Identification of a novel dentin matrix protein-1 (DMP-1) mutation and dental anomalies in a kindred with autosomal recessive hypophosphatemia.

PubMed

Turan, Serap; Aydin, Cumhur; Bereket, Abdullah; Akcay, Teoman; Güran, Tülay; Yaralioglu, Betul Akmen; Bastepe, Murat; Jüppner, Harald

2010-02-01

An autosomal recessive form of hypophosphatemia (ARHP) was recently shown to be caused by homozygous mutations in DMP1, the gene encoding dentin matrix protein-1 (DMP-1), a non-collagenous bone matrix protein with an important role in the development and mineralization of bone and teeth. Here, we describe a previously not reported consanguineous ARHP kindred in which the three affected individuals carry a novel homozygous DMP-1 mutation. The index case presented at the age of 3 years with bowing of his legs and showed hypophosphatemia due to insufficient renal phosphate retention. Serum alkaline phosphatase activity was elevated, with initially normal PTH. FGF23 was inappropriately normal at an older age while being treated with oral phosphate and 1,25(OH)(2)D. Similar clinical and biochemical findings, except for elevated FGF23 levels, were present in his 16-month-old brother and his 12.5-year-old female cousin; the parents of the three affected children are first-degree cousins. Nucleotide sequence analysis was performed on PCR-amplified exons encoding DMP-1 and flanking intronic regions. A novel homozygous frame-shift mutation (c.485Tdel; p.Glu163ArgfsX53) in exon 6 resulting in a premature stop codon was identified in all effected individuals. The parents and available unaffected siblings were heterozygous for c.485Tdel. Tooth growth and shape were normal for the index case, his affected brother and cousin, but their permanent and deciduous teeth displayed enlarged pulp chambers. The identified genetic mutation underscores the importance of DMP-1 mutations in the pathogenesis of ARHP. Furthermore, DMP-1 mutations appear to contribute, through yet unknown mechanisms, to tooth development. (c) 2009 Elsevier Inc. All rights reserved.

DMP-1-mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH.

PubMed

Liu, Zhongbo; Kennedy, Oran D; Cardoso, Luis; Basta-Pljakic, Jelena; Partridge, Nicola C; Schaffler, Mitchell B; Rosen, Clifford J; Yakar, Shoshana

2016-02-01

Bone minerals are acquired during growth and are key determinants of adult skeletal health. During puberty, the serum levels of growth hormone (GH) and its downstream effector IGF-1 increase and play critical roles in bone acquisition. The goal of the current study was to determine how bone cells integrate signals from the GH/IGF-1 to enhance skeletal mineralization and strength during pubertal growth. Osteocytes, the most abundant bone cells, were shown to orchestrate bone modeling during growth. We used dentin matrix protein (Dmp)-1-mediated Ghr knockout (DMP-GHRKO) mice to address the role of the GH/IGF axis in osteocytes. We found that DMP-GHRKO did not affect linear growth but compromised overall bone accrual. DMP-GHRKO mice exhibited reduced serum inorganic phosphate and parathyroid hormone (PTH) levels and decreased bone formation indices and were associated with an impaired response to intermittent PTH treatment. Using an osteocyte-like cell line along with in vivo studies, we found that PTH sensitized the response of bone to GH by increasing Janus kinase-2 and IGF-1R protein levels. We concluded that endogenously secreted PTH and GHR signaling in bone are necessary to establish radial bone growth and optimize mineral acquisition during growth. © FASEB.

Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation.

PubMed

Mäkitie, Outi; Pereira, Renata C; Kaitila, Ilkka; Turan, Serap; Bastepe, Murat; Laine, Tero; Kröger, Heikki; Cole, William G; Jüppner, Harald

2010-10-01

Homozygous inactivating mutations in DMP1 (dentin matrix protein 1), the gene encoding a noncollagenous bone matrix protein expressed in osteoblasts and osteocytes, cause autosomal recessive hypophosphatemia (ARHP). Herein we describe a family with ARHP owing to a novel homozygous DMP1 mutation and provide a detailed description of the associated skeletal dysplasia and carrier phenotype. The two adult patients with ARHP, a 78-year-old man and his 66-year-old sister, have suffered from bone pain and lower extremity varus deformities since early childhood. With increasing age, both patients developed severe joint pain, contractures, and complete immobilization of the spine. Radiographs showed short and deformed long bones, significant cranial hyperostosis, enthesopathies, and calcifications of the paraspinal ligaments. Biochemistries were consistent with hypophosphatemia owing to renal phosphate wasting; markers of bone turnover and serum fibroblast growth factor 23 (FGF-23) levels were increased significantly. Nucleotide sequence analysis of DMP1 revealed a novel homozygous mutation at the splice acceptor junction of exon 6 (IVS5-1G > A). Two heterozygous carriers of the mutation also showed mild hypophosphatemia, and bone biopsy in one of these individuals showed focal areas of osteomalacia. In bone, DMP1 expression was absent in the homozygote but normal in the heterozygote, whereas FGF-23 expression was increased in both subjects but higher in the ARHP patient. The clinical and laboratory observations in this family confirm that DMP1 has an important role in normal skeletal development and mineral homeostasis. The skeletal phenotype in ARHP may be significantly more severe than in other forms of hypophosphatemic rickets.

Long-Term Clinical Outcome and Carrier Phenotype in Autosomal Recessive Hypophosphatemia Caused by a Novel DMP1 Mutation

PubMed Central

Mäkitie, Outi; Pereira, Renata C; Kaitila, Ilkka; Turan, Serap; Bastepe, Murat; Laine, Tero; Kröger, Heikki; Cole, William G; Jüppner, Harald

2010-01-01

Homozygous inactivating mutations in DMP1 (dentin matrix protein 1), the gene encoding a noncollagenous bone matrix protein expressed in osteoblasts and osteocytes, cause autosomal recessive hypophosphatemia (ARHP). Herein we describe a family with ARHP owing to a novel homozygous DMP1 mutation and provide a detailed description of the associated skeletal dysplasia and carrier phenotype. The two adult patients with ARHP, a 78-year-old man and his 66-year-old sister, have suffered from bone pain and lower extremity varus deformities since early childhood. With increasing age, both patients developed severe joint pain, contractures, and complete immobilization of the spine. Radiographs showed short and deformed long bones, significant cranial hyperostosis, enthesopathies, and calcifications of the paraspinal ligaments. Biochemistries were consistent with hypophosphatemia owing to renal phosphate wasting; markers of bone turnover and serum fibroblast growth factor 23 (FGF-23) levels were increased significantly. Nucleotide sequence analysis of DMP1 revealed a novel homozygous mutation at the splice acceptor junction of exon 6 (IVS5-1G > A). Two heterozygous carriers of the mutation also showed mild hypophosphatemia, and bone biopsy in one of these individuals showed focal areas of osteomalacia. In bone, DMP1 expression was absent in the homozygote but normal in the heterozygote, whereas FGF-23 expression was increased in both subjects but higher in the ARHP patient. The clinical and laboratory observations in this family confirm that DMP1 has an important role in normal skeletal development and mineral homeostasis. The skeletal phenotype in ARHP may be significantly more severe than in other forms of hypophosphatemic rickets. © 2010 American Society for Bone and Mineral Research. PMID:20499351

DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

PubMed Central

Lorenz-Depiereux, Bettina; Bastepe, Murat; Benet-Pagès, Anna; Amyere, Mustapha; Wagenstaller, Janine; Müller-Barth, Ursula; Badenhoop, Klaus; Kaiser, Stephanie M; Rittmaster, Roger S; Shlossberg, Alan H; Olivares, José L; Loris, César; Ramos, Feliciano J; Glorieux, Francis; Vikkula, Miikka; Jüppner, Harald; Strom, Tim M

2018-01-01

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression. PMID:17033625

DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.

PubMed

Lorenz-Depiereux, Bettina; Bastepe, Murat; Benet-Pagès, Anna; Amyere, Mustapha; Wagenstaller, Janine; Müller-Barth, Ursula; Badenhoop, Klaus; Kaiser, Stephanie M; Rittmaster, Roger S; Shlossberg, Alan H; Olivares, José L; Loris, César; Ramos, Feliciano J; Glorieux, Francis; Vikkula, Miikka; Jüppner, Harald; Strom, Tim M

2006-11-01

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.

Influences of DMP on the Fertilization Process and Subsequent Embryogenesis of Abalone (Haliotis diversicolor supertexta) by Gametes Exposure

PubMed Central

Cai, Zhong-Hua

2011-01-01

Di-methyl phthalate (DMP), a typical endocrine disrupting chemical (EDC), is ubiquitously distributed in aquatic environments; yet studies regarding its impact on gametes and the resulting effects on embryogenesis in marine gastropods are relatively scarce. In this study, the influences of DMP on the gametes and subsequent developmental process of abalone (Haliotis diversicolor supertexta, a representative marine benthic gastropod) were assessed. Newborn abalone eggs and sperm were exposed separately to different DMP concentrations (1, 10 or 100 ppb) for 60 min. At the end-point of exposure, the DMP-treated eggs and sperm were collected for analysis of their ultra-structures, ATPase activities and total lipid levels, and the fertilized gametes (embryos) were collected to monitor related reproductive parameters (fertilization rate, abnormal development rate and hatching success rate). Treatment with DMP did not significantly alter the structure or total lipid content of eggs at any of the doses tested. Hatching failures and morphological abnormalities were only observed with the highest dose of DMP (100 ppb). However, DMP exposure did suppress sperm ATPase activities and affect the morphological character of their mitochondria. DMP-treated sperm exhibited dose-dependent decreases in fertilization efficiency, morphogenesis and hatchability. Relatively obvious toxicological effects were observed when both sperm and eggs were exposed to DMP. Furthermore, RT-PCR results indicate that treatment of gametes with DMP changed the expression patterns of physiologically-regulated genes (cyp3a, 17β-HSD-11 and 17β-HSD-12) in subsequent embryogenesis. Taken together, this study proofed that pre-fertilization exposure of abalone eggs, sperm or both to DMP adversely affects the fertilization process and subsequent embryogenesis. PMID:22028799

Absolute vibrational excitation cross sections for 1-18 eV electron scattering from condensed dimethyl phosphate (DMP)

NASA Astrophysics Data System (ADS)

Lemelin, V.; Bass, A. D.; Wagner, J. R.; Sanche, L.

2017-12-01

Absolute cross sections (CSs) for vibrational excitation by 1-18 eV electrons incident on condensed dimethyl phosphate (DMP) were measured with a high-resolution electron energy loss (EEL) spectrometer. Absolute CSs were extracted from EEL spectra of DMP condensed on multilayer film of Ar held at about 20 K under ultra-high vacuum (˜1 × 10-11 Torr). Structures observed in the energy dependence of the CSs around 2, 4, 7, and 12 eV were compared with previous results of gas- and solid-phase experiments and with theoretical studies on dimethyl phosphate and related molecules. These structures were attributed to the formation of shape resonances.

Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.

PubMed

Rowe, Peter S N

2012-01-01

More than 300 million years ago, vertebrates emerged from the vast oceans to conquer gravity and the dry land. With this transition, new adaptations occurred that included ingenious changes in reproduction, waste secretion, and bone physiology. One new innovation, the egg shell, contained an ancestral protein (ovocleidin-116) that likely first appeared with the dinosaurs and was preserved through the theropod lineage in modern birds and reptiles. Ovocleidin-116 is an avian homolog of matrix extracellular phosphoglycoprotein (MEPE) and belongs to a group of proteins called short integrin-binding ligand-interacting glycoproteins (SIBLINGs). These proteins are all localized to a defined region on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of SIBLING proteins is an acidic serine aspartate-rich MEPE-associated motif (ASARM). Recent research has shown that the ASARM motif and the released ASARM peptide have regulatory roles in mineralization (bone and teeth), phosphate regulation, vascularization, soft-tissue calcification, osteoclastogenesis, mechanotransduction, and fat energy metabolism. The MEPE ASARM motif and peptide are physiological substrates for PHEX, a zinc metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets (HYP). There is evidence that PHEX interacts with another ASARM motif containing SIBLING protein, dentin matrix protein-1 (DMP1). DMP1 mutations cause bone and renal defects that are identical with the defects caused by a loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both HYP and ARHR, increased FGF23 expression plays a major role in the disease and in autosomal dominant hypophosphatemic rickets (ADHR), FGF23 half-life is increased by activating mutations. ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. FGF23 is a member of the fibroblast growth factor (FGF) family of cytokines, which surfaced 500

Developing Mathematical Processes (DMP). Field Test Evaluation, 1973-1974.

ERIC Educational Resources Information Center

Schall, William; And Others

The Developing Mathematical Processes (DMP) program was field-tested in the kindergarten and first three grades of one parochial and five public schools. DMP is an activity-based program developed around a comprehensive list of behavioral objectives. The program is concerned with the development of intuitive geometric concepts as well as…

Developing Mathematical Processes (DMP). Field Test Evaluation, 1972-1973.

ERIC Educational Resources Information Center

Schall, William E.; And Others

The field test of the Developing Mathematical Processes (DMP) program was conducted jointly by the Falconer Central School, St. Mary's Elementary School in Dunkirk, New York, and the Teacher Education Research Center at the State University College in Fredonia, New York. DMP is a research-based, innovative, process-oriented elementary mathematics…

Evaluating cis-2,6-Dimethylpiperidide (cis-DMP) as a Base Component in Lithium-Mediated Zincation Chemistry

PubMed Central

Armstrong, David R; Garden, Jennifer A; Kennedy, Alan R; Leenhouts, Sarah M; Mulvey, Robert E; O'Keefe, Philip; O'Hara, Charles T; Steven, Alan

2013-01-01

Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N′,N′-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis-DMP

A Novel Nonsense Mutation in the DMP1 Gene Identified by a Genome-Wide Association Study Is Responsible for Inherited Rickets in Corriedale Sheep

PubMed Central

Blair, Hugh T.; Thompson, Keith G.; Rothschild, Max F.; Garrick, Dorian J.

2011-01-01

Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP) loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1) was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X) and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were “T T” genotypes; the 3 carriers were “C T”; 24 phenotypically normal related sheep were either “C T” or “C C”; and 46 unrelated normal control sheep from other breeds were all “C C”. The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective “T” allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis. PMID:21747952

Costs and outcomes of the German disease management programme (DMP) for chronic obstructive pulmonary disease (COPD)-A large population-based cohort study.

PubMed

Achelrod, Dmitrij; Welte, Tobias; Schreyögg, Jonas; Stargardt, Tom

2016-09-01

To curb costs and improve health outcomes in chronic obstructive pulmonary disease (COPD), a nationwide disease management programme (DMP) was introduced in Germany in 2005. Yet, its effectiveness has not been comprehensively evaluated. To examine the effects of the German COPD DMP over three years on costs and health resource utilisation from the payer perspective, process quality, morbidity and mortality. A retrospective, population-based cohort study design is applied, using administrative data. After eliminating differences in observable characteristics between the DMP and the control group with entropy balancing, difference-in-difference estimators were computed to account for time-invariant unobservable heterogeneity. 215,104 individuals were included into the analysis of whom 25,269 were enrolled in the DMP. DMP patients had a reduced mortality hazard ratio (0.89, 95%CI: 0.84-0.94) but incurred excess costs of €553 per year. DMP enrolees reveal higher healthcare utilisation with larger shares of individuals being hospitalised (3.14%), consulting an outpatient clinic due to exacerbations (11.13%) and pharmaceutical prescriptions (2.78). However, average length of hospitalisation due to COPD fell by 0.49 days, adherence to medication guidelines as well as indicators for morbidity improved. The German COPD DMP achieved significant improvements in mortality, morbidity and process quality, but at higher costs. Given the low ICER per life year gained, DMP COPD may constitute a cost-effective option to promote COPD population health. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An indirect competitive biotin-streptavidin enzyme-linked immunosorbent assay for the determination of dimethyl phthalate (DMP) in milk and milk products.

PubMed

Sun, Rui Y; Zhuang, Hui S

2015-01-01

After the "plasticizer event" in Taiwan, phthalic acid esters (PAEs) have been listed in "Inedible materials possibly added into food illegally" and "Commonly abused food additives." As one of the PAEs family, DMP has long been a problem of great concern due to its potential impacts on human health. In order to detect DMP with high sensitivity and specificity, a sensitive indirect competitive biotin-streptavidin enzyme-linked immunosorbent assay (BA-ELISA) has been established in this study. A high-titer rabbit polyclonal antibody (pAb-DMP) targeting DMP was obtained, and the procedures of BA-ELISA were optimized for the determination of DMP in milk and milk products. Under optimal conditions, good linearity was achieved within a range of 0.024 to 6.027 μg L(-1), with low cross-reactivity values for DMP structural analogues (lower than 10%). The median inhibitory concentration (IC50) was 0.356 μg L(-1) and the limit of detection (LOD) was 0.0082 μg L(-1). Finally, the concentrations of DMP in milk and milk products ranged from 1.03 μg kg(-1) to 7.23 μg kg(-1) by BA-ELISA. Satisfactory recoveries (90.26-112.38%) and coefficient of variation (CV) values (5.08-8.46%) were obtained. These results were consistent with those using gas chromatography-mass spectrometry (GC-MS), which further confirmed that the proposed BA-ELISA was accurate, specific, reliable and rapid for routine monitoring trace DMP residues in foodstuff, especially milk and milk products.

Sclerostin antibody (Scl-Ab) improves osteomalacia phenotype in dentin matrix protein 1(Dmp1) knockout mice with little impact on serum levels of phosphorus and FGF23.

PubMed

Ren, Yinshi; Han, Xianglong; Jing, Yan; Yuan, Baozhi; Ke, Huazhu; Liu, Min; Feng, Jian Q

2016-01-01

Unlike treatments for most rickets, the treatment using 1,25-(OH)2 vitamin D3 has little efficacy on patients with hypophosphatemic rickets, a set of rare genetic diseases. Thus, understanding the local cause for osteomalacia in hypophosphatemic rickets and developing an effective treatment to restore mineralization in this rare disease has been a longstanding goal in medicine. Here, we used Dmp1 knockout (KO) mice (whose mutations led to the same type of autosomal recessive hypophosphatemic rickets in humans) as the model in which the monoclonal antibody of sclerostin (Scl-Ab) was tested in two age groups for 8weeks: the prevention group (starting at age 4weeks) and the treatment group (starting at age 12weeks). Applications of Scl-Ab greatly improved the osteomalacia phenotype (>15%) and the biomechanical properties (3-point bending, ~60%) in the treated long-bone group. Our studies not only showed improvement of the osteomalacia in the alveolar bone, which has the highest bone metabolism rate, as well as the long bone phenotypes in treated mice. All these improvements attributed to the use of Scl-Ab are independent of the change in serum levels of phosphorus and FGF23, since Scl-Ab had little efficacy on those parameters. Finally, we propose a model to explain how Scl-Ab can improve the Dmp1 KO osteomalacia phenotype, in which the sclerostin level is already low. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Sclerostin Antibody (Scl-Ab) Improves Osteomalacia Phenotype in Dentin Matrix Protein 1(Dmp1) Knockout Mice with Little Impact on Serum Levels of Phosphorus and FGF23

PubMed Central

Ren, Yinshi; Han, Xianglong; Jing, Yan; Yuan, Baozhi; Ke, Huazhu; Liu, Min; Feng, Jian Q.

2016-01-01

Unlike treatments for most rickets, the treatment using 1,25-(OH)2 vitamin D3 has little efficacy on patients with hypophosphatemic rickets, a set of rare genetic diseases. Thus, understanding the local cause for osteomalacia in hypophosphatemic rickets and developing an effective treatment to restore mineralization in this rare disease has been a longstanding goal in medicine. Here, we used Dmp1 knockout (KO) mice (whose mutations led to the same type of autosomal recessive hypophosphatemic rickets in humans) as the model in which the monoclonal antibody of sclerostin (Scl-Ab) was tested in two age groups for 8 weeks: the prevention group (starting at age 4 weeks) and the treatment group (starting at age 12 weeks). Applications of Scl-Ab greatly improved the osteomalacia phenotype (>15%) and the biomechanical properties (3-point bending, ~60%) in the treated long-bone group. Our studies not only showed improvement of the osteomalacia in the alveolar bone, which has the highest bone metabolism rate, as well as the long bone phenotypes in treated mice. All these improvements attributed to the use of Scl-Ab are independent of the change in serum levels of phosphorus and FGF23, since Scl-Ab had little efficacy on those parameters. Finally, we propose a model to explain how Scl-Ab can improve the Dmp1 KO osteomalacia phenotype, in which the sclerostin level is already low. PMID:26721590

Synthesis and biological evaluation of (99m)Tc-DMP-NGA as a novel hepatic asialoglycoprotein receptor imaging agent.

PubMed

Yang, Wenjiang; Mou, Tiantian; Zhang, Xianzhong; Wang, Xuebin

2010-01-01

A novel bifunctional coupling agents-biomolecular compound DMP-NGA was prepared by coupling the SATP with galactosyl-neoglycoalbumin (NGA). The DMP-NGA was labeled with technetium-99m, and the radiochemical purity in excess of 98% after purified with HPLC. In vivo biodistribution showed that (99m)Tc-DMP-NGA had very high initial liver uptake with good retention. The liver accumulated 99.35+/-9.77%, 74.25+/-3.03%, 52.47+/-7.58% of the injected dose per gram at 5, 30 and 120min after injection, respectively. It had relative higher initial liver uptake and much lower blood uptake than that of (99m)Tc-GSA. The liver/blood ratio reached 83.4 at 30min post-injection, while the ratio of liver/kidney was 14.4. The uptakes in other organs in the abdomen were also slightly low. In addition, the hepatic uptake of (99m)Tc-DMP-NGA was blocked by preinjecting free GSA as blocking agent. The result indicates that (99m)Tc-DMP-NGA has specific binding to ASGP receptor. Images acquired with Kodak In-Vivo Imaging System FX Pro showed significant difference before and after inhibition. The promising biological properties of (99m)Tc-DMP-NGA afford potential applications in liver receptor imaging for assessment of hepatocyte function.

[Management of chronic heart failure - a systematic review of guidelines in the context of the DMP revision].

PubMed

Kötter, Thomas; Bartel, Carmen; Schramm, Susanne; Lange, Petra; Höfer, Eva; Hänsel, Michaela; Waffenschmidt, Siw; Waldt, Susanne Ein; Hoffmann-Eßer, Wiebke; Rüther, Alric; Lühmann, Dagmar; Scherer, Martin

2013-01-01

Disease Management Programmes (DMPs) are structured treatment programmes for chronic diseases. The DMP requirements are primarily derived from evidence-based guidelines. DMPs are regularly revised to ensure that they reflect current best practice and medical knowledge. The aim of this study was to assess the need for updating the German DMP module on heart failure by comparing it to relevant guidelines and identifying recommendations that should be revised. We systematically searched for clinical guidelines on heart failure published in German, English or French, and extracted relevant guideline recommendations. All included guidelines were assessed for methodological quality. To identify revision needs in the DMP, we performed a synoptic analysis of the extracted guideline recommendations and DMP requirements. 27 guidelines were included. The extracted recommendations covered all aspects of the management of heart failure. The comparison of guideline recommendations with DMP requirements showed that, overall, guideline recommendations were more detailed than DMP requirements, and that the guidelines covered topics not included in the DMP module. The DMP module is largely consistent with current guidelines on heart failure. We did not identify any need for significant revision of the DMP requirements. However, some specific recommendations of the DMP module could benefit from revision. Copyright © 2013. Published by Elsevier GmbH.

MEKK1 is a Novel Regulator of the Dmp1-Arf-p53 Pathway and Prognostic Indicator in Breast Cancer

DTIC Science & Technology

2012-12-01

hDMP1, INK4a/ARF, p53 or Hdm2 amplification. Kaplan -Meier analyses have been conducted to study the impact for the impact of loss or gain of each locus on...Palma P, Pellegrini S, Fina P et al. Mdm2 gene alterations and mdm2 protein expression in breast carcinomas. J Pathol 1995; 175: 31–38. 21 Turbin DA

A New Efficient Hybrid Intelligent Model for Biodegradation Process of DMP with Fuzzy Wavelet Neural Networks

PubMed Central

Huang, Mingzhi; Zhang, Tao; Ruan, Jujun; Chen, Xiaohong

2017-01-01

A new efficient hybrid intelligent approach based on fuzzy wavelet neural network (FWNN) was proposed for effectively modeling and simulating biodegradation process of Dimethyl phthalate (DMP) in an anaerobic/anoxic/oxic (AAO) wastewater treatment process. With the self learning and memory abilities of neural networks (NN), handling uncertainty capacity of fuzzy logic (FL), analyzing local details superiority of wavelet transform (WT) and global search of genetic algorithm (GA), the proposed hybrid intelligent model can extract the dynamic behavior and complex interrelationships from various water quality variables. For finding the optimal values for parameters of the proposed FWNN, a hybrid learning algorithm integrating an improved genetic optimization and gradient descent algorithm is employed. The results show, compared with NN model (optimized by GA) and kinetic model, the proposed FWNN model have the quicker convergence speed, the higher prediction performance, and smaller RMSE (0.080), MSE (0.0064), MAPE (1.8158) and higher R2 (0.9851) values. which illustrates FWNN model simulates effluent DMP more accurately than the mechanism model. PMID:28120889

A New Efficient Hybrid Intelligent Model for Biodegradation Process of DMP with Fuzzy Wavelet Neural Networks

NASA Astrophysics Data System (ADS)

Huang, Mingzhi; Zhang, Tao; Ruan, Jujun; Chen, Xiaohong

2017-01-01

A new efficient hybrid intelligent approach based on fuzzy wavelet neural network (FWNN) was proposed for effectively modeling and simulating biodegradation process of Dimethyl phthalate (DMP) in an anaerobic/anoxic/oxic (AAO) wastewater treatment process. With the self learning and memory abilities of neural networks (NN), handling uncertainty capacity of fuzzy logic (FL), analyzing local details superiority of wavelet transform (WT) and global search of genetic algorithm (GA), the proposed hybrid intelligent model can extract the dynamic behavior and complex interrelationships from various water quality variables. For finding the optimal values for parameters of the proposed FWNN, a hybrid learning algorithm integrating an improved genetic optimization and gradient descent algorithm is employed. The results show, compared with NN model (optimized by GA) and kinetic model, the proposed FWNN model have the quicker convergence speed, the higher prediction performance, and smaller RMSE (0.080), MSE (0.0064), MAPE (1.8158) and higher R2 (0.9851) values. which illustrates FWNN model simulates effluent DMP more accurately than the mechanism model.

The (Re)-Relaunching of the DMP, the French Shared Medical Record: New Features to Improve Uptake and Use.

PubMed

Séroussi, Brigitte; Bouaud, Jacques

2018-01-01

Health care delivery for patients with chronic conditions is complex and confusing. Care is often fragmented, less effective, and sometimes harmful. Given the potential for EHRs and other health IT systems to facilitate information flow between providers, patients, and settings, health IT-based measures are of particular interest for care coordination. Health information exchange (HIE) has the potential to improve the quality of healthcare by enabling providers with better access to patient information from multiple sources at the point of care. However, many barriers to HIE use have been reported. Another solution relies on the implementation of a nationwide centralized framework of clinical information sharing with "new" secure online care records stored in specifically created platforms. The French DMP follows this model but the adoption of the tool has been historically poor. In 2016, a renovation of the DMP program was launched in nine pilot French departments and new features have been implemented: the DMP content has been fully specified, patients can create their DMP by themselves, DMPs are automatically filled in by data claims, a mobile app has been developed, and technical issues about DMP and EHRs interoperability have been resolved. In October 2017, over 900,000 people have a DMP with an average new DMP being created every minute. These results have to be confirmed in 2018 when the new DMP will be deployed on the whole French territory.

Colocalization of dentin matrix protein 1 and dentin sialoprotein at late stages of rat molar development.

PubMed

Baba, Otto; Qin, Chunlin; Brunn, Jan C; Wygant, James N; McIntyre, Bradley W; Butler, William T

2004-10-01

Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) are acidic proteins found in the extracellular matrices of bones and teeth. Recent data from gene knockouts, along with those of gene mutations, indicate that these two phosphoproteins are critical for bone and tooth development and/or maintenance. However, the precise functions of the two proteins have not been elucidated. In order to gain insights into their functions in tooth formation, we performed systematic, comparative investigations on the immunolocalization of DMP1 and dentin sialoprotein (DSP, a cleaved fragment of DSPP), using the rat first molar at different developmental stages as a model. Immunohistochemistry (IHC) was performed with specific, monoclonal antibodies against the COOH-terminal fragments of DMP1 and against DSP. In 1-day- and 1-week-old rats, weak immunoreactions for DMP1 were observed in dentinal tubules while stronger reactions for DSP were seen in the tubules and predentin. In rats older than 2 weeks, immunoreactions for DMP1 were found in dentinal tubules, predentin and odontoblasts. In 5-week- and 8-week-old rats, strong immunoreactions for DMP1 were widely distributed in odontoblasts and predentin. The distribution pattern of DSP was strikingly similar to that of DMP1 after 2 weeks and the localization of each was distinctly different from that of bone sialoprotein (BSP). The unique colocalization of DMP1 and DSPP in tooth development suggests that the two proteins play complementary and/or synergistic roles in formation and maintenance of healthy teeth.

Radiological characterization survey of the former Diamond Magnesium Company Company site, 720 Fairport-Nursery Road, Painesville, Ohio (DMP001, DMP002)

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

Foley, R.D.; Carrier, R.F.

1991-12-01

At the request of the US Department of Energy (DOE), a group from Oak Ridge National Laboratory performed an investigative radiological survey at the former Diamond Magnesium Company (DMC) site at 720 Fairport-Nursery Road, Painesville, Ohio, in September 1990. The purpose of the survey was to determine if the site is contaminated with radioactive residues as a result of federal government operation in the development of nuclear energy for defense-related projects. The survey of the site, separate parcels of which are currently owned by the Uniroyal Chemical Company (DMP001) and the Lonza Chemical Company (DMP002), included a gamma scan overmore » the ground surface, determination of gamma exposure rates at the surface and at 1 m above the surface at grid points, collection and radionuclide analysis of soil samples, and directly measured radiation levels inside three buildings used during original DMC processing. Results of the survey revealed widespread radiological contamination outdoors on the Uniroyal property and several isolated spots of elevated radiation levels on the Lonza property. The contaminants consisted of radium, uranium, and thorium in surface and subsurface soil in concentrations exceeding DOE guidelines for the release of property for unrestricted use.« less

Radiological characterization survey of the former Diamond Magnesium Company Company site, 720 Fairport-Nursery Road, Painesville, Ohio (DMP001, DMP002)

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

Foley, R.D.; Carrier, R.F.

At the request of the US Department of Energy (DOE), a group from Oak Ridge National Laboratory performed an investigative radiological survey at the former Diamond Magnesium Company (DMC) site at 720 Fairport-Nursery Road, Painesville, Ohio, in September 1990. The purpose of the survey was to determine if the site is contaminated with radioactive residues as a result of federal government operation in the development of nuclear energy for defense-related projects. The survey of the site, separate parcels of which are currently owned by the Uniroyal Chemical Company (DMP001) and the Lonza Chemical Company (DMP002), included a gamma scan overmore » the ground surface, determination of gamma exposure rates at the surface and at 1 m above the surface at grid points, collection and radionuclide analysis of soil samples, and directly measured radiation levels inside three buildings used during original DMC processing. Results of the survey revealed widespread radiological contamination outdoors on the Uniroyal property and several isolated spots of elevated radiation levels on the Lonza property. The contaminants consisted of radium, uranium, and thorium in surface and subsurface soil in concentrations exceeding DOE guidelines for the release of property for unrestricted use.« less

The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding to the histone-like HU protein

PubMed Central

Ko, Tzu-Ping; Liao, Yi-Ting; Hsu, Kai-Cheng

2017-01-01

DNA mimicry is a direct and effective strategy by which the mimic competes with DNA for the DNA binding sites on other proteins. Until now, only about a dozen proteins have been shown to function via this strategy, including the DNA mimic protein DMP19 from Neisseria meningitides. We have shown previously that DMP19 dimer prevents the operator DNA from binding to the transcription factor NHTF. Here, we provide new evidence that DMP19 monomer can also interact with the Neisseria nucleoid-associated protein HU. Using BS3 crosslinking, gel filtration and isothermal titration calorimetry assays, we found that DMP19 uses its monomeric form to interact with the Neisseria HU dimer. Crosslinking conjugated mass spectrometry was used to investigate the binding mode of DMP19 monomer and HU dimer. Finally, an electrophoretic mobility shift assay (EMSA) confirmed that the DNA binding affinity of HU is affected by DMP19. These results showed that DMP19 is bifunctional in the gene regulation of Neisseria through its variable oligomeric forms. PMID:29220372

Coupling UV-H2O2 to accelerate dimethyl phthalate (DMP) biodegradation and oxidation.

PubMed

Chen, Bin; Song, Jiaxiu; Yang, Lihui; Bai, Qi; Li, Rongjie; Zhang, Yongming; Rittmann, Bruce E

2015-11-01

Dimethyl phthalate (DMP), an important industrial raw material, is an endocrine disruptor of concern for human and environmental health. DMP exhibits slow biodegradation, and its coupled treatment by means of advanced oxidation may enhance its biotransformation and mineralization. We evaluated two ways of coupling UV-H2O2 advanced oxidation to biodegradation: sequential coupling and intimate coupling in an internal circulation baffled biofilm reactor (ICBBR). During sequential coupling, UV-H2O2 pretreatment generated carboxylic acids that depressed the pH, and subsequent biodegradation generated phthalic acid; both factors inhibited DMP biodegradation. During intimately coupled UV-H2O2 with biodegradation, carboxylic acids and phthalic acid (PA) did not accumulate, and the biodegradation rate was 13 % faster than with biodegradation alone and 78 % faster than with biodegradation after UV-H2O2 pretreatment. Similarly, DMP oxidation with intimate coupling increased by 5 and 39 %, respectively, compared with biodegradation alone and sequential coupling. The enhancement effects during intimate coupling can be attributed to the rapid catabolism of carboxylic acids, which generated intracellular electron carriers that directly accelerated di-oxygenation of PA and relieved the inhibition effect of PA and low pH. Thus, intimate coupling optimized the impacts of energy input from UV irradiation used together with biodegradation.

Increasing specialty care access through use of an innovative home telehealth-based spinal cord injury disease management protocol (SCI DMP)

PubMed Central

Seton, Jacinta M.; Washington, Monique; Tomlinson, Suk C.; Phrasavath, Douangmala; Farrell, Karen R.; Goldstein, Barry

2016-01-01

Background A spinal cord injury disease management protocol (SCI DMP) was developed to address the unique medical, physical, functional, and psychosocial needs of those living with spinal cord injuries and disorders (SCI/D). The SCI DMP was piloted to evaluate DMP clinical content and to identify issues for broader implementation across the Veterans Affairs (VA) SCI System of Care. Methods Thirty-three patients with SCI/D from four VA SCI centers participated in a 6-month pilot. Patients received customized SCI DMP questions through a data messaging device (DMD). Nurse home telehealth care coordinators (HTCC) monitored responses and addressed clinical alerts daily. One site administered the Duke Severity of Illness (DUSOI) Checklist and Short Form-8 (SF-8™) to evaluate the changes in comorbidity severity and health-related quality of life while on the SCI DMP. Results Patients remained enrolled an average of 116 days, with a mean response rate of 56%. The average distance between patient's home and their VA SCI center was 59 miles. Feedback on SCI DMP content and the DMD included requests for additional clinical topics, changes in administration frequency, and adapting the DMD for functional impairments. Improvement in clinical outcomes was seen in a subset of patients enrolled on the SCI DMP. Conclusion SCI HTCCs and patients reported that the program was most beneficial for newly injured patients recently discharged from acute rehabilitation that live far from specialty SCI care facilities. SCI DMP content changes and broader implementation strategies are currently being evaluated based on lessons learned from the pilot. PMID:24617497

Increasing specialty care access through use of an innovative home telehealth-based spinal cord injury disease management protocol (SCI DMP).

PubMed

Woo, Christine; Seton, Jacinta M; Washington, Monique; Tomlinson, Suk C; Phrasavath, Douangmala; Farrell, Karen R; Goldstein, Barry

2016-01-01

A spinal cord injury disease management protocol (SCI DMP) was developed to address the unique medical, physical, functional, and psychosocial needs of those living with spinal cord injuries and disorders (SCI/D). The SCI DMP was piloted to evaluate DMP clinical content and to identify issues for broader implementation across the Veterans Affairs (VA) SCI System of Care. Thirty-three patients with SCI/D from four VA SCI centers participated in a 6-month pilot. Patients received customized SCI DMP questions through a data messaging device (DMD). Nurse home telehealth care coordinators (HTCC) monitored responses and addressed clinical alerts daily. One site administered the Duke Severity of Illness (DUSOI) Checklist and Short Form-8 (SF-8™) to evaluate the changes in comorbidity severity and health-related quality of life while on the SCI DMP. Patients remained enrolled an average of 116 days, with a mean response rate of 56%. The average distance between patient's home and their VA SCI center was 59 miles. Feedback on SCI DMP content and the DMD included requests for additional clinical topics, changes in administration frequency, and adapting the DMD for functional impairments. Improvement in clinical outcomes was seen in a subset of patients enrolled on the SCI DMP. SCI HTCCs and patients reported that the program was most beneficial for newly injured patients recently discharged from acute rehabilitation that live far from specialty SCI care facilities. SCI DMP content changes and broader implementation strategies are currently being evaluated based on lessons learned from the pilot.

Use of a Nationwide Personally Controlled Electronic Health Record by Healthcare Professionals and Patients: A Case Study with the French DMP.

PubMed

Seroussi, Brigitte; Bouaud, Jacques

2017-01-01

If the wide adoption of electronic health records (EHRs) is necessary to address health information sharing and care coordination issues, it is not sufficient. In order to address health information sharing, some countries, among which, France, have implemented a centralized framework with "new" nationwide care records. The French DMP is a centralized, nationally shared, electronic medical record, created according to the opt-in model. More than five years after the launching of the DMP project, DMPs have been created for 1.5% of the target population, which demonstrates the poor adoption of the tool by healthcare professionals. Among the 583,997 existing DMPs in June 2016, 41% were empty, and 24% of non-empty DMPs were actually accessed. If these "active" DMPs were equally accessed by both healthcare professionals and patients, patients accessed DMP documents four times more than healthcare professionals.

Neisseria conserved protein DMP19 is a DNA mimic protein that prevents DNA binding to a hypothetical nitrogen-response transcription factor

PubMed Central

Wang, Hao-Ching; Ko, Tzu-Ping; Wu, Mao-Lun; Ku, Shan-Chi; Wu, Hsing-Ju; Wang, Andrew H.-J.

2012-01-01

DNA mimic proteins occupy the DNA binding sites of DNA-binding proteins, and prevent these sites from being accessed by DNA. We show here that the Neisseria conserved hypothetical protein DMP19 acts as a DNA mimic. The crystal structure of DMP19 shows a dsDNA-like negative charge distribution on the surface, suggesting that this protein should be added to the short list of known DNA mimic proteins. The crystal structure of another related protein, NHTF (Neisseria hypothetical transcription factor), provides evidence that it is a member of the xenobiotic-response element (XRE) family of transcriptional factors. NHTF binds to a palindromic DNA sequence containing a 5′-TGTNAN11TNACA-3′ recognition box that controls the expression of an NHTF-related operon in which the conserved nitrogen-response protein [i.e. (Protein-PII) uridylyltransferase] is encoded. The complementary surface charges between DMP19 and NHTF suggest specific charge–charge interaction. In a DNA-binding assay, we found that DMP19 can prevent NHTF from binding to its DNA-binding sites. Finally, we used an in situ gene regulation assay to provide evidence that NHTF is a repressor of its down-stream genes and that DMP19 can neutralize this effect. We therefore conclude that the interaction of DMP19 and NHTF provides a novel gene regulation mechanism in Neisseria spps. PMID:22373915

The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development

PubMed Central

2011-01-01

Background Mitogen-activated protein kinase (MAPK) cascades (p38, JNK, ERK pathways) are involved in cell fate acquisition during development. These kinase modules are associated with scaffold proteins that control their activity. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. Results Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK) in the future intervein cells, thus promoting intervein fate. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Finally, Corto is phosphorylated. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Conclusions Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling. PMID:21401930

Identification of full-length dentin matrix protein 1 in dentin and bone.

PubMed

Huang, Bingzhen; Maciejewska, Izabela; Sun, Yao; Peng, Tao; Qin, Disheng; Lu, Yongbo; Bonewald, Lynda; Butler, William T; Feng, Jian; Qin, Chunlin

2008-05-01

Dentin matrix protein 1 (DMP1) has been identified in the extracellular matrix (ECM) of dentin and bone as the processed NH(2)-terminal and COOH-terminal fragment. However, the full-length form of DMP1 has not been identified in these tissues. The focus of this investigation was to search for the intact full-length DMP1 in dentin and bone. We used two types of anti-DMP1 antibodies to identify DMP1: one type specifically recognizes the NH(2)-terminal region and the other type is only reactive to the COOH-terminal region of the DMP1 amino acid sequence. An approximately 105-kDa protein, extracted from the ECM of rat dentin and bone, was recognized by both types of antibodies; and the migration rate of this protein was identical to the recombinant mouse full-length DMP1 made in eukaryotic cells. We concluded that this approximately 105-kDa protein is the full-length form of DMP1, which is considerably less abundant than its processed fragments in the ECM of dentin and bone. We also detected the full-length form of DMP1 and its processed fragments in the extract of dental pulp/odontoblast complex dissected from rat teeth. In addition, immunofluorescence analysis showed that in MC3T3-E1 cells the NH(2)-terminal and COOH-terminal fragments of DMP1 are distributed differently. Our findings indicate that the majority of DMP1 must be cleaved within the cells that synthesize it and that minor amounts of uncleaved DMP1 molecules are secreted into the ECM of dentin and bone.

Distinct compartmentalization of dentin matrix protein 1 fragments in mineralized tissues and cells.

PubMed

Maciejewska, Izabela; Qin, Disheng; Huang, Bingzhen; Sun, Yao; Mues, Gabrielle; Svoboda, Kathy; Bonewald, Lynda; Butler, William T; Feng, Jerry Q; Qin, Chunlin

2009-01-01

Dentin matrix protein 1 (DMP1) has been shown to be critical for the formation of dentin and bone. However, the precise pathway by which DMP1 participates in dentinogenesis and osteogenesis remains to be clarified. DMP1 is present in the extracellular matrix of dentin and bone as processed NH(2)- and COOH-terminal fragments. The NH(2)-terminal fragment occurs as a proteoglycan, whereas the COOH-terminal fragment is highly phosphorylated. The differences in biochemical properties suggest that these fragments may have different tissue and cell distribution in association with distinct functions. In this study, we analyzed the distribution of the NH(2)- and COOH-terminal fragments of DMP1 in tooth, bone, osteocytes as well as MC3T3-E1 and HEK-293 cells. Immunohistochemical analyses were performed using antibodies specific to the NH(2)- or COOH-terminal region of DMP1. Clear differences in the distribution of these fragments were observed. In the teeth and bone, the NH(2)-terminal fragment was primarily located in the nonmineralized predentin and cartilage of the growth plate, while the COOH-terminal fragment accumulated in the mineralized zones. In osteocytes, the NH(2)-terminal fragment appeared more abundant along cell membrane and processes of osteocytes, while the COOH-terminal fragment was often found in the nuclei. This pattern of distribution in cellular compartments was further confirmed by analyses on MC3T3-E1 and HEK-293 cells transfected with a construct containing DMP1 cDNA. In these cell lines, the COOH-terminal fragment accumulated in cell nuclei, while the NH(2)-terminal fragment was in the cytosol. The different distribution of DMP1 fragments indicates that these DMP1 variants must perform distinct functions. Copyright 2008 S. Karger AG, Basel.

Computational Proficiency and Algorithmic Learning of Sixth-Graders Using DMP Materials: A Formative Evaluation. Technical Report No. 401.

ERIC Educational Resources Information Center

Wiles, Clyde

Two questions were investigated in this study: (1) How did the computational proficiency of sixth graders who had one year's experience with Developing Mathematical Processes (DMP) materials compare with an equivalent group of students who used the usual textbook program; and (2) What occurs when sixth graders study algorithms as sequences of rule…

Genome-wide identification of chromatin-enriched RNA reveals that unspliced dentin matrix protein-1 mRNA regulates cell proliferation in squamous cell carcinoma.

PubMed

Suzuki, Shigeki; Hoshino, Hiroaki; Yoshida, Kazuma; Nakanishi, Jun; Tsuchiya-Hirata, Shizu; Kobuke, Seiji; Haruyama, Naoto; Nishimura, Fusanori; Shiba, Hideki

2018-01-15

Chromatin-enriched noncoding RNAs (ncRNAs) have emerged as key molecules in epigenetic processes by interacting with chromatin-associated proteins. Recently, protein-coding mRNA genes have been reported to be chromatin-tethered, similar with ncRNA. However, very little is known about whether chromatin-enriched mRNA is involved in the chromatin modification process. Here, we comprehensively examined chromatin-enriched RNA in squamous cell carcinoma (SQCC) cells by RNA subcellular localization analysis, which was a combination of RNA fractionation and RNA-seq. We identified 11 mRNAs as highly chromatin-enriched RNAs. Among these, we focused on the dentin matrix protein-1 (DMP-1) gene because its expression in SQCC cells has not been reported. Furthermore, we clarified that DMP-1 mRNA was retained in chromatin in its unspliced form in SQCC in vitro and in vivo. As the inhibition of the unspliced DMP-1 mRNA (unspDMP-1) expression resulted in decreased cellular proliferation in SQCC cells, we performed ChIP-qPCR to identify cell cycle-related genes whose expression was epigenetically modified by unspDMP-1, and found that the CDKN1B promoter became active in SQCC cells by inhibiting unspDMP-1 expression. This result was further validated by the increased CDKN1B gene expression in the cells treated with siRNA for unspDMP-1 and by restoration of the decreased cellular proliferation rate by simultaneously inhibiting CDKN1B expression in SQCC cells. Further, to examine whether unspDMP-1 was able to associate with the CDKN1B promoter region, SQCC cells stably expressing PP7-mCherry fusion protein were transiently transfected with the unspDMP-1 fused to 24 repeats of the PP7 RNA stem loop (unspDMP-1-24xPP7) and we found that unspDMP-1-24xPP7 was efficiently precipitated with the antibody against mCherry and was significantly enriched in the CDKN1B promoter region. Thus, unspDMP-1 is a novel chromatin-enriched RNA that epigenetically regulates cellular proliferation of SQCC

A chondroitin sulfate chain attached to the bone dentin matrix protein 1 NH2-terminal fragment.

PubMed

Qin, Chunlin; Huang, Bingzhen; Wygant, James N; McIntyre, Bradley W; McDonald, Charles H; Cook, Richard G; Butler, William T

2006-03-24

Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein shown by gene ablations to be critical for the proper mineralization of bone and dentin. In the extracellular matrix of these tissues DMP1 is present as fragments representing the NH2-terminal (37 kDa) and COOH-terminal (57 kDa) portions of the cDNA-deduced amino acid sequence. During our separation of bone noncollagenous proteins, we observed a high molecular weight, DMP1-related component (designated DMP1-PG). We purified DMP1-PG with a monoclonal anti-DMP1 antibody affinity column. Amino acid analysis and Edman degradation of tryptic peptides proved that the core protein for DMP1-PG is the 37-kDa fragment of DMP1. Chondroitinase treatments demonstrated that the slower migration rate of DMP1-PG is due to the presence of glycosaminoglycan. Quantitative disaccharide analysis indicated that the glycosaminoglycan is made predominantly of chondroitin 4-sulfate. Further analysis on tryptic peptides led us to conclude that a single glycosaminoglycan chain is linked to the core protein via Ser74, located in the Ser74-Gly75 dipeptide, an amino acid sequence specific for the attachment of glycosaminoglycans. Our findings show that in addition to its existence as a phosphoprotein, the NH2-terminal fragment from DMP1 occurs as a proteoglycan. Amino acid sequence alignment analysis showed that the Ser74-Gly75 dipeptide and its flanking regions are highly conserved among a wide range of species from caiman to the Homo sapiens, indicating that this glycosaminoglycan attachment domain has survived an extremely long period of evolution pressure, suggesting that the glycosaminoglycan may be critical for the basic biological functions of DMP1.

