to January 2008 in Binh Phuoc, Dong Nai, and Ba Ria Vung Tau provinces, Vietnam. Based on the field surveys, the most important pests that damage flushing foliar and floral shoots and young cashew fruits and nuts were mosquito bugs, brown shoot borers, blue shoot borers, and fruit-nut borers. The damage caused by each of these pests was significantly lower on trees with weaver ants compared with trees without the ants, showing that the ants were able to keep these pest damages under the control threshold. Regular monitoring of the field experiment showed that weaver ants were similar to insecticides for controlling mosquito bugs, blue shoot borers, fruit-nut borers, leaf rollers, and leaf miners. Aphids did not become major pests in plot with weaver ants. To manage insect pest assemblage in cashew orchards, an integrated pest management using weaver ants as a major component is discussed. PMID:25195419
Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets
Pastor-Anglada, Marçal; Pérez-Torras, Sandra
Nucleoside and nucleobase analogs are currently used in the treatment of solid tumors, lymphoproliferative diseases, viral infections such as hepatitis and AIDS, and some inflammatory diseases such as Crohn. Two gene families are implicated in the uptake of nucleosides and nucleoside analogs into cells, SCL28 and SLC29. The former encodes hCNT1, hCNT2, and hCNT3 proteins. They translocate nucleosides in a Na+ coupled manner with high affinity and some substrate selectivity, being hCNT1 and hCNT2 pyrimidine- and purine-preferring, respectively, and hCNT3 a broad selectivity transporter. SLC29 genes encode four members, being hENT1 and hENT2 the only two which are unequivocally implicated in the translocation of nucleosides and nucleobases (the latter mostly via hENT2) at the cell plasma membrane. Some nucleoside-derived drugs can also interact with and be translocated by members of the SLC22 gene family, particularly hOCT and hOAT proteins. Inter-individual differences in transporter function and perhaps, more importantly, altered expression associated with the disease itself might modulate the transporter profile of target cells, thereby determining drug bioavailability and action. Drug transporter pharmacology has been periodically reviewed. Thus, with this contribution we aim at providing a state-of-the-art overview of the clinical evidence generated so far supporting the concept that these membrane proteins can indeed be biomarkers suitable for diagnosis and/or prognosis. Last but not least, some of these transporter proteins can also be envisaged as drug targets, as long as they can show "transceptor" functions, in some cases related to their role as modulators of extracellular adenosine levels, thereby providing a functional link between P1 receptors and transporters. PMID:25713533
Effects of cereal fiber on leptin resistance and sensitivity in C57BL/6J mice fed a high-fat/cholesterol diet
Zhang, Ru; Jiao, Jun; Zhang, Wei; Zhang, Zheng; Zhang, Weiguo; Qin, Li-Qiang; Han, Shu-Fen
Background Cereal fiber is reported to be associated with obesity and metabolic diseases. However, whether cereal fiber improves leptin resistance and sensitivity remains unclear. Design For 24 weeks, 48 male C57BL/6J mice were randomly given a normal chow diet (Chow), high-fat/cholesterol diet (HFD), HFD with 0.8% oat fiber (H-oat) or HFD with 0.8% wheat bran fiber (H-wheat). At the end of feeding period, both the serum insulin and leptin levels were determined by ELISA kits. Western blotting was used to assess the protein expressions of the leptin receptor (LepR) and the leptin-signaling pathway in the adipose tissues. Results Our results suggested that mice fed oat or wheat bran fiber exhibited lower body weight, serum lipids, as well as insulin and leptin levels. The two cereal fibers potently increased the protein expressions of LepR in the adipose tissue. In addition, protein expressions of Janus kinase 2 (JAK2) and transcription 3 (STAT3) (induced by LepR), which enhances leptin signaling, were significantly higher and the expression of cytokine signaling-3 (SOCS3), which inhibits leptin signaling, was significantly lower in the two cereal fiber groups than in the HFD group. Conclusion Taken together, our findings suggest that cereal fiber can improve leptin resistance and sensitivity by the JAK2/STAT3 pathway in C57BL/6J mice fed a HFD; furthermore, oat fiber is more effective in the improvement of leptin sensitivity than wheat bran fiber, in this murine model. PMID:27534844
Coral Geochemical Proxy Records Of The East Asian Winter Monsoon And Hydrological Conditions In The Central Vietnam From 1978-2004 AD
NASA Astrophysics Data System (ADS)
Chang, C.; Shen, C.; Chen, Y.; Chiang, H.; Lam, D. D.; Ngai, N.
Monthly-resolution geochemical proxies, including δ18O, δ13C, Sr/Ca, and Ba/Ca, in a living Porites coral head, collected from Son Tra Island, a near-shore island located at the north tip of Vung Da Nang Bay, central Vietnam (16°12'59.4", 108°1'57.1"), was used to quantitatively reconstruct records of sea surface temperature (SST), sea surface salinity (SSS), seasonality of rainfall, and regional terrestrial input during a period of 1978-2004 AD. By comparing the 1/4-century geochemical data, five features are exhibited. (1) The coral Sr/Ca-inferred summer SSTs correspond well with the 1°x1° instrumental data to suggest that the regional SST record can be retrieved from this local coral head. (2) Interannual variation of coral winter SST data does not follow regional instrumental values. The harmonic phenomenon between coral inferred winter SST dynamic and the surface pressure difference, between the southern South China Sea (SCS) (0-10°N, 105-115°E) and the northern SCS (22.5-32.5°N, 112-122°E), indicating that the cold local SST induced by East Asian winter monsoon was addressed in the Son Tra coral. (3) 1‰ seasonal anomaly of δ18O residual (Δδ18O) suggests a 2-4-psu seasonal salinity change between dry and wet seasons. (4) The synchronous intra-annual changes of δ18O and Ba/Ca data suggest that the rainy season is from late summer to winter, which is consistent with the meteorological record. (5) The high Ba/Ca background level of 10 μmol/mol in 1992-2004, 2-3 times larger than the averaged value of 4 μmol/mol in 1978-1992, indicates an enhanced terrestrial sediment discharge into the bay over the past 10 years. Ba records probably reflect an impact of human activity on hydrological change since the Vietnam War.