Dentin matrix protein 1 and phosphate homeostasis are critical for postnatal pulp, dentin and enamel formation

PubMed Central

Rangiani, Afsaneh; Cao, Zheng-Guo; Liu, Ying; Voisey Rodgers, Anika; Jiang, Yong; Qin, Chun-Lin; Feng, Jian-Quan

2012-01-01

Deletion or mutation of dentin matrix protein 1 (DMP1) leads to hypophosphatemic rickets and defects within the dentin. However, it is largely unknown if this pathological change is a direct role of DMP1 or an indirect role of phosphate (Pi) or both. It has also been previously shown that Klotho-deficient mice, which displayed a high Pi level due to a failure of Pi excretion, causes mild defects in the dentinal structure. This study was to address the distinct roles of DMP1 and Pi homeostasis in cell differentiation, apoptosis and mineralization of dentin and enamel. Our working hypothesis was that a stable Pi homeostasis is critical for postnatal tooth formation, and that DMP1 has an antiapoptotic role in both amelogenesis and dentinogenesis. To test this hypothesis, Dmp1-null (Dmp1−/−), Klotho-deficient (kl/kl), Dmp1/Klotho-double-deficient (Dmp1−/−/kl/kl) and wild-type (WT) mice were killed at the age of 6 weeks. Combinations of X-ray, microcomputed tomography (μCT), scanning electron microscopy (SEM), histology, apoptosis and immunohistochemical methods were used for characterization of dentin, enamel and pulp structures in these mutant mice. Our results showed that Dmp1−/− (a low Pi level) or kl/kl (a high Pi level) mice displayed mild dentin defects such as thin dentin and a reduction of dentin tubules. Neither deficient mouse line exhibited any apparent changes in enamel or pulp structure. However, the double-deficient mice (a high Pi level) displayed severe defects in dentin and enamel structures, including loss of dentinal tubules and enamel prisms, as well as unexpected ectopic ossification within the pulp root canal. TUNEL assay showed a sharp increase in apoptotic cells in ameloblasts and odontoblasts. Based on the above findings, we conclude that DMP1 has a protective role for odontoblasts and ameloblasts in a pro-apoptotic environment (a high Pi level). PMID:23258378

Elimination of the azeotropic point of acetone and methanol by 1,3-dimethylimidazolium dimethylphosphate: an ab initio calculation study.

PubMed

Yu, Guangren; Liu, Xiaomin; Zhang, Xiaochun; Chen, Xiaochun; Liu, Zhiping; Abdeltawab, Ahmed A

2017-03-01

1,3-Dimethylimidazolium dimethylphosphate ([C 1 mim][DMP]) was observed experimentally to be able to eliminate the atmospheric azeotropic point of acetone and methanol, which is an important azeotrope generally encountered in furfural production and the Fischer-Tropsch process. Here, we employed ab initio calculation to understand the underlying mechanism of [C 1 mim][DMP] in eliminating the azeotropic point of acetone and methanol. Structure, energy and interaction in binary-, ternary- and quaternary-clusters composed of methanol, acetone, [C 1 mim] + or/and [DMP]‾ were calculated. The σ-hole, AIM and NBO analyses were performed to understand intermolecular interaction with electron density, electron occupancy, charge transfer and molecular orbital interaction. Hydrogen bond interaction plays a key role in azeotropic point elimination; due to the much stronger hydrogen bond interaction between methanol and [C 1 mim][DMP] than that between acetone and [C 1 mim][DMP], [C 1 mim][DMP] prefers to interact with methanol rather than acetone, and the original interaction between methanol and acetone is separated by [C 1 mim][DMP]. The hydrogen bond is from the orbital interaction between O lone-pair-electron orbitals of the hydrogen bond acceptor and σ * (C-H) or σ * (O-H) anti-bonding orbitals of the hydrogen bond donor, where remarkable electron or charge transfer occurs. These theoretical calculation results are in agreement with the experimental observation that [C 1 mim][DMP] eliminates the azeotropic point of methanol and acetone. This work shows that ab initio calculation may be employed to rationalize the design or synthesis of ionic liquids for separating azeotropes. Graphical Abstract Elimination of azeotropic point of acetone and methanol by [C 1 mim][DMP].

A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

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

London, J.E.

1993-03-01

The acute oral LD{sub 30/50} values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

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

London, J.E.

1993-03-01

The acute oral LD[sub 30/50] values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

Facilitating disaster preparedness through local radio broadcasting.

PubMed

Romo-Murphy, Eila; James, Ross; Adams, Mike

2011-10-01

The 2008 Disaster Mitigation Preparedness (DMP) study took place in Aceh province, Indonesia. It sought to help develop radio programmes and messages to increase resilience to disasters. The role of radio was evaluated during and after the 2004 Asian tsunami disaster. The study team interviewed 984 tsunami survivors from nine sub-districts of Banda Aceh, and local nongovernmental organisations convened eight focus groups around the area of Aceh Besar. Six key informant interviews were held with government disaster management agencies. The DMP survey is the first of its kind to interview a representative random sample of Banda Aceh residents. It reveals the importance of community and social networks, during disaster situations, when essential communications are down. A disaster warning information system based on a multi-media approach needs to be developed. The wider community should be involved in the planning, education and training of Banda Aceh and Aceh Besar residents to facilitate appropriate personal and community survival strategies. © 2011 The Author(s). Disasters © Overseas Development Institute, 2011.

Impact of disease-management programs on metabolic control in patients with type 1 diabetes mellitus

PubMed Central

Lin, Kun; Yang, Xiaoping; Wu, Yixi; Chen, Shuru; Yin, Guoshu; Zhan, Jianjun; Lin, Chujia; Xu, Wencan; Chen, Yongsong; Lin, Dan; Xie, Peiwen; Fang, Yishan; Lin, Qiuqiang; Lin, Shaoda

2016-01-01

Abstract The aim of this study is to evaluate the effect of diabetes disease management program (DMP) on glycemic control in type 1 diabetes mellitus (T1DM) patients in Shantou China. A sample of 240 participants recruited from 3C study Shantou subgroup was followed up in DMP for 3 years. The DMP provided self-management education, individualized therapy plan, diabetes complications screening, and laboratory examination periodical according to clinical practice guidelines. Primary outcomes were changes in hemoglobin A1C (HbA1c). Two hundred one of the participants completed the follow-up. There was a significant decrease in the HbA1c levels after DMP implemented. The mean (± SD) pre- and post-intervention HbA1c levels were 10.26% ± 3.30% and 8.57% ± 1.57% respectively with a P value <0.001. General linear mixed model analyse demonstrated that changes in glycemic control were associated with insulin treatment regimen, frequency of Self-Monitoring of Blood Glucose (SMBG), diabetes diet adherence, physical activity, and duration of diabetes. DMP helped to improve glycemic control and should be general implemented in China's T1DM. Individuals with basal-bolus regimen (multiple daily injections or pump therapy), more frequency of SMBG, following a diabetes diet, more physical activity, shorter diabetes duration may derive greater benefits from DMP. PMID:28033258

Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice

PubMed Central

Xiao, Zhousheng; Dallas, Mark; Qiu, Ni; Nicolella, Daniel; Cao, Li; Johnson, Mark; Bonewald, Lynda; Quarles, L. Darryl

2011-01-01

We investigated whether polycystin-1 is a bone mechanosensor. We conditionally deleted Pkd1 in mature osteoblasts/osteocytes by crossing Dmp1-Cre with Pkd1flox/m1Bei mice, in which the m1Bei allele is nonfunctional. We assessed in wild-type and Pkd1-deficient mice the response to mechanical loading in vivo by ulna loading and ex vivo by measuring the response of isolated osteoblasts to fluid shear stress. We found that conditional Pkd1 heterozygotes (Dmp1-Cre;Pkd1flox/+) and null mice (Pkd1Dmp1-cKO) exhibited a ∼40 and ∼90% decrease, respectively, in functional Pkd1 transcripts in bone. Femoral bone mineral density (12 vs. 27%), trabecular bone volume (32 vs. 48%), and cortical thickness (6 vs. 17%) were reduced proportionate to the reduction of Pkd1 gene dose, as were mineral apposition rate (MAR) and expression of Runx2-II, Osteocalcin, Dmp1, and Phex. Anabolic load-induced periosteal lamellar MAR (0.58±0.14; Pkd1Dmp1-cKO vs. 1.68±0.34 μm/d; control) and increases in Cox-2, c-Jun, Wnt10b, Axin2, and Runx2-II gene expression were significantly attenuated in Pkd1Dmp1-cKO mice compared with controls. Application of fluid shear stress to immortalized osteoblasts from Pkd1null/null and Pkd1m1Bei/m1Bei-derived osteoblasts failed to elicit the increments in cytosolic calcium observed in wild-type controls. These data indicate that polycystin-1 is essential for the anabolic response to skeletal loading in osteoblasts/osteocytes.—Xiao, Z., Dallas, M., Qiu, N., Nicolella, D., Cao, L., Johnson, M., Bonewald, L., Quarles, L. D. Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice. PMID:21454365

Evidence for the proteolytic processing of dentin matrix protein 1. Identification and characterization of processed fragments and cleavage sites.

PubMed

Qin, Chunlin; Brunn, Jan C; Cook, Richard G; Orkiszewski, Ralph S; Malone, James P; Veis, Arthur; Butler, William T

2003-09-05

Full-length cDNA coding for dentin matrix protein 1 (DMP1) has been cloned and sequenced, but the corresponding complete protein has not been isolated. In searching for naturally occurring DMP1, we recently discovered that the extracellular matrix of bone contains fragments originating from DMP1. Shortened forms of DMP1, termed 37K and 57K fragments, were treated with alkaline phosphatase and then digested with trypsin. The resultant peptides were purified by a two-dimensional method: size exclusion followed by reversed-phase high performance liquid chromatography. Purified peptides were sequenced by Edman degradation and mass spectrometry, and the sequences compared with the DMP1 sequence predicted from cDNA. Extensive sequencing of tryptic peptides revealed that the 37K fragments originated from the NH2-terminal region, and the 57K fragments were from the COOH-terminal part of DMP1. Phosphate analysis indicated that the 37K fragments contained 12 phosphates, and the 57K fragments had 41. From 37K fragments, two peptides lacked a COOH-terminal lysine or arginine; instead they ended at Phe173 and Ser180 and were thus COOH termini of 37K fragments. Two peptides were from the NH2 termini of 57K fragments, starting at Asp218 and Asp222. These findings indicated that DMP1 is proteolytically cleaved at four bonds, Phe173-Asp174, Ser180-Asp181, Ser217-Asp218, and Gln221-Asp222, forming eight fragments. The uniformity of cleavages at the NH2-terminal peptide bonds of aspartyl residues suggests that a single proteinase is involved. Based on its reported specificity, we hypothesize that these scissions are catalyzed by PHEX protein. We envision that the proteolytic processing of DMP1 plays a crucial role during osteogenesis and dentinogenesis.

ELSID-Diabetes study-evaluation of a large scale implementation of disease management programmes for patients with type 2 diabetes. Rationale, design and conduct--a study protocol [ISRCTN08471887].

PubMed

Joos, Stefanie; Rosemann, Thomas; Heiderhoff, Marc; Wensing, Michel; Ludt, Sabine; Gensichen, Jochen; Kaufmann-Kolle, Petra; Szecsenyi, Joachim

2005-10-04

Diabetes model projects in different regions of Germany including interventions such as quality circles, patient education and documentation of medical findings have shown improvements of HbA1c levels, blood pressure and occurrence of hypoglycaemia in before-after studies (without control group). In 2002 the German Ministry of Health defined legal regulations for the introduction of nationwide disease management programs (DMP) to improve the quality of care in chronically ill patients. In April 2003 the first DMP for patients with type 2 diabetes was accredited. The evaluation of the DMP is essential and has been made obligatory in Germany by the Fifth Book of Social Code. The aim of the study is to assess the effectiveness of DMP by example of type 2 diabetes in the primary care setting of two German federal states (Rheinland-Pfalz and Sachsen-Anhalt). The study is three-armed: a prospective cluster-randomized comparison of two interventions (DMP 1 and DMP 2) against routine care without DMP as control group. In the DMP group 1 the patients are treated according to the current situation within the German-Diabetes-DMP. The DMP group 2 represents diabetic care within ideally implemented DMP providing additional interventions (e.g. quality circles, outreach visits). According to a sample size calculation a sample size of 200 GPs (each GP including 20 patients) will be required for the comparison of DMP 1 and DMP 2 considering possible drop-outs. For the comparison with routine care 4000 patients identified by diabetic tracer medication and age (> 50 years) will be analyzed. This study will evaluate the effectiveness of the German Diabetes-DMP compared to a Diabetes-DMP providing additional interventions and routine care in the primary care setting of two different German federal states.

ELSID-Diabetes study-evaluation of a large scale implementation of disease management programmes for patients with type 2 diabetes. Rationale, design and conduct – a study protocol [ISRCTN08471887

PubMed Central

Joos, Stefanie; Rosemann, Thomas; Heiderhoff, Marc; Wensing, Michel; Ludt, Sabine; Gensichen, Jochen; Kaufmann-Kolle, Petra; Szecsenyi, Joachim

2005-01-01

Background Diabetes model projects in different regions of Germany including interventions such as quality circles, patient education and documentation of medical findings have shown improvements of HbA1c levels, blood pressure and occurrence of hypoglycaemia in before-after studies (without control group). In 2002 the German Ministry of Health defined legal regulations for the introduction of nationwide disease management programs (DMP) to improve the quality of care in chronically ill patients. In April 2003 the first DMP for patients with type 2 diabetes was accredited. The evaluation of the DMP is essential and has been made obligatory in Germany by the Fifth Book of Social Code. The aim of the study is to assess the effectiveness of DMP by example of type 2 diabetes in the primary care setting of two German federal states (Rheinland-Pfalz and Sachsen-Anhalt). Methods/Design The study is three-armed: a prospective cluster-randomized comparison of two interventions (DMP 1 and DMP 2) against routine care without DMP as control group. In the DMP group 1 the patients are treated according to the current situation within the German-Diabetes-DMP. The DMP group 2 represents diabetic care within ideally implemented DMP providing additional interventions (e.g. quality circles, outreach visits). According to a sample size calculation a sample size of 200 GPs (each GP including 20 patients) will be required for the comparison of DMP 1 and DMP 2 considering possible drop-outs. For the comparison with routine care 4000 patients identified by diabetic tracer medication and age (> 50 years) will be analyzed. Discussion This study will evaluate the effectiveness of the German Diabetes-DMP compared to a Diabetes-DMP providing additional interventions and routine care in the primary care setting of two different German federal states. PMID:16202151

Impact of Disease Management Programs on HbA1c Values in Type 2 Diabetes Patients in Germany.

PubMed

Kostev, Karel; Rockel, Timo; Jacob, Louis

2017-01-01

The aim was to analyze the impact of disease management programs on HbA1c values in type 2 diabetes mellitus (T2DM) patients in Germany. This study included 9017 patients followed in disease management programs (DMPs) who started an antihyperglycemic treatment upon inclusion in a DMP. Standard care (SC) patients were included after individual matching (1:1) to DMP cases based on age, gender, physician (diabetologist versus nondiabetologist care), HbA1c values at baseline, and index year. The main outcome was the share of patients with HbA1c <7.5% or 6.5% after at least 6 months and less than 12 months of therapy in DMP and SC groups. Multivariate logistic regression models were fitted with HbA1c level as a dependent variable and the potential predictor (DMP versus SC). The mean age was 64.3 years and 54.7% of the patients were men. The mean HbA1c level at baseline was equal to 8.7%. In diabetologist practices, 64.7% of DMP patients and 55.1% of SC patients had HbA1c levels <7.5%, while 23.4% of DMP patients and 16.9% of SC patients had HbA1c levels <6.5% ( P values < .001). By comparison, in general practices, 72.4% of DMP patients and 65.7% of SC patients had HbA1c levels <7.5%, while 29.0% of DMP patients and 25.4% of SC patients had HbA1c levels <6.5% ( P values < .001). DMPs increased the likelihood of HbA1c levels lower than 7.5% or 6.5% after 6 months of therapy in both diabetologist and general care practices. The present study indicates that the enrollment of T2DM patients in DMPs has a positive impact on HbA1c values in Germany.

Physiological and Morphological Characterization of Organotypic Cocultures of the Chick Forebrain Area MNH and its Main Input Area DMA/DMP

PubMed Central

Endepols, Heike; Jungnickel, Julia; Braun, Katharina

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostrai neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were lightand electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intraceilular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain. PMID:12018771

Physiological and morphological characterization of organotypic cocultures of the chick forebrain area MNH and its main input area DMA/DMP.

PubMed

Endepols, H; Jungnickel, J; Braun, K

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostral neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were light- and electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intracellular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain.

Impact of disease-management programs on metabolic control in patients with type 1 diabetes mellitus: A cohort study in Shantou, China.

PubMed

Lin, Kun; Yang, Xiaoping; Wu, Yixi; Chen, Shuru; Yin, Guoshu; Zhan, Jianjun; Lin, Chujia; Xu, Wencan; Chen, Yongsong; Lin, Dan; Xie, Peiwen; Fang, Yishan; Lin, Qiuqiang; Lin, Shaoda

2016-12-01

The aim of this study is to evaluate the effect of diabetes disease management program (DMP) on glycemic control in type 1 diabetes mellitus (T1DM) patients in Shantou China.A sample of 240 participants recruited from 3C study Shantou subgroup was followed up in DMP for 3 years. The DMP provided self-management education, individualized therapy plan, diabetes complications screening, and laboratory examination periodical according to clinical practice guidelines. Primary outcomes were changes in hemoglobin A1C (HbA1c).Two hundred one of the participants completed the follow-up. There was a significant decrease in the HbA1c levels after DMP implemented. The mean (± SD) pre- and post-intervention HbA1c levels were 10.26% ± 3.30% and 8.57% ± 1.57% respectively with a P value <0.001. General linear mixed model analyse demonstrated that changes in glycemic control were associated with insulin treatment regimen, frequency of Self-Monitoring of Blood Glucose (SMBG), diabetes diet adherence, physical activity, and duration of diabetes.DMP helped to improve glycemic control and should be general implemented in China's T1DM. Individuals with basal-bolus regimen (multiple daily injections or pump therapy), more frequency of SMBG, following a diabetes diet, more physical activity, shorter diabetes duration may derive greater benefits from DMP.

[Effect of the Disease Management Program on HbA1c Value in Type 2 Diabetes Mellitus Patients: A Retrospective Comparison between Disease Management Programs and Standard Care].

PubMed

Wiefarn, Stefan; Kostev, Karel; Heumann, Christian; Rettelbach, Anja

2017-10-01

Background  This retrospective study aims to measure the effect of the disease management program (DMP) for type 2 diabetes mellitus (T2DM) patients on HbA 1c value within Germany. Methods  This study is based on patient data from the Disease Analyzer panel (IMS Health). An adequate control group was created using 2:1 propensity score matching. After matching, the analysis included 14 759 patients. Of these, 5875 participated in a DMP while 8884 received standard care. The DMP effect was estimated on the basis of the matched data, using an unpaired t-test. In addition, subgroups were considered from the perspective of personalized medicine. Results  The reduction in HbA 1c values in the DMP group amounted to an average of 1.0 percentage point (baseline HbA 1c  = 8.1 vs. final HbA 1c  = 7.1), while the SC group was able to achieve an average reduction in HbA 1c values of 0.9 percentage point (baseline HbA 1c  = 8.1 vs. final HbA 1c  = 7.2). The DMP group thus achieved an average reduction in HbA 1c values that exceeded that of the SC group by only 0.1 percentage point (95 % CI: 0.04 - 0.16). Descriptively, it also became apparent that patients from the DMP group received a greater average number of annual prescriptions and had more HbA 1c measurements. The subgroup analysis identified groups of patients who benefit more from DMPs than others. Thus, young patients or patients who are being treated by diabetologists are able to benefit most from a DMP. Furthermore, the baseline HbA 1c value has an influence on the DMP effect. Conclusion  T2DM patients in the DMP exhibit a significantly higher reduction in HbA 1c value. However, it is questionable whether this effect is clinically relevant. Certain groups of patients benefit more from DMPs than others. Nevertheless, further studies are needed in order to better understand the impact of the DMP on HbA 1c value and the reasons for the subgroup effects. Such studies should be carried

[General practitioners' opinion and attitude towards DMPs and the change in practice routines to implement the DMP "diabetes mellitus type 2"].

PubMed

Miksch, Antje; Trieschmann, Johanna; Ose, Dominik; Rölz, Andreas; Heiderhoff, Marc; Szecsenyi, Joachim

2011-01-01

Effective implementation of disease management programmes (DMPs) in primary care practices often requires changes in practice workflows and responsibilities and acceptance by the parties involved. Within the ELSID study (evaluation study of the DMP diabetes mellitus type 2) the physicians' attitudes toward DMPs were obtained and an optimised implementation of DMPs was developed by conducting a quality management cycle with primary care practice teams. The aim was to investigate which practice workflows will have to be changed and what kind of barriers to implement these changes are perceived. In 78 primary care practices of the two German federal states of Rheinland-Pfalz and Sachsen-Anhalt a quality management cycle was conducted using a structured analysis of the current state of DMP workflows and the need for improvement identified. Subsequently, an optimised workflow was developed and targets were agreed upon. After 6 months, the study team called to inquire about the current state of implementation and, if appropriate, actual barriers to change. After 6 months, 71 practices had been interviewed by phone. 64 of them (90.1%) had agreed on at least one target (e.g., to purchase new instrumentation, to regularly discuss feedback reports, to set up a patient registry). On average three targets had been formulated, and 2 out of 3 had been implemented in the meantime. In most cases lack of time was given as the reason for non-implementation. The majority of surveyed practices perceived some need for improvement. But sufficient resources (time, staff and money) are required to ensure efficient implementation of DMPs in primary care practices and their integration with routine processes. A redefinition of responsibilities for DMPs will strengthen the role of medical assistants and promote high-quality implementation of these programmes. Copyright © 2010. Published by Elsevier GmbH.

Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

PubMed Central

Bertazzoni, Umberto; Turci, Marco; Avesani, Francesca; Di Gennaro, Gianfranco; Bidoia, Carlo; Romanelli, Maria Grazia

2011-01-01

Human T-lymphotropic viruses type 1 (HTLV-1) and type 2 (HTLV-2) present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity. PMID:21994745

Use of short-term breath measures to estimate daily methane production by cattle.

PubMed

Velazco, J I; Mayer, D G; Zimmerman, S; Hegarty, R S

2016-01-01

Methods to measure enteric methane (CH4) emissions from individual ruminants in their production environment are required to validate emission inventories and verify mitigation claims. Estimates of daily methane production (DMP) based on consolidated short-term emission measurements are developing, but method verification is required. Two cattle experiments were undertaken to test the hypothesis that DMP estimated by averaging multiple short-term breath measures of methane emission rate did not differ from DMP measured in respiration chambers (RC). Short-term emission rates were obtained from a GreenFeed Emissions Monitoring (GEM) unit, which measured emission rate while cattle consumed a dispensed supplement. In experiment 1 (Expt. 1), four non-lactating cattle (LW=518 kg) were adapted for 18 days then measured for six consecutive periods. Each period consisted of 2 days of ad libitum intake and GEM emission measurement followed by 1 day in the RC. A prototype GEM unit releasing water as an attractant (GEM water) was also evaluated in Expt. 1. Experiment 2 (Expt. 2) was a larger study based on similar design with 10 cattle (LW=365 kg), adapted for 21 days and GEM measurement was extended to 3 days in each of the six periods. In Expt. 1, there was no difference in DMP estimated by the GEM unit relative to the RC (209.7 v. 215.1 g CH(4)/day) and no difference between these methods in methane yield (MY, 22.7 v. 23.7 g CH(4)/kg of dry matter intake, DMI). In Expt. 2, the correlation between GEM and RC measures of DMP and MY were assessed using 95% confidence intervals, with no difference in DMP or MY between methods and high correlations between GEM and RC measures for DMP (r=0.85; 215 v. 198 g CH(4)/day SEM=3.0) and for MY (r=0.60; 23.8 v. 22.1 g CH(4)/kg DMI SEM=0.42). When data from both experiments was combined neither DMP nor MY differed between GEM- and RC-based measures (P>0.05). GEM water-based estimates of DMP and MY were lower than RC and GEM (P<0

Spatially and temporally controlled biomineralization is facilitated by interaction between self-assembled dentin matrix protein 1 and calcium phosphate nuclei in solution.

PubMed

He, Gen; Gajjeraman, Sivakumar; Schultz, David; Cookson, David; Qin, Chunlin; Butler, William T; Hao, Jianjun; George, Anne

2005-12-13

Bone and dentin biomineralization are well-regulated processes mediated by extracellular matrix proteins. It is widely believed that specific matrix proteins in these tissues modulate nucleation of apatite nanoparticles and their growth into micrometer-sized crystals via molecular recognition at the protein-mineral interface. However, this assumption has been supported only circumstantially, and the exact mechanism remains unknown. Dentin matrix protein 1 (DMP1) is an acidic matrix protein, present in the mineralized matrix of bone and dentin. In this study, we have demonstrated using synchrotron small-angle X-ray scattering that DMP1 in solution can undergo oligomerization and temporarily stabilize the newly formed calcium phosphate nanoparticle precursors by sequestering them and preventing their further aggregation and precipitation. The solution structure represents the first low-resolution structural information for DMP1. Atomic force microscopy and transmission electron microscopy studies further confirmed that the nascent calcium phosphate nuclei formed in solution were assembled into ordered protein-mineral complexes with the aid of oligomerized DMP1, recombinant and native. This study reveals a novel mechanism by which DMP1 might facilitate initiation of mineral nucleation at specific sites during bone and dentin mineralization and prevent spontaneous calcium phosphate precipitation in areas in which mineralization is not desirable.

[Experiences with synopses of clinical guidelines using the example of synopses for Disease Management Programmes (DMP)].

PubMed

Siering, Ulrich; Rüther, Alric

2014-01-01

Guideline synopses, i.e. the systematic synthesis of clinical practice guidelines, are used as a basis for Disease Management Programmes (DMPs) in Germany. One of the responsibilities of the German Institute for Quality and Efficiency in Health Care (IQWiG) is the preparation of guideline synopses for DMPs. The article describes the experiences with this methodology. For the preparation of guideline synopses, a systematic search for evidence-based guidelines is conducted, and their recommendations are extracted and synthesised. In parallel, the quality of the guidelines is assessed using the AGREE instrument. The need for updating or supplementing a DMP is justified by means of the Grade of Recommendation (GoR) or, alternatively, the Level of Evidence (LoE). Since 2006 IQWiG has synthesised recommendations from 256 evidence-based guidelines in 12 guideline synopses for DMPs. The results are then used by the Federal Joint Committee (G-BA) to update DMPs. Using the example of the 12 synopses, several analyses were conducted. It was determined that a search for guidelines in guideline databases is sufficient and that a search in bibliographic databases can be dispensed with. Furthermore, the analyses showed that a large proportion of recommendations in evidence-based guidelines are not clearly linked to a GoR or LoE. If GoR and LoE are provided, only about 42% of recommendations with a strong GoR also refer to a strong LoE. It was also shown that only 21 % of the analysed guideline providers supplied information on the handling of unpublished data. With consistent average to high values, the assessment of the methodological quality across all of the prepared synopses allows for the conclusion of a basically acceptable guideline quality, but with a need for improvement. A guideline synopsis is an established tool for identifying health care standards as a basis for developing and updating DMPs. Further methodological development, particularly in collaboration with

Effectiveness of a multidisciplinary heart failure disease management programme on 1-year mortality

PubMed Central

Laborde-Castérot, Hervé; Agrinier, Nelly; Zannad, Faiez; Mebazaa, Alexandre; Rossignol, Patrick; Girerd, Nicolas; Alla, François; Thilly, Nathalie

2016-01-01

Abstract We performed a multicenter prospective observational cohort study (Epidémiologie et Pronostic de l’Insuffisance Cardiaque Aiguë en Lorraine, Epidemiology and Prognosis of Acute Heart Failure in Lorraine [EPICAL2]) to evaluate the effectiveness on mortality of a community-based multidisciplinary disease management programme (DMP) for heart failure (HF) patients. Between October 2011 and October 2012, 1816 patients, who were hospitalized for acute HF or who developed acute HF during a hospitalization, were included from 21 hospitals in a northeast region of France. At hospital admission, their mean age was 77.3 (standard deviation [SD] 11.6) years and mean left ventricular ejection fraction was 45.0 (SD 16.0)%. A subset of patients were enrolled in a multidimensional DMP for HF (n = 312, 17.2%), based on structured patient education, home monitoring visits by HF-trained nurses, and automatic alerts triggered by significant clinical and biological changes to the patient. The DMP involved general practitioners, nurses, and cardiologists collaborating via an individual web-based medical electronic record. The outcome was all-cause mortality from the 3rd to the 12th month after discharge. During the follow-up, a total of 377 (20.8%) patients died: 321 (21.3%) in the control group and 56 (17.9%) in the DMP group. In a propensity score analysis, DMP was associated with lower 1-year all-cause mortality (hazard ratio 0.65, 95% CI 0.46–0.92). Instrumental variable analysis gave similar results (hazard ratio 0.56, 0.27–1.16). In a real world setting, a multidimensional DMP for HF with structured patient education, home nurse monitoring, and appropriate physician alerts may improve survival when implemented after discharge from hospitalization due to worsening HF. PMID:27631204

[Disease management programs in Germany: Validity of the medical documentation].

PubMed

Linder, R; Horenkamp-Sonntag, D; Engel, S; Köppel, D; Heilmann, T; Verheyen, F

2014-01-01

The specific documentation for disease management programs (DMP) in Germany with respect to § 137 Social Code Book V is the basis for evaluating the DMP. DMP run up costs of the order of a billion euro without assessing evidence-based benefit so far. Aim of this study was to question if and to which extent this documentation may be suitable for reliable quality assurance in its present form. Data of nearly 300000 insured persons of a German Statutory Health Insurance (Techniker Krankenkasse, TK) which were continuously registered from July 1st 2009 until December 31st 2010 in a DMP were analyzed. We analyzed how items which were components of claims data and of DMP documentation were matched. With regard to prescriptions there were some considerable differences. Prescription of glibenclamid was documented twice as frequently in the DMP documentation compared to prescriptions filled in pharmacies. Only a fraction of emergency hospitalizations documented in the claims data were found in the DMP documentation. Investigations of the fundus oculi for diabetics are mentioned three times more frequently in the DMP documentation than they are accounted by ophthalmologists. There are considerable differences between claims data and DMP specific documentation. The latter shows a plainly reduced validity for investigated fields in the documentation forms. Reasons for this are manifold. Former evaluations of DM Ps carried out just on the basis of DMP documentation are thus highly questionable. Therefore, the DMPs themselves and their documentation have to be reformed. © Georg Thieme Verlag KG Stuttgart · New York.

Spontaneous Ca(2+) transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine.

PubMed

Baker, Salah A; Drumm, Bernard T; Saur, Dieter; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

2016-06-15

Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it

Spontaneous Ca2+ transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine

PubMed Central

Baker, Salah A.; Drumm, Bernard T.; Saur, Dieter; Hennig, Grant W.; Ward, Sean M.

2016-01-01

Key points Interstitial cells of Cajal at the level of the deep muscular plexus (ICC‐DMP) in the small intestine generate spontaneous Ca2+ transients that consist of localized Ca2+ events and limited propagating Ca2+ waves.Ca2+ transients in ICC‐DMP display variable characteristics: from discrete, highly localized Ca2+ transients to regionalized Ca2+ waves with variable rates of occurrence, amplitude, duration and spatial spread.Ca2+ transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells.Ca2+ transients in ICC‐DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s).Functional intracellular Ca2+ stores are essential for spontaneous Ca2+ transients, and the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump is necessary for maintenance of spontaneity.Ca2+ release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3Rs). Release from these channels is interdependent.ICC express transcripts of multiple RyRs and InsP3Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Abstract Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC‐DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC‐DMP are mediated by activation of Ca2+‐activated Cl− channels; thus, Ca2+ signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca2+ transients in ICC‐DMP within intact jejunal muscles expressing a genetically encoded Ca2+ indicator (GCaMP3) selectively in ICC. ICC‐DMP displayed spontaneous Ca2+ transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca2+ transients was highly variable, and it was

Selection effects may account for better outcomes of the German Disease Management Program for type 2 diabetes

PubMed Central

2010-01-01

Background The nationwide German disease management program (DMP) for type 2 diabetes was introduced in 2003. Meanwhile, results from evaluation studies were published, but possible baseline differences between DMP and usual-care patients have not been examined. The objective of our study was therefore to find out if patient characteristics as socio-demographic variables, cardiovascular risk profile or motivation for life style changes influence the chance of being enrolled in the German DMP for type 2 diabetes and may therefore account for outcome differences between DMP and usual-care patients. Methods Case control study comparing DMP patients with usual-care patients at baseline and follow up; mean follow-up period of 36 ± 14 months. We used chart review data from 51 GP surgeries. Participants were 586 DMP and 250 usual-care patients with type 2 diabetes randomly selected by chart registry. Data were analysed by multivariate logistic and linear regression analyses. Significance levels were p ≤ 0.05. Results There was a better chance for enrolment if patients a) had a lower risk status for diabetes complications, i.e. non-smoking (odds ratio of 1.97, 95% confidence interval of 1.11 to 3.48) and lower systolic blood pressure (1.79 for 120 mmHg vs. 160 mmHg, 1.15 to 2.81); b) had higher activity rates, i.e. were practicing blood glucose self-monitoring (1.67, 1.03 to 2.76) and had been prescribed a diabetes patient education before enrolment (2.32, 1.29 to 4.19) c) were treated with oral medication (2.17, 1.35 to 3.49) and d) had a higher GP-rated motivation for diabetes education (4.55 for high motivation vs. low motivation, 2.21 to 9.36). Conclusions At baseline, future DMP patients had a lower risk for diabetes complications, were treated more intensively and were more active and motivated in managing their disease than usual-care patients. This finding a) points to the problem that the German DMP may not reach the higher risk patients and b) selection bias

Selection effects may account for better outcomes of the German Disease Management Program for type 2 diabetes.

PubMed

Schäfer, Ingmar; Küver, Claudia; Gedrose, Benjamin; von Leitner, Eike-Christin; Treszl, András; Wegscheider, Karl; van den Bussche, Hendrik; Kaduszkiewicz, Hanna

2010-12-31

The nationwide German disease management program (DMP) for type 2 diabetes was introduced in 2003. Meanwhile, results from evaluation studies were published, but possible baseline differences between DMP and usual-care patients have not been examined. The objective of our study was therefore to find out if patient characteristics as socio-demographic variables, cardiovascular risk profile or motivation for life style changes influence the chance of being enrolled in the German DMP for type 2 diabetes and may therefore account for outcome differences between DMP and usual-care patients. Case control study comparing DMP patients with usual-care patients at baseline and follow up; mean follow-up period of 36 ± 14 months. We used chart review data from 51 GP surgeries. Participants were 586 DMP and 250 usual-care patients with type 2 diabetes randomly selected by chart registry. Data were analysed by multivariate logistic and linear regression analyses. Significance levels were p ≤ 0.05. There was a better chance for enrolment if patients a) had a lower risk status for diabetes complications, i.e. non-smoking (odds ratio of 1.97, 95% confidence interval of 1.11 to 3.48) and lower systolic blood pressure (1.79 for 120 mmHg vs. 160 mmHg, 1.15 to 2.81); b) had higher activity rates, i.e. were practicing blood glucose self-monitoring (1.67, 1.03 to 2.76) and had been prescribed a diabetes patient education before enrolment (2.32, 1.29 to 4.19) c) were treated with oral medication (2.17, 1.35 to 3.49) and d) had a higher GP-rated motivation for diabetes education (4.55 for high motivation vs. low motivation, 2.21 to 9.36). At baseline, future DMP patients had a lower risk for diabetes complications, were treated more intensively and were more active and motivated in managing their disease than usual-care patients. This finding a) points to the problem that the German DMP may not reach the higher risk patients and b) selection bias may impair the assessment of differences

[Health locus of control of patients in disease management programmes].

PubMed

Schnee, M; Grikscheit, F

2013-06-01

Health locus of control beliefs plays a major role in improving self-management skills of the chronically ill - a main goal in disease management programmes (DMP). This study aims at characterising participants in disease management regarding their health locus of control. Data are based on 4 cross-sectional postal surveys between spring and autumn of 2006 and 2007 within the Health Care Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A high internal locus of control (HLC) occurs significantly less often in DMP patients than in normal chronically ill patients (and healthy people) controlling for age, gender and social class. With increasing age, a high internal locus of control is also significantly less likely. When comparing healthy people, the chronically ill and the DMP participants a social gradient of a high internal locus of control belief can be observed. The weaker internal and higher doctor-related external locus of control of DMP participants should be carefully observed by the physician when trying to strengthen the patients' self-management skills. Evaluators of DMP should take into account the different baselines of DMP patients and relevant control groups and incorporate these differences into the evaluation. © Georg Thieme Verlag KG Stuttgart · New York.

Intracellular Localization of Arabidopsis Sulfurtransferases1

PubMed Central

Bauer, Michael; Dietrich, Christof; Nowak, Katharina; Sierralta, Walter D.; Papenbrock, Jutta

2004-01-01

Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism. PMID:15181206

No selection, but higher satisfaction of people participating in the disease management programme diabetes type 2 in Germany.

PubMed

Kellner, Christiane; Kuniss, Nadine; Kloos, Christof; Müller, Ulrich Alfons; Müller, Nicolle

2018-04-01

We analysed metabolic control, complications and satisfaction in people with and without DMP participation. We retrospectively analysed the German data of the GUIDANCE study. The general practices included (n = 38) were selected from the physicians' register of the Thuringian Association of Statutory Health Insurance Physicians. Half of the practices (n = 19) participated in the DMP "Diabetes mellitus type 2". Nine hundred and fifty-nine people were included in the analysis. Of these, 541 (56.4%) were enrolled in the DMP and 418 (43.6%) not. There was no difference between the two groups (DMP vs. no DMP) regarding age (67.8 vs. 67.6y), gender (female 50.6 vs. 52.2%), diabetes duration (9.8 vs. 9.5y), BMI (31.3 vs. 30.7 kg/m 2 ), HbA1c (7.2 vs. 7.2%), systolic blood pressure (139 vs. 140 mm Hg) or antihypertensive drug (89.5 vs. 88.8%). More DMP participants had regular screening of diabetic late complications: retinopathy 84.7 versus 69.9% (p < 0.001); polyneuropathy 93.0 versus 52.6% (p < 0.001). Chronic kidney disease was more frequent in DMP participants (15.0 vs. 9.3%, p = 0.005). Treatment satisfaction was higher in participants enrolled in the DMP (31.1 vs. 30.0; p = 0.002). DMP participants do not exhibit positive selection. Process quality and treatment satisfaction are higher in DMP participants.

An Intact Dorsomedial Posterior Arcuate Nucleus is Not Necessary for Photoperiodic Responses in Siberian Hamsters1

PubMed Central

Teubner, Brett J.W.; Leitner, Claudia; Thomas, Michael A.; Ryu, Vitaly; Bartness, Timothy J.

2015-01-01

Seasonal responses of many animal species are triggered by changes in daylength and its transduction into a neuroendocrine signal by the pineal gland through the nocturnal duration of melatonin (MEL) release. The precise central sites necessary to receive, transduce, and relay the short day (SD) fall-winter MEL signals into seasonal responses and changes in physiology and behavior are unclear. In Siberian hamsters, SDs trigger decreases in body and lipid mass, testicular regression and pelage color changes. Several candidate genes and their central sites of expression have been proposed as components of the MEL transduction system with considerable recent focus on the arcuate nucleus (ARC) and its component, the dorsomedial posterior arcuate nucleus (dmpARC). This site has been postulated as a critical relay of SD information through the modulation of a variety of neurochemicals/receptors important for the control of energy balance. Here the necessity of an intact dmpARC for SD responses was tested by making electrolytic lesions of the Siberian hamster dmpARC and then exposing them to either long days (LD) or SDs for 12 weeks. The SD typical decreases in body and fat mass, food intake, testicular volume, serum testosterone concentrations, pelage color change and increased UCP-1 protein expression (a proxy for brown adipose tissue thermogenesis) all occurred despite the lack of an intact dmpARC. Although the Siberian hamster dmpARC contains photoperiod-modulated constituents, these data demonstrate that an intact dmpARC is not necessary for SD responses and not integral to the seasonal energy- and reproductive-related responses measured here. PMID:25647158

Klf10 regulates odontoblast differentiation and mineralization via promoting expression of dentin matrix protein 1 and dentin sialophosphoprotein genes

PubMed Central

Chen, Zhuo; Li, Wentong; Wang, Han; Wan, Chunyan; Luo, Daoshu; Deng, Shuli

2016-01-01

Klf10, a member of the Krüppel-like family of transcription factors, is critical for osteoblast differentiation, bone formation and mineralization. However, whether Klf10 is involved in odontoblastic differentiation and tooth development has not been determined. In this study, we investigate the expression patterns of Klf10 during murine tooth development in vivo and its role in odontoblastic differentiation in vitro. Klf10 protein was expressed in the enamel organ and the underlying mesenchyme, ameloblasts and odontoblasts at early and later stages of murine molar formation. Furthermore, the expression of Klf10, Dmp1, Dspp and Runx2 was significantly elevated during the process of mouse dental papilla mesenchymal differentiation and mineralization. The overexpression of Klf10 induced dental papilla mesenchymal cell differentiation and mineralization as detected by alkaline phosphatase staining and alizarin red S assay. Klf10 additionally up-regulated the expression of odontoblastic differentiation marker genes Dmp1, Dspp and Runx2 in mouse dental papilla mesenchymal cells. The molecular mechanism of Klf10 in controlling Dmp1 and Dspp expression is thus to activate their regulatory regions in a dosage-dependent manner. Our results suggest that Klf10 is involved in tooth development and promotes odontoblastic differentiation via the up-regulation of Dmp1 and Dspp transcription. PMID:26310138

Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets.

PubMed

Wacker, Michael J; Touchberry, Chad D; Silswal, Neerupma; Brotto, Leticia; Elmore, Chris J; Bonewald, Lynda F; Andresen, Jon; Brotto, Marco

2016-01-01

Autosomal recessive hypophosphatemic rickets (ARHR) is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well-characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand in order to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL-fast-twitch muscle), soleus (SOL-slow-twitch muscle), heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum) which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2α or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In summary, these

Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets

PubMed Central

Wacker, Michael J.; Touchberry, Chad D.; Silswal, Neerupma; Brotto, Leticia; Elmore, Chris J.; Bonewald, Lynda F.; Andresen, Jon; Brotto, Marco

2016-01-01

Autosomal recessive hypophosphatemic rickets (ARHR) is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well-characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand in order to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL-fast-twitch muscle), soleus (SOL–slow-twitch muscle), heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum) which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2α or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In summary

Synthesis Characterization and DNA Interaction Studies of a New Zn(II) Complex Containing Different Dinitrogen Aromatic Ligands

PubMed Central

Shahabadi, Nahid; Mohammadi, Somaye

2012-01-01

A mononuclear complex of Zn(II), [Zn(DIP)2 (DMP)] (NO3)2 ·2H2O in which DIP is 4,7-diphenyl-1,10-phenanthroline and DMP is 4,4′-dimethyl-2,2′-bipyridine has been prepared and characterized by 1HNMR spectroscopy, FT-IR, UV-Vis and elemental analysis techniques. DNA-binding properties of the complex were studied using UV-vis spectra, circular dichroism (CD) spectra, fluorescence, cyclic voltammetry (CV), and viscosity measurements. The results indicate that this zinc(II) complex can intercalate into the stacked base pairs of DNA and compete with the strong intercalator ethidium bromide for the intercalative binding sites. PMID:22956919

MLF1-interacting protein is mainly localized in nucleolus through N-terminal bipartite nuclear localization signal.

PubMed

Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Saito, Shinobu; Takeda, Nobuakira; Yamada, Hisashi; Horiguchi-Yamada, Junko

2007-01-01

The myelodysplasia/myeloid leukemia factor 1-interacting protein (MLF1LP, also called KLIP1 and CENP-50) is reported to localize in both the nucleus and the cytoplasm. To investigate the functions of MLF1IP, its subnuclear localization was studied. MLF1IP was tagged with green fluorescent protein (EGFP). Fibrillarin was tagged with red fluorescent protein (DsRed). EGFP-tagged MLF1IP deletion vectors were also constructed. Plasmid-constructs were transfected into human cervical adenocarcinoma HeLa cells or monkey kidney fibroblast COS-7 cells, and the localization was studied by either confocal fluorescence microscopy or fluorescence microscopy. Ectopically expressed MLF1IP was localized mainly in the nucleolus. In some cells, small dot-like particles of MLF1IP fluorescence were observed in the nucleoplasm. Co-staining of fibrillarin disclosed that MLF1IP was co-localized with fibrillarin in the nucleolus. Deletion mutants of MLF1IP revealed that the N-terminal bipartite nuclear localization signal (NLS) was responsible for nucleolar targeting. MLF1IP was localized mainly in the nucleolus through the N-terminal bipartite NLS and partly in the nucleoplasm featuring small dot-like particles. These findings suggest that MLF1IP may have multi-functions and its different localizations may contribute to carcinogenesis.

Social disparities in Disease Management Programmes for coronary heart disease in Germany: a cross-classified multilevel analysis

PubMed Central

Bozorgmehr, Kayvan; Maier, Werner; Brenner, Hermann; Saum, Kai-Uwe; Stock, Christian; Miksch, Antje; Holleczek, Bernd; Szecsenyi, Joachim; Razum, Oliver

2015-01-01

Background Disease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels. Methods Cross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models. Results Among N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates. Conclusions We found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the

Social disparities in Disease Management Programmes for coronary heart disease in Germany: a cross-classified multilevel analysis.

PubMed

Bozorgmehr, Kayvan; Maier, Werner; Brenner, Hermann; Saum, Kai-Uwe; Stock, Christian; Miksch, Antje; Holleczek, Bernd; Szecsenyi, Joachim; Razum, Oliver

2015-11-01

Disease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels. Cross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models. Among N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates. We found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the effects were partly explained by

Gene flow in maize fields with different local pollen densities.

PubMed

Goggi, A Susana; Lopez-Sanchez, Higinio; Caragea, Petrutza; Westgate, Mark; Arritt, Raymond; Clark, Craig A

2007-08-01

The development of maize (Zea mays L.) varieties as factories of pharmaceutical and industrial compounds has renewed interest in controlling pollen dispersal. The objective of this study was to compare gene flow into maize fields of different local pollen densities under the same environmental conditions. Two fields of approximately 36 ha were planted with a nontransgenic, white hybrid, in Ankeny, Iowa, USA. In the center of both fields, a 1-ha plot of a yellow-seeded stacked RR/Bt transgenic hybrid was planted as a pollen source. Before flowering, the white receiver maize of one field was detasseled in a 4:1 ratio to reduce the local pollen density (RPD). The percentage of outcross in the field with RPD was 42.2%, 6.3%, and 1.3% at 1, 10, and 35 m from the central plot, respectively. The percentage of outcross in the white maize with normal pollen density (NPD) was 30.1%, 2.7%, and 0.4%, respectively, at these distances. At distances greater than 100 m, the outcross frequency decreased below 0.1 and 0.03% in the field with RPD and NPD, respectively. A statistical model was used to compare pollen dispersal based on observed outcross percentages. The likelihood ratio test confirmed that the models of outcrossing in the two fields were significantly different (P is practically 0). Results indicated that when local pollen is low, the incoming pollen has a competitive advantage and the level of outcross is significantly greater than when the local pollen is abundant.

LOCALIZATION OF SP22 ON HUMAN SPERM OF DIFFERING QUALITY

EPA Science Inventory

LOCALIZATION OF SP22 ON HUMAN SPERM OF DIFFERING QUALITY. AE Lavers*1, GR Klinefelter2, DW Hamilton1, KP Roberts1, 1University of Minnesota, Minneapolis, MN and 2US EPA, Research Triangle Park, NC.
SP22 is a sperm membrane protein that has been implicated in sperm function d...

Serotype-specific differences in dengue virus non-structural protein 5 nuclear localization.

PubMed

Hannemann, Holger; Sung, Po-Yu; Chiu, Han-Chen; Yousuf, Amjad; Bird, Jim; Lim, Siew Pheng; Davidson, Andrew D

2013-08-02

The four serotypes of dengue virus (DENV-1 to -4) cause the most important arthropod-borne viral disease of humans. DENV non-structural protein 5 (NS5) contains enzymatic activities required for capping and replication of the viral RNA genome that occurs in the host cytoplasm. However, previous studies have shown that DENV-2 NS5 accumulates in the nucleus during infection. In this study, we examined the nuclear localization of NS5 for all four DENV serotypes. We demonstrate for the first time that there are serotypic differences in NS5 nuclear localization. Whereas the DENV-2 and -3 proteins accumulate in the nucleus, DENV-1 and -4 NS5 are predominantly if not exclusively localized to the cytoplasm. Comparative studies on the DENV-2 and -4 NS5 proteins revealed that the difference in DENV-4 NS5 nuclear localization was not due to rapid nuclear export but rather the lack of a functional nuclear localization sequence. Interaction studies using DENV-2 and -4 NS5 and human importin-α isoforms failed to identify an interaction that supported the differential nuclear localization of NS5. siRNA knockdown of the human importin-α isoform KPNA2, corresponding to the murine importin-α isoform previously shown to bind to DENV-2 NS5, did not substantially affect DENV-2 NS5 nuclear localization, whereas knockdown of importin-β did. The serotypic differences in NS5 nuclear localization did not correlate with differences in IL-8 gene expression. The results show that NS5 nuclear localization is not strictly required for virus replication but is more likely to have an auxiliary function in the life cycle of specific DENV serotypes.