Detection of Area Changes in River Mouthbars at the Mekong River Delta using ALOS/PALSAR data
NASA Astrophysics Data System (ADS)
Tanaka, A.; Uehara, K.; Tamura, T.; Saito, Y.
other seasonal changing factors, such as the mean monthly sea level at Vung Tau hydrometeorological station, lower Mekong mainstream monthly discharge at Kratie, eastern Cambodia, and rainfall at Chau Doc in the Mekong River Delta. Moreover, it is highly likely that tidal height at the time of SAR data acquisition clearly reflect the area by examining over half-day intervals for ascending and descending images. To monitor the area changes over longer time intervals further investigation combing another SAR data is required. It will also be useful to apply to other regions to reach more comprehensive and comparable analysis.
Synthesis and biological activities of new side chain and backbone cyclic bradykinin analogues.
Schumann, C; Seyfarth, L; Greiner, G; Paegelow, I; Reissmann, S
A series of conformationally constrained cyclic analogues of the peptide hormone bradykinin (BK, Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) was synthesized to check different turned structures proposed for the bioactive conformation of BK agonists and antagonists. Cycles differing in the size and direction of the lactam bridge were performed at the C- and N-terminal sequences of the molecule. Glutamic acid and lysine were introduced into the native BK sequence at different positions for cyclization through their side chains. Backbone cyclic analogues were synthesized by incorporation of N-carboxy alkylated and N-amino alkylated amino acids into the peptide chain. Although the coupling of Fmoc-glycine to the N-alkylated phenylalanine derivatives was effected with DIC/HOAt in SPPS, the dipeptide building units with more bulky amino acids were pre-built in solution. For backbone cyclization at the C-terminus an alternative building unit with an acylated reduced peptide bond was preformed in solution. Both types of building units were handled in the SPPS in the same manner as amino acids. The agonistic and antagonistic activities of the cyclic BK analogues were determined in rat uterus (RUT) and guinea-pig ileum (GPI) assays. Additionally, the potentiation of the BK-induced effects was examined. Among the series of cyclic BK agonists only compound 3 with backbone cyclization between positions 2 and 5 shows a significant agonistic activity on RUT. To study the influence of intramolecular ring closure we used an antagonistic analogue with weak activity, [D-Phe7]-BK. Side chain as well as backbone cyclization in the N-terminus of [D-Phe7]-BK resulted in analogues with moderate antagonistic activity on RUT. Also, compound 18 in which a lactam bridge between positions 6 and 9 was achieved via an acylated reduced peptide bond has moderate antagonistic activity on RUT. These results support the hypothesis of turn structures in both parts of the molecule as a requirement for BK
Intake-to-delivered-energy ratios for central station and distributed electricity generation in California
NASA Astrophysics Data System (ADS)
Heath, Garvin A.; Nazaroff, William W.
In previous work, we showed that the intake fraction (iF) for nonreactive primary air pollutants was 20 times higher in central tendency for small-scale, urban-sited distributed electricity generation (DG) sources than for large-scale, central station (CS) power plants in California [Heath, G.A., Granvold, P.W., Hoats, A.S., Nazaroff, W.W., 2006. Intake fraction assessment of the air pollutant exposure implications of a shift toward distributed electricity generation. Atmospheric Environment 40, 7164-7177]. The present paper builds on that study, exploring pollutant- and technology-specific aspects of population inhalation exposure from electricity generation. We compare California's existing CS-based system to one that is more reliant on DG units sited in urban areas. We use Gaussian plume modeling and a GIS-based exposure analysis to assess 25 existing CSs and 11 DG sources hypothetically located in the downtowns of California's most populous cities. We consider population intake of three pollutants—PM 2.5, NO x and formaldehyde—directly emitted by five DG technologies—natural gas (NG)-fired turbines, NG internal combustion engines (ICE), NG microturbines, diesel ICEs, and fuel cells with on-site NG reformers. We also consider intake of these pollutants from existing CS facilities, most of which use large NG turbines, as well as from hypothetical facilities located at these same sites but meeting California's best-available control technology standards. After systematically exploring the sensitivity of iF to pollutant decay rate, the iFs for each of the three pollutants for all DG and CS cases are estimated. To efficiently compare the pollutant- and technology-specific exposure potential on an appropriate common basis, a new metric is introduced and evaluated: the intake-to-delivered-energy ratio (IDER). The IDER expresses the mass of pollutant inhaled by an exposed population owing to emissions from an electricity generation unit per quantity of electric
Heterogeneous δ18O in the mantle wedge beneath Medicine Lake and Mt. Shasta volcanoes (California): ancient or modern subduction signature?
NASA Astrophysics Data System (ADS)
Martin, E.; Bindeman, I.; Grove, T.