Serotype-specific Differences in Dengue Virus Non-structural Protein 5 Nuclear Localization*

PubMed Central

Hannemann, Holger; Sung, Po-Yu; Chiu, Han-Chen; Yousuf, Amjad; Bird, Jim; Lim, Siew Pheng; Davidson, Andrew D.

2013-01-01

The four serotypes of dengue virus (DENV-1 to -4) cause the most important arthropod-borne viral disease of humans. DENV non-structural protein 5 (NS5) contains enzymatic activities required for capping and replication of the viral RNA genome that occurs in the host cytoplasm. However, previous studies have shown that DENV-2 NS5 accumulates in the nucleus during infection. In this study, we examined the nuclear localization of NS5 for all four DENV serotypes. We demonstrate for the first time that there are serotypic differences in NS5 nuclear localization. Whereas the DENV-2 and -3 proteins accumulate in the nucleus, DENV-1 and -4 NS5 are predominantly if not exclusively localized to the cytoplasm. Comparative studies on the DENV-2 and -4 NS5 proteins revealed that the difference in DENV-4 NS5 nuclear localization was not due to rapid nuclear export but rather the lack of a functional nuclear localization sequence. Interaction studies using DENV-2 and -4 NS5 and human importin-α isoforms failed to identify an interaction that supported the differential nuclear localization of NS5. siRNA knockdown of the human importin-α isoform KPNA2, corresponding to the murine importin-α isoform previously shown to bind to DENV-2 NS5, did not substantially affect DENV-2 NS5 nuclear localization, whereas knockdown of importin-β did. The serotypic differences in NS5 nuclear localization did not correlate with differences in IL-8 gene expression. The results show that NS5 nuclear localization is not strictly required for virus replication but is more likely to have an auxiliary function in the life cycle of specific DENV serotypes. PMID:23770669

The effect of using different regions of interest on local and mean skin temperature.

PubMed

Maniar, Nirav; Bach, Aaron J E; Stewart, Ian B; Costello, Joseph T

2015-01-01

The dynamic nature of tissue temperature and the subcutaneous properties, such as blood flow, fatness, and metabolic rate, leads to variation in local skin temperature. Therefore, we investigated the effects of using multiple regions of interest when calculating weighted mean skin temperature from four local sites. Twenty-six healthy males completed a single trial in a thermonetural laboratory (mean ± SD): 24.0 (1.2)°C; 56 (8%) relative humidity; <0.1 m/s air speed). Mean skin temperature was calculated from four local sites (neck, scapula, hand and shin) in accordance with International Standards using digital infrared thermography. A 50 mm × 50 mm, defined by strips of aluminium tape, created six unique regions of interest, top left quadrant, top right quadrant, bottom left quadrant, bottom right quadrant, centre quadrant and the entire region of interest, at each of the local sites. The largest potential error in weighted mean skin temperature was calculated using a combination of a) the coolest and b) the warmest regions of interest at each of the local sites. Significant differences between the six regions interest were observed at the neck (P<0.01), scapula (P<0.001) and shin (P<0.05); but not at the hand (P = 0.482). The largest difference (± SEM) at each site was as follows: neck 0.2 (0.1)°C; scapula 0.2 (0.0)°C; shin 0.1 (0.0)°C and hand 0.1 (0.1)°C. The largest potential error (mean ± SD) in weighted mean skin temperature was 0.4 (0.1)°C (P<0.001) and the associated 95% limits of agreement for these differences was 0.2-0.5 °C. Although we observed differences in local and mean skin temperature based on the region of interest employed, these differences were minimal and are not considered physiologically meaningful. Copyright © 2015 Elsevier Ltd. All rights reserved.

Better lipid target achievement for secondary prevention through disease management programs for diabetes mellitus and coronary heart disease in clinical practice in Germany.

PubMed

Gitt, Anselm K; Sonntag, Frank; Jannowitz, Christina; Weizel, Achim; Karmann, Barbara; Schaefer, Juergen R; Pittrow, David; Hildemann, Steven K

2016-01-01

Disease management programs (DMP) for diabetes mellitus (DM) or coronary heart disease (CHD) address the treatment of lipid disorders. The current registry aimed to compare drug utilization, lipid lowering effects and further outcomes of outpatients at high cardiovascular risk in DMP for DM or CHD compared to patients in routine care (no-DMP). This was a prospective non-interventional registry with a 1 year follow-up which enrolled consecutive patients with known DM and/or any vascular disease on simvastatin 40 mg monotherapy, to document lipid target achievement in clinical practice in Germany according to existing guidelines. Drug use (maintenance, add-on, switch, discontinuation) and other components of care were upon the discretion of the treating physician. Of a total of 12,154 patients (mean age 65.8 years, 61.2% males), 3273 were in DMP CHD, 3265 in DMP DM and 1760 in DMP CHD + DM. In DMP patients compared to no-DMP patients, comorbidities/risk factors were more frequent. More patients in the DMP groups attained the target level of low density lipoprotein (LDL-C) <70 mg/dl (1.8 mmol/l) at baseline (8.5% DMP vs. 5.7% no-DMP), at 6 month (10.3% vs. 7.4%) and 12 month follow-up (10.1% vs. 7.1%). Cholesterol absorption inhibitors were added in 16% of the patients at the end of the baseline or at the follow-up visits, while statin treatment (including mean dose) remained largely unchanged. Target achievement rates were highest for all time points in the DMP CHD + DM group. With respect to limitations, this study was restricted to lipid disorders as qualifying diagnosis and simvastatin as qualifying treatment, which is a potential cause of selection bias. Information on non-pharmacological measures was not collected, and the 12-month follow-up period was relatively short. Patients in DMP compared to those not in DMP achieved better LDL-C lowering and higher control rates, but overall lipid target achievement rates need to be improved. Longer

Health related quality of life and comorbidity. A descriptive analysis comparing EQ-5D dimensions of patients in the German disease management program for type 2 diabetes and patients in routine care.

PubMed

Ose, Dominik; Miksch, Antje; Urban, Elisabeth; Natanzon, Iris; Szecsenyi, Joachim; Kunz, Cornelia Ursula; Freund, Tobias

2011-08-02

The co-occurance of multiple medical conditions has a negative impact on health related quality of life (HRQoL) for patients with type 2 diabetes. These patients demand for intensified care programs. Participation in a disease management program (DMP) for type 2 diabetes has shown to counterbalance this effect. However, it remains unclear which dimensions of HRQoL are influenced by the DMP. The aim of this study was to explore the HRQoL dimensions of patients with type 2 diabetes in the German DMP and patients in routine care (RC). This analysis is part of a comparative evaluation of the German DMP for patients with type 2 diabetes. A questionnaire, including the HRQoL measure EQ-5D, was mailed to a random sample of 3,546 patients with type 2 diabetes (59.3% female). The EQ-5D dimensions were analyzed by grouping patients according to their participation in the German DMP for diabetes into DMP and RC. Compared to patients in DMP, patients in RC reported more problems for the dimensions mobility (P < 0.05), self care (P < 0.05) and performing usual activities (P < 0.01). Depending on the number of other conditions, remarkable differences for reporting "no problems" exist for patients with six or more comorbid conditions regarding the dimensions mobility (RC = 8.7%, DMP = 32.3%), self care (RC = 43.5%, DMP = 64.5%), usual activities (RC = 13.0%, DMP = 33.9%) and anxiety or depression (RC = 37.0%, DMP = 48.4%). Patients participating in the German DMP for type 2 diabetes mellitus show significantly higher ratings of their HRQoL in the dimensions mobility, self care and performing usual activities compared to patients in RC. This difference can also be observed in patients with significant comorbidities. As these dimensions are known to be essential for diabetes care, the German DMP may contribute to improved care even for comorbid diabetes patients.

Health related quality of life and comorbidity. A descriptive analysis comparing EQ-5D dimensions of patients in the German disease management program for type 2 diabetes and patients in routine care

PubMed Central

2011-01-01

Background The co-occurance of multiple medical conditions has a negative impact on health related quality of life (HRQoL) for patients with type 2 diabetes. These patients demand for intensified care programs. Participation in a disease management program (DMP) for type 2 diabetes has shown to counterbalance this effect. However, it remains unclear which dimensions of HRQoL are influenced by the DMP. The aim of this study was to explore the HRQoL dimensions of patients with type 2 diabetes in the German DMP and patients in routine care (RC). Methods This analysis is part of a comparative evaluation of the German DMP for patients with type 2 diabetes. A questionnaire, including the HRQoL measure EQ-5D, was mailed to a random sample of 3,546 patients with type 2 diabetes (59.3% female). The EQ-5D dimensions were analyzed by grouping patients according to their participation in the German DMP for diabetes into DMP and RC. Results Compared to patients in DMP, patients in RC reported more problems for the dimensions mobility (P < 0.05), self care (P < 0.05) and performing usual activities (P < 0.01). Depending on the number of other conditions, remarkable differences for reporting "no problems" exist for patients with six or more comorbid conditions regarding the dimensions mobility (RC = 8.7%, DMP = 32.3%), self care (RC = 43.5%, DMP = 64.5%), usual activities (RC = 13.0%, DMP = 33.9%) and anxiety or depression (RC = 37.0%, DMP = 48.4%). Conclusion Patients participating in the German DMP for type 2 diabetes mellitus show significantly higher ratings of their HRQoL in the dimensions mobility, self care and performing usual activities compared to patients in RC. This difference can also be observed in patients with significant comorbidities. As these dimensions are known to be essential for diabetes care, the German DMP may contribute to improved care even for comorbid diabetes patients. PMID:21810241

Modelling of human low frequency sound localization acuity demonstrates dominance of spatial variation of interaural time difference and suggests uniform just-noticeable differences in interaural time difference.

PubMed

Smith, Rosanna C G; Price, Stephen R

2014-01-01

Sound source localization is critical to animal survival and for identification of auditory objects. We investigated the acuity with which humans localize low frequency, pure tone sounds using timing differences between the ears. These small differences in time, known as interaural time differences or ITDs, are identified in a manner that allows localization acuity of around 1° at the midline. Acuity, a relative measure of localization ability, displays a non-linear variation as sound sources are positioned more laterally. All species studied localize sounds best at the midline and progressively worse as the sound is located out towards the side. To understand why sound localization displays this variation with azimuthal angle, we took a first-principles, systemic, analytical approach to model localization acuity. We calculated how ITDs vary with sound frequency, head size and sound source location for humans. This allowed us to model ITD variation for previously published experimental acuity data and determine the distribution of just-noticeable differences in ITD. Our results suggest that the best-fit model is one whereby just-noticeable differences in ITDs are identified with uniform or close to uniform sensitivity across the physiological range. We discuss how our results have several implications for neural ITD processing in different species as well as development of the auditory system.

Is there a survival benefit within a German primary care-based disease management program?

PubMed

Miksch, Antje; Laux, Gunter; Ose, Dominik; Joos, Stefanie; Campbell, Stephen; Riens, Burgi; Szecsenyi, Joachim

2010-01-01

To compare the mortality rate of patients with type 2 diabetes who were enrolled in the German diabetes disease management program (DMP) with the mortality rate of those who were not enrolled. This observational study was part of the ELSID study (Evaluation of a Large Scale Implementation of disease management programs) in Germany. Participants had type 2 diabetes and were either enrolled or not enrolled in the DMP. The DMP provides systems-based, multifaceted, and patient-centered interventions. To reduce imbalances between the groups, a matched sample was created using sex, age, retirement status, federal state, pharmacy-based cost groups, and diagnostic-cost groups as matching criteria. Cox proportional hazards regression model and the Kaplan-Meier method were used to assess overall mortality. The observation period was 3 years beginning on January 1, 2006. A total of 11,079 patients were included in the analysis. As of January 1, 2006, 2300 patients were enrolled in the DMP and 8779 were receiving routine care. There were 1927 matched pairs of patients in the DMP group and the non-DMP group. The overall mortality rate was 11.3% in the DMP and 14.4% in the non-DMP group (log-rank test P <.01). We found an association between participation in the German diabetes DMP and reduced mortality. This reduced mortality cannot be attributed directly to the DMP. However, further research should evaluate whether a primary care-based DMP contributes to increased life expectancy in patients with diabetes.

Patients with type 2 diabetes benefit from primary care-based disease management: a propensity score matched survival time analysis.

PubMed

Drabik, Anna; Büscher, Guido; Thomas, Karsten; Graf, Christian; Müller, Dirk; Stock, Stephanie

2012-08-01

This study aimed to assess the impact of a nationwide German diabetes mellitus disease management program (DMP) on survival time and costs in comparison to routine care. The authors conducted a retrospective observational cohort study using routine administration data from Germany's largest sickness fund to identify insured suffering from diabetes in 2002. A total of 95,443 insured with type 2 diabetes mellitus who were born before January 1, 1962 met the defined inclusion criteria, resulting in 19,888 pairs of DMP participants and nonparticipants matched for socioeconomic and health status using propensity score matching methods. This is the first time propensity score matching has been used to evaluate a survival benefit of DMPs. In the time frame analyzed (3 years), mean survival time for the DMP group was 1045 days vs. 985 days for the routine care group (P<0.001). Mean daily hospital and total costs (including DMP administration and medical costs) were lower for the DMP group in the case of deceased insureds (92€ vs. 139€ and 122€ vs. 169€, respectively) as well as for censored observations (6€ vs. 7€ and 12.9€ vs. 13.4€, respectively). Mean daily drug costs were slightly lower for deceased insured in the DMP group (difference 0.6€), while no identifiable difference was found for censored observations. In this study, insured who were enrolled in a DMP for diabetes mellitus in the German Statutory Health Insurance showed a significant benefit in survival time. They also incurred lower costs compared to propensity score matched insured in routine care.

Two-fold interpenetrating btc based cobaltous coordination polymer: A promising catalyst for solvent free oxidation of 1-hexene

NASA Astrophysics Data System (ADS)

Bora, Sanchay J.; Paul, Rima; Nandi, Mithun; Bhattacharyya, Pradip K.

2017-12-01

This work describes the synthesis of a new 2-D coordination polymer (CP), [Co3(btc)2(dmp)8]n (btc = 1,3,5-benzenetricarboxylate and dmp = 3,5-dimethylpyrazole) and its catalytic activity towards the oxidation reaction of 1-hexene to form oxygenated compounds under solvent free condition. Structural analysis reveals that Co(II) cations in this polymeric compound are linked by btc3- anions with alternate tetrahedral/octahedral coordination forming a two-fold interpenetrated 3-connected hcb underlying net. Electronic spectrum of the cobaltous polymer has been calculated using TDDFT/B3LYP method for making the appropriate assignments of electronic transitions. Catalytic results show good conversions of the starting material to oxygenated products with high selectivities for 1,2-epoxyhexane and 1-hexanal.

Local expression of vaginal Th1 and Th2 cytokines in murine vaginal candidiasis under different immunity conditions.

PubMed

Chen, Shanjuan; Li, Shaohua; Wu, Yan; Liu, Zhixiang; Li, Jiawen

2008-08-01

To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1 (IL-2)/Th2 (IL-4, IL-10, TGF-beta1) cytokines in murine vaginal tissues was determined by RT-PCR. The cykotine in local tissues was increased to different extent under normal immune condition. IL-2 mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-beta1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10, and TGF-beta1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans (C. albicans), and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.

Epidemiological Differences Between Localized and Nonlocalized Low Back Pain.

PubMed

Coggon, David; Ntani, Georgia; Walker-Bone, Karen; Palmer, Keith T; Felli, Vanda E; Harari, Raul; Barrero, Lope H; Felknor, Sarah A; Gimeno, David; Cattrell, Anna; Vargas-Prada, Sergio; Bonzini, Matteo; Solidaki, Eleni; Merisalu, Eda; Habib, Rima R; Sadeghian, Farideh; Kadir, M Masood; Warnakulasuriya, Sudath Sp; Matsudaira, Ko; Nyantumbu, Busisiwe; Sim, Malcolm R; Harcombe, Helen; Cox, Ken; Sarquis, Leila M M; Marziale, Maria H; Harari, Florencia; Freire, Rocio; Harari, Natalia; Monroy, Magda V; Quintana, Leonardo A; Rojas, Marianela; Harris, Elizabeth Clare; Serra, Consol; Martinez, José Miguel; Delclos, George; Benavides, Fernando G; Carugno, Michele; Ferrario, Marco M; Pesatori, Angela C; Chatzi, Leda; Bitsios, Panos; Kogevinas, Manolis; Oha, Kristel; Freimann, Tiina; Sadeghian, Ali; Peiris-John, Roshini J; Sathiakumar, Nalini; Wickremasinghe, A Rajitha; Yoshimura, Noriko; Kelsall, Helen L; Hoe, Victor C W; Urquhart, Donna M; Derrett, Sarah; McBride, David; Herbison, Peter; Gray, Andrew; Salazar Vega, Eduardo J

2017-05-15

A cross-sectional survey with a longitudinal follow-up. The aim of this study was to test the hypothesis that pain, which is localized to the low back, differs epidemiologically from that which occurs simultaneously or close in time to pain at other anatomical sites SUMMARY OF BACKGROUND DATA.: Low back pain (LBP) often occurs in combination with other regional pain, with which it shares similar psychological and psychosocial risk factors. However, few previous epidemiological studies of LBP have distinguished pain that is confined to the low back from that which occurs as part of a wider distribution of pain. We analyzed data from CUPID, a cohort study that used baseline and follow-up questionnaires to collect information about musculoskeletal pain, associated disability, and potential risk factors, in 47 occupational groups (office workers, nurses, and others) from 18 countries. Among 12,197 subjects at baseline, 609 (4.9%) reported localized LBP in the past month, and 3820 (31.3%) nonlocalized LBP. Nonlocalized LBP was more frequently associated with sciatica in the past month (48.1% vs. 30.0% of cases), occurred on more days in the past month and past year, was more often disabling for everyday activities (64.1% vs. 47.3% of cases), and had more frequently led to medical consultation and sickness absence from work. It was also more often persistent when participants were followed up after a mean of 14 months (65.6% vs. 54.1% of cases). In adjusted Poisson regression analyses, nonlocalized LBP was differentially associated with risk factors, particularly female sex, older age, and somatizing tendency. There were also marked differences in the relative prevalence of localized and nonlocalized LBP by occupational group. Future epidemiological studies should distinguish where possible between pain that is limited to the low back and LBP that occurs in association with pain at other anatomical locations. 2.

Selective enrollment in Disease Management Programs for coronary heart disease in Germany - An analysis based on cross-sectional survey and administrative claims data.

PubMed

Röttger, Julia; Blümel, Miriam; Busse, Reinhard

2017-04-04

In 2002, Disease Management Programs (DMPs) were introduced within the German healthcare system with the aim to increase the quality of chronic disease care. Due to the enrollment procedures, it can be assumed a) that only certain patients actively decide to enroll in a DMP and/or b) that only certain patients get the recommendation for DMP enrollment from their physician. How strong this assumed effect of self- and/or professional selection is, is still unclear. We used data from a cross-sectional postal-survey linked on individual level with administrative claims data from a German sickness fund. The sample consisted of individuals suffering from coronary heart disease (CHD) who i) were either enrolled in the respective DMP or ii) fulfilled the disease related criteria for enrollment but were not enrolled. We applied multivariate logistic regression analyses to assess factors on patient level associated with DMP enrollment. We included 7070 individuals in our analyses. Male sex, higher age and receiving old age pension, a higher Charlson Score and a diagnosis of type 2 diabetes increased the odds for DMP-CHD enrollment significantly. Individuals with a diagnosed myocardial infarction (MI) were also more likely to be enrolled in the DMP-CHD. We found a significant interaction effect for MI and sex, indicating that the association between MI and DMP enrollment is stronger for women than for men. DMP-enrollees and non-enrollees differ in various factors. Studies analyzing the effectiveness of DMP-CHD should carefully take into account these group differences. Furthermore, the results suggest that the DMP-CHD assessed reaches men better than women.

Experimental investigation of ionic liquid pretreatment of sugarcane bagasse with 1,3-dimethylimadazolium dimethyl phosphate.

PubMed

Bahrani, Samaneh; Raeissi, Sona; Sarshar, Mohammad

2015-06-01

In this study, an imidazolium-based ionic liquid (IL), 1,3-dimethylimidazolium dimethyl phosphate ([Mmim][DMP]), was applied for pretreating sugarcane bagasse to produce bioethanol. The main goal of this study was to investigate the feasibility of bagasse pretreatment with this IL, and to verify the effect of different operational parameters on the pretreatment process. Results indicated that temperature and duration of IL-pretreatment have optimum values. Within the range investigated, a maximum fermentable sugar conversion of 70.38% was achieved with this IL at 120°C and 120min. The corresponding value was 28.65% for the untreated biomass. The main cause for the observed enhancement in enzymatic hydrolysis was the reduction of cellulose crystallinity in the IL-pretreated biomass, as compared to the untreated sample, because it resulted in higher accessibility of the enzymes to the biomass after pretreatment. Moreover, the results indicated that aqueous [Mmim][DMP] mixtures are not as effective for pretreatment as the pure IL. Copyright © 2015 Elsevier Ltd. All rights reserved.

Local systematic differences in 2MASS positions

NASA Astrophysics Data System (ADS)

Bustos Fierro, I. H.; Calderón, J. H.

2018-01-01

We have found that positions in the 2MASS All-sky Catalog of Point Sources show local systematic differences with characteristic length-scales of ˜ 5 to ˜ 8 arcminutes when compared with several catalogs. We have observed that when 2MASS positions are used in the computation of proper motions, the mentioned systematic differences cause systematic errors in the resulting proper motions. We have developed a method to locally rectify 2MASS with respect to UCAC4 in order to diminish the systematic differences between these catalogs. The rectified 2MASS catalog with the proposed method can be regarded as an extension of UCAC4 for astrometry with accuracy ˜ 90 mas in its positions, with negligible systematic errors. Also we show that the use of these rectified positions removes the observed systematic pattern in proper motions derived from original 2MASS positions.

Biodegradation of phthalate esters by newly isolated Rhizobium sp. LMB-1 and its biochemical pathway of di-n-butyl phthalate.

PubMed

Tang, W-J; Zhang, L-S; Fang, Y; Zhou, Y; Ye, B-C

2016-07-01

To isolate a novel strain that could degrade many kinds PAEs efficiently and investigate the DBP-degrading pathway in this strain. Based on its 16S rRNA gene sequence, the strain was identified as Rhizobium sp. This strain, named LMB-1, can also utilize phthalates, such as DEHP, DMP, DBP and DEP. During the degradation of DBP, six possible metabolites, diethyl phthalate, mono-ethyl phthalate, di-methyl phthalate, mono-methyl phthalate, phthalic acid and tartaric acid, were identified by gas chromatography-mass spectrometry (GC-MS) analysis, and the degradation pathway of DBP was also identified in this study. In summary, strain LMB-1, identified as Rhizobium sp., was found to be capable of efficiently degrading PAEs, and it was determined that the strain degraded DMP completely within 45 h. DEP, DMP, MEP, MMP, PA and tartaric acid were detected during the course of DBP degradation by LMB-1. We propose that this strain could completely degrade DBP or other PAEs. Our results offer a novel and potential candidate, Rhizobium sp. LMB-1, for use in the bioremediation of cultivated soil contaminated by PAEs. This is the first report concerning the complete degradation of phthalate esters by Rhizobium sp. © 2016 The Society for Applied Microbiology.

[Characteristics of Adsorption Leaching and Influencing Factors of Dimethyl Phthalate in Purple Soil].

PubMed

Wang, Qiang; Song, Jiao-yan; Zeng, Wei; Wang, Fa

2016-02-15

The typical soil-purple soil in Three Gorges Reservoir was the tested soil, the characteristics of adsorption leaching of dimethyl phthalate (DMP) in contaminated water by the soil, and the influencing factors in the process were conducted using soil column leaching experiment. The results showed that the parabolic equation was the best equation describing adsorption kinetics of DMP by soils. The concentration of DMP in the leaching solution had significant effect on the adsorption amounts of DMP. With the increasing concentration of DMP in the leaching solution, the adsorption capacities of DMP by purple soil increased linearly. The ionic strength and pH in leaching solution had significant effects on adsorption of DMP. On the whole, increasing of the ionic strength restrained the adsorption. The adsorption amounts at pH 5.0-7.0 were more than those under other pH condition. The addition of exogenous organic matter (OM) in purple soil increased the adsorption amount of DMP by purple soil. However, the adsorption amount was less than those with other addition amounts of exogenous OM when the addition of exogenous OM was too high (> or = 30 g x kg(-1)). The addition of surfactant sodium dodecylbenzene sulfonic acid (SDBS) in purple soil increased the adsorption amount of DMP by purple soil. The adsorption amount was maximal when the addition amount of SDBS was 50 mg x kg(-1). However, the adsorption amounts decreased with increasing addition amounts of SDBS although the adsorption amounts were still more than that of the control group, and the adsorption amount was almost equal to that of the control group when the addition amount of SDBS was 800 mg x kg(-1). Continuous leaching time affected the vertical distribution of DMP in the soil column. When the leaching time was shorter, the upper soil column adsorbed more DMP, while the DMP concentrations in upper and lower soil columns became similar with the extension of leaching time.

The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences.

PubMed

Schäfer, Ingmar; Küver, Claudia; Gedrose, Benjamin; Hoffmann, Falk; Russ-Thiel, Barbara; Brose, Hans-Peter; van den Bussche, Hendrik; Kaduszkiewicz, Hanna

2010-03-03

In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year. Cohort study with a baseline interview and a follow-up after 10.4 +/- 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses. DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have > or = 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up. In the light of patient's experiences the DMP enhances the process quality of medical care for type 2

[Ambulatory care of patients with asthma in Germany and disease management program for asthma from the view of statutory health insured patients. A postal survey of statutory health insured patients].

PubMed

Bücker, B; Löscher, S; Schürer, C; Schaper, K; Abholz, H-H; Wilm, S

2015-03-01

In spite of a decline in mortality due to asthma in Germany various studies point towards deficits in asthma care. Our investigation should collect data about ambulatory care from the view of statutory health insured patients (SHI), who participate in the disease management program asthma (DMP-P) or do not (NP). Primary question was, if there is a difference between asthma control. Secondary questions referred to process parameters. The postal inquiry was conducted in 2010 with 8000 randomly selected members of a SHI company with asthma (4000 DMP-P and 4000 NP). The descriptive evaluation of categorical items was performed with cross-tables. The absolute risk reduction (ARR) and 97.5 %-confidence interval (CI; multiple level 5 %) was used to evaluate the primary question. Secondary questions were analysed by ARR and 95 %-CI. The response rate of the questionnaire accounted for 31.1 % (2565). 49.2 % of all respondents lived with an uncontrolled asthma with no differences between DMP-P and NP (ARR -2.7 %, 97.5 %-CI -7.9 -2.4 %). Results did not alter after adjustment for sex and age. The secondary questions revealed significant differences (DMP-P vs. NP) in participation in asthma trainings 50.6 vs. 32.3 %, use of a peak-flow-meter 49.3 vs. 25.3 % and asthma action plan within reach 21.7 vs. 11.0 %. Half of all respondents lives selfreported - even in the DMP-group - with an uncontrolled asthma. Process parameters showed better results in the DMP-group. It can be considered, that the DMP has its desired effect on patient-centered care, but does not lead to a better therapeutic outcome. Explanations can only be assumed: insufficient impact of the process parameters on the outcome, patient behavior, that minimizes a possible effect, or selection effects, if patients, who were more sick and at the same time more motivated, were mainly included in the DMP. These aspects should be addressed in studies with a prospective design. © Georg Thieme

Rumen-protected lysine, methionine, and histidine increase milk protein yield in dairy cows fed a metabolizable protein-deficient diet.

PubMed

Lee, C; Hristov, A N; Cassidy, T W; Heyler, K S; Lapierre, H; Varga, G A; de Veth, M J; Patton, R A; Parys, C

2012-10-01

The objective of this experiment was to evaluate the effect of supplementing a metabolizable protein (MP)-deficient diet with rumen-protected (RP) Lys, Met, and specifically His on dairy cow performance. The experiment was conducted for 12 wk with 48 Holstein cows. Following a 2-wk covariate period, cows were blocked by DIM and milk yield and randomly assigned to 1 of 4 diets, based on corn silage and alfalfa haylage: control, MP-adequate diet (ADMP; MP balance: +9 g/d); MP-deficient diet (DMP; MP balance: -317 g/d); DMP supplemented with RPLys (AminoShure-L, Balchem Corp., New Hampton, NY) and RPMet (Mepron; Evonik Industries AG, Hanau, Germany; DMPLM); and DMPLM supplemented with an experimental RPHis preparation (DMPLMH). The analyzed crude protein content of the ADMP and DMP diets was 15.7 and 13.5 to 13.6%, respectively. The apparent total-tract digestibility of all measured nutrients, plasma urea-N, and urinary N excretion were decreased by the DMP diets compared with ADMP. Milk N secretion as a proportion of N intake was greater for the DMP diets compared with ADMP. Compared with ADMP, dry matter intake (DMI) tended to be lower for DMP, but was similar for DMPLM and DMPLMH (24.5, 23.0, 23.7, and 24.3 kg/d, respectively). Milk yield was decreased by DMP (35.2 kg/d), but was similar to ADMP (38.8 kg/d) for DMPLM and DMPLMH (36.9 and 38.5kg/d, respectively), paralleling the trend in DMI. The National Research Council 2001model underpredicted milk yield of the DMP cows by an average (±SE) of 10.3 ± 0.75 kg/d. Milk fat and true protein content did not differ among treatments, but milk protein yield was increased by DMPLM and DMPLMH compared with DMP and was not different from ADMP. Plasma essential amino acids (AA), Lys, and His were lower for DMP compared with ADMP. Supplementation of the DMP diets with RP AA increased plasma Lys, Met, and His. In conclusion, MP deficiency, approximately 15% below the National Research Council requirements from 2001, decreased

Removal of dimethyl phthalate from water by ozone microbubbles.

PubMed

Jabesa, Abdisa; Ghosh, Pallab

2017-08-01

This work investigates the removal of dimethyl phthalate (DMP) from water using ozone microbubbles in a pilot plant of 20 dm 3 capacity. Experiments were performed under various reaction conditions to examine the effects of the initial concentration of DMP, pH of the medium, ozone generation rate, and the role of H 2 O 2 on the removal of DMP. The DMP present in water was effectively removed by the ozone microbubbles. The removal was effective in neutral and alkaline media. Increase in the initial concentration of the target pollutant negatively affected its removal efficiency. The removal efficiency dramatically increased from 1% to 99% when the ozone generation rate was increased from 0.28 to 1.94 mg s -1 at pH 7. The total organic carbon measurements revealed that a complete mineralization of DMP was achieved within 1.8 ks at the high ozone feed rate. The use of t-butyl alcohol as the hydroxyl radical scavenger confirmed that the reaction between the target organic compound and ·OH radical dominated over its direct reaction with ozone. The reaction between DMP and ozone followed an overall second-order kinetics. The volumetric mass transfer coefficient of ozone in the reacting system and the enhancement factor increased with increasing initial concentration of DMP. Very low values of Hatta number were obtained at all initial concentrations of DMP and pH, which show that the mass transfer resistance was small.

Treatment of lateral epicondilitis using three different local injection modalities: a randomized prospective clinical trial.

PubMed

Dogramaci, Yunus; Kalaci, Aydiner; Savaş, Nazan; Duman, I Gokhan; Yanat, A Nedim

2009-10-01

To determine the effectiveness of three different local injection modalities in the treatment of lateral epicondilitis. In a prospective randomized study on lateral epicondilitis, 75 patients were divided into three equal groups A, B and C (n = 25) and were treated using three different method of local injection. The patients in group A were treated with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine), those in group B were treated with injection of local anaesthetic (1 mL lidocaine) combined with peppering technique and those in group C with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine) and peppering technique. The outcome was defined by measuring the elbow pain during the activity using a 10-cm visual analogue scale (VAS) and satisfaction with the treatment using a scoring system based on the criteria of the Verhaar et al. at 3 weeks and 6 months after the injection and compared with the pre-treatment condition. There were significant (P = 0.006) differences in the successful outcomes between the three groups at 6 months. In group C in which local steroid + peppering injection technique were used; excellent results were obtained in 84% of patients comparing to 36% and 48% for patients in groups A and B, respectively. The successful outcomes were statistically higher in group C comparing to group A (P = 0.002) and group B (P = 0.011). In all groups, there was a significantly lower pain (VAS) at the 3-week and 6-month follow-ups comparing to the pre-treatment condition. VAS measured at 6-month follow-up were significantly lower in group C comparing to other groups (P = 0.002). In the treatment of lateral epicondilitis, combination of corticosteroid injections with peppering is more effective than corticosteroid injections or peppering injections alone and produces better clinical results.

A prospective examination of disease management program use by complex cardiac outpatients.

PubMed

Gravely, Shannon; Reid, Robert D; Oh, Paul; Ross, Heather; Stewart, Donna E; Grace, Sherry L

2012-01-01

The use of disease management programs (DMPs) by patients with cardiovascular disease (CVD) is associated with improved outcomes. Although rates of cardiac rehabilitation (CR) use are well established, less is known about other DMPs. The objectives of this study were to describe the degree of DMP utilization by CVD outpatients, and examine factors related to use. This study represents a secondary analysis of a larger prospective cohort study. In hospital, 2635 CVD inpatients from 11 hospitals in Ontario Canada completed a survey that assessed factors affecting DMP utilization. One year later, 1803 participants completed a mailed survey that assessed DMP utilization. One thousand seventy-three (59.5%) participants reported using at least 1 DMP. Overall, 951 (52.7%) reported participating in cardiac rehabilitation, and among participants with a comorbid indication, 212 (41.2%) reported attending a diabetes education centre, 28 (25.9%) attended stroke rehabilitation, 35 (12.9%) used a heart failure clinic, and 13 (11.7%) attended a smoking cessation program. A multinomial logistic regression analysis showed that compared with no DMP use, participants that attended 1 or multiple programs were younger, married, diagnosed with a myocardial infarction, less likely to have had a percutaneous coronary intervention and had higher perceptions of personal control over their heart condition. There were few differences between participants that used 1 vs multiple DMPs, however, having diabetes or comorbid stroke significantly increased the likelihood of multiple DMP use. Approximately 40% of CVD outpatients do not access DMPs. An integrated approach to vascular disease management appears warranted. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Impact localization on composite structures using time difference and MUSIC approach

NASA Astrophysics Data System (ADS)

Zhong, Yongteng; Xiang, Jiawei

2017-05-01

1-D uniform linear array (ULA) has the shortcoming of the half-plane mirror effect, which does not allow discriminating between a target placed above the array and a target placed below the array. This paper presents time difference (TD) and multiple signal classification (MUSIC) based omni-directional impact localization on a large stiffened composite structure using improved linear array, which is able to perform omni-directional 360° localization. This array contains 2M+3 PZT sensors, where 2M+1 PZT sensors are arranged as a uniform linear array, and the other two PZT sensors are placed above and below the array. Firstly, the arrival times of impact signals observed by the other two sensors are determined using the wavelet transform. Compared with each other, the direction range of impact source can be decided in general, 0°to 180° or 180°to 360°. And then, two dimensional multiple signal classification (2D-MUSIC) based spatial spectrum formula using the uniform linear array is applied for impact localization by the general direction range. When the arrival times of impact signals observed by upper PZT is equal to that of lower PZT, the direction can be located in x axis (0°or 180°). And time difference based MUSIC method is present to locate impact position. To verify the proposed approach, the proposed approach is applied to a composite structure. The localization results are in good agreement with the actual impact occurring positions.

Disease management programmes for patients with coronary heart disease--an empirical study of German programmes.

PubMed

Gapp, Oliver; Schweikert, Bernd; Meisinger, Christa; Holle, Rolf

2008-12-01

To evaluate healthcare and outcomes of disease management programmes (DMPs) for patients with coronary heart disease (CHD) in primary care, and to assess selection of enrollment for these programmes. A cross-sectional survey of 2330 statutorily insured patients with a history of acute myocardial infarction (AMI) was performed in 2006 by the population-based KORA Myocardial Infarction Register from the region of Augsburg, Germany. Patients enrolled in DMP-CHDs receive evidence-based care, with patients not enrolled receiving standard care. To control for selection bias, a propensity score approach was used. Main factors influencing DMP participation were age (OR 0.98, 95% CI 0.96-0.99), diabetes (OR 1.56, CI 1.25-1.95) and time since last heart attack (OR 0.98, CI 0.95-0.99). Significantly more patients enrolled in DMP-CHDs stated that they received medical counselling for smoking (OR 3.77, CI 1.07-13.34), nutrition (OR 2.15, 1.69-2.74) and for physical activity (OR 2.58, 1.99-3.35). Furthermore, prescription of statins (OR 1.58, CI 1.24-2.00), antiplatelets (OR 1.96, CI 1.43-2.69) and beta-blockers (not significant) were higher in the DMP group. With respect to outcomes, we did not see relevant differences in quality of life and body mass index, and only a minor reduction in smoking. Enrollment into DMPs for CHD exhibits systematic selection effects. Participants tend to experience--at least on a short to medium term and for AMI patients--better quality of healthcare services. However, since DMP-CHDs were initiated only 2 years ago, we were unable to identify significant improvements in health outcomes. Only the reduction in smoking provides a first indication of better quality outcomes following DMP-CHD. Thus, policy-makers must provide appropriate incentives to sickness funds and physicians in order to ensure initiation and continuation of high quality DMPs.

Characteristics, management and attainment of lipid target levels in diabetic and cardiac patients enrolled in Disease Management Program versus those in routine care: LUTZ registry

PubMed Central

2009-01-01

Background Since 2002 the sick funds in Germany have widely implemented disease management programs (DMPs) for patients with type 2 diabetes mellitus (DM) and coronary heart disease (CHD). Little is known about the characteristics, treatment and target attainment lipid levels of these patients enrolled in DMPs compared to patients in routine care (non-DMP). Methods In an open, non-interventional registry (LUTZ) in Germany, 6551 physicians documented 15,211 patients with DM (10,110 in DMP, 5101 in routine care) and 14,222 (6259 in DMP, 7963 in routine care) over a follow-up period of 4 months. They received the NCEP ATP III guidelines as a reminder on lipid level targets. Results While demographic characteristics of DMP patients were similar to routine care patients, the former had higher rates of almost all cardiovascular comorbidities. Patients in DMPs received pharmacological treatment (in almost all drug classes) more often than non-DMP patients (e.g. antiplatelets: in DM 27.0% vs 23.8%; in CHD 63.0% vs. 53.6%). The same applied for educational measures (on life style changes and diet etc.). The rate of target level attainment for low density lipoprotein cholesterol (LDL-C) < 100 mg/dl was somewhat higher in DMP patients at inclusion compared to non-DMP patients (DM: 23.9% vs. 21.3%; CHD: 30.6% vs. 23.8%) and increased after 4 months (DM: 38.3% vs. 36.9%; CHD: 49.8% vs. 43.3%). Individual LDL-C target level attainment rates as assessed by the treating physicians were higher (at 4 months in DM: 59.6% vs. 56.5%; CHD: 49.8% vs 43.3%). Mean blood pressure (BP) and HbA1c values were slightly lowered during follow-up, without substantial differences between DMP and non-DMP patients. Conclusion Patients with DM, and (to a greater extent) with CHD in DMPs compared to non-DMP patients in routine care have a higher burden of comorbidities, but also receive more intensive pharmacological treatment and educational measures. The present data support that the substantial

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

PubMed

Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

2017-04-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes

PubMed Central

Alam, Imranul; Reilly, Austin M.; Alkhouli, Mohammed; Gerard-O’Riley, Rita L.; Kasipathi, Charishma; Oakes, Dana K.; Wright, Weston B.; Acton, Dena; McQueen, Amie K.; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G.; Econs, Michael J.

2017-01-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice over-expressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions. PMID:28013361

Biodegradation of dimethyl phthalate by Sphingomonas sp. isolated from phthalic-acid-degrading aerobic granules.

PubMed

Zeng, Ping; Moy, Benjamin Yan-Pui; Song, Yong-Hui; Tay, Joo-Hwa

2008-10-01

Phthalic acid esters (PAEs) contamination in water, air, and soil is one of the major environmental concerns in many countries. Besides the PAE biodegradation process, the PAE degrading bacteria have become one of the focuses of study. This study reports the successful isolation of one kind of indigenous bacterium PA-02 from phthalic acid (PA)-degrading aerobic granules. Based on its 16S ribosomal DNA sequence, isolate PA-02 was identified as Sphingomonas genus with 100% similarity to Sphingomonas sp. strain D84532. Strain PA-02 was a Gram-negative, rod-shaped bacterium with strong auto-aggregation ability. In particular, the strain PA-02 possessed PAE-degrading ability without acclimation. Results of growth tests showed that strain PA-02 could degrade dimethyl phthalate (DMP), dibutyl phthalate, and diethylhexyl phthalate. The specific degradation rates of DMP and PA were concentration-dependent with maximum values of 0.4 g-DMP g(-1) biomass h(-1) and 1.3 g-PA g(-1) biomass h(-1), respectively. Kinetic studies also revealed that PA-02 was robust under high concentrations of DMP and PA. Even when the PA concentration was increased to 1,000.0 mg l(-1), the specific PA degradation rate was about 0.25 g-PA g(-1) biomass h(-1). The corresponding value for DMP was 0.067 g-DMP g(-1) biomass h(-1) at 1,000 mg l(-1).

Evaluation of a community-based inner-city disease management program for postmyocardial infarction patients: a randomized controlled trial

PubMed Central

Young, Wendy; Rewa, George; Goodman, Shaun G.; Jaglal, Susan Brenda; Cash, Linda; Lefkowitz, Charles; Coyte, Peter C.

2003-01-01

Background Disease management programs (DMPs) that use multidisciplinary teams and specialized clinics reduce hospital admissions and improve quality of life and functional status. Evaluations of cardiac DMPs delivered by home health nurses are required. Methods Between August 1999 and August 2000 we identified consecutive patients admitted to hospital with elevated cardiac enzymes. Patients who agreed were randomly assigned to participate in a DMP or to receive usual care. The DMP included 6 home visits by a cardiac-trained nurse, a standardized nurses' checklist, referral criteria for specialty care, communication with the family physician and patient education. We measured readmission days per 1000 follow-up days for angina, congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD); all-cause readmission days; and provincial claims for emergency department visits, physician visits, diagnostic or therapeutic services and laboratory services. Results We screened 715 consecutive patients admitted with elevated cardiac markers between August 1999 and August 2000. Of those screened 71 DMP and 75 usual care patients met the diagnostic criteria for myocardial infarction, were eligible for visits from a home health nurse and consented to participate in the study. Readmission days for angina, CHF and COPD per 1000 follow-up days were significantly higher for usual care patients than for DMP patients (incidence density ratio [IDR] = 1.59, 95% confidence interval [CI] 1.27–2.00, p < 0.001). All-cause readmission days per 1000 follow-up days were significantly higher for usual care patients than for DMP patients (IDR = 1.53, 95% CI 1.37–1.71, p < 0.001). The difference in emergency department encounters per 1000 follow-up days was significant (IDR = 2.08, 95% CI 1.56–2.77, p < 0.001). During the first 25 days after discharge, there were significantly fewer provincial claims submitted for DMP patients than for usual care patients for emergency

Molecular energy dissipation in nanoscale networks of dentin matrix protein 1 is strongly dependent on ion valence

NASA Astrophysics Data System (ADS)

Adams, J.; Fantner, G. E.; Fisher, L. W.; Hansma, P. K.

2008-09-01

The fracture resistance of biomineralized tissues such as bone, dentin, and abalone is greatly enhanced through the nanoscale interactions of stiff inorganic mineral components with soft organic adhesive components. A proper understanding of the interactions that occur within the organic component, and between the organic and inorganic components, is therefore critical for a complete understanding of the mechanics of these tissues. In this paper, we use atomic force microscope (AFM) force spectroscopy and dynamic force spectroscopy to explore the effect of ionic interactions within a nanoscale system consisting of networks of dentin matrix protein 1 (DMP1) (a component of both bone and dentin organic matrix), a mica surface and an AFM tip. We find that DMP1 is capable of dissipating large amounts of energy through an ion-mediated mechanism, and that the effectiveness increases with increasing ion valence.

Gender differences in global-local perception? Evidence from orientation and shape judgments.

PubMed

Kimchi, Ruth; Amishav, Rama; Sulitzeanu-Kenan, Anat

2009-01-01

Direct examinations of gender differences in global-local processing are sparse, and the results are inconsistent. We examined this issue with a visuospatial judgment task and with a shape judgment task. Women and men were presented with hierarchical stimuli that varied in closure (open or closed shape) or in line orientation (oblique or horizontal/vertical) at the global or local level. The task was to classify the stimuli on the basis of the variation at the global level (global classification) or at the local level (local classification). Women's classification by closure (global or local) was more accurate than men's for stimuli that varied in closure on both levels, suggesting a female advantage in discriminating shape properties. No gender differences were observed in global-local processing bias. Women and men exhibited a global advantage, and they did not differ in their speed of global or local classification, with only one exception. Women were slower than men in local classification by orientation when the to-be-classified lines were embedded in a global line with a different orientation. This finding suggests that women are more distracted than men by misleading global oriented context when performing local orientation judgments, perhaps because women and men differ in their ability to use cognitive schemes to compensate for the distracting effects of the global context. Our findings further suggest that whether or not gender differences arise depends not only on the nature of the visual task but also on the visual context.

Local accumulation times for spatial difference in morphogen concentration

NASA Astrophysics Data System (ADS)

Wen, Xiaoqing; Yin, Hongwei

During development of multicellular organisms, spatial patterns of cells and tissue organizations rely on the action of morphogens, which are signaling molecules and act as dose-dependent regulators of gene expression and cellular differentiation. Since some experimental evidences have indicated that the spatial difference in morphogen concentration regulates cellular proliferation rather than this concentration profile in developing tissues, we propose spatially discrete models to describe this difference for a synthesis-diffusion-degradation process of morphogen in infinite and finite development fields, respectively. For both of models, we respectively derive analytical expressions of local accumulation times, which are required to form the steady state of the spatial difference in morphogen concentration. Our results show that the local accumulation times for the spatial difference in morphogen concentrations are different from the ones for morphogen concentration profiles.

32 CFR 1648.1 - Authority of local board.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Authority of local board. 1648.1 Section 1648.1 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION BY LOCAL BOARD § 1648.1 Authority of local board. A local board shall consider and determine all claims...

32 CFR 1648.1 - Authority of local board.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Authority of local board. 1648.1 Section 1648.1 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION BY LOCAL BOARD § 1648.1 Authority of local board. A local board shall consider and determine all claims...

German diabetes disease management programs are appropriate for restructuring care according to the chronic care model: an evaluation with the patient assessment of chronic illness care instrument.

PubMed

Szecsenyi, Joachim; Rosemann, Thomas; Joos, Stefanie; Peters-Klimm, Frank; Miksch, Antje

2008-06-01

With the introduction of diabetes disease management programs (DMPs) in Germany, there is a necessity to evaluate whether patients receive care that is congruent to the Chronic Care Model (CCM) and evidence-based behavioral counseling. We examined differences as perceived and experienced by patients with type 2 diabetes between those enrolled in a DMP compared with patients receiving usual care in two federal states of Germany. A random, heterogeneous sample of 3,546 patients (59.3% female) received a mailed questionnaire from their regional health fund, including the German version of the Patient Assessment of Chonic Illness Care (PACIC) instrument, which had additional items for behavioral advice (5A). Two weeks later, a general reminder was sent out. A total of 1,532 questionnaires were returned (response rate 42.2%), and valid data could be obtained for 1,399 patients. Mean age of responders was 70.3 years, of which 53.6% were female. Overall, patients enrolled in a DMP scored significantly higher (3.21 of a possible 5) than patients not enrolled in a DMP (2.86) (P < 0.001). Significant differences in the same direction were found on all five subscales of the PACIC. For the 5A scales, similar differences were found for all five subscales plus the sum score (P < 0.001; mean for DMP = 3.08, mean for non-DMP = 2.78). DMPs, as currently established in primary care in Germany, may impact provided care significantly. The changes in daily practice that have been induced by the DMPs are recognized by patients as care that is more structured and that to a larger extent reflects the core elements of the CCM and evidence-based counseling compared with usual care.

Local Structural Differences in Homologous Proteins: Specificities in Different SCOP Classes

PubMed Central

Joseph, Agnel Praveen; Valadié, Hélène; Srinivasan, Narayanaswamy; de Brevern, Alexandre G.

2012-01-01

The constant increase in the number of solved protein structures is of great help in understanding the basic principles behind protein folding and evolution. 3-D structural knowledge is valuable in designing and developing methods for comparison, modelling and prediction of protein structures. These approaches for structure analysis can be directly implicated in studying protein function and for drug design. The backbone of a protein structure favours certain local conformations which include α-helices, β-strands and turns. Libraries of limited number of local conformations (Structural Alphabets) were developed in the past to obtain a useful categorization of backbone conformation. Protein Block (PB) is one such Structural Alphabet that gave a reasonable structure approximation of 0.42 Å. In this study, we use PB description of local structures to analyse conformations that are preferred sites for structural variations and insertions, among group of related folds. This knowledge can be utilized in improving tools for structure comparison that work by analysing local structure similarities. Conformational differences between homologous proteins are known to occur often in the regions comprising turns and loops. Interestingly, these differences are found to have specific preferences depending upon the structural classes of proteins. Such class-specific preferences are mainly seen in the all-β class with changes involving short helical conformations and hairpin turns. A test carried out on a benchmark dataset also indicates that the use of knowledge on the class specific variations can improve the performance of a PB based structure comparison approach. The preference for the indel sites also seem to be confined to a few backbone conformations involving β-turns and helix C-caps. These are mainly associated with short loops joining the regular secondary structures that mediate a reversal in the chain direction. Rare β-turns of type I’ and II’ are also

The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences

PubMed Central

2010-01-01

Background In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year. Methods Cohort study with a baseline interview and a follow-up after 10.4 ± 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses. Results DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have ≥ 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up. Conclusions In the light of patient's experiences the DMP enhances the process

Health system responsiveness and chronic disease care - What is the role of disease management programs? An analysis based on cross-sectional survey and administrative claims data.

PubMed

Röttger, Julia; Blümel, Miriam; Linder, Roland; Busse, Reinhard

2017-07-01

Health system responsiveness is an important aspect of health systems performance. The concept of responsiveness relates to the interpersonal and contextual aspects of health care. While disease management programs (DMPs) aim to improve the quality of health care (e.g. by improving the coordination of care), it has not been analyzed yet whether these programs improve the perceived health system responsiveness. Our study aims to close this gap by analyzing the differences in the perceived health system responsiveness between DMP-participants and non-participants. We used linked survey- and administrative claims data from 7037 patients with coronary heart disease in Germany. Of those, 5082 were enrolled and 1955 were not enrolled in the DMP. Responsiveness was assessed with an adapted version of the WHO responsiveness questionnaire in a postal survey in 2013. The survey covered 9 dimensions of responsiveness and included 17 items for each, GP and specialist care. Each item had five answer categories (very good - very bad). We handled missing values in the covariates by multiple imputation and applied propensity score matching (PSM) to control for differences between the two groups (DMP/non-DMP). We used Wilcoxon-signed-rank and McNemar test to analyze differences regarding the reported responsiveness. The PSM led to a matched and well balanced sample of 1921 pairs. Overall, DMP-participants rated the responsiveness of care more positive. The main difference was found for the coordination of care at the GP, with 62.0% of 1703 non-participants reporting a "good" or "very good" experience, compared to 69.1% of 1703 participants (p < 0.001). The results of our study indicate an overall high responsiveness for CHD-care, as well for DMP-participants as for non-participants. Yet, the results also clearly indicate that there is still a need to improve the coordination of care. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Aplin, H.M.; Hirst, K.L.; Crosby, A.H.

Dentinogenesis imperfecta type II (DGI1) is an autosomal dominant disorder of dentin formation, which has been mapped to human chromosome 4q12-q21. The region most likely to contain the DGI1 locus is a 3.2-cM region surrounding the osteopontin (SPP1) locus. Recently, a novel dentin-specific acidic phosphoprotein (dmp1) has been cloned in the rat and mapped to mouse chromosome 5q21. In the current investigation, we have isolated a cosmid containing the human DMP1 gene. The isolation of a short tandem repeat polymorphism at this locus has allowed us to map the DMP1 locus to human chromosome 4q21 and demonstrate that it ismore » tightly linked to DGI1 in two families (Z{sub max} = 11.01, {theta} = 0.001). The creation of a yeast artificial chromosome contig around SPP1 has further allowed us to demonstrate that DMP1 is located within 150 kb of the bone sialoprotein and 490 kb of the SPP1 loci, respectively. DMP1 is therefore a strong candidate for the DGI1 locus. 12 refs., 2 figs., 1 tab.« less

Discrete maximum principle for the P1 - P0 weak Galerkin finite element approximations

NASA Astrophysics Data System (ADS)

Wang, Junping; Ye, Xiu; Zhai, Qilong; Zhang, Ran

2018-06-01

This paper presents two discrete maximum principles (DMP) for the numerical solution of second order elliptic equations arising from the weak Galerkin finite element method. The results are established by assuming an h-acute angle condition for the underlying finite element triangulations. The mathematical theory is based on the well-known De Giorgi technique adapted in the finite element context. Some numerical results are reported to validate the theory of DMP.

Preliminary site survey report for the Uniroyal Chemical Company, formerly the Diamond Magnesium Company, 720 Fairport-Nursery Road, Painesville, Ohio (DMP001)

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

Foley, R.D.; Floyd, L.M.

1990-03-01

At the request of the US Department of Energy (DOE), a group from Oak Ridge National Laboratory conducted a preliminary radiological survey at the Uniroyal Chemical Company, formerly the Diamond Magnesium Company, 720 Fairport-Nursery Road, Painesville, Ohio (DMP001), in 1988. The purpose of the survey was to determine whether the property was contaminated with radioactive residues from the former Manhattan Engineer District (MED) project. The scope of this preliminary survey primarily covered the area west of the buildings around the railroad car spill containment basin. The survey included direct measurement of gamma radiation levels at the surface and soil samplingmore » for radionuclide analyses. Results of the survey demonstrated radionuclide concentrations in excess of the DOE Formerly Utilized Sites Remedial Action Program criteria for both {sup 238}U and {sup 226}Ra in soil. Based on the results of this radiological assessment, it is recommended that a follow-up, detailed radiological survey of both surface and subsurface environs be performed to more precisely define the extent of the contamination. 5 refs., 10 figs., 3 tabs.« less

Mountain chickadees from different elevations sing different songs: acoustic adaptation, temporal drift or signal of local adaptation?

PubMed Central

Branch, Carrie L.; Pravosudov, Vladimir V.

2015-01-01

Song in songbirds is widely thought to function in mate choice and male–male competition. Song is also phenotypically plastic and typically learned from local adults; therefore, it varies across geographical space and can serve as a cue for an individual's location of origin, with females commonly preferring males from their respective location. Geographical variation in song dialect may reflect acoustic adaptation to different environments and/or serve as a signal of local adaptation. In montane environments, environmental differences can occur over an elevation gradient, favouring local adaptations across small spatial scales. We tested whether food caching mountain chickadees, known to exhibit elevation-related differences in food caching intensity, spatial memory and the hippocampus, also sing different dialects despite continuous distribution and close proximity. Male songs were collected from high and low elevations at two different mountains (separated by 35 km) to test whether song differs between elevations and/or between adjacent populations at each mountain. Song structure varied significantly between high and low elevation adjacent populations from the same mountain and between populations from different mountains at the same elevations, despite a continuous distribution across each mountain slope. These results suggest that elevation-related differences in song structure in chickadees might serve as a signal for local adaptation. PMID:26064641

Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

NASA Astrophysics Data System (ADS)

Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

2018-04-01

Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

Ultrasound assessment of cranial spread during caudal blockade in children: Effect of different volumes of local anesthetic

PubMed Central

Sinha, Chandni; Kumar, Amarjeet; Sharma, Shalini; Singh, Akhilesh Kumar; Majumdar, Somak; Kumar, Ajeet; Sahay, Nishant; Kumar, Bindey; Bhadani, UK

2017-01-01

Background: Ultrasound-guided caudal block injection is a simple, safe, and effective method of anesthesia/analgesia in pediatric patients. The volume of caudal drug required has always been a matter of debate. Materials and Methods: This present prospective, randomized, double-blinded study aimed to measure extent of the cranial spread of caudally administered levobupivacaine in Indian children by means of real-time ultrasonography. Ninety American Society of Anesthesiologists I/II children scheduled for urogenital surgeries were enrolled in this trial. Anesthesia and caudal analgesia were administered in a standardized manner in the patients. The patients received 0.5 ml/kg or 1 ml/kg or 1.25 ml/kg of 0.125% levobupivacaine according to the group allocated. Cranial spread of local anesthetic was noted using ultrasound. Results: There was no difference in the spread when related to age, sex, weight, or body mass index. A significant difference of ultrasound-assessed cranial spread of the local anesthetic was found between Group 1 (0.5 ml/kg) with both Group 2 (1 ml/kg) (P = 0.001) and with Group 3 (1.125 ml/kg) (P < 0.001) but there is no significant difference between Group 2 and Group 3 (P = 0.451) revealing that spinal level spread is only different between 0.5 ml/kg and 1 ml/kg of local anesthetic. Conclusion: In conclusion, the ultrasound assessment of local anesthetic spread after a caudal block showed that cranial spread of the block is dependent on the volume injected into the caudal space. Since there was no difference between 1 ml/kg and 1.25 ml/kg, to achieve a dermatomal blockade up to thoracic level, we might have to increase the dose beyond 1.25 ml/kg, keeping the toxic dose in mind. PMID:29033727

Behavioral and Physiological Findings of Gender Differences in Global-Local Visual Processing

ERIC Educational Resources Information Center

Roalf, David; Lowery, Natasha; Turetsky, Bruce I.

2006-01-01

Hemispheric asymmetries in global-local visual processing are well-established, as are gender differences in cognition. Although hemispheric asymmetry presumably underlies gender differences in cognition, the literature on gender differences in global-local processing is sparse. We employed event related brain potential (ERP) recordings during…

Preosteocytes/Osteocytes Have the Potential to Dedifferentiate Becoming a Source of Osteoblasts

PubMed Central

Torreggiani, Elena; Matthews, Brya G.; Pejda, Slavica; Matic, Igor; Horowitz, Mark C.; Grcevic, Danka; Kalajzic, Ivo

2013-01-01

Presently there is no clear evidence for the ability of mature osteogenic lineage cells to dedifferentiate. In order to identify and trace mature osteogenic lineage cells, we have utilized transgenic mouse models in which the dentin matrix protein 1 (Dmp1) promoter drives expression of GFP (active marker) or Cre recombinase (historic label) in preosteocytes/osteocytes. In long bone chip outgrowth cultures, in which cells on the bone surface were enzymatically removed, cells with previous activity of the Dmp1 promoter migrated onto plastic and down-regulated Dmp1-GFP expression. Dmp1Cre-labeled cells from these cultures had the potential to re-differentiate into the osteogenic lineage, while the negative population showed evidence of adipogenesis. We observed numerous Dmp1Cre-labeled osteoblasts on the surface of bone chips following their in vivo transplantation. Our data indicate that cells embedded in bone matrix are motile, and once given access to the extra bony milieu will migrate out of their lacunae. This population of cells is phenotypically and functionally heterogeneous in vitro. Once the preosteocytes/osteocytes leave lacunae, they can dedifferentiate, potentially providing an additional source of functional osteoblasts. PMID:24040401

Efficiency of the Austrian disease management program for diabetes mellitus type 2: a historic cohort study based on health insurance provider's routine data.

PubMed

Ostermann, Herwig; Hoess, Victoria; Mueller, Michael

2012-06-29

The Austrian diabetes disease management program (DMP) was introduced in 2007 in order to improve health care delivery for diabetics via the promotion of treatment according to guidelines. Considering the current low participation rates in the DMP and the question of further promotion of the program, it is of particular interest for health insurance providers in Austria to assess whether enrollment in the DMP leads to differences in the pattern of the provision of in- and outpatient services, as well as to the subsequent costs in order to determine overall program efficiency. Historic cohort study comparing average annual levels of in- and outpatient health services utilization and its associated costs for patients enrolled and not enrolled in the DMP before (2006) and 2 years after (2009) the implementation of the program in Austria. Data on the use of services and data on costs were extracted from the records of the Austrian Social Insurance Institution for Business. 12,199 persons were identified as diabetes patients treated with anti-diabetic medication or anti-diabetics with insulin throughout the study period. 314 diabetics were enrolled in the DMP. Patients enrolled in the diabetes DMP received a more evolved pattern of outpatient care, featuring higher numbers of services provided by general practitioners and specialists (79 vs. 62), more diagnostic services (22 vs. 15) as well as more services provided by outpatient care centers (9 vs. 6) in line with increased levels of participation in medical assessments as recommended by the treatment guideline in 2009. Hospitalization was lower for DMP patients spending 3.75 days in hospital, as compared to 6.03 days for diabetes patients in regular treatment. Overall, increases in costs of care and medication throughout the study period were lower for enrolled patients (€ 718 vs. € 1.684), resulting in overall costs of € 5,393 p.c. for DMP patients and € 6,416 p.c. for the control group in 2009. Seen from a

Efficiency of the Austrian disease management program for diabetes mellitus type 2: a historic cohort study based on health insurance provider’s routine data

PubMed Central

2012-01-01

Background The Austrian diabetes disease management program (DMP) was introduced in 2007 in order to improve health care delivery for diabetics via the promotion of treatment according to guidelines. Considering the current low participation rates in the DMP and the question of further promotion of the program, it is of particular interest for health insurance providers in Austria to assess whether enrollment in the DMP leads to differences in the pattern of the provision of in- and outpatient services, as well as to the subsequent costs in order to determine overall program efficiency. Methods Historic cohort study comparing average annual levels of in- and outpatient health services utilization and its associated costs for patients enrolled and not enrolled in the DMP before (2006) and 2 years after (2009) the implementation of the program in Austria. Data on the use of services and data on costs were extracted from the records of the Austrian Social Insurance Institution for Business. 12,199 persons were identified as diabetes patients treated with anti-diabetic medication or anti-diabetics with insulin throughout the study period. 314 diabetics were enrolled in the DMP. Results Patients enrolled in the diabetes DMP received a more evolved pattern of outpatient care, featuring higher numbers of services provided by general practitioners and specialists (79 vs. 62), more diagnostic services (22 vs. 15) as well as more services provided by outpatient care centers (9 vs. 6) in line with increased levels of participation in medical assessments as recommended by the treatment guideline in 2009. Hospitalization was lower for DMP patients spending 3.75 days in hospital, as compared to 6.03 days for diabetes patients in regular treatment. Overall, increases in costs of care and medication throughout the study period were lower for enrolled patients (€ 718 vs. € 1.684), resulting in overall costs of € 5,393 p.c. for DMP patients and € 6,416 p.c. for the

Effects of strain differences and vehicles on results of local lymph node assays.

PubMed

Anzai, Takayuki; Ullmann, Ludwig G; Hayashi, Daisuke; Satoh, Tetsuo; Kumazawa, Takeshi; Sato, Keizo

2010-01-01

The Local Lymph Node Assay (LLNA) is now regarded as the worldwide standard. The analysis of accumulated LLNA data reveals that the animal strains and vehicles employed are likely to affect LLNA results. Here we show that an obvious strain difference in the local lymph node response was observed between DMSO-treated CBA/CaOlaHsd and CBA/CaHsdRcc mice. We also show that a vehicle difference in the response was observed when CBA/CaHsdRcc mice were exposed to 6 vehicles; 4:1 v/v acetone/olive oil (AOO), ethanol/water (70% EtOH), N,N-dimethylformamide (DMF), 2-butanone (BN), propylene glycol (PG), and dimethylsulfoxide (DMSO). The dpm/LN level was lowest in the 70% EtOH group and highest in the DMSO group. When alpha-hexylcinnamaldehyde (HCA) was used as a sensitizer for the LLNA, HCA was a weak sensitizer when AOO or DMSO was used as a vehicle, but a moderate sensitizer when the other 4 vehicles were used. This study showed that there are vehicle differences in the local lymph node response (dpm/LN level) in the LLNA and that the sensitization potency of HCA may be classified in different categories when using different vehicles. This suggests that careful consideration should be exercised in selecting a vehicle for the LLNA. A further comprehensive study will be needed to investigate why vehicle differences are observed in the LLNA.

Atypical Local Interference Affects Global Processing in Children with Neurofibromatosis Type 1.

PubMed

Payne, Jonathan M; Porter, Melanie A; Bzishvili, Samantha; North, Kathryn N

2017-05-01

To examine hierarchical visuospatial processing in children with neurofibromatosis type 1 (NF1), a single gene disorder associated with visuospatial impairments, attention deficits, and executive dysfunction. We used a modified Navon paradigm consisting of a large "global" shape composed of smaller "local" shapes that were either congruent (same) or incongruent (different) to the global shape. Participants were instructed to name either the global or local shape within a block. Reaction times, interference ratios, and error rates of children with NF1 (n=30) and typically developing controls (n=24) were compared. Typically developing participants demonstrated the expected global processing bias evidenced by a vulnerability to global interference when naming local stimuli without a cost of congruence when naming global stimuli. NF1 participants, however, experienced significant interference from the unattended level when naming both local and global levels of the stimuli. Findings suggest that children with NF1 do not demonstrate the typical human bias of processing visual information from a global perspective. (JINS, 2017, 23, 446-450).

Evaluation of a disease management program for COPD using propensity matched control group.

PubMed

George, Pradeep Paul; Heng, Bee Hoon; Lim, Tow Keang; Abisheganaden, John; Ng, Alan Wei Keong; Verma, Akash; Lim, Fong Seng

2016-07-01

Disease management programs (DMPs) have proliferated recently as a means of improving the quality and efficiency of care for patients with chronic illness. These programs include education about disease, optimization of evidence-based medications, information and support from case managers, and institution of self-management principles. Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in Singapore and worldwide. DMP aims to reduce mortality, hospitalizations, and average length of stay in such patients. This study assesses the outcomes of the DMP, comparing the propensity score matched DMP patients with controls. DMP patients were compared with the controls, who were COPD patients fulfilling the DMP's inclusion criteria but not included in the program. Control patients were identified from Operations Data Store (ODS) database. The outcomes of interest were average length of stay, number of days admitted to hospital per 100 person days, readmission, and mortality rates per person year. The risk of death and readmission was estimated using Cox, and competing risk regression respectively. Propensity score was estimated to identify the predictors of DMP enrolment. DMP patients and controls were matched on their propensity score. There were 170 matched DMP patients and control patients having 287 and 207 hospitalizations respectively. Program patient had lower mortality than the controls (0.12 vs. 0.27 per person year); cumulative 1-year survival was 91% among program patient and 76% among the control patients. Readmission, and hospital days per 100 person-days was higher for the program patients (0.36 vs. 0.17 per person year), and (2.19 vs. 1.88 per person year) respectively. Participation in "DMP" was associated with lower all-cause mortality when compared to the controls. This survival gain in the program patients was paradoxically associated with an increase in readmission rate and total hospital days.

26 CFR 1.164-4 - Taxes for local benefits.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Taxes for local benefits. 1.164-4 Section 1.164... local benefits. (a) So-called taxes for local benefits referred to in paragraph (g) of § 1.164-2, more properly assessments, paid for local benefits such as street, sidewalk, and other like improvements...

Asthma management practices in adults--findings from the German Health Update (GEDA) 2010 and the German National Health Interview and Examination Survey (DEGS1) 2008-2011.

PubMed

Steppuhn, Henriette; Langen, Ute; Mueters, Stephan; Dahm, Stefan; Knopf, Hildtraud; Keil, Thomas; Scheidt-Nave, Christa

2016-01-01

In Germany, population-wide data on adherence to national asthma management guidelines are lacking, and performance measures (PM) for quality assurance in asthma care are systematically monitored for patients with German national asthma disease management program (DMP) enrollment only. We used national health survey data to assess variation in asthma care PM with respect to patient characteristics and care context, including DMP enrollment. Among adults 18-79 years with self-reported physician-diagnosed asthma in the past 12 months identified from a recent German National Health Interview Survey (GEDA 2010: N = 1096) and the German National Health interview and Examination Survey 2008-2011 (DEGS1: N = 333), variation in asthma care PM was analyzed using logistic regression analysis. Overall, 38.4% (95% confidence interval: 32.5-44.6%) of adults with asthma were on current inhaled corticosteroid therapy. Regarding non-drug asthma management, low coverage was observed for inhaler technique monitoring (35.2%; 31.2-39.3%) and for provision of an asthma management plan (27.3%; 24.2-30.7%), particularly among those with low education. Specific PM were more complete among persons with than without asthma DMP enrollment (adjusted odds ratios ranging up to 10.19; 5.23-19.86), even if asthma patients were regularly followed in a different care context. Guideline adherence appears to be suboptimal, particularly with respect to PM related to patient counseling. Barriers to the translation of recommendations into practice need to be identified and continuous monitoring of asthma care PM at the population level needs to be established.

The sweating foot: local differences in sweat secretion during exercise-induced hyperthermia.

PubMed

Taylor, Nigel A S; Caldwell, Joanne N; Mekjavic, Igor B

2006-10-01

Little is known regarding local differences in foot sweat secretion. Since such information is important to our understanding of sweat gland control for thermoregulatory modeling and for the design of footwear we explored this topic. Local sweat rates were investigated across core temperatures from 37-39 degrees C, achieved using endogenous (cycling) and exogenous heat (water-perfusion garment: 46 degrees C). Six healthy adults (three men, three women) performed one-legged, incremental cycling in a heated, climate-controlled chamber (36 degrees C, 60% relative humidity). Sweat rates were measured at the forehead and stationary (left) foot (capsules 3.16 cm2): three dorsal sites (base of toes, second metatarsal, and mid point), the lateral, and the central plantar surfaces. Terminal core temperatures ranged between 38.3-39.1 oC, with peak heart rates of 155-187 bpm. Most foot sweat rates were < 50% of that observed at the forehead: dorsal 1 (38%); dorsal 2 (54%); dorsal 3 (37%); lateral (24%); and plantar surfaces (18%). When averaged across the trial, local sweat rates were: 2.61 (forehead); 0.98 (dorsal 1); 1.39 (dorsal 2); 0.95 (dorsal 3); 0.62 (lateral); and 0.47 mg cm2 2 min-1 (plantar). Two key observations emerged. First, sweat secretion from the experimental foot averaged 30 ml x h(-1), peaking in the last 5 min at 50 ml x h(-1). Second, approximately 70% of the measured sweat flow emanated from the upper skin surfaces, with only 30% coming from the plantar surface.

PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1.

PubMed

Kumar, Vikash; Kaur, Jasweer; Singh, Amrit P; Singh, Vineeta; Bisht, Anjali; Panda, Jiban J; Mishra, Prakash C; Hora, Rachna

2018-01-01

Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric (PHIST) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHISTc subfamily, PFD1140w and PF11_0503, and compared these with a well-characterized member, PFI1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton-binding protein-1 (PfSBP-1), and P. falciparum erythrocyte membrane protein-1 (PfEMP-1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of PfEMP-1 and a novel interaction with PfSBP-1. Interestingly, PFD1140w interacts with PfEMP-1 and PfSBP-1 simultaneously in vitro leading to formation of a complex. These two distant PHISTc members also bind PfEMP-1 on distinct sites, despite sharing the Phist domain. Our data re-emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, PfSBP-1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family. © 2017 Federation of European Biochemical Societies.

Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 Gene

PubMed Central

Levy-Litan, Varda; Hershkovitz, Eli; Avizov, Luba; Leventhal, Neta; Bercovich, Dani; Chalifa-Caspi, Vered; Manor, Esther; Buriakovsky, Sophia; Hadad, Yair; Goding, James; Parvari, Ruti

2010-01-01

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1. PMID:20137772

48 CFR 52.229-1 - State and Local Taxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false State and Local Taxes. 52....229-1 State and Local Taxes. As prescribed in 29.401-1, insert the following clause: State and Local Taxes (APR 1984) Notwithstanding the terms of the Federal, State, and Local Taxes clause, the contract...

48 CFR 52.229-1 - State and Local Taxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false State and Local Taxes. 52....229-1 State and Local Taxes. As prescribed in 29.401-1, insert the following clause: State and Local Taxes (APR 1984) Notwithstanding the terms of the Federal, State, and Local Taxes clause, the contract...

Local participation in biodiversity conservation initiatives: a comparative analysis of different models in South East Mexico.

PubMed

Méndez-López, María Elena; García-Frapolli, Eduardo; Pritchard, Diana J; Sánchez González, María Consuelo; Ruiz-Mallén, Isabel; Porter-Bolland, Luciana; Reyes-Garcia, Victoria

2014-12-01

In Mexico, biodiversity conservation is primarily implemented through three schemes: 1) protected areas, 2) payment-based schemes for environmental services, and 3) community-based conservation, officially recognized in some cases as Indigenous and Community Conserved Areas. In this paper we compare levels of local participation across conservation schemes. Through a survey applied to 670 households across six communities in Southeast Mexico, we document local participation during the creation, design, and implementation of the management plan of different conservation schemes. To analyze the data, we first calculated the frequency of participation at the three different stages mentioned, then created a participation index that characterizes the presence and relative intensity of local participation for each conservation scheme. Results showed that there is a low level of local participation across all the conservation schemes explored in this study. Nonetheless, the payment for environmental services had the highest local participation while the protected areas had the least. Our findings suggest that local participation in biodiversity conservation schemes is not a predictable outcome of a specific (community-based) model, thus implying that other factors might be important in determining local participation. This has implications on future strategies that seek to encourage local involvement in conservation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Contactless measurement of canine retraction by digital macrophotogrammetry during hybrid retractor application.

PubMed

Sander, Christian; Geiger, Martin; Sander, Franz-Günter

2002-11-01

A new contactless method for measuring tooth movements is presented. Digital macrophotogrammetry (DMP) enables the orthodontist to obtain information on the three-dimensional movement of a tooth at each session. Analysis of the DMP images provides information on the translation and toration of a tooth during treatment. It is conceivable that the introduction of DMP will make an important contribution to quality assurance.DMP application during canine retraction with the Hybrid Retractor((R)) has pave the way for the orthodontic appliance to be correctly adjusted at each session. Despite intra- and interindividual differences during canine movement, for which the anisotropy of the bone seems to be basically responsible, a movement velocity of ca 1.2 mm is to be expected over the entire treatment period. The preconditions for the three-dimensional orientation and description of canine movement are:1. The markers on the brackets and attachments must be clearly visible throughout the treatment.2. The teeth to which the scaling frame is fixed should not move during treatment.3. Four measuring points should be visible on each bracket.4. The control points on the frame must be positioned three-dimensionally, and it must be possible to determine their position with sufficient accuracy in advance. In vitro calibration of the photogrammetry presented here yielded a resolution of 1 micrometer for translation and of better than 1/10 degrees for rotation around the three spatial axes under optimal conditions.

Racial Differences in the Surgical Care of Medicare Beneficiaries With Localized Prostate Cancer.

PubMed

Schmid, Marianne; Meyer, Christian P; Reznor, Gally; Choueiri, Toni K; Hanske, Julian; Sammon, Jesse D; Abdollah, Firas; Chun, Felix K H; Kibel, Adam S; Tucker-Seeley, Reginald D; Kantoff, Philip W; Lipsitz, Stuart R; Menon, Mani; Nguyen, Paul L; Trinh, Quoc-Dien

2016-01-01

top 50% of blacks spent $1185.50 (95% CI , $804.85-1 $1566.10; P < .001) more than the top 50% of non-Hispanic whites). There was no difference in PCa-specific mortality (P = .16) or all-cause mortality (P = .64) between black and non-Hispanic white men. Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared with non-Hispanic white men; however, this does not translate into a difference in PCa-specific or all-cause mortality.

Local and average structures of BaTiO 3-Bi(Zn 1/2Ti 1/2)O 3

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

Usher, Tedi-Marie; Iamsasri, Thanakorn; Forrester, Jennifer S.

The complex crystallographic structures of (1-x)BaTiO 3-xBi(Zn 1/2Ti 1/2)O 3 (BT-xBZT) are examined using high resolution synchrotron X-ray diffraction, neutron diffraction, and neutron pair distribution function (PDF) analyses. The short-range structures are characterized from the PDFs, and a combined analysis of the X-ray and neutron diffraction patterns is used to determine the long-range structures. Our results demonstrate that the structure appears different when averaged over different length scales. In all compositions, the local structures determined from the PDFs show local tetragonal distortions (i.e., c/a > 1). But, a box-car fitting analysis of the PDFs reveals variations at different length scales.more » For 0.80BT-0.20BZT and 0.90BT-0.10BZT, the tetragonal distortions decrease at longer atom-atom distances (e.g., 30 vs. 5 ). When the longest distances are evaluated (r > 40 ), the lattice parameters approach cubic. Neutron and X-ray diffraction yield further information about the long-range structure. Compositions 0.80BT-0.20BZT and 0.90BT-0.10BZT appear cubic by Bragg diffraction (no peak splitting), consistent with the PDFs at long distances. However, these patterns cannot be adequately fit using a cubic lattice model; modeling their structures with the P4mm space group allows for a better fit to the patterns because the space group allows for c-axis atomic displacements that occur at the local scale. Furthermore, for the compositions 0.92BT-0.08BZT and 0.94BT-0.06BZT, strong tetragonal distortions are observed at the local scale and a less-distorted tetragonal structure is observed at longer length scales. In Rietveld refinements, the latter is modeled using a tetragonal phase. Since the peak overlap in these two-phase compositions limits the ability to model the local-scale structures as tetragonal, it is approximated in the refinements as a cubic phase. These results demonstrate that alloying BT with BZT results in increased disorder and

Local and average structures of BaTiO 3-Bi(Zn 1/2Ti 1/2)O 3

DOE PAGES

Usher, Tedi-Marie; Iamsasri, Thanakorn; Forrester, Jennifer S.; ...

2016-11-11

The complex crystallographic structures of (1-x)BaTiO 3-xBi(Zn 1/2Ti 1/2)O 3 (BT-xBZT) are examined using high resolution synchrotron X-ray diffraction, neutron diffraction, and neutron pair distribution function (PDF) analyses. The short-range structures are characterized from the PDFs, and a combined analysis of the X-ray and neutron diffraction patterns is used to determine the long-range structures. Our results demonstrate that the structure appears different when averaged over different length scales. In all compositions, the local structures determined from the PDFs show local tetragonal distortions (i.e., c/a > 1). But, a box-car fitting analysis of the PDFs reveals variations at different length scales.more » For 0.80BT-0.20BZT and 0.90BT-0.10BZT, the tetragonal distortions decrease at longer atom-atom distances (e.g., 30 vs. 5 ). When the longest distances are evaluated (r > 40 ), the lattice parameters approach cubic. Neutron and X-ray diffraction yield further information about the long-range structure. Compositions 0.80BT-0.20BZT and 0.90BT-0.10BZT appear cubic by Bragg diffraction (no peak splitting), consistent with the PDFs at long distances. However, these patterns cannot be adequately fit using a cubic lattice model; modeling their structures with the P4mm space group allows for a better fit to the patterns because the space group allows for c-axis atomic displacements that occur at the local scale. Furthermore, for the compositions 0.92BT-0.08BZT and 0.94BT-0.06BZT, strong tetragonal distortions are observed at the local scale and a less-distorted tetragonal structure is observed at longer length scales. In Rietveld refinements, the latter is modeled using a tetragonal phase. Since the peak overlap in these two-phase compositions limits the ability to model the local-scale structures as tetragonal, it is approximated in the refinements as a cubic phase. These results demonstrate that alloying BT with BZT results in increased disorder and

Effects of dietary protein concentration and coconut oil supplementation on nitrogen utilization and production in dairy cows.

PubMed

Lee, C; Hristov, A N; Heyler, K S; Cassidy, T W; Long, M; Corl, B A; Karnati, S K R

2011-11-01

The objective of this study was to investigate the effect of metabolizable protein (MP) deficiency and coconut oil supplementation on N utilization and production in lactating dairy cows. The hypothesis of the study was that a decrease in ruminal protozoal counts with coconut oil would increase microbial protein synthesis in the rumen, thus compensating for potential MP deficiency. The experiment was conducted for 10 wk with 36 cows (13 primiparous and 23 multiparous), including 6 ruminally cannulated cows. The experimental period, 6 wk, was preceded by 2-wk adaptation and 2-wk covariate periods. Cows were blocked by parity, days in milk, milk yield, and rumen cannulation and randomly assigned to one of the following diets: a diet with a positive MP balance (+44 g/d) and 16.7% dietary crude protein (CP) concentration (AMP); a diet deficient in MP (-156 g/d) and 14.8% CP concentration (DMP); or DMP supplemented with approximately 500 g of coconut oil/head per day (DMPCO). Ruminal ammonia tended to be greater and plasma urea N (20.1, 12.8, and 13.1 mg/dL, for AMP, DMP, and DMPCO diets, respectively) and milk urea N (12.5, 8.3, and 9.5mg/dL, respectively) were greater for AMP compared with DMP and DMPCO. The DMPCO diet decreased total protozoa counts (by 60%) compared with DMP, but had no effect on the methanogens profile in the rumen. Total tract apparent digestibility of dry matter and CP was decreased by DMP compared with AMP. Fiber digestibility was lower for both DMP and DMPCO compared with AMP. Urinary N excretion was decreased (by 37%) by both DMP and DMPCO compared with AMP. The DMP and DMPCO diets resulted in greater milk N efficiency compared with AMP (32.0 and 35.1 vs. 27.6%, respectively). Milk yield was decreased by both DMP and DMPCO compared with AMP (36.2, 34.4, and 39.3 kg/d, respectively) and coconut oil supplementation suppressed feed intake and caused milk fat depression. Coconut oil supplementation decreased short-chain fatty acid (C4:0, C6:0, and

Patient-experienced effect of an active implementation of a disease management programme for COPD – a randomised trial

PubMed Central

2013-01-01

Background People living with chronic disease currently account for the majority of the total healthcare costs. The Central Denmark Region implemented a disease management programme (DMP) for chronic obstructive pulmonary disease (COPD) in 2008. This presented an opportunity to examine the effect of an evidence-based, planned and proactive implementation of a DMP compared to the usual implementation strategy. Methods We performed a block- and cluster-randomised controlled trial with two groups and an extra external control group. The primary outcome was patients’ assessment of their care after using an active implementation model for a DMP for COPD measured with the Patient-Assessment-of-Chronic-Illness-Care (PACIC) instrument. At baseline, questionnaires were sent to 2,895 patients identified by an algorithm based on health registry data on lung-related contacts to the healthcare system. Patients were asked to confirm or refute their diagnosis of COPD. Of those who responded, 1,445 (72.8%) confirmed their diagnosis. PACIC data were collected at baseline and at a 12-month follow-up for 744 (51.1%) patients. Results Comparing the three groups after the implementation of the DMP, we found a statistically significantly higher change in the PACIC score in the intervention group than in the control groups. No statistically significant differences were found between the control and the external control groups in any of the dimensions. Conclusions Reinforcing the role of general practice as coordinator for care-and self-management-support with an active implementation of a DMP for COPD made patients score higher on the PACIC instrument, which indicates a better experience of the received healthcare. Trial registration NCT01228708. PMID:24088417

Patient-experienced effect of an active implementation of a disease management programme for COPD - a randomised trial.

PubMed

Smidth, Margrethe; Olesen, Frede; Fenger-Grøn, Morten; Vedsted, Peter

2013-10-03

People living with chronic disease currently account for the majority of the total healthcare costs. The Central Denmark Region implemented a disease management programme (DMP) for chronic obstructive pulmonary disease (COPD) in 2008. This presented an opportunity to examine the effect of an evidence-based, planned and proactive implementation of a DMP compared to the usual implementation strategy. We performed a block- and cluster-randomised controlled trial with two groups and an extra external control group. The primary outcome was patients' assessment of their care after using an active implementation model for a DMP for COPD measured with the Patient-Assessment-of-Chronic-Illness-Care (PACIC) instrument. At baseline, questionnaires were sent to 2,895 patients identified by an algorithm based on health registry data on lung-related contacts to the healthcare system. Patients were asked to confirm or refute their diagnosis of COPD. Of those who responded, 1,445 (72.8%) confirmed their diagnosis. PACIC data were collected at baseline and at a 12-month follow-up for 744 (51.1%) patients. Comparing the three groups after the implementation of the DMP, we found a statistically significantly higher change in the PACIC score in the intervention group than in the control groups. No statistically significant differences were found between the control and the external control groups in any of the dimensions. Reinforcing the role of general practice as coordinator for care-and self-management-support with an active implementation of a DMP for COPD made patients score higher on the PACIC instrument, which indicates a better experience of the received healthcare. NCT01228708.

Joint working. Local differences.

PubMed

Hudson, B

1997-09-18

The interface between social care and primary healthcare remains underdeveloped. Where joint working is effective, it is the result of co-operation, trust and mutual respect. Successful local networks take account of professional autonomy.

An Immunohistochemical Study of Matrix Proteins in the Craniofacial Cartilage in Midterm Human Fetuses

PubMed Central

Shibata, S.; Sakamoto, Y.; Baba, O.; Qin, C.; Murakami, G.; Cho, B.H.

2013-01-01

Immunohistochemical localization of collagen types I, II, and X, aggrecan, versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein (MEPE) were performed for Meckel’s cartilage, cranial base cartilage, and mandibular condylar cartilage in human midterm fetuses; staining patterns within the condylar cartilage were compared to those within other cartilaginous structures. Mandibular condylar cartilage contained aggrecan; it also had more type I collagen and a thicker hypertrophic cell layer than the other two types of cartilage; these three characteristics are similar to those of the secondary cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage matrix of all types of cartilage in the human fetuses and in Meckel’s cartilage of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in the primary spongiosa. These results indicated that MEPE is a component of cartilage matrix and may be involved in cartilage mineralization. DMP-1 immunoreactivity first became evident in human bone lacunae walls and canaliculi; this pattern of expression was comparable to the pattern seen in rodents. In addition, chondroid bone was evident in the mandibular (glenoid) fossa of the temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1 immunoreactivity; these findings indicated that chondroid bone in this region has phenotypic expression indicative of both hypertrophic chondrocytes and osteocytes. PMID:24441192

48 CFR 26.202-1 - Local area set-aside.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Local area set-aside. 26... SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Disaster or Emergency Assistance Activities 26.202-1 Local area set-aside. The contracting officer may set aside solicitations to allow only local firms within a...

Local amygdala structural differences with 3T MRI in patients with Alzheimer disease

PubMed Central

Cavedo, E.; Boccardi, M.; Ganzola, R.; Canu, E.; Beltramello, A.; Caltagirone, C.; Thompson, P.M.

2011-01-01

Objective: Histologic studies show that the amygdala is affected by Alzheimer disease (AD) pathology, and its medial aspect is the most involved. We aimed to assess in vivo local structural differences in the amygdala of patients with AD using high-field MRI. Methods: A total of 19 patients with AD (mean age 76, SD 6 years, mean Mini-Mental State Examination score [MMSE] 13, SD 4) and 19 healthy elderly controls (age 74, SD 5, MMSE 29, SD 1) were enrolled. The radial atrophy mapping technique was used to reconstruct the 3-dimensional surface of the amygdala. Maps of surface tissue loss in patients with AD vs controls were computed and statistically tested with permutation tests thresholded at p < 0.05, to correct for multiple comparisons. A digital atlas of the amygdalar nuclei was used to infer which nuclei were involved. Results: Both amygdalar volumes were significantly smaller in patients with AD (right 1,508 mm3, SD 418; left 1,646, SD 419) than controls (right 2,129 mm3, SD 316; left 2,077, SD 376; p < 0.002). In the dorsomedial part, significant local tissue loss (20%–30%) was mapped in the medial and central nuclei. Ventrally, the lateral nucleus (La) and the basolateral ventral medial nucleus (BLVM) were also involved (20%–30% loss). Conclusions: We found in vivo local structural differences in the amygdala of patients with AD. The nuclei involved have known connections to the hippocampus (BLVM, La) and olfactory system (medial nucleus) and with cholinergic pathways (central nucleus). This pattern is consistent with the known pathophysiology of neural systems affected by AD. PMID:21339500

Recognizing the bank robber and spotting the difference: emotional state and global vs. local attentional set.

PubMed

Pacheco-Unguetti, Antonia Pilar; Acosta, Alberto; Lupiáñez, Juan

2014-01-01

In two experiments (161 participants in total), we investigated how current mood influences processing styles (global vs. local). Participants watched a video of a bank robbery before receiving a positive, negative or neutral induction, and they performed two tasks: a face-recognition task about the bank robber as global processing measure, and a spot-the-difference task using neutral pictures (Experiment-1) or emotional scenes (Experiment-2) as local processing measure. Results showed that positive mood induction favoured a global processing style, enhancing participants' ability to correctly identify a face even when they watched the video before the mood-induction. This shows that, besides influencing encoding processes, mood state can be also related to retrieval processes. On the contrary, negative mood induction enhanced a local processing style, making easier and faster the detection of differences between nearly identical pictures, independently of their valence. This dissociation supports the hypothesis that current mood modulates processing through activation of different cognitive styles.

International-local remuneration differences across six countries: do they undermine poverty reduction work?

PubMed

Carr, Stuart C; McWha, Ishbel; Maclachlan, Malcolm; Furnham, Adrian

2010-10-01

Despite the rhetoric of a single global economy, professionals in poorer countries continue to be remunerated differently depending on whether they are compensated at a local vs. international rate. Project ADDUP (Are Development Discrepancies Undermining Performance?) surveyed 1290 expatriate and local professionals (response rate = 47%) from aid, education, government, and business sectors in (1) Island Nations (Papua New Guinea, Solomon Islands), (2) landlocked economies (Malaŵi, Uganda), and (3) emerging economies (India, China). Difference in pay was estimated using purchasing power parity, from the World Bank's World Development Indicators 2007. Psychological measures included self-reported pay and benefits (remuneration), self-attributed ability, remuneration comparison, sense of justice in remuneration, remuneration-related motivation, thoughts of turnover and thoughts about international mobility. We included control measures of candour, culture shock, cultural values (horizontal/vertical individualism/collectivism), personality (from the "big five"), job satisfaction and work engagement. Controlling for these and country (small effects) and organization effects (medium), (a) pay ratios between international and local workers exceeded what were perceived to be acceptable pay thresholds among respondents remunerated locally; who also reported a combination of a sense of relative (b) injustice and demotivation; which (c) together with job satisfaction/work engagement predicted turnover and international mobility. These findings question the wisdom of dual salary systems in general, expose and challenge a major contradiction between contemporary development policy and practice, and have a range of practical, organizational, and theoretical implications for poverty reduction work.

MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis.

PubMed

Lafita-Navarro, Maria Del Carmen; Blanco, Rosa; Mata-Garrido, Jorge; Liaño-Pons, Judit; Tapia, Olga; García-Gutiérrez, Lucía; García-Alegría, Eva; Berciano, María T; Lafarga, Miguel; León, Javier

2016-10-25

MXD1 is a protein that interacts with MAX, to form a repressive transcription factor. MXD1-MAX binds E-boxes. MXD1-MAX antagonizes the transcriptional activity of the MYC oncoprotein in most models. It has been reported that MYC overexpression leads to augmented RNA synthesis and ribosome biogenesis, which is a relevant activity in MYC-mediated tumorigenesis. Here we describe that MXD1, but not MYC or MNT, localizes to the nucleolus in a wide array of cell lines derived from different tissues (carcinoma, leukemia) as well as in embryonic stem cells. MXD1 also localizes in the nucleolus of primary tissue cells as neurons and Sertoli cells. The nucleolar localization of MXD1 was confirmed by co-localization with UBF. Co-immunoprecipitation experiments showed that MXD1 interacted with UBF and proximity ligase assays revealed that this interaction takes place in the nucleolus. Furthermore, chromatin immunoprecipitation assays showed that MXD1 was bound in the transcribed rDNA chromatin, where it co-localizes with UBF, but also in the ribosomal intergenic regions. The MXD1 involvement in rRNA synthesis was also suggested by the nucleolar segregation upon rRNA synthesis inhibition by actinomycin D. Silencing of MXD1 with siRNAs resulted in increased synthesis of pre-rRNA while enforced MXD1 expression reduces it. The results suggest a new role for MXD1, which is the control of ribosome biogenesis. This new MXD1 function would be important to curb MYC activity in tumor cells.

MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis

PubMed Central

Lafita-Navarro, Maria del Carmen; Blanco, Rosa; Mata-Garrido, Jorge; Liaño-Pons, Judit; Tapia, Olga; García-Gutiérrez, Lucía; García-Alegría, Eva; Berciano, María T.; Lafarga, Miguel; León, Javier

2016-01-01

MXD1 is a protein that interacts with MAX, to form a repressive transcription factor. MXD1-MAX binds E-boxes. MXD1-MAX antagonizes the transcriptional activity of the MYC oncoprotein in most models. It has been reported that MYC overexpression leads to augmented RNA synthesis and ribosome biogenesis, which is a relevant activity in MYC-mediated tumorigenesis. Here we describe that MXD1, but not MYC or MNT, localizes to the nucleolus in a wide array of cell lines derived from different tissues (carcinoma, leukemia) as well as in embryonic stem cells. MXD1 also localizes in the nucleolus of primary tissue cells as neurons and Sertoli cells. The nucleolar localization of MXD1 was confirmed by co-localization with UBF. Co-immunoprecipitation experiments showed that MXD1 interacted with UBF and proximity ligase assays revealed that this interaction takes place in the nucleolus. Furthermore, chromatin immunoprecipitation assays showed that MXD1 was bound in the transcribed rDNA chromatin, where it co-localizes with UBF, but also in the ribosomal intergenic regions. The MXD1 involvement in rRNA synthesis was also suggested by the nucleolar segregation upon rRNA synthesis inhibition by actinomycin D. Silencing of MXD1 with siRNAs resulted in increased synthesis of pre-rRNA while enforced MXD1 expression reduces it. The results suggest a new role for MXD1, which is the control of ribosome biogenesis. This new MXD1 function would be important to curb MYC activity in tumor cells. PMID:27588501

Biodegradation of Dimethyl Phthalate by Freshwater Unicellular Cyanobacteria.

PubMed

Zhang, Xiaohui; Liu, Lincong; Zhang, Siping; Pan, Yan; Li, Jing; Pan, Hongwei; Xu, Shiguo; Luo, Feng

2016-01-01

The biodegradation characteristics of dimethyl phthalate (DMP) by three freshwater unicellular organisms were investigated in this study. The findings revealed that all the organisms were capable of metabolizing DMP; among them, Cyanothece sp. PCC7822 achieved the highest degradation efficiency. Lower concentration of DMP supported the growth of the Cyanobacteria; however, with the increase of DMP concentration growth of Cyanobacteria was inhibited remarkably. Phthalic acid (PA) was detected to be an intermediate degradation product of DMP and accumulated in the culture solution. The optimal initial pH value for the degradation was detected to be 9.0, which mitigated the decrease of pH resulting from the production of PA. The optimum temperature for DMP degradation of the three species of organisms is 30°C. After 72 hours' incubation, no more than 11.8% of the residual of DMP aggregated in Cyanobacteria cells while majority of DMP remained in the medium. Moreover, esterase was induced by DMP and the activity kept increasing during the degradation process. This suggested that esterase could assist in the degradation of DMP.

Biodegradation of Dimethyl Phthalate by Freshwater Unicellular Cyanobacteria

PubMed Central

Zhang, Xiaohui; Liu, Lincong; Zhang, Siping; Pan, Yan; Li, Jing; Pan, Hongwei

2016-01-01

The biodegradation characteristics of dimethyl phthalate (DMP) by three freshwater unicellular organisms were investigated in this study. The findings revealed that all the organisms were capable of metabolizing DMP; among them, Cyanothece sp. PCC7822 achieved the highest degradation efficiency. Lower concentration of DMP supported the growth of the Cyanobacteria; however, with the increase of DMP concentration growth of Cyanobacteria was inhibited remarkably. Phthalic acid (PA) was detected to be an intermediate degradation product of DMP and accumulated in the culture solution. The optimal initial pH value for the degradation was detected to be 9.0, which mitigated the decrease of pH resulting from the production of PA. The optimum temperature for DMP degradation of the three species of organisms is 30°C. After 72 hours' incubation, no more than 11.8% of the residual of DMP aggregated in Cyanobacteria cells while majority of DMP remained in the medium. Moreover, esterase was induced by DMP and the activity kept increasing during the degradation process. This suggested that esterase could assist in the degradation of DMP. PMID:28078293

Cellular Localization of Aquaporin-1 in the Human and Mouse Trigeminal Systems

PubMed Central

Gu, Minxia; Marshall, Charles; Ding, Jiong; Hu, Gang; Xiao, Ming

2012-01-01

Previous studies reported that a subpopulation of mouse and rat trigeminal neurons express water channel aquaporin-1 (AQP1). In this study we make a comparative investigation of AQP1 localization in the human and mouse trigeminal systems. Immunohistochemistry and immunofluorescence results showed that AQP1 was localized to the cytoplasm and cell membrane of some medium and small-sized trigeminal neurons. Additionally, AQP1 was found in numerous peripheral trigeminal axons of humans and mice. In the central trigeminal root and brain stem, AQP1 was specifically expressed in astrocytes of humans, but was restricted to nerve fibers within the central trigeminal root and spinal trigeminal tract and nucleus in mice. Furthermore, AQP1 positive nerve fibers were present in the mucosal and submucosal layers of human and mouse oral tissues, but not in the muscular and subcutaneous layers. Fluorogold retrograde tracing demonstrated that AQP1 positive trigeminal neurons innervate the mucosa but not skin of cheek. These results reveal there are similarities and differences in the cellular localization of AQP1 between the human and mouse trigeminal systems. Selective expression of AQP1 in the trigeminal neurons innervating the oral mucosa indicates an involvement of AQP1 in oral sensory transduction. PMID:23029502

RDMO - Research Data Management Organiser

NASA Astrophysics Data System (ADS)

Klar, Jochen; Engelhardt, Claudia; Neuroth, Heike; Enke, Harry; Ludwig, Jens

2017-04-01

The Research Data Management Organiser (RDMO) is a new tool to support the structured planning and implementation of the research data management in a scientific project and, in addition, provide the scientist with a textual Data Management Plan (DMP). While DMP are in principle a great tool to optimise the data management during all stages of a research project and to serve as a roadmap for the various data management tasks, their current usage is strongly focused on the requirements of funding agencies. Existing software tools for DMP creation and editing are useful in that respect, but do not sufficiently support the full data life cycle of a project. The RDMO is meant to be a companion for data management issues during and after the whole project. Starting from a structured interview about the project and the data involved, it organizes the data management along tasks and comprises all relevant stakeholders, i.e. researchers, PIs, institutional data managers, IT departments. Adaptations to discipline-specific or institutional needs are supported. The installation of the tool into local environments and its integration into existing administrative IT infrastructure and work flows is given special consideration. The tool is multilingual (at first German and English). In my talk, I will present the different features of the software, show its current stage of development, and how RDMO can be deployed for your institution.