This study presents new analyses of O-isotopes in olivine phenocrysts from most primitive high alumina olivine tholeiite (HAOT) from Medicine Lake volcano (MLV; California) with MgO > 8%. The measured δ18OOl-values range from 4.69‰ to 5.49‰, with an average of 5.07‰ (n = 12), which is low relatively to the mantle olivine values (5.2‰±±0.2‰). We compare these data to O-isotopes measured in olivine phenocrysts from the most primitive lavas from Mount Shasta, which show high δ18OOl-values relatively to the olivine mantle value, 5.89-6.08‰ in HAOT (n = 2), 5.31-5.81‰ in basaltic andesite (BA; n = 7) and 5.54-5.85‰ in primitive magnesian andesite (PMA; n = 5). The primitive crystal poor nature of these lavas, Mg# > 0.65, and the fact that we analyzed olivine, the first mineral to crystallize in these lavas, allow us a good assessment to mantle-derived magmas. The HOAT are known to be generated by nearly anhydrous melting of spinel peridotite, which makes them a good indicator of the composition of the mantle unaffected by the present day subduction fluids. Therefore it appears that the mantle beneath MLV has a low- to mantle-like δ18OOl with variation of up to 0.8‰. However, beneath Mt Shasta the mantle has a relatively high δ18OOl and more homogeneous (based on two samples). Overall, it appears that the arc mantle of the South Cascade segment is heterogeneous with more than 1.3‰ variation in δ18OOl. The question that we address here is: Is the high-δ18O signature measured in olivine phenocrysts from BA and PMA from Mt Shasta come from the preexisting mantle source itself or from the present subduction fluids? If we consider BA and PMA to be generated by high-δ18O fluids flux melting in the present subduction environment, how can we explain high-δ18O values measured in HAOT? The heterogeneous character of the mantle in the South Cascades could be due to ancient subduction fluids more and more depleted during the slab dehydration that fluxed
[Risk factors for smoking in persons over 45].
Jóźwiak, Paulina; Wierzejska, Ewelina; Szmagaj, Aleksandra; Biskupska, Maria
cigarettes was associated with hinh level of LDL cholesterol. The smokers aged over 45 can be generally characterized as strongly addicted and have been smoking for many years. Anti-tobacco activities targeted at this group should be intensified in order to reduce the number of cigarettes smoked daily. These interventions should take into account group characteristics and its needs. PMID:25799855
Late Pleistocene-Holocene seismic stratigraphy of the Southeast Vietnam Shelf
NASA Astrophysics Data System (ADS)
Dung, Bui Viet; Stattegger, Karl; Unverricht, Daniel; Phach, Phung Van; Thanh, Nguyen Trung
The Late Pleistocene-Holocene sedimentary architecture of the Southeast (SE) Vietnam Shelf was investigated using high-resolution seismic profiles and core samples. Three systems tracts and a prominent seismic reflection surface at the base of the sequence were revealed. This surface (SB1) is interpreted as a sequence boundary formed by subaerial processes during the Late Pleistocene sea-level fall and subsequent marine reworking during transgression. A surface map of the lowstand surface, compiled from seismic profiles and sediment cores, revealed the W-E to N-S oriented incised-valley system of the paleo-Mekong River. The incised valleys show a clear change in morphology from the north to the south in the study area. The northern incised-valley system off Vung Tau appears as a narrow and deep V-shape in cross-section (< 5 km wide and tens of meters deep) likely as a result of the high-gradient morphology of the paleo-shelf. In contrast, the wide and low-gradient paleo-shelf off the modern Mekong Delta and Ca Mau Peninsula created shallow incised-valleys (5-15 km wide and < 15 m deep) on the exposed shelf. The lowstand systems tract (LST) consists of a prograding outer shelf delta-wedge formed during the Last Glacial Maximum (LGM) sea-level lowstand period. The transgressive systems tract (TST) was well preserved in the incised-valleys, where its thickness reaches 15-25 m. Sediment core analysis results and seismic facies reveal that the TST deposits within the incised-channels were marked by a transition from fluvial deposits at the base to marine deposits in the upper part of the channels. On the exposed shelf and the interfluvial area of the incised-channels, the TST is a sandy layer overlying the sequence boundary SB1. Thickness of the TST on the shelf varies from 0 to 15 m. The highstand systems tract (HST) consists of thick mud clinoforms of the modern Mekong subaqueous delta. The HST wedge prograded onto the shelf primarily after the mid-Holocene sea


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subset: commoncrawl


text:
Im recently 20 years young, living at home currently in Knockrow NSW, working as a nurse in Ballina and love to explore. I was born and bred here in the Northern Rivers, I moved to Sydney for 4 months early 2016 and worked as a nanny and lived in Neutral Bay and Manly. Im a bright and bubbly individual who loves to cook, create, listen to music, chat and adventure. I love the beach and being active! I do have a little cat (Banjo) and may be getting a puppy but would only bring one with me when I move out, and leave the other at home with the parents. I really enjoy going out, relaxing with friends, and also having quiet time to do art ect ect. Of course I respect others space, but would always be up to cook up a feast for all in the house Im going to be studying my Bachelor of Nursing 2018 at SCU Lismore. And then go from there!
I am a quiet, independent and happy soul. I enjoy cooking- vegetarian, walks and yoga. I am a primary school teacher working casual relief at the moment. I am also studying Steiner Education. I have a gorgeous cat Lily who is an inside cat - for her sake and the wildlife! So I am looking for somewhere that is cat friendly. I'm going away over Easter so would be looking to move in at the beginning of second term - early May.
Hello We are two korean girls who work full time. We are looking for a room to stay about 3 months can be longer. We are pretty clean and quiet person and love to go swim on the weekend. Pls contact me if you would love to show your house and meet us. Mobile Regards Molley
I am an Australian, working as a trainer/teacher. I'm a non-smoker and don't have kids or pets though I love animals. I enjoy being fit, love food & a glass of wine on the deck. I'm private and home owner so I understand to keep a place clean and respected. I am flexible with my length of stay from 3 months to over 12 months depending on the place. References available.
Shae - 25 Year Old Female / Eliza - 29 Year Old Female We are currently based in Melbourne and are looking to relocate up the coast. We love animals, dancing, music, drinking with good company and meeting new people! As much as we love to socialize we do enjoy quiet time, going for walks and reading. Both tidy and respectful, warm souls.