48 CFR 970.5229-1 - State and local taxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false State and local taxes. 970... for Management and Operating Contracts 970.5229-1 State and local taxes. As prescribed in 970.2904-1(b... prescribed in paragraph (a) of the clause may be broadened to include all State and local taxes which may be...

48 CFR 970.5229-1 - State and local taxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false State and local taxes. 970... for Management and Operating Contracts 970.5229-1 State and local taxes. As prescribed in 970.2904-1(b... prescribed in paragraph (a) of the clause may be broadened to include all State and local taxes which may be...

Analysing horizontal equity in enrolment in Disease Management Programmes for coronary heart disease in Germany 2008-2010.

PubMed

Bozorgmehr, Kayvan; San Sebastian, Miguel; Brenner, Hermann; Razum, Oliver; Maier, Werner; Saum, Kai-Uwe; Holleczek, Bernd; Miksch, Antje; Szecsenyi, Joachim

2015-03-10

Disease Management Programmes (DMPs) have been introduced in Germany ten years ago with the aim to improve effectiveness and equity of care, but little is known about the degree to which enrolment in the programme meets the principles of equity in health care. We aimed to analyse horizontal equity in DMP enrolment among patients with coronary heart disease (CHD). Cross-sectional analysis of horizontal inequities in physician-reported enrolment in the DMP for CHD in a large population-based cohort-study in Germany (2008-2010). We calculated horizontal inequity indices (HII) and their 95% confidence intervals [95%CI] for predicted need-standardised DMP enrolment across two measures of socio-economic status (SES) (educational attainment, regional deprivation) stratified by sex. Need-standardised DMP enrolment was predicted in multi-level logistic regression models. Among N = 1,280 individuals aged 55-84 years and diagnosed with CHD, DMP enrolment rates were 22.2% (women) and 35.0% (men). Education-related inequities in need-standardised DMP enrolment favoured groups with lower education, but HII estimates were not significant. Deprivation-related inequities among women significantly favoured groups with higher SES (HII = 0.086 [0.007 ; 0.165]. No such deprivation-related inequities were seen among men (HII = 0.014 [-0.048 ; 0.077]). Deprivation-related inequities across the whole population favoured groups with higher SES (HII estimates not significant). Need-standardised DMP enrolment was fairly equitable across educational levels. Deprivation-related inequities in DMP enrolment favoured women living in less deprived areas relative to those living in areas with higher deprivation. Further research is needed to gain a better understanding of the mechanisms that contribute to deprivation-related horizontal inequities in DMP enrolment among women.

Immunocytochemical localization of muscarinic, adrenergic and AT1 receptors.

PubMed

Schulze, W; Fu, M L

1996-01-01

By indirect immunofluorescence and post-embedding EM gold technique, the localization of alpha 1-adrenergic, M2-muscarinic and angiotensin II receptor-I (AT1) were determinated. With antipeptide antibodies directed against the second extracellular loops of all three receptors, these receptors were found to be localized at the sarcolemma of adult rat cardiomyocytes and at the surface membranes of cultivated neonatal heart cells. Additionally, M2 receptors were localized along T-tubule membranes of both rat and human adult cardiomyocytes. alpha 1-Adrenergic receptors were found intracellular near the surface of atrial granules (ANF-granules). By using M2 and alpha 1-adrenergic receptor antibodies the strongest fluorescence was found in the right atrium of the rat. Besides the localization in cardiomyocytes, AT1 receptors were also localized in outer plasma membranes and the endoplasmic reticulum of fibroblasts, and the surface of smooth muscle cells of the major arteries and veins. Likewise, the muscarinic M2 receptors were found along the outer membranes of endothelial cells from capillaries and endocardium.

Ultrasound assessment of cranial spread during caudal blockade in children: the effect of different volumes of local anaesthetics.

PubMed

Brenner, L; Marhofer, P; Kettner, S C; Willschke, H; Machata, A-M; Al-Zoraigi, U; Lundblad, M; Lönnqvist, P A

2011-08-01

Despite the large amount of literature on caudal anaesthesia in children, the issue of volume of local anaesthetics and cranial spread is still not settled. Thus, the aim of the present prospective randomized study was to evaluate the cranial spread of caudally administered local anaesthetics in children by means of real-time ultrasound, with a special focus on the effects of using different volumes of local anaesthetics. Seventy-five children, 1 month to 6 yr, undergoing inguinal hernia repair or more distal surgery were randomized to receive a caudal block with 0.7, 1.0, or 1.3 ml kg(-1) ropivacaine. The cranial spread of the local anaesthetic within the spinal canal was assessed by real-time ultrasound scanning; the absolute cranial segmental level and the cranial level relative to the conus medullaris were determined. All the blocks were judged to be clinically successful. A significant correlation was found between the injected volume and the cranial level reached by the local anaesthetic both with regards to the absolute cranial segmental level and the cranial level relative to the conus medullaris. The main finding of the present study was positive, but numerically small correlation between injected volumes of local anaesthetic and the cranial spread of caudally administered local anaesthetics. Therefore, the prediction of the cranial spread of local anaesthetic, depending on the injected volume of the local anaesthetic, was not possible. EudraCT Number: 2008-007627-40.

Changes in histopathology and cytokeratin AE1/AE3 expression in skin graft with different time on Indonesian local cats.

PubMed

Erwin; Etriwati; Gunanti; Handharyani, Ekowati; Noviana, Deni

2017-06-01

A good skin graft histopathology is followed by formation of hair follicle, sweat gland, sebaceous gland, blood vessel, lightly dense connective tissue, epidermis, and dermis layer. This research aimed to observe histopathology feature and cytokeratin AE1/AE3 expression on cat skin post skin grafting within a different period of time. Nine male Indonesian local cats aged 1-2 years old weighing 3-4 kg were separated into three groups. First surgery created defect wound of 2 cm × 2 cm in size to whole groups. The wounds were left alone for several days, differing in interval between each group, respectively: Group I (for 2 days), Group II (for 4 days), and Group III (for 6 days). The second surgery was done to each group which harvested skin of thoracic area and applied it on recipient wound bed. On day 24 th post skin graft was an examination of histopathology and cytokeratin AE1/AE3 immunohistochemistry. Group I donor skin's epidermis layer had not formed completely whereas epidermis of donor skin of Groups II and III had completely formed. In all group hair follicle, sweat gland, sebaceous gland, and neovascularization were found. The density of connective tissue in Group I was very solid than other groups. Cytokeratin AE1/AE3 expression was found on donor skin's epithelial cell in epidermis and dermis layer with very brown intensity for Group II, brown intensity for Group II, and lightly brown for Group I. Histopathological structure and cytokeratin AE1/AE3 expression post skin graft are better in Groups II and III compared to Group I.

Impacts of dimethyl phthalate on the bacterial community and functions in black soils

PubMed Central

Wang, Zhi-Gang; Hu, Yun-Long; Xu, Wei-Hui; Liu, Shuai; Hu, Ying; Zhang, Ying

2015-01-01

Dimethyl phthalate (DMP), a known endocrine disruptor and one of the phthalate esters (PAEs), is a ubiquitous pollutant. Its impacts on living organisms have aroused great concern. In this study, the impacts of DMP contamination on bacterial communities and functions were tested by using microcosm model in black soils. The results showed that the operational taxonomic unit (OTUs) richness and bacterial diversity were reduced by DMP contamination. The relative percentages of some genera associated with nitrogen metabolism were increased by DMP contamination, while the relative percentages of some other genera that were extremely beneficial to soil health were decreased by DMP contamination. Further, the relative percentages of some genera that possessed the capability to degrade DMP were increased by the DMP treatment at low concentrations (5, 10, and 20 mg/kg), but were decreased by the high concentration DMP treatment (40 mg/kg). Clearly, DMP contamination changed the bacterial community structure and disturbed the metabolic activity and functional diversity of the microbes in black soils. Our results suggest that DMP pollution can alter the metabolism and biodiversity of black soil microorganisms, thereby directly impact fertility and ecosystem functions. PMID:25999932

Non-local thermodynamic equilibrium 1.5D modeling of red giant stars

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

Young, Mitchell E.; Short, C. Ian, E-mail: myoung@ap.smu.ca

Spectra for two-dimensional (2D) stars in the 1.5D approximation are created from synthetic spectra of one-dimensional (1D) non-local thermodynamic equilibrium (NLTE) spherical model atmospheres produced by the PHOENIX code. The 1.5D stars have the spatially averaged Rayleigh-Jeans flux of a K3-4 III star while varying the temperature difference between the two 1D component models (ΔT {sub 1.5D}) and the relative surface area covered. Synthetic observable quantities from the 1.5D stars are fitted with quantities from NLTE and local thermodynamic equilibrium (LTE) 1D models to assess the errors in inferred T {sub eff} values from assuming horizontal homogeneity and LTE. Fivemore » different quantities are fit to determine the T {sub eff} of the 1.5D stars: UBVRI photometric colors, absolute surface flux spectral energy distributions (SEDs), relative SEDs, continuum normalized spectra, and TiO band profiles. In all cases except the TiO band profiles, the inferred T {sub eff} value increases with increasing ΔT {sub 1.5D}. In all cases, the inferred T {sub eff} value from fitting 1D LTE quantities is higher than from fitting 1D NLTE quantities and is approximately constant as a function of ΔT {sub 1.5D} within each case. The difference between LTE and NLTE for the TiO bands is caused indirectly by the NLTE temperature structure of the upper atmosphere, as the bands are computed in LTE. We conclude that the difference between T {sub eff} values derived from NLTE and LTE modeling is relatively insensitive to the degree of the horizontal inhomogeneity of the star being modeled and largely depends on the observable quantity being fit.« less

Glucocorticoid-induced bone loss can be reversed by the actions of PTH and Risedronate on different pathways for bone formation and mineralization

PubMed Central

Yao, Wei; Cheng, Zhiqiang; Pham, Aaron; Busse, Cheryl; Zimmermann, Elizabeth A.; Ritchie, Robert O.; Lane, Nancy E.

2008-01-01

Glucocorticoid (GC) excess decreases bone mineralization and microarchitecture and lead to reduced bone strength. Both anabolic (PTH) and anti-resorptive agents are used to prevent and treat GC-induced bone loss, yet these bone active agents alter bone turnover by very different mechanisms. Our study objective was to determine how PTH and risedronate (Ris) alter bone quality following GC excess. Five-month-old Swiss-Webster male mice were treated with the glucocorticoid (GC) prednisolone (5 mg/kg 60-day slow-release pellet) or placebo (PL)]. At day 28−56, two groups of GC-treated animals had either PTH (5μg/kg, 5x/wk) or Ris (5μg/kg, 5x/wk) intervention. Bone quality and quantity measurements include x-ray tomography microscopy (XTM) for the degree of bone mineralization (DBM), microCT for bone microarchitecture, compression testing for trabecular bone strength, biochemistry and histomorphometry for bone turnover. In addition, real-time PCR and immunohistochemistry were performed to monitor the expression of several key genes regulating Wnt signaling (bone formation) and mineralization. Results Compared to the placebo treated mice, GC treatment decreased trabecular bone volume (BV/TV) and serum osteocalcin, but increased serum CTX and osteoclast surface with a peak at day 28. GC+PTH increased and GC+Ris restored BV/TV to the PL levels after a 28 day treatment period. Average DBM was lowered after GC treatment (−27%), and it was restored to PL level with GC+Ris and GC+PTH. At day 56, RT-PCR revealed that continuous exposure to GC and GC+PTH increased, while GC+Ris decreased the expression of genes that inhibit bone mineralization (Dmp1 and Phex), compared to the PL group. Wnt signaling antagonists Dkk1, Sost and Wif1 were up-regulated by GC treatment but were down-regulated after GC+PTH treatment. Immunohistochemistry of bone sections found GC increased N terminal dmp-1 while PTH treatment increased both N and C terminal dmp-1 staining around osteocytes

Cancer detection rates following enrolment in a disease management programme for type 2 diabetes.

PubMed

Geier, A S; Wellmann, J; Wellmann, I; Kajüter, H; Heidinger, O; Hempel, G; Hense, H W

2013-09-01

Recent prospective studies found an elevated cancer risk shortly after diabetes diagnosis, and this was probably due to increased ascertainment. This study investigated whether site-specific cancer risks are also raised following enrolment in a disease management programme for type 2 diabetes mellitus (DMP-DM2). We linked records from a DMP-DM2 to population cancer registry data. The study period was from June 2003 to December 2009. Standardised incidence ratios (SIRs) were calculated for time intervals following DMP enrolment using the cancer incidence rates of the general source population. Additionally, Poisson regression with natural splines was used to assess time-dependent cancer incidence by diabetes duration. There were 2,034 first invasive cancer cases identified over 163,738 person-years of follow-up. Pancreatic cancer risk was significantly increased mainly in the first year after enrolment (SIR 1.62); the increment was only seen for patients in whom diabetes had been diagnosed less than 1 year before DMP-DM2 enrolment. Risk of endometrial cancer was similarly raised in the first year after DMP-DM2 enrolment among individuals newly diagnosed with diabetes but decreased rapidly thereafter. There was no time dependence in the incidence of cancers of the liver, lung, colon, breast and prostate. Enrolment in a DMP-DM2 did not appear to induce ascertainment bias for most cancers. Cancer risks were initially increased, especially for pancreatic cancer, potentially as a result of reverse causality. Ascertainment bias and time-dependent incidence of cancer appear to be less of a problem in settings using DMP-like structures for the study of the association between diabetes duration, glucose-lowering medication and cancer incidence.

The effectiveness of German disease management programs (DMPs) in patients with type 2 diabetes mellitus and coronary heart disease: results from an observational longitudinal study.

PubMed

Laxy, Michael; Stark, Renée; Meisinger, Christa; Kirchberger, Inge; Heier, Margit; von Scheidt, Wolfgang; Holle, Rolf

2015-01-01

Although the population-based German disease management programs (DMPs) for diabetes mellitus (DM) and coronary heart disease (CHD) are among the biggest worldwide, evidence on the effectiveness of these programs is still inconclusive or missing, particularly for high risk patients with comorbidities. The objective of this study was therefore to analyze the impact of DMPs on process and outcome parameters in patients with both, type 2 DM and CHD. Analyses are based on two postal surveys of patients from the KORA myocardial infarction registry (southern Germany) with type 2 DM and on two postal validation studies with patients' general physicians (2006, n = 312 and 2011, n = 212). The association between DMP enrollment (being enrolled in either DMP-DM or DMP-CHD) and guideline care (defined by several process indicators) at baseline (2006) and its development until follow-up (2011) was analyzed using logistic regression models accounting for the repeated measurements structure. The impact of DMP enrollment/guideline care on cumulated (quality-adjusted) life years ((QA)LYs) over a 4-year time horizon (2006-2010) was assessed using multiple linear regression methods. Logistic regression models were applied to analyze the association between DMP status and patient self-management at follow-up. Being enrolled in a DMP was associated with better guideline care at baseline [OR = 2.3 (95 % CI 1.27-4.03)], but not at follow-up [OR = 0.80 (95 % CI 0.40-1.58); p value for time-interaction <0.01]. DMP enrollment was not significantly [+0.15 LYs (95 % CI -0.07, 0.37); +0.06 QALYs (95 % CI -0.15, 0.26)], but treatment according to guideline care significantly [+0.40 LYs (95 % CI 0.21-0.60); +0.28 QALYs (95 % CI 0.10-0.45)] associated with higher (quality-adjusted) survival over the 4-year follow-up period. DMP enrollees further reported a somewhat better self-management than patients not being enrolled into a DMP. The results of this study concerning the

43 CFR 8365.1-7 - State and local laws.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false State and local laws. 8365.1-7 Section... and local laws. Except as otherwise provided by Federal law or regulation, State and local laws and ordinances shall apply and be enforced by the appropriate State and local authorities. This includes, but is...

43 CFR 8365.1-7 - State and local laws.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false State and local laws. 8365.1-7 Section... and local laws. Except as otherwise provided by Federal law or regulation, State and local laws and... not limited to, State and local laws and ordinances governing: (a) Operation and use of motor vehicles...

Molecular Tracers of Saturated and Polycyclic Aromatic Hydrocarbon Inputs into Central Park Lake, New York City

PubMed Central

YAN, BEIZHAN; ABRAJANO, TEOFILO A.; BOPP, RICHARD F.; CHAKY, DAMON A.; BENEDICT, LUCILLE A.; CHILLRUD, STEVEN N.

2011-01-01

Saturated hydrocarbons (SH) and polycyclic aromatic hydrocarbons (PAHs) have been quantified in a sediment core obtained from Central Park Lake, New York City. Radionuclides 210Pb and 137Cs were used to assign approximate dates to each individual section in the core. The dating profile based on 210Pb matches very well with the time constraints provided by 137Cs. Radionuclide-derived depositional dates are consistent with temporal information from the petroleum-indicator ratio U/R [the ratio of unresolved complex mixture (UCM) to saturated hydrocarbons in the aliphatic fraction] and the history of fuel use in the NYC area. Ratios of 1,7-dimethylphenanthrane (DMP) to 1,7-DMP plus 2,6-DMP [1,7/(1,7 + 2,6)-DMP], retene to retene plus chrysene [Ret/(Ret + Chy)], and fluoranthene to fluoranthene plus pyrene [Fl/(Fl + Py)] provide additional source discrimination throughout the core. Results show that the ratio U/R is sensitive to petroleum inputs and Ret/(Ret + Chy) is responsive to contributions from softwood combustion, whereas both Fl/(Fl + Py) and 1,7/(1,7 + 2,6)-DMP can be used to discriminate among wood, coal, and petroleum combustion sources. Combined use of these ratios suggests that in New York City, wood combustion dominated 100 years ago, with a shift to coal combustion occurring from the 1900s to the 1950s. Petroleum use began around the 1920s and has dominated since the 1940s. PMID:16201624

Molecular tracers of saturated and polycyclic aromatic hydrocarbon inputs into Central Park Lake, New York City.

PubMed

Yan, Beizhan; Abrajano, Teofilo A; Bopp, Richard F; Chaky, Damon A; Benedict, Lucille A; Chillrud, Steven N

2005-09-15

Saturated hydrocarbons (SH) and polycyclic aromatic hydrocarbons (PAHs) have been quantified in a sediment core obtained from Central Park Lake, New York City. Radionuclides 210Pb and 137Cs were used to assign approximate dates to each individual section in the core. The dating profile based on 210Pb matches very well with the time constraints provided by 137Cs. Radionuclide-derived depositional dates are consistent with temporal information from the petroleum-indicator ratio U/R [the ratio of unresolved complex mixture (UCM)to saturated hydrocarbons in the aliphatic fraction] and the history of fuel use in the NYC area. Ratios of 1,7-dimethylphenanthrane (DMP) to 1,7-DMP plus 2,6-DMP [1,7/(1,7 + 2,6)-DMP], retene to retene plus chrysene [Ret/(Ret + Chy)], and fluoranthene to fluoranthene plus pyrene [FI/(FI + Py)] provide additional source discrimination throughoutthe core. Results show that the ratio U/R is sensitive to petroleum inputs and Ret/(Ret + Chy) is responsive to contributions from softwood combustion, whereas both FI/(FI + Py) and 1,7/ (1,7 + 2,6)-DMP can be used to discriminate among wood, coal, and petroleum combustion sources. Combined use of these ratios suggests that in New York City, wood combustion dominated 100 years ago, with a shift to coal combustion occurring from the 1900s to the 1950s. Petroleum use began around the 1920s and has dominated since the 1940s.

Potentialities of a membrane reactor with laccase grafted membranes for the enzymatic degradation of phenolic compounds in water.

PubMed

Chea, Vorleak; Paolucci-Jeanjean, Delphine; Sanchez, José; Belleville, Marie-Pierre

2014-10-06

This paper describes the degradation of phenolic compounds by laccases from Trametes versicolor in an enzymatic membrane reactor (EMR). The enzymatic membranes were prepared by grafting laccase on a gelatine layer previously deposited onto α-alumina tubular membranes. The 2,6-dimethoxyphenol (DMP) was selected  from among the three different phenolic compounds tested (guaiacol, 4-chlorophenol and DMP) to study the performance of the EMR in dead end configuration. At the lowest feed substrate concentration tested (100 mg·L-1), consumption increased with flux (up to 7.9 × 103 mg·h-1·m-2 at 128 L·h-1·m-2), whereas at the highest substrate concentration (500 mg·L-1), it was shown that the reaction was limited by the oxygen content.

Potentialities of a Membrane Reactor with Laccase Grafted Membranes for the Enzymatic Degradation of Phenolic Compounds in Water

PubMed Central

Chea, Vorleak; Paolucci-Jeanjean, Delphine; Sanchez, José; Belleville, Marie-Pierre

2014-01-01

This paper describes the degradation of phenolic compounds by laccases from Trametes versicolor in an enzymatic membrane reactor (EMR). The enzymatic membranes were prepared by grafting laccase on a gelatine layer previously deposited onto α-alumina tubular membranes. The 2,6-dimethoxyphenol (DMP) was selected  from among the three different phenolic compounds tested (guaiacol, 4-chlorophenol and DMP) to study the performance of the EMR in dead end configuration. At the lowest feed substrate concentration tested (100 mg·L−1), consumption increased with flux (up to 7.9 × 103 mg·h−1·m−2 at 128 L·h−1·m−2), whereas at the highest substrate concentration (500 mg·L−1), it was shown that the reaction was limited by the oxygen content. PMID:25295628

Isolation and functional analysis of an immortalized murine cementocyte cell line, IDG-CM6

PubMed Central

Duan, Peipei; Prideaux, Matthew; Zhao, Hong; Foster, Brian L.; Somerman, Martha J.; Bonewald, Lynda F.

2016-01-01

The dental cementum covering the tooth root is similar to bone in several respects, but remains poorly understood in terms of development and differentiation of cementoblasts, as well as the potential function(s) of cementocytes residing in the cellular cementum. It is not known if the cementocyte is a dynamic actor in cementum metabolism, comparable to the osteocyte in the bone. Cementocytes exhibit irregular spacing and lacunar shape, with fewer canalicular connections compared to osteocytes. Immunohistochemistry and quantitative PCR (qPCR) revealed that the in vivo expression profile of cementocytes paralleled that of osteocytes, including expression of dentin matrix protein 1 (Dmp1/DMP1), Sost/sclerostin, E11/gp38/podoplanin, Tnfrsf11b (osteoprotegerin; OPG), and Tnfsf11 (receptor activator of NF-kB ligand; RANKL). We used the Immortomouse+/−; Dmp1-GFP+/− mice to isolate cementocytes as Dmp1-expressing cells followed by immortalization using the interferon (IFN)-γ-inducible promoter driving expression of a thermolabile large T antigen to create the first immortalized line of cementocytes, IDG-CM6. This cell line reproduced the expression profile of cementocytes observed in vivo, including alkaline phosphatase activity and mineralization. IDG-CM6 cells expressed higher levels of Tnfrsf11b, and lower levels of Tnfsf11 compared to IDG-SW3 osteocytes, and under fluid flow shear stress, IDG-CM6 cells significantly increased OPG while decreasing RANKL, leading to a significantly increased OPG/RANKL ratio, which would inhibit osteoclast activation. These studies indicate similarities yet potentially important differences in the function of cementocytes as compared to osteocytes and support cementocytes as mechanically responsive cells. PMID:26274352

Species differences in the localization and number of CNS beta adrenergic receptors: Rat versus guinea pig

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

Booze, R.M.; Crisostomo, E.A.; Davis, J.N.

1989-06-01

The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of (125I)cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in themore » thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions (1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, (2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and (3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species.« less

The mutual influence of speciation and combination of Cu and Pb on the photodegradation of dimethyl o-phthalate.

PubMed

Jiang, Xinshu; Wang, Zhe; Zhang, Yiyue; Wang, Fei; Zhu, Mijia; Yao, Jun

2016-12-01

Specific industrial application of dimethyl o-phthalate (DMP) in ore flotation has led to DMP-heavy metals combined pollution, which causes the abiotic degradation of DMP in the environment more complex. This study focused on the effect of Cu and Pb on photodegradation of DMP. The major mechanism of inhibiting effect of Cu and Pb on degradation of DMP involved their speciation and combination. It was found that the Cu (5 mg/L, I = 95.4%) and Pb (5 mg/L, I = 100%) could inhibit the photodegradation of DMP. The main species that inhibit the DMP degradation were Cu(OH) + and Pb(OH) + , respectively. The intensity of the UV-Vis absorbance of DMP was obviously related to the concentration of Cu 2+ (R 2  = 0.8655) or Pb 2+ (R 2  = 0.9019) ions. Fluorescence quenching effect of Cu 2+ (R 2  > 0.9946), Pb 2+ (R 2  > 0.6879) on DMP is strongly correlated with the concentration of ions. And the equilibrium membrane dialysis experiment has also verified the combination of DMP and Cu, Pb. These results are useful to understand the effect mechanism of metal species on the photodegradation of organic chemicals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inequality measures perform differently in global and local assessments: An exploratory computational experiment

NASA Astrophysics Data System (ADS)

Chiang, Yen-Sheng

2015-11-01

Inequality measures are widely used in both the academia and public media to help us understand how incomes and wealth are distributed. They can be used to assess the distribution of a whole society-global inequality-as well as inequality of actors' referent networks-local inequality. How different is local inequality from global inequality? Formalizing the structure of reference groups as a network, the paper conducted a computational experiment to see how the structure of complex networks influences the difference between global and local inequality assessed by a selection of inequality measures. It was found that local inequality tends to be higher than global inequality when population size is large; network is dense and heterophilously assorted, and income distribution is less dispersed. The implications of the simulation findings are discussed.

Risk of Nonfatal Stroke in Type 2 Diabetes Mellitus Patients: A Retrospective Comparison Between Disease Management Programs and Standard Care.

PubMed

Wiefarn, Stefan; Heumann, Christian; Rettelbach, Anja; Kostev, Karel

2017-07-01

The present retrospective study examines the influence of disease management programs on nonfatal stroke in type 2 diabetes mellitus (T2DM) patients in Germany. The evaluation is based on retrospective patient data from the Disease Analyzer (IMS Health). The analysis included 169 414 T2DM patients aged 40 years and older with an initial prescription of antihyperglycemic therapy between January 2004 and December 2014. A total of 86 713 patients participated in a disease management program (DMP) for T2DM and 82 701 patients received standard care. The main outcome measure of this study was nonfatal stroke. Kaplan-Meier curves of DMP and SC patients were compared using log rank test. The Cox proportional hazards model was used to provide an adjusted estimate of the DMP effect. It is apparent from the baseline characteristics that the general health of patients receiving standard care was poorer than that of patients participating in a DMP. The baseline HbA1c value was 7.6% in the DMP group and 7.8% in the SC group. Furthermore, the SC group had a higher proportion of preexisting conditions, such as coronary heart disease (CHD), peripheral arterial occlusive disease (pAOD), and renal insufficiency. The proportion of patients who received insulin in first year therapy was higher in the SC group. Time to event analysis showed that DMP was associated with a delayed occurrence of stroke, because stroke occurred an average of 350 days later in DMP patients than in patients receiving SC (DMP: 1.216 days, RV: 866 days). The Cox model with covariable adjustment confirmed the significant association of DMPs with nonfatal stroke in patients with type 2 diabetes mellitus (HR 0.71; 95% CI: 0.69-0.74). The present study indicates that DMPs are positively associated with stroke. The possible reasons for this must be verified in further studies.

Risk of Nonfatal Stroke in Type 2 Diabetes Mellitus Patients: A Retrospective Comparison Between Disease Management Programs and Standard Care

PubMed Central

Wiefarn, Stefan; Heumann, Christian; Rettelbach, Anja; Kostev, Karel

2017-01-01

Objective: The present retrospective study examines the influence of disease management programs on nonfatal stroke in type 2 diabetes mellitus (T2DM) patients in Germany. Methods: The evaluation is based on retrospective patient data from the Disease Analyzer (IMS Health). The analysis included 169 414 T2DM patients aged 40 years and older with an initial prescription of antihyperglycemic therapy between January 2004 and December 2014. A total of 86 713 patients participated in a disease management program (DMP) for T2DM and 82 701 patients received standard care. The main outcome measure of this study was nonfatal stroke. Kaplan-Meier curves of DMP and SC patients were compared using log rank test. The Cox proportional hazards model was used to provide an adjusted estimate of the DMP effect. Results: It is apparent from the baseline characteristics that the general health of patients receiving standard care was poorer than that of patients participating in a DMP. The baseline HbA1c value was 7.6% in the DMP group and 7.8% in the SC group. Furthermore, the SC group had a higher proportion of preexisting conditions, such as coronary heart disease (CHD), peripheral arterial occlusive disease (pAOD), and renal insufficiency. The proportion of patients who received insulin in first year therapy was higher in the SC group. Time to event analysis showed that DMP was associated with a delayed occurrence of stroke, because stroke occurred an average of 350 days later in DMP patients than in patients receiving SC (DMP: 1.216 days, RV: 866 days). The Cox model with covariable adjustment confirmed the significant association of DMPs with nonfatal stroke in patients with type 2 diabetes mellitus (HR 0.71; 95% CI: 0.69-0.74). Conclusion: The present study indicates that DMPs are positively associated with stroke. The possible reasons for this must be verified in further studies. PMID:28300432

Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene.

PubMed

Levy-Litan, Varda; Hershkovitz, Eli; Avizov, Luba; Leventhal, Neta; Bercovich, Dani; Chalifa-Caspi, Vered; Manor, Esther; Buriakovsky, Sophia; Hadad, Yair; Goding, James; Parvari, Ruti

2010-02-12

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

High-Resolution pH Imaging of Living Bacterial Cells To Detect Local pH Differences

PubMed Central

Morimoto, Yusuke V.; Kami-ike, Nobunori; Miyata, Tomoko; Kawamoto, Akihiro; Kato, Takayuki

2016-01-01

ABSTRACT Protons are utilized for various biological activities such as energy transduction and cell signaling. For construction of the bacterial flagellum, a type III export apparatus utilizes ATP and proton motive force to drive flagellar protein export, but the energy transduction mechanism remains unclear. Here, we have developed a high-resolution pH imaging system to measure local pH differences within living Salmonella enterica cells, especially in close proximity to the cytoplasmic membrane and the export apparatus. The local pH near the membrane was ca. 0.2 pH unit higher than the bulk cytoplasmic pH. However, the local pH near the export apparatus was ca. 0.1 pH unit lower than that near the membrane. This drop of local pH depended on the activities of both transmembrane export components and FliI ATPase. We propose that the export apparatus acts as an H+/protein antiporter to couple ATP hydrolysis with H+ flow to drive protein export. PMID:27923921

Subcellular localization of the Snf1 kinase is regulated by specific β subunits and a novel glucose signaling mechanism

PubMed Central

Vincent, Olivier; Townley, Robert; Kuchin, Sergei; Carlson, Marian

2001-01-01

The Snf1/AMP-activated protein kinase family has broad roles in transcriptional, metabolic, and developmental regulation in response to stress. In Saccharomyces cerevisiae, Snf1 is required for the response to glucose limitation. Snf1 kinase complexes contain the α (catalytic) subunit Snf1, one of the three related β subunits Gal83, Sip1, or Sip2, and the γ subunit Snf4. We present evidence that the β subunits regulate the subcellular localization of the Snf1 kinase. Green fluorescent protein fusions to Gal83, Sip1, and Sip2 show different patterns of localization to the nucleus, vacuole, and/or cytoplasm. We show that Gal83 directs Snf1 to the nucleus in a glucose-regulated manner. We further identify a novel signaling pathway that controls this nuclear localization in response to glucose phosphorylation. This pathway is distinct from the glucose signaling pathway that inhibits Snf1 kinase activity and responds not only to glucose but also to galactose and sucrose. Such independent regulation of the localization and the activity of the Snf1 kinase, combined with the distinct localization of kinases containing different β subunits, affords versatility in regulating physiological responses. PMID:11331606

Epigenome-wide association study reveals longitudinally stable DNA methylation differences in CD4+ T cells from children with IgE-mediated food allergy.

PubMed

Martino, David; Joo, Jihoon E; Sexton-Oates, Alexandra; Dang, Thanh; Allen, Katrina; Saffery, Richard; Prescott, Susan

2014-07-01

Food allergy is mediated by a combination of genetic and environmental risk factors, potentially mediated by epigenetic mechanisms. CD4+ T-cells are key drivers of the allergic response, and may therefore harbor epigenetic variation in association with the disease phenotype. Here we retrospectively examined genome-wide DNA methylation profiles (~450,000 CpGs) from CD4+ T-cells on a birth cohort of 12 children with IgE-mediated food allergy diagnosed at 12-months, and 12 non-allergic controls. DNA samples were available at two time points, birth and 12-months. control comparisons of CD4+ methylation profiles identified 179 differentially methylated probes (DMP) at 12-months and 136 DMP at birth (FDR-adjusted P value<0.05, delta β>0.1). Approximately 30% of DMPs were coincident with previously annotated SNPs. A total of 92 [corrected] allergy-associated non-SNP DMPs were present at birth when individuals were initially disease-free, potentially implicating these loci in the causal pathway. Pathway analysis of differentially methylated genes identified several MAP kinase signaling molecules. Mass spectrometry was used to validate 15 CpG sites at 3 candidate genes. Combined analysis of differential methylation with gene expression profiles revealed gene expression differences at some but not all allergy associated differentially methylated genes. Thus, dysregulation of DNA methylation at MAPK signaling-associated genes during early CD4+ T-cell development may contribute to suboptimal T-lymphocyte responses in early childhood associated with the development of food allergy.

[Dmt(1)]DALDA analogues with enhanced μ opioid agonist potency and with a mixed μ/κ opioid activity profile.

PubMed

Bai, Longxiang; Li, Ziyuan; Chen, Jiajia; Chung, Nga N; Wilkes, Brian C; Li, Tingyou; Schiller, Peter W

2014-04-01

Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity, were prepared by replacing Phe(3) with various 2',6'-dialkylated Phe analogues, including 2',6'-dimethylphenylalanine (Dmp), 2',4',6'-trimethylphenylalanine (Tmp), 2'-isopropyl-6'-methylphenylalanine (Imp) and 2'-ethyl-6'-methylphenylalanine (Emp), or with the bulky amino acids 3'-(1-naphthyl)alanine (1-Nal), 3'-(2-naphthyl)alanine (2-Nal) or Trp. Several compounds showed significantly increased μ agonist potency, retained μ receptor selectivity and are of interest as drug candidates for neuropathic pain treatment. Surprisingly, the Dmp(3)-, Imp(3)-, Emp(3)- and 1-Nal(3)-containing analogues showed much increased κ receptor binding affinity and had mixed μ/κ properties. In these cases, molecular dynamics studies indicated conformational preorganization of the unbound peptide ligands due to rotational restriction around the C(β)C(γ) bond of the Xxx(3) residue, in correlation with the observed κ receptor binding enhancement. Compounds with a mixed μ/κ opioid activity profile are known to have therapeutic potential for treatment of cocaine abuse. Copyright © 2014 Elsevier Ltd. All rights reserved.

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

PubMed Central

Ma, Shu; Liu, Genxia; Jin, Lin; Pang, Xiyao; Wang, Yanqiu; Wang, Zilu; Yu, Yan; Yu, Jinhua

2016-01-01

Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed that hsa-let-7c low-expression can significantly promote the mineralization of IGF-1 treated SCAPs, while hsa-let-7c over-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, COL-I/COL-I, DSPP/DSP, and DMP-1/DMP-1) in IGF-1 treated SCAPs were significantly upregulated in Let-7c-low group. On the contrary, hsa-let-7c over-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated in Let-7c-low SCAPs but inhibited in Let-7c-over SCAPs. Together, the IGF-1/IGF-1R/hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways. PMID:27833148

[Can the local energy minimization refine the PDB structures of different resolution universally?].

PubMed

Godzi, M G; Gromova, A P; Oferkin, I V; Mironov, P V

2009-01-01

The local energy minimization was statistically validated as the refinement strategy for PDB structure pairs of different resolution. Thirteen pairs of structures with the only difference in resolution were extracted from PDB, and the structures of 11 identical proteins obtained by different X-ray diffraction techniques were represented. The distribution of RMSD value was calculated for these pairs before and after the local energy minimization of each structure. The MMFF94 field was used for energy calculations, and the quasi-Newton method was used for local energy minimization. By comparison of these two RMSD distributions, the local energy minimization was proved to statistically increase the structural differences in pairs so that it cannot be used for refinement purposes. To explore the prospects of complex refinement strategies based on energy minimization, randomized structures were obtained by moving the initial PDB structures as far as the minimized structures had been moved in a multidimensional space of atomic coordinates. For these randomized structures, the RMSD distribution was calculated and compared with that for minimized structures. The significant differences in their mean values proved the energy surface of the protein to have only few minima near the conformations of different resolution obtained by X-ray diffraction for PDB. Some other results obtained by exploring the energy surface near these conformations are also presented. These results are expected to be very useful for the development of new protein refinement strategies based on energy minimization.

Evaluation of a disease management program for COPD using propensity matched control group

PubMed Central

George, Pradeep Paul; Heng, Bee Hoon; Lim, Tow Keang; Abisheganaden, John; Ng, Alan Wei Keong; Lim, Fong Seng

2016-01-01

Background Disease management programs (DMPs) have proliferated recently as a means of improving the quality and efficiency of care for patients with chronic illness. These programs include education about disease, optimization of evidence-based medications, information and support from case managers, and institution of self-management principles. Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in Singapore and worldwide. DMP aims to reduce mortality, hospitalizations, and average length of stay in such patients. This study assesses the outcomes of the DMP, comparing the propensity score matched DMP patients with controls. Methods DMP patients were compared with the controls, who were COPD patients fulfilling the DMP’s inclusion criteria but not included in the program. Control patients were identified from Operations Data Store (ODS) database. The outcomes of interest were average length of stay, number of days admitted to hospital per 100 person days, readmission, and mortality rates per person year. The risk of death and readmission was estimated using Cox, and competing risk regression respectively. Propensity score was estimated to identify the predictors of DMP enrolment. DMP patients and controls were matched on their propensity score. Results There were 170 matched DMP patients and control patients having 287 and 207 hospitalizations respectively. Program patient had lower mortality than the controls (0.12 vs. 0.27 per person year); cumulative 1-year survival was 91% among program patient and 76% among the control patients. Readmission, and hospital days per 100 person-days was higher for the program patients (0.36 vs. 0.17 per person year), and (2.19 vs. 1.88 per person year) respectively. Conclusions Participation in “DMP” was associated with lower all-cause mortality when compared to the controls. This survival gain in the program patients was paradoxically associated with an increase in readmission rate and

Intracultural Differences in Local Botanical Knowledge and Knowledge Loss among the Mexican Isthmus Zapotecs.

PubMed

Saynes-Vásquez, Alfredo; Vibrans, Heike; Vergara-Silva, Francisco; Caballero, Javier

2016-01-01

This study reports on the socio-demographic and locality factors that influence ethnobiological knowledge in three communities of Zapotec indigenous people of the Isthmus of Tehuantepec, Mexico. It uses local botanical nomenclature as a proxy for general ethnobiological knowledge. In each of these communities (one urban and two rural), 100 adult men were interviewed aided with a field herbarium. Fifty had a background in farming, and 50 worked in the secondary or tertiary sector as their main economic activity, totaling 300 interviews. Using a field herbarium with samples of 30 common and rare wild regional species, we documented visual recognition, knowledge of the local life form, generic and specific names and uses (five knowledge levels measuring knowledge depth). The relationship between sociodemographic variables and knowledge was analyzed with simple correlations. Differences between the three communities and the five knowledge levels were then evaluated with a discriminant analysis. A general linear analysis identified factors and covariables that influenced the observed differences. Differences between the groups with different economic activities were estimated with a t-test for independent samples. Most of the relationships found between sociodemographic variables and plant knowledge were expected: age and rurality were positively related with knowledge and years of formal schooling was negatively related. However, the somewhat less rural site had more traditional knowledge due to local circumstances. The general linear model explained 70-77% of the variation, a high value. It showed that economic activity was by far the most important factor influencing knowledge, by a factor of five. The interaction of locality and economic activity followed. The discriminant analysis assigned interviewees correctly to their localities in 94% of the cases, strengthening the evidence for intracultural variation. Both sociodemographic and historic intracultural

Intracultural Differences in Local Botanical Knowledge and Knowledge Loss among the Mexican Isthmus Zapotecs

PubMed Central

Saynes-Vásquez, Alfredo; Vibrans, Heike; Vergara-Silva, Francisco; Caballero, Javier

2016-01-01

This study reports on the socio-demographic and locality factors that influence ethnobiological knowledge in three communities of Zapotec indigenous people of the Isthmus of Tehuantepec, Mexico. It uses local botanical nomenclature as a proxy for general ethnobiological knowledge. In each of these communities (one urban and two rural), 100 adult men were interviewed aided with a field herbarium. Fifty had a background in farming, and 50 worked in the secondary or tertiary sector as their main economic activity, totaling 300 interviews. Using a field herbarium with samples of 30 common and rare wild regional species, we documented visual recognition, knowledge of the local life form, generic and specific names and uses (five knowledge levels measuring knowledge depth). The relationship between sociodemographic variables and knowledge was analyzed with simple correlations. Differences between the three communities and the five knowledge levels were then evaluated with a discriminant analysis. A general linear analysis identified factors and covariables that influenced the observed differences. Differences between the groups with different economic activities were estimated with a t-test for independent samples. Most of the relationships found between sociodemographic variables and plant knowledge were expected: age and rurality were positively related with knowledge and years of formal schooling was negatively related. However, the somewhat less rural site had more traditional knowledge due to local circumstances. The general linear model explained 70–77% of the variation, a high value. It showed that economic activity was by far the most important factor influencing knowledge, by a factor of five. The interaction of locality and economic activity followed. The discriminant analysis assigned interviewees correctly to their localities in 94% of the cases, strengthening the evidence for intracultural variation. Both sociodemographic and historic intracultural

Production, purification and biochemical characterization of two laccase isoforms produced by Trametes versicolor grown on oak sawdust.

PubMed

Martínez-Morales, Fernando; Bertrand, Brandt; Pasión Nava, Angélica A; Tinoco, Raunel; Acosta-Urdapilleta, Lourdes; Trejo-Hernández, María R

2015-02-01

Two laccase isoforms (lcc1 and lcc2) produced by Trametes versicolor, grown on oak sawdust under solid-state fermentation conditions, were purified and characterized. The two isoforms showed significant biochemical differences. Lcc1 and lcc2 had MWs of 60 and 100 kDa, respectively. Both isoforms had maximal activity at pH 3 with ABTS and 2,6-dimethyloxyphenol (DMP). Lcc1 was the most attractive isoform due to its greater affinity towards all the laccase substrates used. Lcc1 had Km values of 12, 10, 15 and 17 mM towards ABTS, DMP, guaiacol and syringaldazine, respectively. Lcc2 had equivalent values of 45, 47, 15 and 39 mM. The biochemical properties of lcc1 substantiate the potential of this enzyme for application in the treatment of contaminated water with low pH values and high phenolic content.

48 CFR 26.202-1 - Local area set-aside.

Code of Federal Regulations, 2010 CFR

2010-10-01

... shall also determine whether a local area set-aside should be further restricted to small business... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Local area set-aside. 26... area set-aside. The contracting officer may set aside solicitations to allow only local firms within a...

Effectiveness of a Peer Support Programme versus Usual Care in Disease Management of Diabetes Mellitus Type 2 regarding Improvement of Metabolic Control: A Cluster-Randomised Controlled Trial.

PubMed

Johansson, Tim; Keller, Sophie; Winkler, Henrike; Ostermann, Thomas; Weitgasser, Raimund; Sönnichsen, Andreas C

2016-01-01

Testing the effectiveness of peer support additionally to a disease management programme (DMP) for type 2 diabetes patients. Unblinded cluster-randomised controlled trial (RCT) involving 49 general practices, province of Salzburg, Austria. All patients enrolled in the DMP were eligible, n = 337 participated (intervention: 148 in 19 clusters; control: 189 in 20 clusters). The peer support intervention ran over 24 months and consisted of peer supporter recruitment and training, and group meetings weekly for physical exercise and monthly for discussion of diabetes related topics. At two-year follow-up, adjusted analysis revealed a nonsignificant difference in HbA1c change of 0.14% (21.97 mmol/mol) in favour of the intervention (95% CI -0.08 to 0.36%, p = 0.22). Baseline values were 7.02 ± 1.25% in the intervention and 7.08 ± 1.25 in the control group. None of the secondary outcome measures showed significant differences except for improved quality of life (EQ-5D-VAS) in controls (4.3 points on a scale of 100; 95% CI 0.08 to 8.53, p = 0.046) compared to the intervention group. Our peer support intervention as an additional DMP component showed no significant effect on HbA1c and secondary outcome measures. Further RTCs with a longer follow-up are needed to reveal whether peer support will have clinically relevant effects. This trial has been registered with Current Controlled Trials Ltd. (ISRCTN10291077).

Alimentary tract absorption (f1 values) for radionuclides in local and regional fallout from nuclear tests.

PubMed

Ibrahim, Shawki A; Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L

2010-08-01

This paper presents gastrointestinal absorption fractions (f1 values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f1 values are based on specific circumstances of weapons test conditions and a review of reported f1 values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f1 values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f1 values for different circumstances where persons are exposed to radioactive fallout (e.g., local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f1 values are similar to those adopted by the International Commission on Radiological Protection (ICRP) (e.g., iodine and most actinides). However, f1 values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f1 values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively). The f1 values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout.

Alimentary Tract Absorption (f1 Values) for Radionuclides in Local and Regional Fallout from Nuclear Tests

PubMed Central

Ibrahim, Shawki; Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold

2009-01-01

This paper presents gastrointestinal absorption fractions (f1 values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f1 values are based on specific circumstances of weapons test conditions and a review of reported f1 values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f1 values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f1 values for different circumstances where persons are exposed to radioactive fallout (e.g. local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f1 values are similar to those adopted by the ICRP (e.g. iodine and most actinides). However, f1 values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f1 values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively. The f1 values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout. PMID:20622554

Macromolecules of extracellular matrix: determination of selective structures and their functional significance.

PubMed

Butler, William T

2008-01-01

In this brief review, I recount events and scientific endeavors in which I have been privileged to participate. The descriptive information includes discovery and characterization of hydroxylysine glycosides from collagen, isolation of dentin sialoprotein (DSP), investigations on dentin phosphoprotein (DPP), and the discovery of a single gene for both DSP and DPP that requires posttranslational proteolytic cleavage of the parent DSPP molecule to generate the two fragments. Finally, I address our unexpected finding of fragments of DMP1 in bone extracts. These fragments are from the NH2-terminal (37 kDa) and COOH-terminal (57 kDa) regions of DMP1. Our studies showed that, similar to DSPP, DMP1 is proteolytically processed by cleavages at X-Asp bonds.

Health promoting schools and children’s oral health related quality of life

PubMed Central

2013-01-01

Background The study objective was to compare children’s oral health related quality of life (OHRQoL) in schools with 6 years of implementation of a health promoting school model in Malaysia, i.e. the Doktor Muda Programme (DMP) and in schools without the DMP. Methods This report was part of a larger study to evaluate the DMP impact on schoolchildren’s oral health knowledge, attitudes, behaviour, caries progression and OHRQoL. It was conducted in Negri Sembilan state. The sample comprised 3455, Year 6 (11–12 year old) children; 1282 from DMP (intervention) and 2173 from non-DMP (control) schools. The Malay Child-OIDP index was used to evaluate children’s levels of oral impacts on 8 daily performances after 6 years of DMP implementation (2006–2011). Prevalence, score, impact intensity, causes and extent of impacts were compared. Chi-square and Mann–Whitney tests were used in the data analysis. Results Overall response rate was 95.1%. Prevalence of overall impacts was 57.8% and 60.8% (mean total impact score was 7.10 and 7.77) in the intervention and control group, respectively. The three most frequently affected performances in both groups were eating, cleaning teeth and emotional stability. Significantly less DMP children had oral impact on cleaning teeth (p = 0.034). The majority of children with impacts in both groups reported ‘very little’ to ‘moderate’ levels of impact intensity. Significantly more DMP children reported having ‘very little’ and ‘little’ levels of impact intensity on cleaning teeth (p = 0.037) and emotional stability (p = 0.020), respectively. Significantly less DMP children reported having ‘very severe’ level of impact intensity on speaking (p = 0.038). The most prevalent cause of impacts in both groups was toothache. Significantly less DMP children reported bleeding gums (p = 0.016) and presence of plaque/calculus as causes of impacts (p = 0.032). About 75% of children with impacts in both groups reported having

Pin1At regulates PIN1 polar localization and root gravitropism

PubMed Central

Xi, Wanyan; Gong, Ximing; Yang, Qiaoyun; Yu, Hao; Liou, Yih-Cherng

2016-01-01

Root gravitropism allows plants to establish root systems and its regulation depends on polar auxin transport mediated by PIN-FORMED (PIN) auxin transporters. PINOID (PID) and PROTEIN PHOSPHATASE 2A (PP2A) act antagonistically on reversible phosphorylation of PINs. This regulates polar PIN distribution and auxin transport. Here we show that a peptidyl-prolyl cis/trans isomerase Pin1At regulates root gravitropism. Downregulation of Pin1At suppresses root agravitropic phenotypes of pp2aa and 35S:PID, while overexpression of Pin1At affects root gravitropic responses and enhances the pp2aa agravitropic phenotype. Pin1At also affects auxin transport and polar localization of PIN1 in stele cells, which is mediated by PID and PP2A. Furthermore, Pin1At catalyses the conformational change of the phosphorylated Ser/Thr-Pro motifs of PIN1. Thus, Pin1At mediates the conformational dynamics of PIN1 and affects PID- and PP2A-mediated regulation of PIN1 polar localization, which correlates with the regulation of root gravitropism. PMID:26791759

Pin1At regulates PIN1 polar localization and root gravitropism.

PubMed

Xi, Wanyan; Gong, Ximing; Yang, Qiaoyun; Yu, Hao; Liou, Yih-Cherng

2016-01-21

Root gravitropism allows plants to establish root systems and its regulation depends on polar auxin transport mediated by PIN-FORMED (PIN) auxin transporters. PINOID (PID) and PROTEIN PHOSPHATASE 2A (PP2A) act antagonistically on reversible phosphorylation of PINs. This regulates polar PIN distribution and auxin transport. Here we show that a peptidyl-prolyl cis/trans isomerase Pin1At regulates root gravitropism. Downregulation of Pin1At suppresses root agravitropic phenotypes of pp2aa and 35S:PID, while overexpression of Pin1At affects root gravitropic responses and enhances the pp2aa agravitropic phenotype. Pin1At also affects auxin transport and polar localization of PIN1 in stele cells, which is mediated by PID and PP2A. Furthermore, Pin1At catalyses the conformational change of the phosphorylated Ser/Thr-Pro motifs of PIN1. Thus, Pin1At mediates the conformational dynamics of PIN1 and affects PID- and PP2A-mediated regulation of PIN1 polar localization, which correlates with the regulation of root gravitropism.

Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections.

PubMed

Chalmet, Kristen; Staelens, Delfien; Blot, Stijn; Dinakis, Sylvie; Pelgrom, Jolanda; Plum, Jean; Vogelaers, Dirk; Vandekerckhove, Linos; Verhofstede, Chris

2010-09-07

The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission. Baseline HIV-1 pol sequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients' demographics, laboratory and clinical data, were retrieved anonymously. Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics. Multivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection with Chlamydia (p = 0.01) and infection with Hepatitis C virus (p = 0.017). More and larger transmission-clusters were identified among the subtype B infections (p < 0.001). Overall, in multivariate analysis, clustering was significantly associated with Caucasian origin, infection through homosexual contact and younger age (all p < 0.001). Bivariate analysis additionally showed a correlation between clustering and syphilis (p < 0.001), higher CD4 counts (p = 0.002), Chlamydia infection (p = 0.013) and primary HIV (p = 0.017). Combination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions. This finding elucidates observed epidemiological trends through molecular analysis, and

Decision Gate Process for Assessment of a NASA Technology Development Portfolio

NASA Technical Reports Server (NTRS)

Kohli, Rajiv; Fishman, Julianna L.; Hyatt, Mark J.

2012-01-01

The NASA Dust Management Project (DMP) was established to provide technologies (to Technology Readiness Level (TRL) 6) required to address adverse effects of lunar dust to humans and to exploration systems and equipment, to reduce life cycle cost and risk, and to increase the probability of sustainable and successful lunar missions. The technology portfolio of DMP consisted of different categories of technologies whose final product was either a technology solution in itself, or one that contributes toward a dust mitigation strategy for a particular application. A Decision Gate Process (DGP) was developed to assess and validate the achievement and priority of the dust mitigation technologies as the technologies progress through the development cycle. The DGP was part of continuous technology assessment and was a critical element of DMP risk management. At the core of the process were technology-specific criteria developed to measure the success of each DMP technology in attaining the technology readiness levels assigned to each decision gate. The DGP accounts for both categories of technologies and qualifies the technology progression from technology development tasks to application areas. The process provided opportunities to validate performance, as well as to identify non-performance in time to adjust resources and direction. This paper describes the overall philosophy of the DGP and the methodology for implementation for DMP, and describes the method for defining the technology evaluation criteria. The process is illustrated by example of an application to a specific DMP technology.

Decision Gate Process for Assessment of a Technology Development Portfolio

NASA Technical Reports Server (NTRS)

Kohli, Rajiv; Fishman, Julianna; Hyatt, Mark

2012-01-01

The NASA Dust Management Project (DMP) was established to provide technologies (to TRL 6 development level) required to address adverse effects of lunar dust to humans and to exploration systems and equipment, which will reduce life cycle cost and risk, and will increase the probability of sustainable and successful lunar missions. The technology portfolio of DMP consisted of different categories of technologies whose final product is either a technology solution in itself, or one that contributes toward a dust mitigation strategy for a particular application. A Decision Gate Process (DGP) was developed to assess and validate the achievement and priority of the dust mitigation technologies as the technologies progress through the development cycle. The DGP was part of continuous technology assessment and was a critical element of DMP risk management. At the core of the process were technology-specific criteria developed to measure the success of each DMP technology in attaining the technology readiness levels assigned to each decision gate. The DGP accounts for both categories of technologies and qualifies the technology progression from technology development tasks to application areas. The process provided opportunities to validate performance, as well as to identify non-performance in time to adjust resources and direction. This paper describes the overall philosophy of the DGP and the methodology for implementation for DMP, and describes the method for defining the technology evaluation criteria. The process is illustrated by example of an application to a specific DMP technology.

Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK

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

Dahl, A.R.; Muggenburg, B.A.; Thornton-Manning, J.R.

1996-12-31

A diffusion model predicts that highly lipophilic toxicants penetrate the comparatively thick epithelium of the conducting airways much more slowly than less lipophilic toxicants. To validate this model, the tracheal walls of a Beagle dog were sprayed with very small quantities of tritiated, highly lipophilic benzo(a)pyrene (BaP), moderately lipophilic pyrene, or slightly lipophilic 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone-(NNK). The concentration of the hydrocarbons and their metabolites were measured in the circulating blood for up to 6 hr, and tissue retention was determined at the end of the experiment. Differences in absorption of these compounds into blood were manifested in several independent measurements. Themore » highly lipophilic toxicant manifested: (1) a much slower penetration into azygous vein blood, the principal drainage system from the exposed area of the trachea; (2) a much slower appearance in the systemic circulation and (3) a much greater retention in the tracheal tissues at the end of the exposure. Increased retention mm in the airway mucosa allowed a grew fraction of lipophilic toxicants to be metabolized locally in the airway walls. This finding led us to conclude that, for example, if the carcinogens BaP and NNK are deposited at the same surface density on the airway mucosa, the highly lipophilic BaP will reach a far higher concentration in the airway epithelium than will the less lipophilic NNK. Such sharp differences in local dosimetry should be considered in order to improve the accuracy of risk assessment models for inhalants.« less

Development of Lithium Dimethyl Phosphate as an Electrolyte Additive for Lithium Ion Batteries

DOE PAGES

Milien, Mickdy S.; Tottempudi, Usha; Son, Miyoung; ...

2016-04-27

The novel electrolyte additive lithium dimethyl phosphate (LiDMP) has been synthesized and characterized. Incorporation of LiDMP (0.1% wt) into LiPF 6 in ethylene carbonate (EC) / ethyl methyl carbonate (EMC) (3:7 wt) results in improved rate performance and reduced impedance for graphite / LiNi 1/3Mn 1/3Co 1/3O 2 cells. Ex-situ surface analysis of the electrodes suggests that incorporation of LiDMP results in a modification of the solid electrolyte interphase (SEI) on the anode. A decrease in the concentration of lithium alkyl carbonates and an increase in the concentration of lithium fluoro phosphates are observed. The change in the anode SEImore » structure is responsible for the increased rate performance and decreased cell impedance.« less

TFE-induced local unfolding and fibrillation of SOD1: bridging the experiment and simulation studies.

PubMed

Kumar, Vijay; Prakash, Amresh; Pandey, Preeti; Lynn, Andrew M; Hassan, Md Imtaiyaz

2018-05-18

Misfolding and aggregation of Cu, Zn Superoxide dismutase (SOD1) is involved in the neurodegenerative disease, amyotrophic lateral sclerosis. Many studies have shown that metal-depleted, monomeric form of SOD1 displays substantial local unfolding dynamics and is the precursor for aggregation. Here, we have studied the structure and dynamics of different apo monomeric SOD1 variants associated with unfolding and aggregation in aqueous trifluoroethanol (TFE) through experiments and simulation. TFE induces partially unfolded β-sheet-rich extended conformations in these SOD1 variants, which subsequently develops aggregates with fibril-like characteristics. Fibrillation was achieved more easily in disulfide-reduced monomeric SOD1 when compared with wild-type and mutant monomeric SOD1. At higher concentrations of TFE, a native-like structure with the increase in α-helical content was observed. The molecular dynamics simulation results illustrate distinct structural dynamics for different regions of SOD1 variants and show uniform local unfolding of β-strands. The strands protected by the zinc-binding and electrostatic loops were found to unfold first in 20% (v/v) TFE, leading to a partial unfolding of β-strands 4, 5, and 6 which are prone to aggregation. Our results thus shed light on the role of local unfolding and conformational dynamics in SOD1 misfolding and aggregation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

HIV-1 nucleocapsid protein localizes efficiently to the nucleus and nucleolus

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

Yu, Kyung Lee; Lee, Sun Hee; Lee, Eun Soo

The HIV-1 nucleocapsid (NC) is an essential viral protein containing two highly conserved retroviral-type zinc finger (ZF) motifs, which functions in multiple stages of the HIV-1 life cycle. Although a number of functions for NC either in its mature form or as a domain of Gag have been revealed, little is known about the intracellular localization of NC and, moreover, its role in Gag protein trafficking. Here, we have investigated various forms of HIV-1 NC protein for its cellular localization and found that the NC has a strong nuclear and nucleolar localization activity. The linker region, composed of a stretchmore » of basic amino acids between the two ZF motifs, was necessary and sufficient for the activity. - Highlights: • HIV-1 NC possess a NLS and leads to nuclear and nucleolus localization. • Mutations in basic residues between two ZFs in NC decrease the nucleus localization. • ZFs of NC affect cytoplasmic organelles localization rather than nucleus localization.« less

Can we reduce preventable heart failure readmissions in patients enrolled in a Disease Management Programme?

PubMed

Phelan, D; Smyth, L; Ryder, M; Murphy, N; O'Loughlin, C; Conlon, C; Ledwidge, M; McDonald, K

2009-06-01

Disease Management Programmes (DMPs) are successful in reducing hospital readmissions in heart failure (HF). However, there remain a number of patients enrolled in a DMP who are readmitted with HF. The primary aim of the study was to determine the proportion of preventable readmissions (PR). The secondary aim was to recognise patient characteristics which would identify certain patients at risk of having a PR. A retrospective chart search was performed on patients readmitted over a 1-year period. 38.5% of readmissions were classified as PR. None of these patients made prior contact with the DMP. Admission levels of BNP, potassium, urea and creatinine were significantly lower in the PR group. DMP have proven benefits in reducing hospital readmission nonetheless a significant proportion of these readmissions are preventable. Further work is required to prospectively analyse why these patients fail to contact the DMP.

Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity.

PubMed

Vinciguerra, Manlio; Santini, Maria Paola; Claycomb, William C; Ladurner, Andreas G; Rosenthal, Nadia

2009-12-10

Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD(+)-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic.

Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity

PubMed Central

Vinciguerra, Manlio; Santini, Maria Paola; Claycomb, William C.; Ladurner, Andreas G.; Rosenthal, Nadia

2010-01-01

Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD+-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic. PMID:20228935

Localization behavior at bound Bi complex states in GaA s 1 - x B i x

DOE PAGES

Alberi, K.; Christian, T. M.; Fluegel, B.; ...

2017-07-01

While bismuth-related states are known to localize carriers in GaAs 1-xBi x alloys, the localization behavior of distinct Bi pair, triplet and cluster states bound above the valence band is less well understood. We probe localization at three different Bi complex states in dilute GaAs 1-xBi x alloys using magneto-photoluminescence and time-resolved photoluminescence spectroscopy. The mass of electrons Coulomb-bound to holes trapped at Bi pair states is found to increase relative to the average electron mass in the alloy. This increase is attributed to enhanced local compressive strain in the immediate vicinity of the pairs. The dependence of energy transfermore » between these states on composition is also explored.« less

Content based Image Retrieval based on Different Global and Local Color Histogram Methods: A Survey

NASA Astrophysics Data System (ADS)

Suhasini, Pallikonda Sarah; Sri Rama Krishna, K.; Murali Krishna, I. V.

2017-02-01

Different global and local color histogram methods for content based image retrieval (CBIR) are investigated in this paper. Color histogram is a widely used descriptor for CBIR. Conventional method of extracting color histogram is global, which misses the spatial content, is less invariant to deformation and viewpoint changes, and results in a very large three dimensional histogram corresponding to the color space used. To address the above deficiencies, different global and local histogram methods are proposed in recent research. Different ways of extracting local histograms to have spatial correspondence, invariant colour histogram to add deformation and viewpoint invariance and fuzzy linking method to reduce the size of the histogram are found in recent papers. The color space and the distance metric used are vital in obtaining color histogram. In this paper the performance of CBIR based on different global and local color histograms in three different color spaces, namely, RGB, HSV, L*a*b* and also with three distance measures Euclidean, Quadratic and Histogram intersection are surveyed, to choose appropriate method for future research.

[Introduction of disease management programmes in Germany as reflected by differing interests of health insurance companies and the federal association of statutory health insurance physicians].

PubMed

Erler, A

2002-11-01

On 1st January 2002 a law was enacted by the German Federal Government reorganising the reinsurance pool known as the "risk compensation scheme" (RSA) of the German health insurance system. This enactment contemplates a gradual restructuring of the RSA to shift from a system that considered only certain demographic criteria to one that reflects actual morbidity rates, with the shift to be phased in before full implementation by 2007. The enactment also introduced disease management programmes (DMP) for patients with certain chronic illnesses. Insurance companies will now receive additional payments from the RSA for patients with a chronic condition who are enrolled in a DMP. The intent is to improve the poor medical care for chronically ill patients in Germany - as had been stated by the advisory council of the Concerted Action in Health Care - and to reduce the natural tendency of insurance companies to prefer young healthy members over chronically ill patients. Possible consequences of the legal changes are discussed from the point of view of the various insurance companies as well as the Federal Association of Statutory Health Insurance Physicians.

ILS Localizer Performance Prediction of an Alford 1B Array Near a Limited Access Road at the New Orleans Airport.

DOT National Transportation Integrated Search

1974-08-01

The Transportation Systems Center (TSC) ILS Localizer Performance Prediction Model was used to predict the derogation to an Alford 1B Localizer caused by vehicular traffic traveling on a roadway to be located in front of the localizer. Several differ...

Detection of phenols using engineered bacteria

DOEpatents

Wise, Arlene A.; Kuske, Cheryl R.; Terwilliger, Thomas C.

2007-12-04

Detection of phenols using engineered bacteria. A biosensor can be created by placing a reporter gene under control of an inducible promoter. The reporter gene produces a signal when a cognate transcriptional activator senses the inducing chemical. Creation of bacterial biosensors is currently restricted by limited knowledge of the genetic systems of bacteria that catabolize xenobiotics. By using mutagenic PCR to change the chemical specificity of the Pseudomonas species CF600 DmpR protein, the potential for engineering novel biosensors for detection of phenols has been demonstrated. DmpR, a well-characterized transcriptional activator of the P. CF600's dmp operon mediates growth on simple phenols. Transcription from Po, the promoter heading the dmp operon, is activated when the sensor domain of DmpR interacts with phenol and mono-substituted phenols. By altering the sensor domain of the DmpR, a group of DmpR derivatives that activate transcription of a Po-lacZ fusion in response to eight of the EPA's eleven priority pollutant phenols has been created. The assays and the sensor domain mutations that alter the chemical specificity of DmpR is described.

Detection of phenols using engineered bacteria

DOEpatents

Wise, Arlene A.; Kuske, Cheryl R.; Terwilliger, Thomas C.

2004-08-10

Detection of phenols using engineered bacteria. A biosensor can be created by placing a reporter gene under control of an inducible promoter. The reporter gene produces a signal when a cognate transcriptional activator senses the inducing chemical. Creation of bacterial biosensors is currently restricted by limited knowledge of the genetic systems of bacteria that catabolize xenobiotics. By using mutagenic PCR to change the chemical specificity of the Pseudomonas species CF600 DmpR protein, the potential for engineering novel biosensors for detection of phenols has been demonstrated. DmpR, a well-characterized transcriptional activator of the P. CF600's dmp operon mediates growth on simple phenols. Transcription from Po, the promoter heading the dmp operon, is activated when the sensor domain of DmpR interacts with phenol and mono-substituted phenols. By altering the sensor domain of the DmpR, a group of DmpR derivatives that activate transcription of a Po-lacZ fusion in response to eight of the EPA's eleven priority pollutant phenols has been created. The assays and the sensor domain mutations that alter the chemical specificity of DmpR is described.

Adaptation in sound localization processing induced by interaural time difference in amplitude envelope at high frequencies.

PubMed

Kawashima, Takayuki; Sato, Takao

2012-01-01

When a second sound follows a long first sound, its location appears to be perceived away from the first one (the localization/lateralization aftereffect). This aftereffect has often been considered to reflect an efficient neural coding of sound locations in the auditory system. To understand determinants of the localization aftereffect, the current study examined whether it is induced by an interaural temporal difference (ITD) in the amplitude envelope of high frequency transposed tones (over 2 kHz), which is known to function as a sound localization cue. In Experiment 1, participants were required to adjust the position of a pointer to the perceived location of test stimuli before and after adaptation. Test and adapter stimuli were amplitude modulated (AM) sounds presented at high frequencies and their positional differences were manipulated solely by the envelope ITD. Results showed that the adapter's ITD systematically affected the perceived position of test sounds to the directions expected from the localization/lateralization aftereffect when the adapter was presented at ±600 µs ITD; a corresponding significant effect was not observed for a 0 µs ITD adapter. In Experiment 2, the observed adapter effect was confirmed using a forced-choice task. It was also found that adaptation to the AM sounds at high frequencies did not significantly change the perceived position of pure-tone test stimuli in the low frequency region (128 and 256 Hz). The findings in the current study indicate that ITD in the envelope at high frequencies induces the localization aftereffect. This suggests that ITD in the high frequency region is involved in adaptive plasticity of auditory localization processing.

Research on the degradation mechanism of dimethyl phthalate in drinking water by strong ionization discharge

NASA Astrophysics Data System (ADS)

Hong, ZHAO; Chengwu, YI; Rongjie, YI; Huijuan, WANG; Lanlan, YIN; I, N. MUHAMMAD; Zhongfei, MA

2018-03-01

The degradation mechanism of dimethyl phthalate (DMP) in the drinking water was investigated using strong ionization discharge technology in this study. Under the optimized condition, the degradation efficiency of DMP in drinking water was up to 93% in 60 min. A series of analytical techniques including high-performance liquid chromatography, liquid chromatography mass spectrometry, total organic carbon analyzer and ultraviolet-visible spectroscopy were used in the study. It was found that a high concentration of ozone (O3) produced by dielectric barrier discharge reactor was up to 74.4 mg l-1 within 60 min. Tert-butanol, isopropyl alcohol, carbonate ions ({{{{CO}}}3}2-) and bicarbonate ions ({{{{HCO}}}3}-) was added to the sample solution to indirectly prove the presence and effect of hydroxyl radicals (·OH). These analytical findings indicate that mono-methyl phthalate, phthalic acid (PA) and methyl ester PA were detected as the major intermediates in the process of DMP degradation. Finally, DMP and all products were mineralized into carbon dioxide (CO2) and water (H2O) ultimately. Based on these analysis results, the degradation pathway of DMP by strong ionization discharge technology were proposed.

Epididymal protein CRISP1 plays different roles during the fertilization process.

PubMed

Cohen, Débora J; Maldera, Julieta A; Vasen, Gustavo; Ernesto, Juan I; Muñoz, Mariana Weigel; Battistone, María A; Cuasnicú, Patricia S

2011-01-01

Rat epididymal CRISP1, the first described member of the evolutionarily conserved Cysteine-RIch Secretory Protein (CRISP) family, is expressed in the proximal regions of the epididymis and associates with the sperm during epididymal transit. Evidence indicates the existence of 2 populations of CRISP1 in spermatozoa: a major one, loosely bound, which is released during capacitation and, therefore, proposed as a decapacitating factor; and a minor one, strongly associated with spermatozoa that remains on the cells after capacitation and is proposed to participate in gamete interaction. Originally localized to the dorsal region of capacitated sperm, CRISP1 migrates to the equatorial segment with capacitation and acrosome reaction. Consistent with these localizations, in vitro fertilization experiments support the involvement of CRISP1 in the first step of sperm-zona pellucida (ZP) interaction and subsequent gamete fusion through its interaction with egg-complementary sites. The potential roles of CRISP1 in capacitation and fertilization have been further supported by the finding that capacitated spermatozoa from CRISP1 "knockout" animals exhibit low levels of protein tyrosine phosphorylation and have an impaired ability to fertilize zona-intact and zona-free eggs in vitro. Moreover, recent evidence from mutant spermatozoa reveals that CRISP1 mediates the stage of sperm binding to the ZP. Altogether, these observations support the view that CRISP1 is a multifunctional protein playing different roles during fertilization through its different associations with and localizations on spermatozoa. We believe these results contribute to a better understanding of the molecular mechanisms involved in both the fertilization process and the acquisition of sperm-fertilizing ability that occurs during epididymal maturation.

Phase coherence of 0.1 Hz microvascular tone oscillations during the local heating

NASA Astrophysics Data System (ADS)

Mizeva, I. A.

2017-06-01

The origin of the mechanisms of blood flow oscillations at low frequencies is discussed. It is known that even isolated arteriole demonstrates oscillations with the frequency close to 0.1 Hz, which is caused by the synchronous activity of myocyte cells. On the other hand, oscillations with close frequency are found in the heart rate, which are associated with quite different mechanism. The main purpose of this work is to study phase coherence of the blood flow oscillations in the peripheral vessels under basal and perturbed conditions. Local heating which locally influences the microvascular tone, as one of currently elucidated in sufficient detail physiological test, was chosen. During such provocation blood flow though the small vessels significantly increases because of vasodilation induced by the local synthesis of nitric oxide. In the first part of the paper microvascular response to the local test is quantified in healthy and pathological conditions of diabetes mellitus type 1. It is obtained that regardless of the pathology, subjects with high basal perfusion had lower reserve for vasodilation, which can be caused by the low elasticity of microvascular structure. Further synchronization of pulsations of the heated and undisturbed skin was evaluated on the base of wavelet phase coherency analysis. Being highly synchronised in basal conditions 0.1 Hz pulsations became more independent during heating, especially during NO-mediated vasodilation.

Sustained Attention to Local and Global Target Features Is Different: Performance and Tympanic Membrane Temperature

ERIC Educational Resources Information Center

Helton, William S.; Hayrynen, Lauren; Schaeffer, David

2009-01-01

Vision researchers have investigated the differences between global and local feature perception. No one has, however, examined the role of global and local feature discrimination in sustained attention tasks. In this experiment participants performed a sustained attention task requiring either global or local letter target discriminations or…

TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans

PubMed Central

McCallum, Katie C.; Liu, Bin; Fierro-González, Juan Carlos; Swoboda, Peter; Arur, Swathi; Miranda-Vizuete, Antonio; Garsin, Danielle A.

2016-01-01

The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. PMID:26920757

TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.

PubMed

McCallum, Katie C; Liu, Bin; Fierro-González, Juan Carlos; Swoboda, Peter; Arur, Swathi; Miranda-Vizuete, Antonio; Garsin, Danielle A

2016-05-01

The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Copyright © 2016 by the Genetics Society of America.

Titanium surface bio-functionalization using osteogenic peptides: Surface chemistry, biocompatibility, corrosion and tribocorrosion aspects.

PubMed

Trino, Luciana D; Bronze-Uhle, Erika S; Ramachandran, Amsaveni; Lisboa-Filho, Paulo N; Mathew, Mathew T; George, Anne

2018-05-01

Titanium (Ti) is widely used in biomedical devices due to its recognized biocompatibility. However, implant failures and subsequent clinical side effects are still recurrent. In this context, improvements can be achieved by designing biomaterials where the bulk and the surface of Ti are independently tailored. The conjugation of biomolecules onto the Ti surface can improve its bioactivity, thus accelerating the osteointegration process. Ti was modified with TiO 2 , two different spacers, 3-(4-aminophenyl) propionic acid (APPA) or 3-mercaptopropionic acid (MPA) and dentin matrix protein 1 (DMP1) peptides. X-ray photoelectron spectroscopy analysis revealed the presence of carbon and nitrogen for all samples, indicating a success in the functionalization process. Furthermore, DMP1 peptides showed an improved coverage area for the samples with APPA and MPA spacers. Biological tests indicated that the peptides could modulate cell affinity, proliferation, and differentiation. Enhanced results were observed in the presence of MPA. Moreover, the immobilization of DMP1 peptides through the spacers led to the formation of calcium phosphate minerals with a Ca/P ratio near to that of hydroxyapatite. Corrosion and tribocorrosion results indicated an increased resistance to corrosion and lower mass loss in the functionalized materials, showing that this new type of functional material has attractive properties for biomaterials application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Localization of SERBP1 in stress granules and nucleoli.

PubMed

Lee, Yu-Jen; Wei, Hung-Ming; Chen, Ling-Yun; Li, Chuan

2014-01-01

SERPINE1 mRNA-binding protein 1 (SERBP1) is an arginine-methylated RNA-binding protein whose modification affects protein interaction and intracellular localization. In the present study, we show that, under normal growth conditions without stress, SERBP1 interacts with arginine-methylated and stress granule-associated proteins such as heterogeneous nuclear ribonucleoprotein A1, fragile X mental retardation protein and fragile X mental retardation syndrome-related protein 1 in an RNA-dependent manner. We also show that, after arsenite treatment, a proportion of full-length SERBP1 protein co-localizes with the typical stress granule marker T-cell intracellular antigen-1 in the cytoplasmic stress granules. Truncated SERBP1 with an N-terminal, central RG or C-terminal deletion, or single-domain segments comprising the N-terminal, central or C-terminal region, were recruited to stress granules upon arsenite treatment but with reduced efficiency. In addition, upon arsenite treatment, the localization of SERBP1 changed from a diffuse cytoplasmic localization to nuclear-dominant (concentrated in the nucleolus) A similar distribution was observed when cells were treated with the methylation inhibitor adenosine periodate, and was also detected for N- or C-terminal domain deletions and all three single-domain fragments even without stress induction. We further demonstrate that adenosine periodate treatment delays the association/dissociation of SERBP1 with stress granules. Hypomethylation retains SERBP1 in the nucleus/nucleolus regardless of arsenite treatment. Our study indicates that arginine methylation is correlated with recruitment of SERBP to stress granules and nucleoli and its retention therein. To our knowledge, this is the first report of an RNA-binding protein that is shifted simultaneously to cytoplasmic stress granules and nucleoli, two ribonucleoprotein-enriched subcellular compartments, upon stress. © 2013 FEBS.

Membrane permeable local anesthetics modulate NaV1.5 mechanosensitivity

PubMed Central

Beyder, Arthur; Strege, Peter R.; Bernard, Cheryl; Farrugia, Gianrico

2012-01-01

Voltage-gated sodium selective ion channel NaV1.5 is expressed in the heart and the gastrointestinal tract, which are mechanically active organs. NaV1.5 is mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local anesthetic and antiarrhythmic drugs act upon NaV1.5 to modulate activity by multiple mechanisms. This study examined whether NaV1.5 mechanosensitivity is modulated by local anesthetics. NaV1.5 channels wereexpressed in HEK-293 cells, and mechanosensitivity was tested in cell-attached and excised inside-out configurations. Using a novel protocol with paired voltage ladders and short pressure pulses, negative patch pressure (-30 mmHg) in both configurations produced a hyperpolarizing shift in the half-point of the voltage-dependence of activation (V1/2a) and inactivation (V1/2i) by about -10 mV. Lidocaine (50 µM) inhibited the pressure-induced shift of V1/2a but not V1/2i. Lidocaine inhibited the tonic increase in pressure-induced peak current in a use-dependence protocol, but it did not otherwise affect use-dependent block. The local anesthetic benzocaine, which does not show use-dependent block, also effectively blocked a pressure-induced shift in V1/2a. Lidocaine inhibited mechanosensitivity in NaV1.5 at the local anesthetic binding site mutated (F1760A). However, a membrane impermeable lidocaine analog QX-314 did not affect mechanosensitivity of F1760A NaV1.5 when applied from either side of the membrane. These data suggest that the mechanism of lidocaine inhibition of the pressure-induced shift in the half-point of voltage-dependence of activation is separate from the mechanisms of use-dependent block. Modulation of NaV1.5 mechanosensitivity by the membrane permeable local anesthetics may require hydrophobic access and may involve membrane-protein interactions. PMID:22874086

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues

PubMed Central

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M.; Zhou, Xinchun

2014-01-01

Aims Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. Methods We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data were then compared in benign and malignant tissues from the same organ/tissue using the student t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. Results We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (either in nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas

Racial differences in clinically localized prostate cancers of black and white men.

PubMed

deVere White, R W; Deitch, A D; Jackson, A G; Gandour-Edwards, R; Marshalleck, J; Soares, S E; Toscano, S N; Lunetta, J M; Stewart, S L

1998-06-01

Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.

Local and Global Spatial Organization of Interaural Level Difference and Frequency Preferences in Auditory Cortex

PubMed Central

Panniello, Mariangela; King, Andrew J; Dahmen, Johannes C; Walker, Kerry M M

2018-01-01

Abstract Despite decades of microelectrode recordings, fundamental questions remain about how auditory cortex represents sound-source location. Here, we used in vivo 2-photon calcium imaging to measure the sensitivity of layer II/III neurons in mouse primary auditory cortex (A1) to interaural level differences (ILDs), the principal spatial cue in this species. Although most ILD-sensitive neurons preferred ILDs favoring the contralateral ear, neurons with either midline or ipsilateral preferences were also present. An opponent-channel decoder accurately classified ILDs using the difference in responses between populations of neurons that preferred contralateral-ear-greater and ipsilateral-ear-greater stimuli. We also examined the spatial organization of binaural tuning properties across the imaged neurons with unprecedented resolution. Neurons driven exclusively by contralateral ear stimuli or by binaural stimulation occasionally formed local clusters, but their binaural categories and ILD preferences were not spatially organized on a more global scale. In contrast, the sound frequency preferences of most neurons within local cortical regions fell within a restricted frequency range, and a tonotopic gradient was observed across the cortical surface of individual mice. These results indicate that the representation of ILDs in mouse A1 is comparable to that of most other mammalian species, and appears to lack systematic or consistent spatial order. PMID:29136122

First microwave map of the Moon with Chang'E-1 data: The role of local time in global imaging

NASA Astrophysics Data System (ADS)

Zheng, Y. C.; Tsang, K. T.; Chan, K. L.; Zou, Y. L.; Zhang, F.; Ouyang, Z. Y.

2012-05-01

Among recent lunar orbiters, only the Chinese Chang'E-1 (CE-1) was equipped with a passive microwave radiometer (MRM) to measure the natural microwave emission from the lunar surface. The microwave emission, characterized by a frequency-dependent brightness temperature (TB), is related to the physical temperature and dielectric properties of the lunar surface. By measuring the brightness temperature at different frequencies, detailed thermal behavior and properties of the lunar surface can be retrieved. Using CE-1's microwave data, we present here a set of microwave maps of the Moon constructed through a rescaling of TB to noontime or midnight. The adopted processing technique helps to reduce the effect of mixing up the temporal and spatial variations introduced by the satellite's localized measurements which cover different locations of the globe at different lunar local times. The resulting maps show fine structures unseen in previous microwave maps that disregarded the local time effect. We discussed the new features revealed and their possible connections with the lunar geology.

Analysis of the subcellular localization of the human histone methyltransferase SETDB1

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

Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp; Gotoh, Eiko; Kawamata, Natsuko

2015-10-02

SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that methylates lysine 9 on histone H3. Although it is important to know the localization of proteins to elucidate their physiological function, little is known of the subcellular localization of human SETDB1. In the present study, to investigate the subcellular localization of hSETDB1, we established a human cell line constitutively expressing enhanced green fluorescent protein fused to hSETDB1. We then generated a monoclonal antibody against the hSETDB1 protein. Expression of both exogenous and endogenous hSETDB1 was observed mainly in the cytoplasm of various human cell lines. Combined treatment with the nuclearmore » export inhibitor leptomycin B and the proteasome inhibitor MG132 led to the accumulation of hSETDB1 in the nucleus. These findings suggest that hSETDB1, localized in the nucleus, might undergo degradation by the proteasome and be exported to the cytosol, resulting in its detection mainly in the cytosol. - Highlights: • Endogenous human SETDB1 was localized mainly in the cytoplasm. • Combined treatment with LMB and MG132 led to accumulation of human SETDB1 in the nucleus. • HeLa cells expressing EFGP-hSETDB1 are useful for subcellular localization analyses.« less

Revealing the cellular localization of STAT1 during the cell cycle by super-resolution imaging

PubMed Central

Gao, Jing; Wang, Feng; Liu, Yanhou; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Wang, Hongda

2015-01-01

Signal transducers and activators of transcription (STATs) can transduce cytokine signals and regulate gene expression. The cellular localization and nuclear trafficking of STAT1, a representative of the STAT family with multiple transcriptional functions, is tightly related with transcription process, which usually happens in the interphase of the cell cycle. However, these priority questions regarding STAT1 distribution and localization at the different cell-cycle stages remain unclear. By using direct stochastic optical reconstruction microscopy (dSTORM), we found that the nuclear expression level of STAT1 increased gradually as the cell cycle carried out, especially after EGF stimulation. Furthermore, STAT1 formed clusters in the whole cell during the cell cycle, with the size and the number of clusters also increasing significantly from G1 to G2 phase, suggesting that transcription and other cell-cycle related activities can promote STAT1 to form more and larger clusters for fast response to signals. Our work reveals that the cellular localization and clustering distribution of STAT1 are associated with the cell cycle, and further provides an insight into the mechanism of cell-cycle regulated STAT1 signal transduction. PMID:25762114

Discriminant locality preserving projections based on L1-norm maximization.

PubMed

Zhong, Fujin; Zhang, Jiashu; Li, Defang

2014-11-01

Conventional discriminant locality preserving projection (DLPP) is a dimensionality reduction technique based on manifold learning, which has demonstrated good performance in pattern recognition. However, because its objective function is based on the distance criterion using L2-norm, conventional DLPP is not robust to outliers which are present in many applications. This paper proposes an effective and robust DLPP version based on L1-norm maximization, which learns a set of local optimal projection vectors by maximizing the ratio of the L1-norm-based locality preserving between-class dispersion and the L1-norm-based locality preserving within-class dispersion. The proposed method is proven to be feasible and also robust to outliers while overcoming the small sample size problem. The experimental results on artificial datasets, Binary Alphadigits dataset, FERET face dataset and PolyU palmprint dataset have demonstrated the effectiveness of the proposed method.

Defective Mineralization in X-Linked Hypophosphatemia Dental Pulp Cell Cultures.

PubMed

Coyac, B R; Hoac, B; Chafey, P; Falgayrac, G; Slimani, L; Rowe, P S; Penel, G; Linglart, A; McKee, M D; Chaussain, C; Bardet, C

2018-02-01

X-linked hypophosphatemia (XLH) is a skeletal disease caused by inactivating mutations in the PHEX gene. Mutated or absent PHEX protein/enzyme leads to a decreased serum phosphate level, which cause mineralization defects in the skeleton and teeth (osteomalacia/odontomalacia). It is not yet altogether clear whether these manifestations are caused solely by insufficient circulating phosphate availability for mineralization or also by a direct, local intrinsic effect caused by impaired PHEX activity. Here, we evaluated the local role of PHEX in a 3-dimensional model of extracellular matrix (ECM) mineralization. Dense collagen hydrogels were seeded either with human dental pulp cells from patients with characterized PHEX mutations or with sex- and age-matched healthy controls and cultured up to 24 d using osteogenic medium with standard phosphate concentration. Calcium quantification, micro-computed tomography, and histology with von Kossa staining for mineral showed significantly lower mineralization in XLH cell-seeded scaffolds, using nonparametric statistical tests. While apatitic mineralization was observed along collagen fibrils by electron microscopy in both groups, Raman microspectrometry indicated that XLH cells harboring the PHEX mutation produced less mineralized scaffolds having impaired mineral quality with less carbonate substitution and lower crystallinity. In the XLH cultures, immunoblotting revealed more abundant osteopontin (OPN), dentin matrix protein 1 (DMP1), and matrix extracellular phosphoglycoprotein (MEPE) than controls, as well as the presence of fragments of these proteins not found in controls, suggesting a role for PHEX in SIBLING protein degradation. Immunohistochemistry revealed altered OPN and DMP1 associated with an increased alkaline phosphatase staining in the XLH cultures. These results are consistent with impaired PHEX activity having local ECM effects in XLH. Future treatments for XLH should target both systemic and local

Selective phenol methylation to 2,6-dimethylphenol in a fluidized bed of iron-chromium mixed oxide catalyst with o-cresol circulation.

PubMed

Zukowski, Witold; Berkowicz, Gabriela; Baron, Jerzy; Kandefer, Stanisław; Jamanek, Dariusz; Szarlik, Stefan; Wielgosz, Zbigniew; Zielecka, Maria

2014-01-01

2,6-dimethylphenol (2,6-DMP) is a product of phenol methylation, especially important for the plastics industry. The process of phenol methylation in the gas phase is strongly exothermic. In order to ensure good temperature equalization in the catalyst bed, the process was carried out using a catalyst in the form of a fluidized bed - in particular, the commercial iron-chromium catalyst TZC-3/1. Synthesis of 2,6-dimethylphenol from phenol and methanol in fluidized bed of iron-chromium catalyst was carried out and the fluidization of the catalyst was examined. Stable state of fluidized bed of iron-chromium catalyst was achieved. The measured velocities allowed to determine the minimum flow of reactants, ensuring introduction of the catalyst bed in the reactor into the state of fluidization. Due to a high content of o-cresol in products of 2,6-dimethylphenol synthesis, circulation in the technological node was proposed. A series of syntheses with variable amount of o-cresol in the feedstock allowed to determine the parameters of stationary states. A stable work of technological node with o-cresol circulation is possible in the temperature range of350-380°C, and o-cresolin/phenolin molar ratio of more than 0.48. Synthesis of 2,6-DMP over the iron-chromium catalyst is characterized by more than 90% degree of phenol conversion. Moreover, the O-alkylation did not occur (which was confirmed by GC-MS analysis). By applying o-cresol circulation in the 2,6-DMP process, selectivity of more than 85% degree of 2,6-DMP was achieved. The participation levels of by-products: 2,4-DMP and 2,4,6-TMP were low. In the optimal conditions based on the highest yield of 2,6-DMP achieved in the technological node applying o-cresol circulation, there are 2%mol. of 2,4-DMP and 6%mol. of 2,4,6-TMP in the final mixture, whereas 2,4,6-TMP can be useful as a chain stopper and polymer's molar mass regulator during the polymerization of 2,6-DMP.

Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children.

PubMed

Yu, C-J; Du, J-C; Chiou, H-C; Chung, M-Y; Yang, W; Chen, Y-S; Fuh, M-R; Chien, L-C; Hwang, B; Chen, M-L

2016-07-01

Attention-deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low-level organophosphate pesticide exposure with childhood ADHD cross-sectionally and prospectively. However, the results have been inconsistent. A first case-control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 μg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose-response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose-response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD. © 2016 American Society of Andrology and European Academy of Andrology.

Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

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

Higgins, Kristin A., E-mail: kristin.higgins@duke.edu; Chino, Junzo P.; Berry, Mark

2012-06-01

Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non-small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non-small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995-2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meiermore » method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.« less

Super-resolution Microscopical Localization of Dopamine Receptors 1 and 2 in Rat Hippocampal Synaptosomes.

PubMed

Miklosi, Andras G; Del Favero, Giorgia; Bulat, Tanja; Höger, Harald; Shigemoto, Ryuichi; Marko, Doris; Lubec, Gert

2018-06-01

Although dopamine receptors D1 and D2 play key roles in hippocampal function, their synaptic localization within the hippocampus has not been fully elucidated. In order to understand precise functions of pre- or postsynaptic dopamine receptors (DRs), the development of protocols to differentiate pre- and postsynaptic DRs is essential. So far, most studies on determination and quantification of DRs did not discriminate between subsynaptic localization. Therefore, the aim of the study was to generate a robust workflow for the localization of DRs. This work provides the basis for future work on hippocampal DRs, in light that DRs may have different functions at pre- or postsynaptic sites. Synaptosomes from rat hippocampi isolated by a sucrose gradient protocol were prepared for super-resolution direct stochastic optical reconstruction microscopy (dSTORM) using Bassoon as a presynaptic zone and Homer1 as postsynaptic density marker. Direct labeling of primary validated antibodies against dopamine receptors D1 (D1R) and D2 (D2R) with Alexa Fluor 594 enabled unequivocal assignment of D1R and D2R to both, pre- and postsynaptic sites. D1R immunoreactivity clusters were observed within the presynaptic active zone as well as at perisynaptic sites at the edge of the presynaptic active zone. The results may be useful for the interpretation of previous studies and the design of future work on DRs in the hippocampus. Moreover, the reduction of the complexity of brain tissue by the use of synaptosomal preparations and dSTORM technology may represent a useful tool for synaptic localization of brain proteins.

The Evaluation of the Effectiveness of Austrians Disease Management Program in Patients with Type 2 Diabetes Mellitus - A Population-Based Retrospective Cohort Study.

PubMed

Riedl, Regina; Robausch, Martin; Berghold, Andrea

2016-01-01

To evaluate the effectiveness of the Austrian Disease Management Program (DMP) 'Therapie aktiv-Diabetes im Griff' for patients with type 2 diabetes mellitus concerning patient-relevant outcomes (mortality, myocardial infarction and stroke) and costs. Based on routine health insurance data, we conducted a population-based retrospective cohort study using a propensity score (PS) matched control group design. The DMP-group consists of participants enrolled in the program during 2008 and 2009 (n = 7181). Out of 208.532 patients with no participation in the DMP up to 2013, PS-matched controls were selected with a matching ratio 1:3. In the PS-model, patient's characteristics, form of antidiabetic drug therapy, several prescriptions, the number of hospital admissions and days, main discharge diagnoses and costs at baseline were included. Over a follow-up period of four years, we observed a significantly lower mortality rate in the DMP-group (9.4%) in comparison with the control group (15.9%, p<0.001). The cumulative number of hospital days and mean annual hospital costs were lower for DMP-participants resulting in significantly lower mean annual total costs, amounting to € 8226.80 per patient in the DMP-group and € 9231.10 in the control group respectively (p<0.001). The evaluation shows a survival benefit and an average reduction of costs for participants in the DMP compared with the control-group. Despite we took great effort to ensure comparable groups, we cannot entirely rule out an influence by residual and unmeasured confounding due to the observational study design and the use of routine data. However, the results indicate that the disease management program implemented in Austria improves quality of care for patients with type 2 diabetes mellitus.

Crossover from weak to strong localization in quasi-1D = conductors.

NASA Astrophysics Data System (ADS)

Gershenson, M. E.; Khavin, Y. B.; Mikhalchuk, A. G.; Bozler, H. M.; Bogdanov, A. L.

1997-03-01

A crossover from weak localization (WL) to strong localization (SL) with decreasing temperature has been observed in the resistance of quasi-1D channels in Si delta-doped GaAs structures. The crossover occurs when the phase-breaking length becomes comparable to the localization length. In the SL regime, an activation temperature dependence R(T) is observed. The activation energy is very close to the spacing between the energy levels of the localized electrons within the localization domain. The activation energy decreases by half in strong magnetic fields, as a result, an exponentially strong negative magnetoresistance is developed. All the features of the magnetoresistance in the SL regime are in good agreement with the theory of doubling of the localization length in quasi-1D conductors in strong fields. The magnetoresistance provides a direct measurement of the localization length. Supported by RNFBR, INTAS 943862, and NSF DRM-9623716 (A.G.M. and H.M.B.)

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues.

PubMed

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M; Zhou, Xinchun

2014-10-01

Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft

Two-year outcome of a prospective, controlled study of a disease management programme for elderly patients with heart failure.

PubMed

Del Sindaco, Donatella; Pulignano, Giovanni; Minardi, Giovanni; Apostoli, Antonella; Guerrieri, Luca; Rotoloni, Marina; Petri, Gabriella; Fabrizi, Lino; Caroselli, Attilia; Venusti, Rita; Chiantera, Angelo; Giulivi, Alessia; Giovannini, Ezio; Leggio, Francesco

2007-05-01

Elderly heart failure patients are at high risk of events. Available studies and systematic reviews suggest that elderly patients benefit from disease management programmes (DMPs). However, important questions remain open, including the optimal follow-up intensity and duration and whether such interventions are cost-effective during long-term follow-up and in different healthcare systems. The aim of this study was to determine the long-term efficacy of a hybrid DMP in consecutive older outpatients. Intervention consisted in combined hospital-based (cardiologists and nurse-coordinators from two heart failure clinics) and home-based (patient's general practitioner visits) care. The components of the DMP were the following: discharge planning, education, therapy optimisation, improved communication, early attention to signs and symptoms. Intensive follow-up was based on scheduled hospital visits (starting within 14 days of discharge), nurse's phone call and home general practitioner visits. A group of 173 patients aged > or =70 years (mean age 77 +/- 6 years, 48% women) was randomly assigned to DMP (n = 86) or usual care (n = 87). At 2-year follow-up, a 36% reduction in all-cause death and heart failure hospital admissions was observed in DMP vs. usual care. All-cause and heart failure admissions as well as the length of hospital stay were also reduced. DMP patients reported, compared to baseline, significant improvements in functional status, quality of life and beta-blocker prescription rate. The intervention was cost-effective with a mean saving of euro 982.04 per patient enrolled. A hybrid DMP for elderly heart failure patients improves outcomes and is cost-effective over a long-term follow-up.

Sex-specific strategy use and global-local processing: a perspective toward integrating sex differences in cognition.

PubMed

Pletzer, Belinda

2014-01-01

This article reviews the literature on sex-specific strategy use in cognitive tasks with the aim to carve out a link between sex differences in different cognitive tasks. I conclude that male strategies are commonly holistic and oriented toward global stimulus aspects, while female strategies are commonly decomposed and oriented toward local stimulus aspects. Thus, the strategies observed in different tasks, may depend on sex differences in attentional focus and hence sex differences in global-local processing. I hypothesize that strategy use may be sex hormone dependent and hence subject to change over the menstrual cycle as evidenced by findings in global-local processing and emotional memory. Furthermore, I propose sex hormonal modulation of hemispheric asymmetries as one possible neural substrate for this theory, thereby building on older theories, emphasizing the importance of sex differences in brain lateralization. The ideas described in the current article represent a perspective toward a unifying approach to the study of sex differences in cognition and their neural correlates.