Hi guys. I'm looking for a place in or around Lennox Head. I have two jobs, one as a bar manager and the other as a group trainer, so I'm pretty easy to live with as I'm not home all that much. I'd say I'm fairy laid back and just look for a house to be tidy and well-maintained. I think I'm a fairly active person so I try to be out and about keeping active when I have free time. Any questions, feel free to message or call
New to the area. Easygoing single lady of the 1960's decade, love to cook, enjoy great food & wine (in moderation), books, movies & world music. Inspired by travelling, (have seen a fair bit of the world & Oz) love getting out & about on adventures in my 4WD. Looking to share with mature single who enjoy similar interests. Clean & respectful of other
Happy, relaxed, fun, considerate, flexible traveller looking to settle. 31yrs old from the UK. I have been travelling and working for the past 7 years and looking to settle in to land life for hopefully a year or 2 in the Byron area. Looking for somewhere from mid May for a few months at least :)
Hi All, I'm moving to the Ballina area around the end of April for work as an environmental professional. I'm easy going, clean, respectful and looking for a laid back place to call home. Interested in all sports, the outdoors and keen to explore the local area. Cheers
Easy going, self sufficient, friendly and tidy, that's the dog, Salty. The human is OK too. I am interested in places in the general region, moving to the area from far South Coast NSW and intending to rent for a year or so while I get to know the region and choose a home to buy. I am active and creative and busy keeping up with the demands of a multi-faceted career. I like cooking and baking, gardening and growing food. I am fortunate to love my work. I sometimes travel for work but mostly work from home or nearby workshop. I'm good to live with because I am respectful of the space/time/social needs of others. I ask, listen and am able to express my own needs and perspective. I do not like drama. I make sure Salty is happy and other members of the household are comfortable with him and understand his cues and commands. Salty is pretty friendly, a desexed red Smithfield, he likes most humans and other animals, he walks away from drama with other dogs rather than be involved in aggression. I live a mostly healthy lifestyle, lots of dog walking and swimming - not much party these days! I still love music and dance. I drink alcohol now and then and I do smoke occasionally. I always make sure no one is offended or adversely affected by my smoking.
Hi, I am a professional male and just commenced a new managerial job in a NSW State Government authority in Byron Bay. My family and I live in Brisbane. I will be travelling to work and seeking accomodation Monday to Thursday nights only. I am clean, quiet and generally easy going in nature.
Hi!! Keat and I are a couple from Geelong who have decided to move to Ballina/ Lennox heads. Keat is already living in Lismore and I will be relocating at the start of may. We both are easy going, tidy, enjoy a drink, a laugh and keeping active. We have a dopey 2 year old golden retriever named Winnie who is really well behaved and can brighten up any bad day. We're happy to do team ups to lease the property we have just landed in east ballina!!
Hi! I'm looking for a room to rent in a share house or similar. I'm clean, tidy, trustworthy and reliable. I have lived in sharehouse for over a year in the local area. Looking for somewhere new and fun. Long stay preferred if I can find something suitable :) I'm 23 and work full time.
I am lucky to spend some time in Australia. I am 26 years old and a student from Austria. I lived with many people in shared accommodations so far and what I´ve learned from that is that I like it tidy and that responsibilities are shared between flat mates. I like to live with people and cook together and spend free time if wanted. :)
Hi my name is Sammy, I'm 21 and looking for a shared house on the north coast of NSW. I am moving from Sydney to work full time as a journalist for a newspaper in Lismore. I am organised, tidy, friendly, outgoing and fun.
I'm over the Sydney life, so have decided to move up to north coast NSW. I'm looking for a room for about 6 months while I check out the real estate. I'm a self-employed digital strategist and life coach with clients in Sydney, so I'll be flying back one week out of four. I'm a bit of a neat freak but also laid back. Spiritual but not religious, meditate often and live authentically. I have plenty of friends for references and all my own furniture (but that can stay in storage for the time being if necessary). I'm looking for a cool, cruisey person to share an awesome home with.
Very easy going, Im based in Coffs Harbour, but spending Tuesday to Friday in Ballina/Byron for work, so will only be around during the week. Like music, surfing and cricket.
interested in long or short term rental, from $100-$300 per week. i look and act younger than most 35 year olds. i'm not a party animal but love a chilled drink & a social chat. love music, the sun & the beach! have lived in many share houses, very clean. healthy lifestyle, vegetarian. have a gorgeous super friendly blue staffy who would love to meet you!
Currently doing an apprenticeship in Byron Bay, and looking to move around Pottsville area and also the Goldcoast. I am clean, easy going and like to socialise! Looking for a place by myself, a room in a share house or people to team up with. Message me if your interested!
Hi! 😊 I'm a professional muso, gigging the East Coast on weekends. I'm currently also studying digital photography online and about to start another course at Kingscliffe Tafe starting in July. My friends say I'm funny, spiritual, creative, honest, respectful & communicative.. and I agree with them 😊 I've lived in sharehouses before and understand the dynamics of respecting personal & shared spaces, honest communication, financial responsibilities & contribution. I'd be away most weekends and in study mode most weekdays with spurts of social activities like dinners and enjoy bodyboarding and brisk walks when I can. I'm looking for either a big bedroom or space for music/camera/office use. A small studio if you will. Maybe a garage or study if bedroom isn't big enough. I would also like to keep my caravan off the street between weekends. Anything else, just ask 😊
My names Jonathan , im 28 years of age and im fijian. I work as a scaffolder for wiggins scaffolding in lennox head. Iv moved here from adelaide 1 year and a half ago to start fresh in the new year. I like to keep to myself, clean person , like meeting new people. My hobbys are composing music. I like writing poetry , swimming and food lol .
Hi, I`m Matteo 28 from Italy and I here in working holiday with a friend. I like so much surfing and listening music.
Nice spacious house on great quiet street. Semi rural so peaceful. We have a pool and great outside area. A pool table, vegi patch and gym setup. 5/10 min walk ride to town/beach. Garden requires regular work as does pool so must be willing to help out with that weekly (well when its shared between the house it's really only every few weeks). Rent is paid fortnightly by direct debit. Electricity is extra can fluctuate from 8-13/wk. Gas and lawns are extra bit aren't much at all. MUST be active, motivated, respectful, honest, environmentally aware and positive to fit in. I'm trying to make a warm welcoming comfortable harmonious that all gets along! Looking for preferably for someone in their 30's.
Clean, conscientious, polite, considerate and relaxed. I am very easy going. I don't mind hanging out and having a chat or a meal together but also like my space and quiet time. I want my home to be my sanctuary - It should be clean, relaxing and relatively quiet. I have been in Byron nearly two years and am keen to stay here for much longer. I am a landscape architect. I love gardening and growing food to eat. I am fit and healthy, play hockey, try to surf and have a horse on a property at coopers shoot. Feel free to ask me anything else you are curious about.
2 mins to lennox head shops by car.Own entrance and lounge room.Quiet street with rural outlook.Share with one other and 2 dogs.Some solar electricity and hot water.House has a pool and internet.


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Sommer Ray Is the Babe of the Day
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This document's objective (EU-GREAT! deliverable 4.2) is to provide guidance and support tools for the design and development of investment plans for Large-scale RDI Initiatives (LSI), in particular for the 5-6 LSI cases that were selected in Task 4.1 and that will be analysed during Task 4.3.
This report includes in particular the relevant conceptual background, the proposed approach or methodology, an evaluation method to assess the proposals for development and implementation of (new) LSI, including examples of business plans, evaluation criteria and key performance indicators (KPIs), and a template for (new) LSIs investment plans. The template proposed is especially applicable in the design of an initial investment plan to be used in the presentation and negotiation of an LSI with potential investors and includes a detailed business plan.
LSIs are recognised to have a large positive impact in innovation, contributing to address societal changes and create economic value. Such fact is supported by the numerous answers to the public survey conducted by EU-GREAT! (Task 2.2) who have identified numerous specific positive impacts resulting from those LSIs' activities. To provide a solid conceptual background, D4.2 includes relevant concepts and definitions, such as "LSI" definition, its possible structures, type, life cycle, and level of openness. The LSI lifecycle proposed considers the following main phases: initial design and viability check, detailed design and investment planning, set-up/installation, operation, renewal/upgrade, and finally, termination or integration.
Some detailed information about these phases' costs is then presented, including: • Start-up costs, referring to the costs incurred before the first project can start within a LSI • Infrastructure costs are resulting from the purchase of physical infrastructure • Project costs result from the implementation of projects in the context of an LSI • Operational costs resulting from the day-to-day operation of the LSI
The approach proposed for the development of these investment plans is a step-by-step operational procedure, comprising the following main stages:
Then, a checklist to assess the completeness and soundness of an LSI investment plan is presented, comprising issues such as the mission and vision, objectives, economic sustainability, SWOT analysis, funding instruments considered, alignment with smart specialisation strategies and priorities, and intellectual property rights issues.
An evaluation method is also proposed based on relevant sources. The method is based on 3 main criteria: Excellence, Impact, and Implementation. Sub-criteria and a scoring system is also proposed. Along with this descriptive part of the method, a series of KPIs is also presented (in annex). Part of the indicators were already presented in WP3 during the selection process of the LSIs, to which new ones are added to complete the evaluation of the intended characteristics such as the stage of development, the TRLs, or the target markets. Finally, the template for developing the investment plans is presented. Its main sections are:
The comprehensive approach described in this document is a solid support tool for the development of LSIs' investment plans, both for the EU-GREAT! planned activities as well as to the development of LSI investment plans developed by other interested parties.
27 May 2015
06 May 2016
12 April 2016


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text: Foramina parietalia permagna: familial and radiological evaluation of two cases and review of literature.Larissa Gabor, Huseyin Canaz, Gokhan Canaz, Nursu Kara, Elif Yilmaz Gulec, Ibrahim AlatasChild's nervous system : ChNS : official journal…2016PURPOSE Foramina parietalia permagna is a variable intramembranous ossification defect of the parietal bones. Foramina parietalia permagna have an autosomal dominant inheritance, and it is showed that mutations in chromosome 5 and 11 are causing this anomaly. Enlarged parietal foramina occurs extremely rare. They are usually asymptomatic, but occasional… (More)


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Brooklyn Paper
Talk about an art studio!
Vacant apartments in a soon-to-be occupied Bushwick rental building have become the neighborhood's newest exhibition spaces as a part of a month-long art show that organizers hope will rival Manhattan's Armory show.
The so-called "Brooklyn Artillery" festival - which runs on weekends until Oct. 31 in a Troutman Avenue rental building called "Castle Braid" - offers more than a dozen artists, galleries and curators space in uninhabited apartments on the first two floors, plus courtyards and other facilities inside the 144-unit structure.
Curator Leia Doran said the arts festival is a great way encourage the neighborhood's thriving art community and help find creative tenants for landlord Mayer Schwartz - the property owner, who also owns Bedford Avenue's Mini Mall.
"They really do want this to be an artists' community, and I think something like this will attract people," said Doran, who helped organize the event with the Williamsburg Gallery Association.
Some artworks in the rental building - which is planning to charge rents ranging from $1,650 for a one-bedroom to $2,925 for a three bedroom - aim to reflect the exhibition's setting as a domestic environment.