Two solanesyl diphosphate synthases with different subcellular localizations and their respective physiological roles in Oryza sativa

PubMed Central

Ohara, Kazuaki; Sasaki, Kanako; Yazaki, Kazufumi

2010-01-01

Long chain prenyl diphosphates are crucial biosynthetic precursors of ubiquinone (UQ) in many organisms, ranging from bacteria to humans, as well as precursors of plastoquinone in photosynthetic organisms. The cloning and characterization of two solanesyl diphosphate synthase genes, OsSPS1 and OsSPS2, in Oryza sativa is reported here. OsSPS1 was highly expressed in root tissue whereas OsSPS2 was found to be high in both leaves and roots. Enzymatic characterization using recombinant proteins showed that both OsSPS1 and OsSPS2 could produce solanesyl diphosphates as their final product, while OsSPS1 showed stronger activity than OsSPS2. However, an important biological difference was observed between the two genes: OsSPS1 complemented the yeast coq1 disruptant, which does not form UQ, whereas OsSPS2 only very weakly complemented the growth defect of the coq1 mutant. HPLC analyses showed that both OsSPS1 and OsSPS2 yeast transformants produced UQ9 instead of UQ6, which is the native yeast UQ. According to the complementation study, the UQ9 levels in OsSPS2 transformants were much lower than that of OsSPS1. Green fluorescent protein fusion analyses showed that OsSPS1 localized to mitochondria, while OsSPS2 localized to plastids. This suggests that OsSPS1 is involved in the supply of solanesyl diphosphate for ubiquinone-9 biosynthesis in mitochondria, whereas OsSPS2 is involved in providing solanesyl diphosphate for plastoquinone-9 formation. These findings indicate that O. sativa has a different mechanism for the supply of isoprenoid precursors in UQ biosynthesis from Arabidopsis thaliana, in which SPS1 provides a prenyl moiety for UQ9 at the endoplasmic reticulum. PMID:20421194

Two solanesyl diphosphate synthases with different subcellular localizations and their respective physiological roles in Oryza sativa.

PubMed

Ohara, Kazuaki; Sasaki, Kanako; Yazaki, Kazufumi

2010-06-01

Long chain prenyl diphosphates are crucial biosynthetic precursors of ubiquinone (UQ) in many organisms, ranging from bacteria to humans, as well as precursors of plastoquinone in photosynthetic organisms. The cloning and characterization of two solanesyl diphosphate synthase genes, OsSPS1 and OsSPS2, in Oryza sativa is reported here. OsSPS1 was highly expressed in root tissue whereas OsSPS2 was found to be high in both leaves and roots. Enzymatic characterization using recombinant proteins showed that both OsSPS1 and OsSPS2 could produce solanesyl diphosphates as their final product, while OsSPS1 showed stronger activity than OsSPS2. However, an important biological difference was observed between the two genes: OsSPS1 complemented the yeast coq1 disruptant, which does not form UQ, whereas OsSPS2 only very weakly complemented the growth defect of the coq1 mutant. HPLC analyses showed that both OsSPS1 and OsSPS2 yeast transformants produced UQ9 instead of UQ6, which is the native yeast UQ. According to the complementation study, the UQ9 levels in OsSPS2 transformants were much lower than that of OsSPS1. Green fluorescent protein fusion analyses showed that OsSPS1 localized to mitochondria, while OsSPS2 localized to plastids. This suggests that OsSPS1 is involved in the supply of solanesyl diphosphate for ubiquinone-9 biosynthesis in mitochondria, whereas OsSPS2 is involved in providing solanesyl diphosphate for plastoquinone-9 formation. These findings indicate that O. sativa has a different mechanism for the supply of isoprenoid precursors in UQ biosynthesis from Arabidopsis thaliana, in which SPS1 provides a prenyl moiety for UQ9 at the endoplasmic reticulum.

Augmented Lagrange Programming Neural Network for Localization Using Time-Difference-of-Arrival Measurements.

PubMed

Han, Zifa; Leung, Chi Sing; So, Hing Cheung; Constantinides, Anthony George

2017-08-15

A commonly used measurement model for locating a mobile source is time-difference-of-arrival (TDOA). As each TDOA measurement defines a hyperbola, it is not straightforward to compute the mobile source position due to the nonlinear relationship in the measurements. This brief exploits the Lagrange programming neural network (LPNN), which provides a general framework to solve nonlinear constrained optimization problems, for the TDOA-based localization. The local stability of the proposed LPNN solution is also analyzed. Simulation results are included to evaluate the localization accuracy of the LPNN scheme by comparing with the state-of-the-art methods and the optimality benchmark of Cramér-Rao lower bound.

Local but not long-range microstructural differences of the ventral temporal cortex in developmental prosopagnosia

PubMed Central

Song, Sunbin; Garrido, Lúcia; Nagy, Zoltan; Mohammadi, Siawoosh; Steel, Adam; Driver, Jon; Dolan, Ray J.; Duchaine, Bradley; Furl, Nicholas

2015-01-01

Individuals with developmental prosopagnosia (DP) experience face recognition impairments despite normal intellect and low-level vision and no history of brain damage. Prior studies using diffusion tensor imaging in small samples of subjects with DP (n=6 or n=8) offer conflicting views on the neurobiological bases for DP, with one suggesting white matter differences in two major long-range tracts running through the temporal cortex, and another suggesting white matter differences confined to fibers local to ventral temporal face-specific functional regions of interest (fROIs) in the fusiform gyrus. Here, we address these inconsistent findings using a comprehensive set of analyzes in a sample of DP subjects larger than both prior studies combined (n=16). While we found no microstructural differences in long-range tracts between DP and age-matched control participants, we found differences local to face-specific fROIs, and relationships between these microstructural measures with face recognition ability. We conclude that subtle differences in local rather than long-range tracts in the ventral temporal lobe are more likely associated with developmental prosopagnosia. PMID:26456436

The corrosion mechanism of the sintered (Ce, Nd)-Fe-B magnets prepared by double main phase and single main phase approaches

NASA Astrophysics Data System (ADS)

Shi, Xiaoning; Zhu, Minggang; Zhou, Dong; Song, Liwei; Guo, Zhaohui; Li, Jia; Li, Wei

2018-05-01

The sintered (Ce, Nd)-Fe-B magnets were produced widely by Double Main Phase (DMP) method in China as the magnetic properties of the DMP magnets are superior to those of single main phase (SMP) magnets with the same nominal composition. In this work, the microstructure and corrosion mechanism of the sintered (Ce0.2Nd0.8)30FebalB (wt.%) magnets prepared by DMP and SMP method were studied in detail. Compared to SMP magnets, the DMP magnets have more positive corrosion potential, lower corrosion current density, larger electron transfer resistance, and lower mass loss of the free corrosion experiment in 0.5mol/l Na2SO4 aqueous solution. All of the results show that the DMP magnets have better corrosion resistance than SMP magnets. The back scattered electron images show that the crystalline grains of the DMP magnets are sphericity with a smooth surface while the SMP ones have plenty of edges and corners. Besides, the distribution of Ce/Nd is much more uneven in both magnetic phase and rare earth (Re)-rich phase of the DMP magnets than those of SMP magnets. After corrosion, DMP magnets show eroded magnetic phase and intact Re-rich phase, which indicate that galvanic corrosion of the Re-rich phase acting as the cathode appears.

Re-examination of the dates of large blade technology in China: a comparison of Shuidonggou Locality 1 and Locality 2.

PubMed

Li, Feng; Kuhn, Steven L; Gao, Xing; Chen, Fu-You

2013-02-01

The presence and age of large blade technology at the Shuidonggou site is a pivotal issue in discussions of the spread of blade technology in East Eurasia. Madsen and colleagues' influential work uses the dates (24,000-29,000 rcy BP [radiocarbon years before present]) they obtained from Shuidonggou Locality 2 to estimate the age of blade technology in this region, and suggested a very late arrival of Levallois-like blade technology from the north. This paper re-examines the evidence for the age of blade technology at Shuidonggou by comparing the lithic assemblages from the new excavations at Locality 2 with those from Locality 1. Several important points are demonstrated: (1) the lithic industry of cultural layers 1 through 4 at Locality 2 is not based on large blades, so reported dates from these layers cannot be an indicator of the age of large blade technology; (2) comparing Locality 1 and 2, the age of large blade technology appears to be around 34,000-38,000 calendar years BP (before present) in this region, suggesting a relatively rapid technology dispersal from the west and/or north; (3) the so-called 'Shuidonggou lower cultural layer' at Locality 1 includes both large blade and simple flake industries. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC

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

Choi, Joungil, E-mail: jochoi@som.umaryland.edu; Veterans Affairs Medical Center, Baltimore, MD 21201; Batchu, Vera Venkatanaresh Kumar

2013-06-14

Highlights: •Novel 35 kDa PGC-1α localizes to mitochondrial inner membrane and matrix in brain. •Mitochondrial localization of 35 kDa PGC-1α depends on VDAC protein. •Mitochondrial localization of 35 kDa PGC-1α depends on membrane potential. •The 35 kDa PGC-1α associates and colocalizes with PINK in brain mitochondria. -- Abstract: Peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) and PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1α isoform localizes to the mitochondrial inner membrane and matrix in brain as determined by protease protection and carbonate extraction assays, as well asmore » by immunoelectron microscopy. Immunoelectron microscopy and import experiments in vitro revealed that 35 kDa PGC-1α colocalizes and interacts with the voltage-dependent anion channel (VDAC), and that its import depends on VDAC. Valinomycin treatment which depolarizes the membrane potential, abolished mitochondrial localization of the 35 kDa PGC-1α. Using blue native-PAGE, co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 35 kDa PGC-1α binds and colocalizes with PINK1 in brain mitochondria. This is the first report regarding mitochondrial localization of a novel 35 kDa PGC-1α isoform and its association with PINK1, suggesting possible regulatory roles for mitochondrial function in the brain.« less

Nuclear Localization of Suppressor of Cytokine Signaling-1 Regulates Local Immunity in the Lung

PubMed Central

Zimmer, Jana; Weitnauer, Michael; Boutin, Sébastien; Küblbeck, Günter; Thiele, Sabrina; Walker, Patrick; Lasitschka, Felix; Lunding, Lars; Orinska, Zane; Vock, Christina; Arnold, Bernd; Wegmann, Michael; Dalpke, Alexander

2016-01-01

Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet, the in vivo importance of nuclear translocation is unknown. We generated transgenic mice containing mutated Socs1ΔNLS that fails to translocate in the cell nucleus (MGLtg mice). Whereas mice fully deficient for SOCS1 die within the first 3 weeks due to excessive interferon signaling and multiorgan inflammation, mice expressing only non-nuclear Socs1ΔNLS (Socs1−/−MGLtg mice) were rescued from early lethality. Canonical interferon gamma signaling was still functional in Socs1−/−MGLtg mice as shown by unaltered tyrosine phosphorylation of STAT1 and whole genome expression analysis. However, a subset of NFκB inducible genes was dysregulated. Socs1−/−MGLtg mice spontaneously developed low-grade inflammation in the lung and had elevated Th2-type cytokines. Upon ovalbumin sensitization and challenge, airway eosinophilia was increased in Socs1−/−MGLtg mice. Decreased transepithelial electrical resistance in trachea epithelial cells from Socs1−/−MGLtg mice suggests disrupted epithelial cell barrier. The results indicate that nuclear SOCS1 is a regulator of local immunity in the lung and unravel a so far unrecognized function for SOCS1 in the cell nucleus. PMID:27917175

Enhanced dimethyl phthalate biodegradation by accelerating phthalic acid di-oxygenation.

PubMed

Tang, Yingxia; Zhang, Yongming; Jiang, Ling; Yang, Chao; Rittmann, Bruce E

2017-12-01

The aerobic biodegradation of dimethyl phthalate (DMP) is initiated with two hydrolysis reactions that generate an intermediate, phthalic acid (PA), that is further biodegraded through a two-step di-oxygenation reaction. DMP biodegradation is inhibited when PA accumulates, but DMP's biodegradation can be enhanced by adding an exogenous electron donor. We evaluated the effect of adding succinate, acetate, or formate as an exogenous electron donor. PA removal rates were increased by 15 and 30% for initial PA concentrations of 0.3 and 0.6 mM when 0.15 and 0.30 mM succinate, respectively, were added as exogenous electron donor. The same electron-equivalent additions of acetate and formate had the same acceleration impacts on PA removal. Consequently, the DMP-removal rate, even PA coexisting with DMP simultaneously, was accelerated by 37% by simultaneous addition of 0.3 mM succinate. Thus, lowering the accumulation of PA by addition of an electron increased the rate of DMP biodegradation.

AN ASSESSMENT OF THE TOXICITY OF PHTHALATE ESTERS TO FRESHWATER BENTHOS. 1. AQUEOUS EXPOSURES

EPA Science Inventory

Tests were performed with the freshwater invertebrates, Hyalella azteca, Chironomus tentans, and Lumbriculus variegatus to determine the acute toxicity of six phthalate esters, including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butylbenzyl ph...

Localized Arm Volume Index: A New Method for Body Type-Corrected Evaluation of Localized Arm Lymphedematous Volume Change.

PubMed

Yamamoto, Takumi; Yamamoto, Nana; Yoshimatsu, Hidehiko

2017-10-01

Volume measurement is a common evaluation for upper extremity lymphedema. However, volume comparison between different patients with different body types may be inappropriate, and it is difficult to evaluate localized limb volume change using arm volume. Localized arm volumes (Vk, k = 1-5) and localized arm volume indices (LAVIk) at 5 points (1, upper arm; 2, elbow; 3, forearm; 4, wrist; 5, hand) of 106 arms of 53 examinees with no arm edema were calculated based on physical measurements (arm circumferences and lengths and body mass index [BMI]). Interrater and intrarater reliabilities of LAVIk were assessed, and Vk and LAVIk were compared between lower BMI (BMI, <22 kg/m) group and higher BMI (BMI, ≥22 kg/m) group. Interrater and intrarater reliabilities of LAVIk were all high (all, r > 0.98). Between lower and higher BMI groups, significant differences were observed in all Vk (V1 [P = 6.8 × 10], V2 [P = 3.1 × 10], V3 [P = 1.1 × 10], V4 [P = 8.3 × 10], and V5 [P = 3.0 × 10]). Regarding localized arm volume index (LAVI) between groups, significant differences were seen in LAVI1 (P = 9.7 × 10) and LAVI5 (P = 1.2 × 10); there was no significant difference in LAVI2 (P = 0.60), LAVI3 (P = 0.61), or LAVI4 (P = 0.22). Localized arm volume index is a convenient and highly reproducible method for evaluation of localized arm volume change, which is less affected by body physique compared with arm volumetry.

Differences in Spending in School Districts across Geographic Locales in Minnesota. Summary. Issues & Answers. REL 2012-No. 124

ERIC Educational Resources Information Center

Wan, Yinmei; Norbury, Heather; Molefe, Ayrin C.; Gerdeman, R. Dean; Meyers, Coby V.; Burke, Matthew

2012-01-01

This study examines differences in spending in school districts across geographic locales in Minnesota and factors that might contribute to these differences. The study finds that district spending per student in 2008/09 varied across locale types in Minnesota. These differences are largely accounted for by differences in regional characteristics…

Multicompare tests of the performance of different metaheuristics in EEG dipole source localization.

PubMed

Escalona-Vargas, Diana Irazú; Lopez-Arevalo, Ivan; Gutiérrez, David

2014-01-01

We study the use of nonparametric multicompare statistical tests on the performance of simulated annealing (SA), genetic algorithm (GA), particle swarm optimization (PSO), and differential evolution (DE), when used for electroencephalographic (EEG) source localization. Such task can be posed as an optimization problem for which the referred metaheuristic methods are well suited. Hence, we evaluate the localization's performance in terms of metaheuristics' operational parameters and for a fixed number of evaluations of the objective function. In this way, we are able to link the efficiency of the metaheuristics with a common measure of computational cost. Our results did not show significant differences in the metaheuristics' performance for the case of single source localization. In case of localizing two correlated sources, we found that PSO (ring and tree topologies) and DE performed the worst, then they should not be considered in large-scale EEG source localization problems. Overall, the multicompare tests allowed to demonstrate the little effect that the selection of a particular metaheuristic and the variations in their operational parameters have in this optimization problem.

Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the Subcellular Localization of the Tax-DLG1 Interaction

PubMed Central

Marziali, Federico; Bugnon Valdano, Marina; Brunet Avalos, Clarisse; Moriena, Lucía; Cavatorta, Ana Laura; Gardiol, Daniela

2017-01-01

Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain–containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1 interaction results in a cytoplasmic co-localization pattern resembling vesicular aggregates, the nature of which is still unknown. To further explore the role of PDZ proteins in HTLV-1 cell transformation, we deeply investigated the Tax-DLG1 association. By fluorescence resonance energy transfer (FRET), we detected, for the first time, the direct binding of Tax to DLG1 within the cell. We showed that the interaction specifically affects the cellular distribution of not only DLG1, but also Tax. After studying different cell structures, we demonstrated that the aggregates distribute into the Golgi apparatus in spatial association with the microtubule-organizing center (MTOC). This study contributes to understand the biological significance of Tax-PDZ interactions. PMID:29168728

Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the Subcellular Localization of the Tax-DLG1 Interaction.

PubMed

Marziali, Federico; Bugnon Valdano, Marina; Brunet Avalos, Clarisse; Moriena, Lucía; Cavatorta, Ana Laura; Gardiol, Daniela

2017-11-23

Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain-containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1 interaction results in a cytoplasmic co-localization pattern resembling vesicular aggregates, the nature of which is still unknown. To further explore the role of PDZ proteins in HTLV-1 cell transformation, we deeply investigated the Tax-DLG1 association. By fluorescence resonance energy transfer (FRET), we detected, for the first time, the direct binding of Tax to DLG1 within the cell. We showed that the interaction specifically affects the cellular distribution of not only DLG1, but also Tax. After studying different cell structures, we demonstrated that the aggregates distribute into the Golgi apparatus in spatial association with the microtubule-organizing center (MTOC). This study contributes to understand the biological significance of Tax-PDZ interactions.

GEP, a local growth factor, is critical for odontogenesis and amelogenesis.

PubMed

Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q

2010-11-25

Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development.

GEP, a Local Growth Factor, is Critical for Odontogenesis and Amelogenesis

PubMed Central

Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q.

2010-01-01

Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development. PMID:21152114

Cytoplasm localization of aminopeptidase M1 and its functional activity in root hair cells and BY-2 cells.

PubMed

Lee, Ok Ran; Cho, Hyung-Taeg

2012-12-01

Aminopeptidase M1 (APM1) was the first M1 metallopeptidase family member identified in Arabidopsis, isolated by its affinity for the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). A loss-of-function mutation showed various developmental defects in cell division and auxin transport. APM1 was shown to be localized in endomembrane structures, the cytoplasm, and the plasma membrane. These previous results suggested that APM1 has diverse functional roles in different cell and tissue types. Here we report that APM1 localized to the cytoplasm, and its over-expression in the root hair cell caused longer root hair phenotypes. Treatment of aminopeptidase inhibitors caused internalization of auxin efflux PIN-FORMED proteins in root hair cells and suppressed short root hair phenotype of PIN3 overexpression line (PIN3ox). APM1 also localized to the cytoplasm in tobacco BY-2 cells, its over-expression had little effect on auxin transport in these cells.

Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury

PubMed Central

Pedigo, Christopher E.; Ducasa, Gloria Michelle; Leclercq, Farah; Sloan, Alexis; Hashmi, Tahreem; Molina-David, Judith; Ge, Mengyuan; Lassenius, Mariann I.; Groop, Per-Henrik; Kretzler, Matthias; Martini, Sebastian; Reich, Heather; Wahl, Patricia; Ghiggeri, GianMarco; Burke, George W.; Kretz, Oliver; Huber, Tobias B.; Mendez, Armando J.; Merscher, Sandra

2016-01-01

High levels of circulating TNF and its receptors, TNFR1 and TNFR2, predict the progression of diabetic kidney disease (DKD), but their contribution to organ damage in DKD remains largely unknown. Here, we investigated the function of local and systemic TNF in podocyte injury. We cultured human podocytes with sera collected from DKD patients, who displayed elevated TNF levels, and focal segmental glomerulosclerosis (FSGS) patients, whose TNF levels resembled those of healthy patients. Exogenous TNF administration or local TNF expression was equally sufficient to cause free cholesterol–dependent apoptosis in podocytes by acting through a dual mechanism that required a reduction in ATP-binding cassette transporter A1–mediated (ABCA1-mediated) cholesterol efflux and reduced cholesterol esterification by sterol-O-acyltransferase 1 (SOAT1). TNF-induced albuminuria was aggravated in mice with podocyte-specific ABCA1 deficiency and was partially prevented by cholesterol depletion with cyclodextrin. TNF-stimulated free cholesterol–dependent apoptosis in podocytes was mediated by nuclear factor of activated T cells 1 (NFATc1). ABCA1 overexpression or cholesterol depletion was sufficient to reduce albuminuria in mice with podocyte-specific NFATc1 activation. Our data implicate an NFATc1/ABCA1-dependent mechanism in which local TNF is sufficient to cause free cholesterol–dependent podocyte injury irrespective of TNF, TNFR1, or TNFR2 serum levels. PMID:27482889

Localization of alpha 1-adrenoceptors in rat and human hearts by immunocytochemistry.

PubMed

Schulze, W; Fu, M L

1996-01-01

The localization of the alpha 1 adrenoceptors (alpha 1-AR) in the heart tissues from rat and human and in the cultured heart cells from neonatal rats was studied by indirect immunofluorescence and postembedding electronmicroscopical immuno-gold technique. With antipeptide antibodies directed against the second extracellular loop of the human alpha 1-AR (AS sequence 192-218), this receptor was found to be localized along the sarcolemma in both human and rat hearts. Similar localization sites were detected in cultivated rat neonatal cardiomyocytes. Beside the localization in cardiomyocytes, alpha 1-AR were identified in endothelial cells of capillaries and smooth muscle cells of coronary vessels, in neuronal endings, in mast cells of cultivated heart cells but not, or in less amount in fibroblasts. Interestingly, in the right atrium of rat heart the localization of alpha 1-AR was found to be near or on atrial natriuretic factor (ANF) granules, providing the basis for the alpha-adrenergic influence on ANF release. The immunocytochemical studies further confirm and complete the findings known by using autoradiographic binding studies with specific ligands.

Excitation Localization/Delocalization Isomerism in a Strongly Coupled Covalent Dimer of 1,3-Diphenylisobenzofuran

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

Schrauben, Joel N.; Akdag, Akin; Wen, Jin

Two isomers of both the lowest excited singlet (S1) and triplet (T1) states of the directly para, para'-connected covalent dimer of the singlet-fission chromophore 1,3-diphenylisobenzofuran have been observed. In one isomer, excitation is delocalized over both halves of the dimer, and in the other, it is localized on one or the other half. For a covalent dimer in solution, such 'excitation isomerism' is extremely rare. The vibrationally relaxed isomers do not interconvert, and their photophysical properties, including singlet fission, differ significantly.

26 CFR 1.501(c)(4)-1 - Civic organizations and local associations of employees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... employees. 1.501(c)(4)-1 Section 1.501(c)(4)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(c)(4)-1 Civic organizations and local associations of employees. (a) Civic organizations—(1) In general. A civic...

15 years of monitoring occupational exposure to respirable dust and quartz within the European industrial minerals sector.

PubMed

Zilaout, Hicham; Vlaanderen, Jelle; Houba, Remko; Kromhout, Hans

2017-07-01

In 2000, a prospective Dust Monitoring Program (DMP) was started in which measurements of worker's exposure to respirable dust and quartz are collected in member companies from the European Industrial Minerals Association (IMA-Europe). After 15 years, the resulting IMA-DMP database allows a detailed overview of exposure levels of respirable dust and quartz over time within this industrial sector. Our aim is to describe the IMA-DMP and the current state of the corresponding database which due to continuation of the IMA-DMP is still growing. The future use of the database will also be highlighted including its utility for the industrial minerals producing sector. Exposure data are being obtained following a common protocol including a standardized sampling strategy, standardized sampling and analytical methods and a data management system. Following strict quality control procedures, exposure data are consequently added to a central database. The data comprises personal exposure measurements including auxiliary information on work and other conditions during sampling. Currently, the IMA-DMP database consists of almost 28,000 personal measurements which have been performed from 2000 until 2015 representing 29 half-yearly sampling campaigns. The exposure data have been collected from 160 different worksites owned by 35 industrial mineral companies and comes from 23 European countries and approximately 5000 workers. The IMA-DMP database provides the European minerals sector with reliable data regarding worker personal exposures to respirable dust and quartz. The database can be used as a powerful tool to address outstanding scientific issues on long-term exposure trends and exposure variability, and importantly, as a surveillance tool to evaluate exposure control measures. The database will be valuable for future epidemiological studies on respiratory health effects and will allow for estimation of quantitative exposure response relationships. Copyright © 2017 The

Expression and subcellular localization of ORC1 in Leishmania major

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

Kumar, Diwakar; Mukherji, Agnideep; Saha, Swati

2008-10-10

The mechanism of DNA replication is highly conserved in eukaryotes, with the process being preceded by the ordered assembly of pre-replication complexes (pre-RCs). Pre-RC formation is triggered by the association of the origin replication complex (ORC) with chromatin. Leishmania major appears to have only one ORC ortholog, ORC1. ORC1 in other eukaryotes is the largest of the ORC subunits and is believed to play a significant role in modulating replication initiation. Here we report for the first time, the cloning of ORC1 from L. major, and the analysis of its expression in L. major promastigotes. In human cells ORC1 levelsmore » have been found to be upregulated in G1 and subsequently degraded, thus playing a role in controlling replication initiation. We examine the subcellular localization of L. major ORC1 in relation to the different stages of the cell cycle. Our results show that, unlike what is widely believed to be the case with ORC1 in human cells, ORC1 in L. major is nuclear at all stages of the cell cycle.« less

Treating colon cancer with a suicide gene delivered by self-assembled cationic MPEG-PCL micelles

NASA Astrophysics Data System (ADS)

Duan, Xingmei; Wang, Pan; Men, Ke; Gao, Xiang; Huang, Meijuan; Gou, Maling; Chen, Lijuan; Qian, Zhiyong; Wei, Yuquan

2012-03-01

Biodegradable cationic micelles show promise for applications in gene delivery. In this article, we used DOTAP to modify monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL, MP) micelles in one step, creating novel cationic self-assembled DOTAP and MPEG-PCL hybrid micelles (DMP). These micelles had a mean particle size of 46 +/- 5.6 nm and a zeta potential of 41.8 +/- 0.5 mV, and had the capacity to bind DNA. Compared with PEI25K (the gold standard), DMP micelles had higher transfection efficiency and lower cytotoxicity. Moreover, we used DMP to deliver the Survivin-T34A gene (S-T34A, a suicide gene) to treat colon cancer. DMP delivered the Survivin-T34A gene (DMP/S-T34A) and could induce apoptosis in cancer cells, resulting in inhibition of the growth of C-26 colon cancer cells in vitro. An in vivo study indicated that intraperitoneal administration of DMP micelles delivered the Survivin-T34A gene and efficiently inhibited the growth of abdominal metastatic C-26 colon cancer and the malignant ascites. These data suggest that DMP may be a novel gene carrier, and its delivery of the S-T34A gene may have promising applications in the treatment of colon cancer.

Decomposition and Mineralization of Dimethyl Phthalate in an Aqueous Solution by Wet Oxidation

PubMed Central

Ji, Dar-Ren; Chang, Chia-Chi; Chen, Shih-Yun; Chiu, Chun-Yu; Tseng, Jyi-Yeong; Chang, Ching-Yuan; Chang, Chiung-Fen; Chiang, Sheng-Wei; Hung, Zang-Sie; Shie, Je-Lueng; Yuan, Min-Hao

2015-01-01

Dimethyl phthalate (DMP) was treated via wet oxygen oxidation process (WOP). The decomposition efficiency η DMP of DMP and mineralization efficiency η TOC of total organic carbons were measured to evaluate the effects of operation parameters on the performance of WOP. The results revealed that reaction temperature T is the most affecting factor, with a higher T offering higher η DMP and η TOC as expected. The η DMP increases as rotating speed increases from 300 to 500 rpm with stirring enhancement of gas liquid mass transfer. However, it exhibits reduction effect at 700 rpm due to purging of dissolved oxygen by overstirring. Regarding the effects of pressure P T, a higher P T provides more oxygen for the forward reaction with DMP, while overhigh P T increases the absorption of gaseous products such as CO2 and decomposes short-chain hydrocarbon fragments back into the solution thus hindering the forward reaction. For the tested P T of 2.41 to 3.45 MPa, the results indicated that 2.41 MPa is appropriate. A longer reaction time of course gives better performance. At 500 rpm, 483 K, 2.41 MPa, and 180 min, the η DMP and η TOC are 93 and 36%, respectively. PMID:26236768

Tung Tree DGAT1 and DGAT2 Have Nonredundant Functions in Triacylglycerol Biosynthesis and Are Localized to Different Subdomains of the Endoplasmic Reticulum[W

PubMed Central

Shockey, Jay M.; Gidda, Satinder K.; Chapital, Dorselyn C.; Kuan, Jui-Chang; Dhanoa, Preetinder K.; Bland, John M.; Rothstein, Steven J.; Mullen, Robert T.; Dyer, John M.

2006-01-01

Seeds of the tung tree (Vernicia fordii) produce large quantities of triacylglycerols (TAGs) containing ∼80% eleostearic acid, an unusual conjugated fatty acid. We present a comparative analysis of the genetic, functional, and cellular properties of tung type 1 and type 2 diacylglycerol acyltransferases (DGAT1 and DGAT2), two unrelated enzymes that catalyze the committed step in TAG biosynthesis. We show that both enzymes are encoded by single genes and that DGAT1 is expressed at similar levels in various organs, whereas DGAT2 is strongly induced in developing seeds at the onset of oil biosynthesis. Expression of DGAT1 and DGAT2 in yeast produced different types and proportions of TAGs containing eleostearic acid, with DGAT2 possessing an enhanced propensity for the synthesis of trieleostearin, the main component of tung oil. Both DGAT1 and DGAT2 are located in distinct, dynamic regions of the endoplasmic reticulum (ER), and surprisingly, these regions do not overlap. Furthermore, although both DGAT1 and DGAT2 contain a similar C-terminal pentapeptide ER retrieval motif, this motif alone is not sufficient for their localization to specific regions of the ER. These data suggest that DGAT1 and DGAT2 have nonredundant functions in plants and that the production of storage oils, including those containing unusual fatty acids, occurs in distinct ER subdomains. PMID:16920778

NGO initiatives in risk reduction: an overview.

PubMed

Benson, C; Twigg, J; Myers, M

2001-09-01

NGOs appear to be well placed to play a significant role in natural disaster mitigation and preparedness (DMP), working, as they do, with poorer and marginalised groups in society. However, there is little information on the scale or nature of NGO DMP activities. This paper reports the findings of a study seeking to address that gap. It confirms that NGOs are involved in a diverse range of DMP activities but that a number of them are not labelled as such. Moreover, evidence of the demonstrable quality and benefits of DMP involvement is poor. The paper concludes that a number of problems need to be overcome before DMP can be satisfactorily mainstreamed into NGO development and post-disaster rehabilitation programmes. However, there are some early indications of momentum for change.

The impact of a disease management programme for type 2 diabetes on health-related quality of life: multilevel analysis of a cluster-randomised controlled trial.

PubMed

Panisch, Sigrid; Johansson, Tim; Flamm, Maria; Winkler, Henrike; Weitgasser, Raimund; Sönnichsen, Andreas C

2018-01-01

Type 2 diabetes is a chronic disease associated with poorer health outcomes and decreased health related quality of life (HRQoL). The aim of this analysis was to explore the impact of a disease management programme (DMP) in type 2 diabetes on HRQoL. A multilevel model was used to explain the variation in EQ-VAS. A cluster-randomized controlled trial-analysis of the secondary endpoint HRQoL. Our study population were general practitioners and patients in the province of Salzburg. The DMP "Therapie-Aktiv" was implemented in the intervention group, and controls received usual care. Outcome measure was a change in EQ-VAS after 12 months. For comparison of rates, we used Fisher's Exact test; for continuous variables the independent T test or Welch test were used. In the multilevel modeling, we examined various models, continuously adding variables to explain the variation in the dependent variable, starting with an empty model, including only the random intercept. We analysed random effects parameters in order to disentangle variation of the final EQ-VAS. The EQ-VAS significantly increased within the intervention group (mean difference 2.19, p = 0.005). There was no significant difference in EQ-VAS between groups (mean difference 1.00, p = 0.339). In the intervention group the improvement was more distinct in women (2.46, p = 0.036) compared to men (1.92, p = 0.063). In multilevel modeling, sex, age, family and work circumstances, any macrovascular diabetic complication, duration of diabetes, baseline body mass index and baseline EQ-VAS significantly influence final EQ-VAS, while DMP does not. The final model explains 28.9% (EQ-VAS) of the total variance. Most of the unexplained variance was found on patient-level (95%) and less on GP-level (5%). DMP "Therapie-Aktiv" has no significant impact on final EQ-VAS. The impact of DMPs in type 2 diabetes on HRQoL is still unclear and future programmes should focus on patient specific needs and predictors in

Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

PubMed Central

Weir, Scott M.; Talent, Larry G.; Anderson, Todd A.; Salice, Christopher J.

2014-01-01

Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals. PMID

Unraveling the relative importance of oral and dermal contaminant exposure in reptiles: insights from studies using the western fence lizard (Sceloporus occidentalis).

PubMed

Weir, Scott M; Talent, Larry G; Anderson, Todd A; Salice, Christopher J

2014-01-01

Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals.

Pannexin2 oligomers localize in the membranes of endosomal vesicles in mammalian cells while Pannexin1 channels traffic to the plasma membrane.

PubMed

Boassa, Daniela; Nguyen, Phuong; Hu, Junru; Ellisman, Mark H; Sosinsky, Gina E

2014-01-01

Pannexin2 (Panx2) is the largest of three members of the pannexin proteins. Pannexins are topologically related to connexins and innexins, but serve different functional roles than forming gap junctions. We previously showed that pannexins form oligomeric channels but unlike connexins and innexins, they form only single membrane channels. High levels of Panx2 mRNA and protein in the Central Nervous System (CNS) have been documented. Whereas Pannexin1 (Panx1) is fairly ubiquitous and Pannexin3 (Panx3) is found in skin and connective tissue, both are fully glycosylated, traffic to the plasma membrane and have functions correlated with extracellular ATP release. Here, we describe trafficking and subcellular localizations of exogenous Panx2 and Panx1 protein expression in MDCK, HeLa, and HEK 293T cells as well as endogenous Panx1 and Panx2 patterns in the CNS. Panx2 was found in intracellular localizations, was partially N-glycosylated, and localizations were non-overlapping with Panx1. Confocal images of hippocampal sections immunolabeled for the astrocytic protein GFAP, Panx1 and Panx2 demonstrated that the two isoforms, Panx1 and Panx2, localized at different subcellular compartments in both astrocytes and neurons. Using recombinant fusions of Panx2 with appended genetic tags developed for correlated light and electron microscopy and then expressed in different cell lines, we determined that Panx2 is localized in the membrane of intracellular vesicles and not in the endoplasmic reticulum as initially indicated by calnexin colocalization experiments. Dual immunofluorescence imaging with protein markers for specific vesicle compartments showed that Panx2 vesicles are early endosomal in origin. In electron tomographic volumes, cross-sections of these vesicles displayed fine structural details and close proximity to actin filaments. Thus, pannexins expressed at different subcellular compartments likely exert distinct functional roles, particularly in the nervous system.

SAFARI-1: Achieving conversion to LEU - A local challenge

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

Piani, C.S.B.

2008-07-15

Two years have passed since the South African Department of Minerals and Energy authorised the conversion from High Enriched Uranium (HEU) to Low Enriched Uranium (LEU) of the South African Research Reactor (SAFARI-1) and the associated fuel manufacturing at Pelindaba. The scheduling, as originally proposed, allowed approximately three years for the full conversion of the reactor, anticipating simultaneous manufacturing ability from the fuel production plant. Due to technical difficulties experienced in the conversion of the local manufacturing plant from HEU (UAl alloy) to LEU (U Silicide) and the uncertainty as to costing and scheduling of such an achievement, the conversionmore » of SAFARI-1 based on local supply has been allocated a lower priority. The acquisition in mid-2006 of 2 LEU silicide elements of SA design, manufactured by AREVA- CERCA and irradiated as test elements in SAFARI-1 to burn-ups of {approx}65% each; was successfully accomplished within 9 cycles of irradiation each. Furthermore, four 'Hybrid' elements (AREVA-CERCA plates assembled locally at Pelindaba) are ready for irradiation and have received regulatory authorisation to load. This will enable the SAFARI-1 conversion program to continue systematically according to an agreed schedule. This paper will trace the developments of the above and reflect the current status and the rescheduled conversion phases of the reactor according to latest expectations. (author)« less

Brain parcellation choice affects disease-related topology differences increasingly from global to local network levels.

PubMed

Lord, Anton; Ehrlich, Stefan; Borchardt, Viola; Geisler, Daniel; Seidel, Maria; Huber, Stefanie; Murr, Julia; Walter, Martin

2016-03-30

Network-based analyses of deviant brain function have become extremely popular in psychiatric neuroimaging. Underpinning brain network analyses is the selection of appropriate regions of interest (ROIs). Although ROI selection is fundamental in network analysis, its impact on detecting disease effects remains unclear. We investigated the impact of parcellation choice when comparing results from different studies. We investigated the effects of anatomical (AAL) and literature-based (Dosenbach) parcellation schemes on comparability of group differences in 35 female patients with anorexia nervosa and 35 age- and sex-matched healthy controls. Global and local network properties, including network-based statistics (NBS), were assessed on resting state functional magnetic resonance imaging data obtained at 3T. Parcellation schemes were comparably consistent on global network properties, while NBS and local metrics differed in location, but not metric type. Location of local metric alterations varied for AAL (parietal and cingulate cortices) versus Dosenbach (insula, thalamus) parcellation approaches. However, consistency was observed for the occipital cortex. Patient-specific global network properties can be robustly observed using different parcellation schemes, while graph metrics characterizing impairments of individual nodes vary considerably. Therefore, the impact of parcellation choice on specific group differences varies depending on the level of network organization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Organophosphate Urinary Metabolite Levels during Pregnancy, Delivery and Postpartum in Women Living in Agricultural Areas in Thailand

PubMed Central

Kongtip, Pornpimol; Nankongnab, Noppanun; Woskie, Susan; Phamonphon, Akkarat; Tharnpoophasiam, Prapin; Wilaiwan, Kitsiluck; Srasom, Punnee

2018-01-01

Organophosphate Urinary Metabolite Levels during Pregnancy, Delivery and Postpartum in Women Living in Agricultural Areas in Thailand: Pornpimol Kongtip, et al. Department of Occupational Health and Safety, Faculty of Public Health, Mahidol University, Thailand Objective Prenatal exposure to organophosphate pesticides can lead to developmental neurotoxicity. A longitudinal birth cohort was established to investigate pesticide exposures from different agricultural activities. Maternal urinary organophosphate metabolites were measured at 28 weeks of pregnancy (n=86), delivery (n=67) and 2 months postpartum (n=51). Method Subjects were interviewed with questionnaires about work, home and behavioral factors potentially associated with pesticide exposures, and spot urine samples were also collected. The urine samples were analyzed for dimethyl phosphate (DMP), diethyl phosphate (DEP), diethyl thiophosphate (DETP) and diethyl dithiophosphate (DEDTP), using gas chromatography-mass spectrometry. Results The urinary DMP and dialkyl phosphate (DAP) concentrations at 28 weeks of pregnancy and delivery were not significantly different, but the DMP and DAP concentrations at 28 weeks of pregnancy and DAP concentrations at delivery were significantly different (p<0.05) from those at 2 months postpartum. The factors influencing the urinary DAP concentrations at 28 weeks of pregnancy included insecticide used in the home, living close to agricultural farmland, frequency of agricultural field visits during the first and second trimesters of pregnancies, occupation of subjects, pesticide used and other agricultural activities. Conclusions The urinary organophosphate metabolites, DMP, DEP, DETP, DEDTP, total DEP and DAPs, at 28 weeks of pregnancy, delivery and 2 months postpartum fluctuated depending on their pesticide exposures both at home and in agricultural fields. PMID:23892639

Mental practice with interactive 3D visual aids enhances surgical performance.

PubMed

Yiasemidou, Marina; Glassman, Daniel; Mushtaq, Faisal; Athanasiou, Christos; Williams, Mark-Mon; Jayne, David; Miskovic, Danilo

2017-10-01

Evidence suggests that Mental Practice (MP) could be used to finesse surgical skills. However, MP is cognitively demanding and may be dependent on the ability of individuals to produce mental images. In this study, we hypothesised that the provision of interactive 3D visual aids during MP could facilitate surgical skill performance. 20 surgical trainees were case-matched to one of three different preparation methods prior to performing a simulated Laparoscopic Cholecystectomy (LC). Two intervention groups underwent a 25-minute MP session; one with interactive 3D visual aids depicting the relevant surgical anatomy (3D-MP group, n = 5) and one without (MP-Only, n = 5). A control group (n = 10) watched a didactic video of a real LC. Scores relating to technical performance and safety were recorded by a surgical simulator. The Control group took longer to complete the procedure relative to the 3D&MP condition (p = .002). The number of movements was also statistically different across groups (p = .001), with the 3D&MP group making fewer movements relative to controls (p = .001). Likewise, the control group moved further in comparison to the 3D&MP condition and the MP-Only condition (p = .004). No reliable differences were observed for safety metrics. These data provide evidence for the potential value of MP in improving performance. Furthermore, they suggest that 3D interactive visual aids during MP could potentially enhance performance, beyond the benefits of MP alone. These findings pave the way for future RCTs on surgical preparation and performance.

Global-local processing relates to spatial and verbal processing: implications for sex differences in cognition.

PubMed

Pletzer, Belinda; Scheuringer, Andrea; Scherndl, Thomas

2017-09-05

Sex differences have been reported for a variety of cognitive tasks and related to the use of different cognitive processing styles in men and women. It was recently argued that these processing styles share some characteristics across tasks, i.e. male approaches are oriented towards holistic stimulus aspects and female approaches are oriented towards stimulus details. In that respect, sex-dependent cognitive processing styles share similarities with attentional global-local processing. A direct relationship between cognitive processing and global-local processing has however not been previously established. In the present study, 49 men and 44 women completed a Navon paradigm and a Kimchi Palmer task as well as a navigation task and a verbal fluency task with the goal to relate the global advantage (GA) effect as a measure of global processing to holistic processing styles in both tasks. Indeed participants with larger GA effects displayed more holistic processing during spatial navigation and phonemic fluency. However, the relationship to cognitive processing styles was modulated by the specific condition of the Navon paradigm, as well as the sex of participants. Thus, different types of global-local processing play different roles for cognitive processing in men and women.

Subcellular localization and cytoplasmic complex status of endogenous Keap1.

PubMed

Watai, Yoriko; Kobayashi, Akira; Nagase, Hiroko; Mizukami, Mio; McEvoy, Justina; Singer, Jeffrey D; Itoh, Ken; Yamamoto, Masayuki

2007-10-01

Keap1 acts as a sensor for oxidative/electrophilic stress, an adaptor for Cullin-3-based ubiquitin ligase, and a regulator of Nrf2 activity through the interaction with Nrf2 Neh2 domain. However, the mechanism(s) of Nrf2 migration into the nucleus in response to stress remains largely unknown due to the lack of a reliable antibody for the detection of endogenous Keap1 molecule. Here, we report the generation of a new monoclonal antibody for the detection of endogenous Keap1 molecules. Immunocytochemical analysis of mouse embryonic fibroblasts with the antibody revealed that under normal, unstressed condition, Keap1 is localized primarily in the cytoplasm with minimal amount in the nucleus and endoplasmic reticulum. This subcellular localization profile of Keap1 appears unchanged after treatment of cells with diethyl maleate, an electrophile, and/or Leptomycin B, a nuclear export inhibitor. Subcellular fractionation analysis of mouse liver cells showed similar results. No substantial change in the subcellular distribution profile could be observed in cells isolated from butylated hydroxyanisole-treated mice. Analyses of sucrose density gradient centrifugation of mouse liver cells indicated that Keap1 appears to form multiprotein complexes in the cytoplasm. These results demonstrate that endogenous Keap1 remains mostly in the cytoplasm, and electrophiles promote nuclear accumulation of Nrf2 without altering the subcellular localization of Keap1.

Communication: Near-locality of exchange and correlation density functionals for 1- and 2-electron systems

NASA Astrophysics Data System (ADS)

Sun, Jianwei; Perdew, John P.; Yang, Zenghui; Peng, Haowei

2016-05-01

The uniform electron gas and the hydrogen atom play fundamental roles in condensed matter physics and quantum chemistry. The former has an infinite number of electrons uniformly distributed over the neutralizing positively charged background, and the latter only one electron bound to the proton. The uniform electron gas was used to derive the local spin density approximation to the exchange-correlation functional that undergirds the development of the Kohn-Sham density functional theory. We show here that the ground-state exchange-correlation energies of the hydrogen atom and many other 1- and 2-electron systems are modeled surprisingly well by a different local spin density approximation (LSDA0). LSDA0 is constructed to satisfy exact constraints but agrees surprisingly well with the exact results for a uniform two-electron density in a finite, curved three-dimensional space. We also apply LSDA0 to excited or noded 1-electron densities, where it works less well. Furthermore, we show that the localization of the exact exchange hole for a 1- or 2-electron ground state can be measured by the ratio of the exact exchange energy to its optimal lower bound.

Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins.

PubMed

Molzan, Manuela; Ottmann, Christian

2013-03-01

Myeloid leukemia factor 1 (MLF1) is associated with the development of leukemic diseases such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, information on the physiological function of MLF1 is limited and mostly derived from studies identifying MLF1 interaction partners like CSN3, MLF1IP, MADM, Manp and the 14-3-3 proteins. The 14-3-3-binding site surrounding S34 is one of the only known functional features of the MLF1 sequence, along with one nuclear export sequence (NES) and two nuclear localization sequences (NLS). It was recently shown that the subcellular localization of mouse MLF1 is dependent on 14-3-3 proteins. Based on these findings, we investigated whether the subcellular localization of human MLF1 was also directly 14-3-3-dependent. Live cell imaging with GFP-fused human MLF1 was used to study the effects of mutations and deletions on its subcellular localization. Surprisingly, we found that the subcellular localization of full-length human MLF1 is 14-3-3-independent, and is probably regulated by other as-yet-unknown proteins.

Degradation of Phthalate Esters by Fusarium sp. DMT-5-3 and Trichosporon sp. DMI-5-1 Isolated from Mangrove Sediments.

PubMed

Luo, Zhu-Hua; Pang, Ka-Lai; Wu, Yi-Rui; Gu, Ji-Dong; Chow, Raymond K K; Vrijmoed, L L P

2012-01-01

Phthalate esters (PAEs) are important industrial compounds mainly used as plasticizers to increase flexibility and softness of plastic products. PAEs are of major concern because of their widespread use, ubiquity in the environment, and endocrine-disrupting toxicity. In this study, two fungal strains, Fusarium sp. DMT-5-3 and Trichosporon sp. DMI-5-1 which had the capability to degrade dimethyl phthalate esters (DMPEs), were isolated from mangrove sediments in the Futian Nature Reserve of Shenzhen, China, by enrichment culture technique. These fungi were identified on the basis of spore morphology and molecular typing using 18S rDNA sequence. Comparative investigations on the biodegradation of three isomers of DMPEs, namely dimethyl phthalate (DMP), dimethyl isophthalate (DMI), and dimethyl terephthalate (DMT), were carried out with these two fungi. It was found that both fungi could not completely mineralize DMPEs but transform them to the respective monomethyl phthalate or phthalate acid. Biochemical degradation pathways for different DMPE isomers by both fungi were different. Both fungi could transform DMT to monomethyl terephthalate (MMT) and further to terephthalic acid (TA) by stepwise hydrolysis of two ester bonds. However, they could only carry out one-step ester hydrolysis to transform DMI to monomethyl isophthalate (MMI). Further metabolism of MMI did not proceed. Only Trichosporon sp. was able to transform DMP to monomethyl phthalate (MMP) but not Fusarium sp. The optimal pH for DMI and DMT degradation by Fusarium sp. was 6.0 and 4.5, respectively, whereas for Trichosporon sp., the optimal pH for the degradation of all the three DMPE isomers was at 6.0. These results suggest that the fungal esterases responsible for hydrolysis of the two ester bonds of PAEs are highly substrate specific.

Does enhanced diabetes management reduce the risk and improve the outcome of tuberculosis?