Artist Ellie Famutimi has turned one of the pristine new apartments into a series of messy bedrooms meant to tell the story of the rooms' imagined inhabitants, one of whom happens to be Ariel from Disney's "The Little Mermaid." Guests are encouraged to interact and touch all parts of her exhibit.
When apartments in the building finally welcome their rental tenants next week, those residents will have the chance to live alongside the art festival for its final month.
"The show is going to stay up in the apartments around the courtyard when the building opens," said Doran. "If somebody specifically wants an apartment that an exhibitor is in, then the exhibitor will be moved. It's great [for tenants]. It's like they'll be living in art for four weeks."


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Court again finds intentional voter discrimination in Texas
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AUSTIN, Texas (AP) — A Republican-drawn map setting the boundaries of Texas' statehouse districts violates the U.S. Constitution by intentionally discriminating against minority voters, a […]
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Every spring, wise homeowners go through a checklist to make certain their property is ready for the upcoming seasons. Most remember to clean up the […]
North Korea first test of President Trump according to John McCain
KTAR.com | April 16, 2017 9:46 am
The recent tensions on the Korean peninsula are going to be the first major test of President Donald Trump according to Arizona senator John McCain.
Iowa Republicans back 'fetal heartbeat' abortion legislation
Associated Press | March 28, 2017 3:28 pm
DES MOINES, Iowa (AP) — Republicans in the Iowa Legislature are backing newly filed legislation that would ban abortions once a fetal heartbeat is detected, […]
White House defends GOP lawmaker's decision to brief Trump
Associated Press | March 23, 2017 12:44 am
WASHINGTON (AP) — The White House on Thursday defended the House intelligence committee chairman's extraordinary decision to openly discuss and brief President Donald Trump on […]
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Associated Press | March 21, 2017 11:33 pm
PHOENIX (AP) — The parents of a 9-year-old boy who was shot in the head in their Phoenix home put off calling 911 as they […]
Top prosecutor pleads not guilty in gifts-for-favors case
Associated Press | March 21, 2017 9:12 pm
PHILADELPHIA (AP) — Philadelphia's top prosecutor pleaded not guilty to federal bribery and extortion charges on Wednesday as pressure mounted from the mayor and others […]
Prosecutor charged with taking $100,000 in gifts, trips
Associated Press | March 21, 2017 9:37 am
PHILADELPHIA (AP) — The city's top prosecutor accepted more than $100,000 in luxury gifts, Caribbean trips and cash, often in exchange for official favors including […]
The Latest: Sweet 16 set after 2 more major upsets
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The Latest on the NCAA Tournament (all times Eastern): 12 a.m. The Sweet 16 is set after a Sunday filled with close games and two […]
Associated Press | April 23, 2017 4:28 amUS officials say pirates have returned to waters off Somalia


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Definition of Ctenizidae
: a family of large burrowing spiders — see trap-door spider
Love words? You must — there are over 200,000 words in our free online dictionary, but you are looking for one that's only in the Merriam-Webster Unabridged Dictionary.
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Origin and Etymology of ctenizidae
New Latin, from Cteniza, type genus (from Greek ktenizion, diminutive of kten-, kteis comb) + -idae — more at pectinate
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Slowing Down Communication: Designs Inspired by Quality, Intimacy, and Humanity
Stefan Agamanolis, Chief Executive/Research Director, Distance Lab
Date: Friday, October 30
Time: 11:50 - 12:05 PM
Location: Transformatorhuis
Stefan Agamanolis explores how the same design thinking that led to fast food has led to the modern mobile phone. Based on his work at MIT and Distance Lab, he reports on some trends in communication design that lead in a different direction. Examples will include sports games you play over a distance, telephones crossed with flotation tanks, and communication systems designed for a bedroom environment. He will introduce the notion of "slow communication", an extension of ideas from the Slow Food movement into the design of communication technologies and techniques that suggests that the broad palette of technologies at our disposal and the increasingly wide availability of bandwidth have not been exploited nearly to the degree that they could be to provide us with communication experiences that are higher in quality, tailored to the nature of the relationship or context, and enable a greater sense of intimacy and immersion.


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Building a better bike trail
By Becky Lang
Published on: 4/11/2006
Mountain biking trails can be gateways to a road less traveled. But if they aren't built properly, they can cause extensive damage.
Thus, the Department of Natural Resources says two full-time professional trail experts from the International Mountain Biking Association will teach proper trail-building April 29-30.
The instruction will take place at Hartman Creek State Park near Waupaca.
There will be classroom instruction and hands-on work on a single-track trail in the park.
Check out
bike trails


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Elmhurst, IL
Writing help from a published author50/hour
...It is my personal goal to help your child succeed and see first hand the outcome of their hard work. Most of my past students have some type of performance and / or school anxiety. I find this as the main... read moreSee Tutors Like This


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- Friday changeover
- Sleeps 2
- 1 Bedroom
- 1 Bathroom
- 2 Pets allowed
- Sorry, no Garden/courtyard
- Sorry, no Private parking
This perfect boutique-style apartment for two provides ground floor accommodation for a seaside break and therefore suitable for all ages. The Blyth has recently been renovated and offers contemporary furnishings all of the highest standard and sea views from the right side of the bay window in the open plan room. The promenade is just at the end of this prime road and all amenities are just around the corner. The Blyth is part of Suffolk House and can be booked together with The Lighthouse and The Pier. Shop: 175 yards Pub: 175 yards.
Entrance: Communal entrance hallway from Dunwich Road into Suffolk House.
Open Plan Room with Sitting Area: Samsung 40 inch TV, sea views. Dining Area: Table and chairs. Kitchen Area: Electric oven and hob, fridge with ice box, microwave, slimline dishwasher, washer dryer.
Bedroom: Double bed.
Bathroom: Bath with hand-held shower only, washbasin and wc.
Parking: Roadside.
Heating: Gas heating.
Pets: Two small well-behaved dogs welcome.
Notes: Wi-Fi and towels provided. Travel cot and highchair available to use.
Southwold Pier Area - It is often said that nothing changes in Southwold. However, the much-acclaimed pier was rebuilt in 2001 and was the first to be constructed in England in over fifty years. It now fits in well with the painted beach huts, promenade and colourful flowerbeds. There is a shop, cafes and an alternative amusement arcade there. The selection of properties' hereabouts makes it an ideal location to stay in Southwold if you require quiet accommodation that is also close to the beach, town centre and the many footpaths across the marshes leading you to the less explored areas of the town.
- Friday changeover
- Sleeps 2
- 1 Bedroom
- 1 Bathroom
- 2 Pets allowed
- Sorry, no Garden/courtyard
- Sorry, no Private parking
- 1 Double bed
- WiFi available
- Equipped with a highchair
- Travel cot available
- Bath towels included
- Bed linen included
- Equipped with a dishwasher
- Equipped with a tumble dryer
- Equipped with a washing machine
- All on one level
|Date Range
|7 night price *
|21st April 2017 - 25th May 2017
|26th May 2017 - 1st June 2017
|2nd June 2017 - 13th July 2017
|14th July 2017 - 20th July 2017
|21st July 2017 - 31st August 2017
|1st September 2017 - 14th September 2017
|15th September 2017 - 21st September 2017
|22nd September 2017 - 19th October 2017
|20th October 2017 - 26th October 2017
|27th October 2017 - 2nd November 2017
|3rd November 2017 - 21st December 2017
|22nd December 2017 - 24th December 2017
|New Year
* Please note: guide prices are based on the current year's prices and do not include optional items such as pet fees.
A great holiday! The whole experience, from my initial phone call to the helpful and knowledgeable staff, right through to dropping the keys back at the end of a fab break was completely positive. Lovely welcome pack too! I will definitely be booking again with So Southwold and Suffolk Secrets.Ms J Dockery - 16th March 2017
Holiday Extras
Holiday Extras
We've hand-picked a selection of Holiday Extras from trusted partners to make your holiday extra special. When you make your booking, you'll see all the Extras on offer at your chosen property and be able to add them to your holiday. Booking them in advance gives you more time to relax when you arrive, and remember - many of these offers are exclusive so you won't find them anywhere else.
Virgin Wines 12 Bottle Classic Wine Selection
This classic case oozes class and is perfect to give you various flavours from across the globe! Enjoy 2 bottles of each wine to encourage sharing or indulgence...
- Normal price
- £115.87
- Price
- £95.50
Virgin Wines 12 Bottle Luxury Wine Selection
This 12 bottle case is packed full of wines to blow you away with flavours and complexities all round – a case guaranteed to impress all who get the pleas...
- Normal price
- £175.87
- Price
- £131.90
Virgin Wines 6 Bottle Celebratory Wine Selection
A true Prosecco lovers case! No excuse is needed for this beautiful selection (so don't let others tell you any different!). Start with the wonderful flor...
- Normal price
- £74.93
- Price
- £61.75
Virgin Wines 6 Bottle Classic Wine Selection
This 6 bottle classic case is perfect for those wanting to try something of everything – carefully selected to incorporate crowd pleasers from across the ...
- Normal price
- £60.93
- Price
- £47.95
Sue Hudson Bread Making Friends & Family Bake Off
Always wanted to make your own bread but not known where to start? Enjoy a bread making workshop for just £36pp.
Dineindulge Dineindulge - private dining service
Enjoy private dining in the comfort of your holiday property. Dineindulge offer a personal chef service with restaurant quality cuisine from only £23.95 per pe...
Dawn Pretty Private art class - Paint a souvenir
Enjoy a 2½ hour art class at a location of your choice with leading local artist Dawn Pretty and take home your masterpiece as a souvenir. Just £25/person.
Southwold Golf Club Unlimited Golf Packages at Southwold Golf Club
Enjoy unlimited golf at this lovely seaside golf course with our exclusive packages from only £49 per person.
Brasserie Bleue Afternoon Tea for Four
Sit back and relax with a truly scrumptious afternoon tea at Aldeburgh's Brasserie Bleue. Price: £40 for four people.
Visiting Spa Company Bespoke Treatment Package
Make your holiday extra special by tailoring a luxurious pamper treatment package to suit your exact requirements. We'll contact you to agree details and pr...


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What is your first impression after coming to this site? There is not much sense in looking for other collections like this one since there is an incredible variety of interesting offers presented below. Can you already decide on something or do you want to spend some more time here?
crib with storage installed and trundle bed underneath for parents on rough nights with baby...amazing.
IKEA Hackers: sniglar crib with storage
Great crib with storage beneath. And gorgeous grasscloth wallpaper. House of Turquoise: Coastal Inspired Nursery
Cute crib, great storage, would look great with some pretty drawer pulls from Anthropologie.
The Classic Shelby Crib and Changer is designed to convert easily into a toddler bed with night stand as your baby grows older. The crib features an attached changing table with a large cabinet and three shelf storage for all things baby.
Keepsake Baby Crib with Storage (Greywash)
Thinking about this one for the little man with such small space!
Sorelle Princeton 4-in-1 Convertible Crib & Changer - Espresso - C International - Babies "R" Us <3 it
Mayfair 4-in-1 Convertible Crib with Toddler Rail | Franklin & Ben It might come in gray or white. Not sure.
The most AWESOME bed EVER for a kid with a small room!!!
Transitional Kids' Rooms from Lina Khatib : Designers' Portfolio 4133 : Home & Garden Television. The previously spacious dining room in the young couple's one bedroom apartment gave way to this serene and enchanting baby girl's room all done in pink
My Small Home: Lauren's Small Space Solutions | Problem: A tiny nursery with no closet - My Solution: Find creative places for storage
Basic Crib converts to Toddler Bed. Also like the drawer beneath for baby bedding, extra storage
**Reuse, for her toy/movie room! only adding the crib mattress too!!! and I love the extra storage!!
Turn a crib into a table with minimal effort. | 51 Insanely Easy Ways To Transform Your Everyday Things
bench made from a headboard (and I already have a twin headboard! Yeah!)
With practical storage and a pretty pale gray color, the GONATT crib is a great choice for a baby boy or girl.
I like this idea but as a wall hanging by the bed for the books/barbies/pieces of paper that get lost in the bed that the kids play with on their bed before bedtime during "Wind-down"
Folding Travel Crib Bed & Diaper Play Station // folds up to the size of a small tote bag, perfect for travelling with a small baby. #product_design
Photobucket Pictures, Images and Photos
Seek out a crib with built-In changing table. | 25 Hacks To Make Room For A Baby In Your Tiny Home
Morgan Convertible Crib
Vittoria Convertible Crib
From Outstanding to Easy: 20 DIY Toddler Beds. I think this would be a neat bed for my daughter!
Beautiful blue grey nursery - -- See what else you need for the nursery and baby
One wall of the nursery is lined with wood to break up the white-walled space. This baby quilt from Ivie Baby and gifted Artecnica mobile (designed by Clara von Zweigbergk) set the color palette for Parker's room and inspired me to hang one of my Curios
Cute & cheap: Under-crib storage using buckets covered with pretty fabric
I love this for any child's room and written on the leaves, I imagine-- wishes, dreams, prayers, positive affirmations, etc-- added to so that the tree grows with the child
Babyletto Mercer 3-in-1 Convertible Crib with Toddler Rail - White from Target has a drawer for storage underneath
Probably already pinned this but I just love this room so much! The color of the wall, the rug, the bookcases/built-in, the pops of orange!
Thanks to a seriously handy dad, baby Eliot had his crib literally built into the closet, complete with storage shelves below and above the bed.
Love the idea of storage bins under the crib - #nursery #storage #organization
if it turns out to be a boy....this is what I plan on doing in Jack and said baby brothers room
The right furniture choices can unlock the potential of a smaller room. This crib has a slim profile and drawers that make smart storage space beneath. Bedding in tonal pinks and browns with a mix of stripes, polka dots and birdies is sweet and whimsical.
Love gray, tangerine, and aqua...just realized I pinned this exact nursery earlier. Guess I really love those colors.
Fantastic Mr. Fox nursery theme | 100 Layer Cakelet - OMG THIS IS MY DREAM NURSERY!!!
i like the shelves on either side of the window...maybe for the small bedroom
Taylor Sterling's Nursery/Office Makeover |
Somehow a shower, pedestal sink and toilet were all miraculously made to fit in this tiny little room. Needless to say, there is absolutely no space for any sort of storage for all the items that typically a guest might need to find in a bathroom. What ca
going to paint my wall gray and aqua stripes for 1 wall, the rest aqua with a few purple things to match my bedspread!! Love the striped walls, easy and super cute!!!
Baby Cribs Furniture Anything with Extra storage for a baby is key!
26 Baby boys bedroom design ideas with modern and best theme Cool Baby Boy Room Ideas
Omg this is so cool! Such a great space saver. I would love this for little girl.
Liking the daybed plus crib idea for a small room with limited storage and possibly 2 kids one day
Project Nursery - White Baby Crib with Storage Drawers
Storage for Kids: long bookcase with legs and a cushion makes a great reading bench
Crib with storage... babyletto Mercer 3-in-1 Convertible Crib in White | AllModern
DIY-toddler-loft-bed-from-old-crib-tutorial. This a wonderful solution for families on a budget...with children who seem to keep growing! It looks fun - from a kids' perspective!
Cheap idea for disguising under crib storage
love the colors, under bed storage, and string of lights


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Gambling addiction charities worried by the introduction of Las Vegas-style supercasinos have warned the new move could have devastating social consequences.
What do you think about extended hours for bookmakers? Tell us in readers' comments below...
Bookmakers are currently allowed to stay open until 10pm in summer and 6.30pm in winter. But, from September 1, when the 2005 Gambling Act takes effect, they will be able to do business until 10pm all-year around - subject to local authority approval.
Gambling addiction charity Gamcare said: "Betting shops are one of the prime instances of problem gambling. Local authorities must protect their population."
And Captain Matt Spencer, of the Salvation Army, said: "Any increased opportunity to gamble is of great concern, particularly in terms of the effect on vulnerable people such as children and problem gamblers."
Higher staff costs may deter some bookmakers from taking advantage of the extended hours, but many are expected to seize the opportunity.
A spokesman for Ladbrokes said: "We are still at the planning stage but we will certainly be looking at extending opening hours at many of our branches."
Longer hours will boost profits as punters place more bets on foreign horse-racing, night-time football matches and 'virtual' games.
A spokesman for the Department for Culture, Media and Sport said: "What the Act does is to remove uncertainty and confusion by creating uniform maximum opening hours that will apply all year round."
Last month Ministers granted permission for the UK's first supercasino to be built in Manchester with 1,250 machines and unlimited jackpots.
The go-ahead was also given for eight large casinos and the same number of smaller ones across Scotland, England and Wales.
A study last year claimed the amount gambled by Britons had risen seven-fold from 2001 to 2005 - up from £7billion to £50billion.
Experts say the surge is linked to Chancellor Gordon Brown's decision to cut betting tax.
Last year Britain's bookmakers made a gross profit of £433million.
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