PubMed

Lo, H-Y; Yang, S-L; Lin, H-H; Bai, K-J; Lee, J-J; Lee, T-I; Chiang, C-Y

2016-03-01

The Bureau of National Health Insurance (NHI) has implemented a pay-for-performance (p4p) programme for diabetes mellitus (DM) in Taiwan. To investigate whether patients with DM enrolled in the p4p programme (DM-p4p) are less likely to develop tuberculosis (TB) and whether they have a better outcome than patients with DM not enrolled in the p4p programme (DM-non-p4p) if they do develop TB. A random sample of 79,471 DM-p4p, 100,000 DM-non-p4p and 100,000 non-diabetic patients (non-DM) was obtained from the 2008-2009 NHI database, and the patients were matched with the National TB Registry to determine whether they had developed TB by the end of 2010. The average annual incidence of TB was respectively 259.9 (95%CI 230.2-293.4), 137.5 (95%CI 116.4-162.5) and 74.1 (95%CI 59.0-93.0) per 100,000 population among DM-non-p4p, DM-p4p and non-DM patients. The relative risk of death over treatment success was 1.79 (95%CI 1.05-3.04) among DM-non-p4p and 1.69 (95%CI 0.84-3.40) among non-DM patients, relative to DM-p4p patients. Enhanced case management of DM reduced risk and improved outcomes of TB among patients with DM.

HIV-1 nucleocapsid protein localizes efficiently to the nucleus and nucleolus.

PubMed

Yu, Kyung Lee; Lee, Sun Hee; Lee, Eun Soo; You, Ji Chang

2016-05-01

The HIV-1 nucleocapsid (NC) is an essential viral protein containing two highly conserved retroviral-type zinc finger (ZF) motifs, which functions in multiple stages of the HIV-1 life cycle. Although a number of functions for NC either in its mature form or as a domain of Gag have been revealed, little is known about the intracellular localization of NC and, moreover, its role in Gag protein trafficking. Here, we have investigated various forms of HIV-1 NC protein for its cellular localization and found that the NC has a strong nuclear and nucleolar localization activity. The linker region, composed of a stretch of basic amino acids between the two ZF motifs, was necessary and sufficient for the activity. Copyright © 2016 Elsevier Inc. All rights reserved.

A Meta-Analysis of Circulating Microvesicles in Patients with Myocardial Infarction.

PubMed

Wang, Zhida; Cai, Wang; Hu, Shaolan; Xia, Yufei; Wang, Yao; Zhang, Qi; Chen, Liming

2017-07-10

Cell-derived microvesicles (MVs) are vesicles released from activated or apoptotic cells. However, the levels of MVs in myocardial infarction have been found inconsistent in researches. To assess the association between MVs and myocardial infarction by conducting a meta-analysis. A systematic literature search on PubMed, Embase, Cochran, Google Scholar electronic database was conducted. Comparison of the MVs levels between myocardial infarction patients and healthy persons were included in our study. Standard Mean Difference (SMD) and 95% confidence interval (CI) in groups were calculated and meta-analyzed. 11 studies with a total of 436 participants were included. Compared with the health persons, AMVs [SMD = 3.65, 95% CI (1.03, 6.27)], PMVs [SMD = 2.88, 95% CI (1.82, 3.93),] and EMVs [SMD = 2.73, 95% CI (1.13, 4.34)], levels were higher in patients with myocardial infarction. However, LMVs levels [SMD = 0.73, 95% CI (-0.57, 2.03)] were not changed significantly in patients with myocardial infarction. AMVs, PMVs and EMVs might be potential biomarkers for myocardial infarction. As microvesículas derivadas de células (MVs) são vesículas liberadas de células ativadas ou apoptóticas. No entanto, os níveis de MVs no infarto do miocárdio foram encontrados inconsistentes nas pesquisas. Avaliar a associação entre MV e infarto do miocárdio por meio de uma meta-análise. Foi realizada uma pesquisa sistemática na literatura em PubMed, Embase, Cochran e no banco de dados eletrônico do Google Scholar. Uma comparação dos níveis de MV entre pacientes com infarto do miocárdio e pessoas saudáveis foi incluída no nosso estudo. A Diferença Média Padrão (DMP) e o intervalo de confiança (IC) de 95% nos grupos foram calculadas e meta-analisadas. Foram incluídos 11 estudos com um total de 436 participantes. Em comparação com as pessoas saudáveis, as MVA [DMP = 3,65, IC 95% (1,03, 6,27)], MVPs [DMP = 2,88, IC 95% (1,82, 3,93)] e MVEs [DMP = 2,73, IC 95% (1

26 CFR 1.501(c)(12)-1 - Local benevolent life insurance associations, mutual irrigation and telephone companies, and like...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Local benevolent life insurance associations, mutual irrigation and telephone companies, and like organizations. 1.501(c)(12)-1 Section 1.501(c)(12)-1...) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(c)(12)-1 Local benevolent life insurance...

26 CFR 1.501(c)(12)-1 - Local benevolent life insurance associations, mutual irrigation and telephone companies, and like...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Local benevolent life insurance associations, mutual irrigation and telephone companies, and like organizations. 1.501(c)(12)-1 Section 1.501(c)(12)-1...) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(c)(12)-1 Local benevolent life insurance...

Investigation of global and local network properties of music perception with culturally different styles of music.

PubMed

Li, Yan; Rui, Xue; Li, Shuyu; Pu, Fang

2014-11-01

Graph theoretical analysis has recently become a popular research tool in neuroscience, however, there have been very few studies on brain responses to music perception, especially when culturally different styles of music are involved. Electroencephalograms were recorded from ten subjects listening to Chinese traditional music, light music and western classical music. For event-related potentials, phase coherence was calculated in the alpha band and then constructed into correlation matrices. Clustering coefficients and characteristic path lengths were evaluated for global properties, while clustering coefficients and efficiency were assessed for local network properties. Perception of light music and western classical music manifested small-world network properties, especially with a relatively low proportion of weights of correlation matrices. For local analysis, efficiency was more discernible than clustering coefficient. Nevertheless, there was no significant discrimination between Chinese traditional and western classical music perception. Perception of different styles of music introduces different network properties, both globally and locally. Research into both global and local network properties has been carried out in other areas; however, this is a preliminary investigation aimed at suggesting a possible new approach to brain network properties in music perception. Copyright © 2014 Elsevier Ltd. All rights reserved.

Life prolonging of disease management programs in patients with type 2 diabetes is cost-effective.

PubMed

Drabik, A; Büscher, G; Sawicki, P T; Thomas, K; Graf, C; Müller, D; Stock, S

2012-02-01

Our objective was to examine the cost-effectiveness of disease management programs (DMPs) for type 2 diabetes mellitus (T2DM) taking into account their life prolonging effect. We compared real life costs in 19,888 propensity score matched pairs of T2DM DMP participants and T2DM patients in routine care (RC) according to sickness funds data. We estimated mean annual costs for survivors, last year of life costs for decedents, the influence of ageing on costs, incremental cost-effectiveness ratio and effects on hospitalization. Annual costs for survivors were 3,318€ (DMP) and 3,570€ (RC). The mean costs in the last year of life were 16,911€ (DMP) and 15,763€ (RC). Ageing had a cost triggering effect for survivors (30€/36€ per year in DMP-/RC-group; p<0.001) and a cost decreasing effect in the last year of life (546€/483€ per year in DMP-/RC-group; p<0.001). The incremental cost-effectiveness ratio of the DMP vs. RC was -1396€ per life-year gained. Hospitalizations increased with age in case of survival and decreased with age in case of death but were always lower in the DMP-group. Despite increase in costs due to longer life DMPs are cost-effective. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Localization and expression of clarin-1, the Clrn1 gene product, in auditory hair cells and photoreceptors

PubMed Central

Zallocchi, Marisa; Meehan, Daniel T.; Delimont, Duane; Askew, Charles; Garrige, Suneetha; Gratton, Michael Anne; Rothermund-Franklin, Christie A.; Cosgrove, Dominic

2009-01-01

The Usher syndrome 3A (CLRN1) gene encodes clarin-1, which is a member of the tetraspanin family of transmembrane proteins. Although identified more than 6 years ago, little is known about its localization or function in the eye and ear. We developed a polyclonal antibody that react with all clarin-1 isoforms and used it to characterize protein expression in cochlea and retina. In the cochlea, we observe clarin-1expression in the stereocilia of P0 mice, and in synaptic terminals present at the base of the auditory hair cells from E18 to P6. In the retina, clarin-1 localizes to the connecting cilia, inner segment of photoreceptors and to the ribbon synapses. RT-PCR from P0 cochlea and P28 retina show mRNAs encoding only isoforms 2 and 3. Western-blots show that only isoform 2 is present in protein extracts from these same tissues. We examined clarin-1 expression in the immortomouse-derived hair cell line UB/OC-1. Only isoform 2 is expressed in UB/OC-1 at both mRNA and protein levels, suggesting this isoform is biologically relevant to hair cell function. The protein co-localizes with microtubules and post-transgolgi vesicles. The sub-cellular localization of clarin-1 in hair cells and photoreceptors suggests it functions at both the basal and apical poles of neurosensoriepithelia. PMID:19539019

ADP1 Affects Plant Architecture by Regulating Local Auxin Biosynthesis

PubMed Central

Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

2014-01-01

Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs. PMID:24391508

ADP1 affects plant architecture by regulating local auxin biosynthesis.

PubMed

Li, Ruixi; Li, Jieru; Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

2014-01-01

Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs.

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

PubMed Central

Lange, Stefan; Donges, Jonathan F.; Volkholz, Jan; Kurths, Jürgen

2015-01-01

A faithful modeling of real-world dynamical systems necessitates model evaluation. A recent promising methodological approach to this problem has been based on complex networks, which in turn have proven useful for the characterization of dynamical systems. In this context, we introduce three local network difference measures and demonstrate their capabilities in the field of climate modeling, where these measures facilitate a spatially explicit model evaluation. Building on a recent study by Feldhoff et al. [1] we comparatively analyze statistical and dynamical regional climate simulations of the South American monsoon system. Three types of climate networks representing different aspects of rainfall dynamics are constructed from the modeled precipitation space-time series. Specifically, we define simple graphs based on positive as well as negative rank correlations between rainfall anomaly time series at different locations, and such based on spatial synchronizations of extreme rain events. An evaluation against respective networks built from daily satellite data provided by the Tropical Rainfall Measuring Mission 3B42 V7 reveals far greater differences in model performance between network types for a fixed but arbitrary climate model than between climate models for a fixed but arbitrary network type. We identify two sources of uncertainty in this respect. Firstly, climate variability limits fidelity, particularly in the case of the extreme event network; and secondly, larger geographical link lengths render link misplacements more likely, most notably in the case of the anticorrelation network; both contributions are quantified using suitable ensembles of surrogate networks. Our model evaluation approach is applicable to any multidimensional dynamical system and especially our simple graph difference measures are highly versatile as the graphs to be compared may be constructed in whatever way required. Generalizations to directed as well as edge- and node

Myosin-1C uses a novel phosphoinositide-dependent pathway for nuclear localization.

PubMed

Nevzorov, Ilja; Sidorenko, Ekaterina; Wang, Weihuan; Zhao, Hongxia; Vartiainen, Maria K

2018-02-01

Accurate control of macromolecule transport between nucleus and cytoplasm underlines several essential biological processes, including gene expression. According to the canonical model, nuclear import of soluble proteins is based on nuclear localization signals and transport factors. We challenge this view by showing that nuclear localization of the actin-dependent motor protein Myosin-1C (Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear membrane proteins. We show that Myo1C constantly shuttles in and out of the nucleus and that its nuclear localization does not require soluble factors, but is dependent on phosphoinositide binding. Nuclear import of Myo1C is preceded by its interaction with the endoplasmic reticulum, and phosphoinositide binding is specifically required for nuclear import, but not nuclear retention, of Myo1C. Our results therefore demonstrate, for the first time, that membrane association and binding to nuclear partners is sufficient to drive nuclear localization of also soluble proteins, opening new perspectives to evolution of cellular protein sorting mechanisms. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Impact of Refugees on Local Health Systems: A Difference-in-Differences Analysis in Cameroon.

PubMed

Tatah, Lambed; Delbiso, Tefera Darge; Rodriguez-Llanes, Jose Manuel; Gil Cuesta, Julita; Guha-Sapir, Debarati

2016-01-01

Hosting refugees may represent a drain on local resources, particularly since external aid is frequently insufficient. Between 2004 and 2011, over 100,000 refugees settled in the eastern border of Cameroon. With little known on how refugee influx affects health services of the hosting community, we investigated the impact of refugees on mother and child health (MCH) services in the host community in Cameroon. We used Cameroon's 2004 and 2011 Demographic and Health Surveys to evaluate changes in MCH indicators in the refugee hosting community. Our outcome variables were antenatal care (ANC) coverage, caesarean delivery rate, place of delivery and child vaccination coverage; whereas the exposure variable was residence in the refugee hosting community. We used a difference-in-differences analysis to compare indicators of the refugee hosting community to a control group selected through propensity score matching from the rest of the country. A total of 10,656 women were included in our 2004 analysis and 7.6% (n = 826) of them resided in the refugee hosting community. For 2011, 15,426 women were included and 5.8% (n = 902) of them resided in the hosting community. Between 2004 and 2011, both the proportion of women delivering outside health facilities and children not completing DPT3 vaccination in the refugee hosting community decreased by 9.0% (95% Confidence Interval (CI): 3.9-14.1%) and 9.6% (95% CI: 7.9-11.3%) respectively. However, ANC attendance and caesarean delivery did not show any significant change. Our findings demonstrate that none of the evaluated MCH service indicators deteriorated (in fact, two of them improved: delivery in health facilities and completing DPT3 vaccine) with the presence of refugees. This suggests evidence disproving the common belief that refugees always have a negative impact on their hosting community.

Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles

PubMed Central

Li, Ruohan; Harvey, Alan R.; Hodgetts, Stuart I.

2017-01-01

Large numbers of long noncoding RNAs have been discovered in recent years, but only a few have been characterized. NEAT1 (nuclear paraspeckle assembly transcript 1) is a mammalian long noncoding RNA that is important for the reproductive physiology of mice, cancer development, and the formation of subnuclear bodies termed paraspeckles. The two major isoforms of NEAT1 (3.7 kb NEAT1_1 and 23 kb NEAT1_2 in human) are generated from a common promoter and are produced through the use of alternative transcription termination sites. This gene structure has made the functional relationship between the two isoforms difficult to dissect. Here we used CRISPR-Cas9 genome editing to create several different cell lines: total NEAT1 knockout cells, cells that only express the short form NEAT1_1, and cells with twofold more NEAT1_2. Using these reagents, we obtained evidence that NEAT1_1 is not a major component of paraspeckles. In addition, our data suggest NEAT1_1 localizes in numerous nonparaspeckle foci we termed “microspeckles,” which may carry paraspeckle-independent functions. This study highlights the complexity of lncRNA and showcases how genome editing tools are useful in dissecting the structural and functional roles of overlapping transcripts. PMID:28325845

Tissue oxidative metabolism can increase the difference between local temperature and arterial blood temperature by up to 1.3oC: Implications for brain, brown adipose tissue, and muscle physiology.

PubMed

Zaretsky, Dmitry V; Romanovsky, Andrej A; Zaretskaia, Maria V; Molkov, Yaroslav I

2018-01-01

Tissue temperature increases, when oxidative metabolism is boosted. The source of nutrients and oxygen for this metabolism is the blood. The blood also cools down the tissue, and this is the only cooling mechanism, when direct dissipation of heat from the tissue to the environment is insignificant, e.g. , in the brain. While this concept is relatively simple, it has not been described quantitatively. The purpose of the present work was to answer two questions: 1) to what extent can oxidative metabolism make the organ tissue warmer than the body core, and, 2) how quickly are changes in the local metabolism reflected in the temperature of the tissue? Our theoretical analysis demonstrates that, at equilibrium, given that heat exchange with the organ is provided by the blood, the temperature difference between the organ tissue and the arterial blood is proportional to the arteriovenous difference in oxygen content, does not depend on the blood flow, and cannot exceed 1.3 o C. Unlike the equilibrium temperature difference, the rate of change of the local temperature, with respect to time, does depend on the blood flow. In organs with high perfusion rates, such as the brain and muscles, temperature changes occur on a time scale of a few minutes. In organs with low perfusion rates, such changes may have characteristic time constants of tens or hundreds of minutes. Our analysis explains, why arterial blood temperature is the main determinant of the temperature of tissues with limited heat exchange, such as the brain.

Stress Chaperone GRP-78 Functions in Mineralized Matrix Formation*

PubMed Central

Ravindran, Sriram; Gao, Qi; Ramachandran, Amsaveni; Blond, Sylvie; Predescu, Sanda A.; George, Anne

2011-01-01

Mineralized matrix formation is a well orchestrated event requiring several players. Glucose-regulated protein-78 (GRP-78) is an endoplasmic reticulum chaperone protein that has been implicated in functional roles ranging from involvement in cancer biology to serving as a receptor for viruses. In the present study we explored the role of GRP-78 in mineralized matrix formation. Differential expression of GRP-78 mRNA and protein was observed upon in vitro differentiation of primary mouse calvarial cells. An interesting observation was that GRP-78 was identified in the secretome of these cells and in the bone matrix, suggesting an extracellular function during matrix formation. In vitro nucleation experiments under physiological concentrations of calcium and phosphate ions indicated that GRP-78 can induce the formation of calcium phosphate polymorphs by itself, when bound to immobilized type I collagen and on demineralized collagen wafers. We provide evidence that GRP-78 can bind to DMP1 and type I collagen independent of each other in a simulated extracellular environment. Furthermore, we demonstrate the cell surface localization of GRP-78 and provide evidence that it functions as a receptor for DMP1 endocytosis in pre-osteoblasts and primary calvarial cells. Overall, this study represents a paradigm shift in the biological function of GRP-78. PMID:21239500

The variance of the locally measured Hubble parameter explained with different estimators

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

Odderskov, Io; Hannestad, Steen; Brandbyge, Jacob, E-mail: isho07@phys.au.dk, E-mail: sth@phys.au.dk, E-mail: jacobb@phys.au.dk

We study the expected variance of measurements of the Hubble constant, H {sub 0}, as calculated in either linear perturbation theory or using non-linear velocity power spectra derived from N -body simulations. We compare the variance with that obtained by carrying out mock observations in the N-body simulations, and show that the estimator typically used for the local Hubble constant in studies based on perturbation theory is different from the one used in studies based on N-body simulations. The latter gives larger weight to distant sources, which explains why studies based on N-body simulations tend to obtain a smaller variancemore » than that found from studies based on the power spectrum. Although both approaches result in a variance too small to explain the discrepancy between the value of H {sub 0} from CMB measurements and the value measured in the local universe, these considerations are important in light of the percent determination of the Hubble constant in the local universe.« less

Ambiguity resolving based on cosine property of phase differences for 3D source localization with uniform circular array

NASA Astrophysics Data System (ADS)

Chen, Xin; Wang, Shuhong; Liu, Zhen; Wei, Xizhang

2017-07-01

Localization of a source whose half-wavelength is smaller than the array aperture would suffer from serious phase ambiguity problem, which also appears in recently proposed phase-based algorithms. In this paper, by using the centro-symmetry of fixed uniform circular array (UCA) with even number of sensors, the source's angles and range can be decoupled and a novel ambiguity resolving approach is addressed for phase-based algorithms of source's 3-D localization (azimuth angle, elevation angle, and range). In the proposed method, by using the cosine property of unambiguous phase differences, ambiguity searching and actual-value matching are first employed to obtain actual phase differences and corresponding source's angles. Then, the unambiguous angles are utilized to estimate the source's range based on a one dimension multiple signal classification (1-D MUSIC) estimator. Finally, simulation experiments investigate the influence of step size in search and SNR on performance of ambiguity resolution and demonstrate the satisfactory estimation performance of the proposed method.

[Tissue localization and expression difference of endogenous beta-glucosidase in digestive system of Musca domestica third instar larvae].

PubMed

Hu, Rong; Zhang, Shu; Wu, Jian-Wei; Guo, Guo; Fu, Ping

2013-08-01

To study the tissue localization and expression difference of endogenous beta-glucosidase in digestive system of Musca domestica third instar larvae. The digestive system of the 3rd instar larvae of Musca domestic was taken for the below tests. Tissue localization of endogenous beta-glucosidase mRNA was identified by in situ hybridization. Cellulase was localized by immunohistochemistry. The enzymatic activity of beta-glucosidase was measured by 3, 5-dinitrosalicylic acid(DNS) assay. The relative mRNA expression levels of M. domestica beta-glucosidase gene in these organs were determined by RT-PCR. Beta-glucosidase mRNA, with in situ hybridization, was shown in the epithelial cells of midgut, salivary glands and foregut of the larvae. The immunohistochemical analysis on larvae tissues revealed that cellulase was produced and secreted by the epithelial cells of the midgut, salivary glands and foregut. beta-glucosidase activity in salivary glands, foregut, midgut, and hindgut was (0.80 +/- 0.06), (0.38 +/- 0.02), (1.20 +/- 0.05) and (0.26 +/- 0.02) IU/mg, respectively. There was significant difference in beta-glucosidase activity among these digestive organs (P < 0.05). The activity level of beta-glucosidase was highest in midgut [(45.45 +/- 1.27)%], and lowest in hindgut [(9.85 +/- 0.88)%]. However, beta-glucosidase gene were only expressed in the salivary gland, foregut and midgut. Significant differences in gene expression level of beta-glucosidase was found among these organs (P < 0.05). The relative expression quantity of beta-glucosidase gene in midgut and salivary glands were 5 and 3 times higher than that in foregut. The endogenous beta-glucosidase gene is expressed in the foregut, midgut and salivary glands. The midgut and salivary glands of Musca domestica 3rd instar larvae are the primary organs of this enzyme secretion.

Quantifying Differences and Similarities in Whole-Brain White Matter Architecture Using Local Connectome Fingerprints

PubMed Central

Singh, Aarti; Poczos, Barnabas; Erickson, Kirk I.; Tseng, Wen-Yih I.; Verstynen, Timothy D.

2016-01-01

Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N = 213), we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns for repeat scans acquired within 3 months. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings, relative to differences between unrelated subjects. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome. PMID:27846212

Local Delivery Is Critical for Monocyte Chemotactic Protein-1 Mediated Site-Specific Murine Aneurysm Healing.

PubMed

Hourani, Siham; Motwani, Kartik; Wajima, Daisuke; Fazal, Hanain; Jones, Chad H; Doré, Sylvain; Hosaka, Koji; Hoh, Brian L

2018-01-01

Local delivery of monocyte chemotactic protein-1 (MCP-1/CCL2) via our drug-eluting coil has been shown to promote intrasaccular aneurysm healing via an inflammatory pathway. In this study, we validate the importance of local MCP-1 in murine aneurysm healing. Whether systemic, rather than local, delivery of MCP-1 can direct site-specific aneurysm healing has significant translational implications. If systemic MCP-1 is effective, then MCP-1 could be administered as a pill rather than by endovascular procedure. Furthermore, we confirm that MCP-1 is the primary effector in our MCP-1 eluting coil-mediated murine aneurysm healing model. We compare aneurysm healing with repeated intraperitoneal MCP-1 versus vehicle injection, in animals with control poly(lactic-co-glycolic) acid (PLGA)-coated coils. We demonstrate elimination of the MCP-1-associated tissue-healing response by knockout of MCP-1 or CCR2 (MCP-1 receptor) and by selectively inhibiting MCP-1 or CCR2. Using immunofluorescent probing, we explore the cell populations found in healed aneurysm tissue following each intervention. Systemically administered MCP-1 with PLGA coil control does not produce comparable aneurysm healing, as seen with MCP-1 eluting coils. MCP-1-directed aneurysm healing is eliminated by selective inhibition of MCP-1 or CCR2 and in MCP-1-deficient or CCR2-deficient mice. No difference was detected in M2 macrophage and myofibroblast/smooth muscle cell staining with systemic MCP-1 versus vehicle in aneurysm wall, but a significant increase in these cell types was observed with MCP-1 eluting coil implant and attenuated by MCP-1/CCR2 blockade or deficiency. We show that systemic MCP-1 concurrent with PLGA-coated platinum coil implant is not sufficient to produce site-specific aneurysm healing. MCP-1 is a critical, not merely complementary, actor in the aneurysm healing pathway.

Benefit and adherence of the disease management program "diabetes 2": a comparison of Turkish immigrants and German natives with diabetes.

PubMed

Makowski, Anna Christin; Kofahl, Christopher

2014-09-17

There is an ongoing debate about equity and equality in health care, and whether immigrants benefit equally from services as the non-immigrant population. The study focuses on benefits from and adherence to the diabetes mellitus type 2 (DM 2) disease management program (DMP) among Turkish immigrants in Germany. So far, it has not been researched whether this group benefits from enrollment in the DMP as well as diabetics from the non-immigrant population. Data on the non-immigrant sample (N = 702) stem from a survey among members of a German health insurance, the Turkish immigrant sample (N = 102) was recruited in the area of Hamburg. Identical questions in both surveys enable comparing major components. Regarding process quality, Turkish diabetics do not differ from the non-immigrant sample; moreover, they have significantly more often received documentation and diabetes training. In terms of outcome quality however, results display a greater benefit on behalf of the non-immigrant sample (e.g., blood parameters and body mass index), and they also met more of the DMP criteria. This underlines the need of diabetics with Turkish background for further education and information in order to become the empowered patient as is intended by the DMP as well as to prevent comorbidities.

Toxic effects of several phthalate esters on the embryos and larvae of abalone Haliotis diversicolor supertexta

NASA Astrophysics Data System (ADS)

Yang, Zhihui; Zhang, Xiangjing; Cai, Zhonghua

2009-05-01

As the most widely used plasticizers in the world, phthalate esters (PAEs) are potential endocrine disruption compounds (EDCs). In the present study, the toxicity of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), di (2-ethylhexyl) phthalate (DEHP) on embryogenesis and larvae development of the marine univalve Haliotis diversicolor supertexta was examined in laboratory. The results show that the malformation of embryos appeared during the experiment, such as embryos died or lysed, small transparent flocculent rings studded on the periphery of the embryo, and the larvae could failed to hatch. In embryo toxic test, embryos incubated at the highest concentration of DMP, DEP and DBP solutions showed significantly high abnormal rate compared with the control, while DEHP solutions displayed no significant difference. In larval toxic test, in all concentrations of DMP, DEP and DBP solutions, larval settlement rates were low significantly than that of the control. Similarly, DEHP solutions show nearly no effect on the larval settlement. The order of toxicity on embryos and larvae is DBP>DEP>DMP>DEHP. Being a simple and easy stimulation to indoor spawn, sensitive to environmental factors, and short culture time, the embryos of H. diversicolor supertexta can be used to indicate toxicity of the PAEs.

Benefit and Adherence of the Disease Management Program “Diabetes 2”: A Comparison of Turkish Immigrants and German Natives with Diabetes

PubMed Central

Makowski, Anna Christin; Kofahl, Christopher

2014-01-01

There is an ongoing debate about equity and equality in health care, and whether immigrants benefit equally from services as the non-immigrant population. The study focuses on benefits from and adherence to the diabetes mellitus type 2 (DM 2) disease management program (DMP) among Turkish immigrants in Germany. So far, it has not been researched whether this group benefits from enrollment in the DMP as well as diabetics from the non-immigrant population. Data on the non-immigrant sample (N = 702) stem from a survey among members of a German health insurance, the Turkish immigrant sample (N = 102) was recruited in the area of Hamburg. Identical questions in both surveys enable comparing major components. Regarding process quality, Turkish diabetics do not differ from the non-immigrant sample; moreover, they have significantly more often received documentation and diabetes training. In terms of outcome quality however, results display a greater benefit on behalf of the non-immigrant sample (e.g., blood parameters and body mass index), and they also met more of the DMP criteria. This underlines the need of diabetics with Turkish background for further education and information in order to become the empowered patient as is intended by the DMP as well as to prevent comorbidities. PMID:25233016

Panconnectivity of Locally Connected K(1,3)-Free Graphs

DTIC Science & Technology

1989-10-15

Graph Theory, 3 (1979) p. 351-356. 22 7. Cun-Quan Zhang, Cycles of Given Lengths in KI, 3-Free Graphs, Discrete Math ., (1988) to appear. I. f 2.f 𔃽. AA A V V / (S. ...Locally Connected and Hamiltonian-Connected Graphs, Isreal J. Math., 33 (1979) p. 5-8. 4. V. Chvatal and P. Erd6s, A Note on Hamiltonian Circuits, Discrete ... Math ., 2 (1972) p. 111-113. 5. S. V. Kanetkar and P. R. Rao, Connected and Locally 2- Connected, K1.3-Free Graphs are Panconnected, J. Graph Theory, 8

Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine

PubMed Central

Werneck de Castro, Joao Pedro; Fonseca, Tatiana L.; Ueta, Cintia B.; McAninch, Elizabeth A.; Abdalla, Sherine; Wittmann, Gabor; Lechan, Ronald M.; Gereben, Balazs; Bianco, Antonio C.

2015-01-01

The current treatment for patients with hypothyroidism is levothyroxine (L-T4) along with normalization of serum thyroid-stimulating hormone (TSH). However, normalization of serum TSH with L-T4 monotherapy results in relatively low serum 3,5,3′-triiodothyronine (T3) and high serum thyroxine/T3 (T4/T3) ratio. In the hypothalamus-pituitary dyad as well as the rest of the brain, the majority of T3 present is generated locally by T4 deiodination via the type 2 deiodinase (D2); this pathway is self-limited by ubiquitination of D2 by the ubiquitin ligase WSB-1. Here, we determined that tissue-specific differences in D2 ubiquitination account for the high T4/T3 serum ratio in adult thyroidectomized (Tx) rats chronically implanted with subcutaneous L-T4 pellets. While L-T4 administration decreased whole-body D2-dependent T4 conversion to T3, D2 activity in the hypothalamus was only minimally affected by L-T4. In vivo studies in mice harboring an astrocyte-specific Wsb1 deletion as well as in vitro analysis of D2 ubiquitination driven by different tissue extracts indicated that D2 ubiquitination in the hypothalamus is relatively less. As a result, in contrast to other D2-expressing tissues, the hypothalamus is wired to have increased sensitivity to T4. These studies reveal that tissue-specific differences in D2 ubiquitination are an inherent property of the TRH/TSH feedback mechanism and indicate that only constant delivery of L-T4 and L-T3 fully normalizes T3-dependent metabolic markers and gene expression profiles in Tx rats. PMID:25555216

Subcellular localization of rat CYP2E1 impacts metabolic efficiency toward common substrates.

PubMed

Hartman, Jessica H; Martin, H Cass; Caro, Andres A; Pearce, Amy R; Miller, Grover P

2015-12-02

Cytochrome P450 2E1 (CYP2E1) detoxifies or bioactivates many low molecular-weight compounds. Most knowledge about CYP2E1 activity relies on studies of the enzyme localized to endoplasmic reticulum (erCYP2E1); however, CYP2E1 undergoes transport to mitochondria (mtCYP2E1) and becomes metabolically active. We report the first comparison of in vitro steady-state kinetic profiles for erCYP2E1 and mtCYP2E1 oxidation of probe substrate 4-nitrophenol and pollutants styrene and aniline using subcellular fractions from rat liver. For all substrates, metabolic efficiency changed with substrate concentration for erCYP2E1 reflected in non-hyperbolic kinetic profiles but not for mtCYP2E1. Hyperbolic kinetic profiles for the mitochondrial enzyme were consistent with Michaelis-Menten mechanism in which metabolic efficiency was constant. By contrast, erCYP2E1 metabolism of 4-nitrophenol led to a loss of enzyme efficiency at high substrate concentrations when substrate inhibited the reaction. Similarly, aniline metabolism by erCYP2E1 demonstrated negative cooperativity as metabolic efficiency decreased with increasing substrate concentration. The opposite was observed for erCYP2E1 oxidation of styrene; the sigmoidal kinetic profile indicated increased efficiency at higher substrate concentrations. These mechanisms and CYP2E1 levels in mitochondria and endoplasmic reticulum were used to estimate the impact of CYP2E1 subcellular localization on metabolic flux of pollutants. Those models showed that erCYP2E1 mainly carries out aniline metabolism at all aniline concentrations. Conversely, mtCYP2E1 dominates styrene oxidation at low styrene concentrations and erCYP2E1 at higher concentrations. Taken together, subcellular localization of CYP2E1 results in distinctly different enzyme activities that could impact overall metabolic clearance and/or activation of substrates and thus impact the interpretation and prediction of toxicological outcomes. Copyright © 2015 Elsevier Ireland Ltd

Integration Processes Compared: Cortical Differences for Consistency Evaluation and Passive Comprehension in Local and Global Coherence.

PubMed

Egidi, Giovanna; Caramazza, Alfonso

2016-10-01

This research studies the neural systems underlying two integration processes that take place during natural discourse comprehension: consistency evaluation and passive comprehension. Evaluation was operationalized with a consistency judgment task and passive comprehension with a passive listening task. Using fMRI, the experiment examined the integration of incoming sentences with more recent, local context and with more distal, global context in these two tasks. The stimuli were stories in which we manipulated the consistency of the endings with the local context and the relevance of the global context for the integration of the endings. A whole-brain analysis revealed several differences between the two tasks. Two networks previously associated with semantic processing and attention orienting showed more activation during the judgment than the passive listening task. A network previously associated with episodic memory retrieval and construction of mental scenes showed greater activity when global context was relevant, but only during the judgment task. This suggests that evaluation, more than passive listening, triggers the reinstantiation of global context and the construction of a rich mental model for the story. Finally, a network previously linked to fluent updating of a knowledge base showed greater activity for locally consistent endings than inconsistent ones, but only during passive listening, suggesting a mode of comprehension that relies on a local scope approach to language processing. Taken together, these results show that consistency evaluation and passive comprehension weigh differently on distal and local information and are implemented, in part, by different brain networks.

Localization and quantitative co-localization of enamelin with amelogenin.

PubMed

Gallon, Victoria; Chen, Lisha; Yang, Xiudong; Moradian-Oldak, Janet

2013-08-01

Enamelin and amelogenin are vital proteins in enamel formation. The cooperative function of these two proteins controls crystal nucleation and morphology in vitro. We quantitatively analyzed the co-localization between enamelin and amelogenin by confocal microscopy and using two antibodies, one raised against a sequence in the porcine 32 kDa enamelin region and the other raised against full-length recombinant mouse amelogenin. We further investigated the interaction of the porcine 32 kDa enamelin and recombinant amelogenin using immuno-gold labeling. This study reports the quantitative co-localization results for postnatal days 1-8 mandibular mouse molars. We show that amelogenin and enamelin are secreted into the extracellular matrix on the cuspal slopes of the molars at day 1 and that secretion continues to at least day 8. Quantitative co-localization analysis (QCA) was performed in several different configurations using large (45 μm height, 33 μm width) and small (7 μm diameter) regions of interest to elucidate any patterns. Co-localization patterns in day 8 samples revealed that enamelin and amelogenin co-localize near the secretory face of the ameloblasts and appear to be secreted approximately in a 1:1 ratio. The degree of co-localization decreases as the enamel matures, both along the secretory face of ameloblasts and throughout the entire thickness of the enamel. Immuno-reactivity against enamelin is concentrated along the secretory face of ameloblasts, supporting the theory that this protein together with amelogenin is intimately involved in mineral induction at the beginning of enamel formation. Copyright © 2013 Elsevier Inc. All rights reserved.

Potential toxicity of phthalic acid esters plasticizer: interaction of dimethyl phthalate with trypsin in vitro.

PubMed

Wang, Yaping; Zhang, Guowen; Wang, Langhong

2015-01-14

Dimethyl phthalate (DMP) is widely used as a plasticizer in industrial processes and has been reported to possess potential toxicity to the human body. In this study, the interaction between DMP and trypsin in vitro was investigated. The results of fluorescence, UV–vis, circular dichroism, and Fourier transform infrared spectra along with cyclic voltammetric measurements indicated that the remarkable fluorescence quenching and conformational changes of trypsin resulted from the formation of a DMP–trypsin complex, which was driven mainly by hydrophobic interactions. The molecular docking and trypsin activity assay showed that DMP primarily interacted with the catalytic triad of trypsin and led to the inhibition of trypsin activity. The dimensions of the individual trypsin molecules were found to become larger after binding with DMP by atomic force microscopy imaging. This study offers a comprehensive picture of DMP–trypsin interaction, which is expected to provide insights into the toxicological effect of DMP.

Unit 1, downstream from Laurel Run Johnstown Local Flood ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Unit 1, downstream from Laurel Run - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

Blue copper model complexes with distorted tetragonal geometry acting as effective electron-transfer mediators in dye-sensitized solar cells.

PubMed

Hattori, Shigeki; Wada, Yuji; Yanagida, Shozo; Fukuzumi, Shunichi

2005-07-06

The electron self-exchange rate constants of blue copper model complexes, [(-)-sparteine-N,N'](maleonitriledithiolato-S,S')copper ([Cu(SP)(mmt)])(0/)(-), bis(2,9-dimethy-1,10-phenanthroline)copper ([Cu(dmp)(2)](2+/+)), and bis(1,10-phenanthroline)copper ([Cu(phen)(2)](2+/+)) have been determined from the rate constants of electron transfer from a homologous series of ferrocene derivatives to the copper(II) complexes in light of the Marcus theory of electron transfer. The resulting electron self-exchange rate constant increases in the order: [Cu(phen)(2)](2+/+) < [Cu(SP)(mmt)](0/)(-) < [Cu(dmp)(2)](2+/+), in agreement with the order of the smaller structural change between the copper(II) and copper(I) complexes due to the distorted tetragonal geometry. The dye-sensitized solar cells (DSSC) were constructed using the copper complexes as redox couples to compare the photoelectrochemical responses with those using the conventional I(3)(-)/I(-) couple. The light energy conversion efficiency (eta) values under illumination of simulated solar light irradiation (100 mW/cm(2)) of DSSCs using [Cu(phen)(2)](2+/+), [Cu(dmp)(2)](2+/+), and [Cu(SP)(mmt)](0/)(-) were recorded as 0.1%, 1.4%, and 1.3%, respectively. The maximum eta value (2.2%) was obtained for a DSSC using the [Cu(dmp)(2)](2+/+) redox couple under the light irradiation of 20 mW/cm(2) intensity, where a higher open-circuit voltage of the cell was attained as compared to that of the conventional I(3)(-)/I(-) couple.

Synthesis and characterization of a family of structurally characterized dysprosium alkoxides for improved fatigue-resistance characteristics of PDyZT thin films.

PubMed

Boyle, Timothy J; Bunge, Scott D; Clem, Paul G; Richardson, Jacob; Dawley, Jeffrey T; Ottley, Leigh Anna M; Rodriguez, Mark A; Tuttle, Bruce A; Avilucea, Gabriel R; Tissot, Ralph G

2005-03-07

Using either an ammoniacal route, the reaction between DyCl3, Na0, and HOR in liquid ammonia, or preferentially reacting Dy(N(SiMe3)2)3 with HOR in a solvent, we isolated a family of dysprosium alkoxides as [Dy(mu-ONep)2(ONep)]4 (1), (ONep)2Dy[(mu3-ONep)(mu-ONep)Dy(ONep)(THF)]2(mu-ONep) (2), (ONep)2Dy[(mu3-ONep)(mu-ONep)Dy(ONep)(py)]2(mu-ONep) (3), [Dy3(mu3-OBut)2(mu-OBut3(OBut)4(HOBut)2] (4), [Dy3(mu3-OBut)2(mu-OBut)3(OBut)4(THF)2] (5), [Dy3(mu3-OBut)2(mu-OBut)3(OBut)4(py)2] (6), (DMP)Dy(mu-DMP)4[Dy(DMP)2(NH3)]2 (7), [Dy(eta6-DMP)(DMP)2]2 (8), Dy(DMP)3(THF)3 (9), Dy(DMP)3(py)3 (10), Dy(DIP)3(NH3)2 (11), [Dy(eta6-DIP)(DIP)2]2 (12), Dy(DIP)3(THF)2 (13), Dy(DIP)3(py)3 (14), Dy(DBP)3(NH3) (15), Dy(DBP)3 (16), Dy(DBP)3(THF) (17), Dy(DBP)3(py)2 (18), [Dy(mu-TPS)(TPS2]2 (19), Dy(TPS)3(THF)3 (20), and Dy(TPS)3(py)3 (21), where ONep = OCH2CMe3, OBut) = OCMe3, DMP = OC6H3(Me)(2)-2,6, DIP = OC6H3(CHMe2)(2)-2,6, DBP = OC6H3(CMe3)(2)-2,6, TPS = OSi(C6H5)3, tol = toluene, THF = tetrahydrofuran, and py = pyridine. We were not able to obtain X-ray quality crystals of compounds 2, 8, and 9. The structures observed and data collected for the Dy compounds are consistent with those reported for its other congeners. A number of these precursors were used as Dy dopants in Pb(Zr0.3Ti0.7)O3 (PZT 30/70) thin films, with compound 12 yielding the highest-quality films. The resulting Pb0.94Dy0.04(Zr0.3Ti0.7)O3 [PDyZT (4/30/70)] had similar properties to PZT (30/70), but showed substantial resistance to polarization reversal fatigue.

Laccase-catalyzed removal of 2,4-dimethylphenol from synthetic wastewater: effect of polyethylene glycol and dissolved oxygen.

PubMed

Ghosh, J P; Taylor, K E; Bewtra, J K; Biswas, N

2008-04-01

The potential use of laccase (SP-504) in an advanced oxidation-based treatment technology to remove 2,4-dimethylphenol (DMP) from water was investigated with and without the additive, polyethylene glycol (PEG). The DMP concentration was varied between 1.0 and 5.0 mM. The optimization of pH and enzyme concentration in the presence and absence of PEG was carried out. All experiments were carried out in continuously stirred reactors for 3h at room temperature. The reaction was initiated by adding enzyme to the reaction mixture. For more than 95% removal of DMP, the presence of PEG reduced the inactivation of enzyme so that the required enzyme concentrations were reduced by about 2-fold compared to the same reactions in the absence of PEG. Finally, the PEG concentrations were optimized to obtain the minimum dose required. For higher substrate concentrations, the availability of oxygen was insufficient in achieving 95% or more removal. Therefore, the effect of increasing dissolved oxygen at higher substrate concentration was investigated. The laccase studied was capable of efficiently removing DMP at very low enzyme concentrations and hence shows great potential for cost-effective industrial applications.

Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia

PubMed Central

Feng, Jian Q.; Clinkenbeard, Erica L.; Yuan, Baozhi; White, Kenneth E.; Drezner, Marc K.

2013-01-01

Although recent studies have established that osteocytes function as secretory cells that regulate phosphate metabolism, the biomolecular mechanism(s) underlying these effects remain incompletely defined. However, investigations focusing on the pathogenesis of X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR), heritable disorders characterized by abnormal renal phosphate wasting and bone mineralization, have clearly implicated FGF23 as a central factor in osteocytes underlying renal phosphate wasting, documented new molecular pathways regulating FGF23 production, and revealed complementary abnormalities in osteocytes that regulate bone mineralization. The seminal observations leading to these discoveries were the following: 1) mutations in FGF23 cause ADHR by limiting cleavage of the bioactive intact molecule, at a subtilisin-like protein convertase (SPC) site, resulting in increased circulating FGF23 levels and hypophosphatemia; 2) mutations in DMP1 cause ARHR, not only by increasing serum FGF23, albeit by enhanced production and not limited cleavage, but also by limiting production of the active DMP1 component, the C-terminal fragment, resulting in dysregulated production of DKK1 and β-catenin, which contributes to impaired bone mineralization; and 3) mutations in PHEX cause XLH both by altering FGF23 proteolysis and production and causing dysregulated production of DKK1 and β-catenin, similar to abnormalities in ADHR and ARHR, but secondary to different central pathophysiological events. These discoveries indicate that ADHR, XLH, and ARHR represent three related heritable hypophosphatemic diseases that arise from mutations in, or dysregulation of, a single common gene product, FGF23 and, in ARHR and XLH, complimentary DMP1 and PHEX directed events that contribute to abnormal bone mineralization. PMID:23403405

Sound-localization experiments with barn owls in virtual space: influence of broadband interaural level different on head-turning behavior.

PubMed

Poganiatz, I; Wagner, H

2001-04-01

Interaural level differences play an important role for elevational sound localization in barn owls. The changes of this cue with sound location are complex and frequency dependent. We exploited the opportunities offered by the virtual space technique to investigate the behavioral relevance of the overall interaural level difference by fixing this parameter in virtual stimuli to a constant value or introducing additional broadband level differences to normal virtual stimuli. Frequency-specific monaural cues in the stimuli were not manipulated. We observed an influence of the broadband interaural level differences on elevational, but not on azimuthal sound localization. Since results obtained with our manipulations explained only part of the variance in elevational turning angle, we conclude that frequency-specific cues are also important. The behavioral consequences of changes of the overall interaural level difference in a virtual sound depended on the combined interaural time difference contained in the stimulus, indicating an indirect influence of temporal cues on elevational sound localization as well. Thus, elevational sound localization is influenced by a combination of many spatial cues including frequency-dependent and temporal features.

Local metric dimension of circulant graph c i r c (n :1 ,2 ,…,n/+1 2 )

NASA Astrophysics Data System (ADS)

Rimadhany, Ruzika; Darmaji

2017-08-01

Let G be a connected graph with two vertices u and v. The distance between u and v, denoted by d(u, v), is defined as length of the shortest path from u to v in G. For an ordered set W = {w1, w2, w3, … , wk} of k distinct vertices in a nontrivial connected graph G, the representation of a vertex v of V(G) respect to W is r(v|W) = (d(v, w1), d(v, w2), … , d(v, wk)). The set W is a resolving set of G if r(v|W) for each vertex v ∈ V(G) is distinct. A resolving set of minimum cardinality is a metric dimension and denoted by dim(G). The set W is a local resolving set of G if r(v|W) for every two adjacent vertices of V(G) is distinct. The minimum cardinality of local resolving set of G is a local metric dimension and denoted by ldim(G). In this research, we determine local metric dimension of circulant graph c i r c (n :1 ,2 ,3 ,…,n/+1 2 ) .

Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1.

PubMed

Midro, Alina T; Zollino, Marcella; Wiland, Ewa; Panasiuk, Barbara; Iwanowski, Piotr S; Murdolo, Marina; Śmigiel, Robert; Sąsiadek, Maria; Pilch, Jacek; Kurpisz, Maciej

2016-02-01

The purpose of this study was to compare meiotic segregation in sperm cells from two carriers with t(4;8)(p16;p23.1) reciprocal chromosome translocations (RCTs), differing in localization of the breakpoint positions at the 4p subband-namely, 4p16.3 (carrier 1) and 4p16.1 (carrier 2)-and to compare data of the pedigree analyses performed by direct method. Three-color fluorescent in situ hybridization (FISH) on sperm cells and FISH mapping for the evaluation of the breakpoint positions, data from pedigrees, and direct segregation analysis of the pedigrees were performed. Similar proportions of normal/balanced and unbalanced sperm cells were found in both carriers. The most common was an alternate type of segregation (about 52 % and about 48 %, respectively). Unbalanced adjacent I and adjacent II karyotypes were found in similar proportions about 15 %. The direct segregation analysis (following Stengel-Rutkowski) of the pedigree of carriers of t(4;8)(p16.1;p23.1) was performed and results were compared with the data of the pedigree segregation analysis obtained earlier through the indirect method. The probability of live-born progeny with unbalanced karyotype for carriers of t(4;8)(p16.1;p23.1) was moderately high at 18.8 %-comparable to the value obtained using the indirect method for the same carriership, which was 12 %. This was, however, markedly lower than the value of 41.2 % obtained through the pedigree segregation indirect analysis estimated for carriers of t(4;8)(p16.3;p23.1), perhaps due to the unique composition of genes present within the 4p16.1-4p 16.3 region. Revealed differences in pedigree segregation analysis did not correspond to the very similar profile of meiotic segregation patterns presented by carrier 1 and carrier 2. Most probably, such discordances may be due to differences in embryo survival rates arising from different genetic backgrounds.

Enzyme activity in dialkyl phosphate ionic liquids

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

Thomas, M.F.; Dunn, J.; Li, L.-L.

2011-12-01

The activity of four metagenomic enzymes and an enzyme cloned from the straw mushroom, Volvariellavolvacea were studied in the following ionic liquids, 1,3-dimethylimidazolium dimethyl phosphate, [mmim][dmp], 1-ethyl-3-methylimidazolium dimethyl phosphate, [emim][dmp], 1-ethyl-3-methylimidazolium diethyl phosphate, [emim][dep] and 1-ethyl-3-methylimidazolium acetate, [emim][OAc]. Activity was determined by analyzing the hydrolysis of para-nitrobenzene carbohydrate derivatives. In general, the enzymes were most active in the dimethyl phosphate ionic liquids, followed by acetate. Generally speaking, activity decreased sharply for concentrations of [emim][dep] above 10% v/v, while the other ionic liquids showed less impact on activity up to 20% v/v.

Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif.

PubMed

Hernández-Sánchez, Itzell E; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P; Jiménez-Bremont, Juan F

2015-01-01

The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization.

Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

PubMed Central

Hernández-Sánchez, Itzell E.; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P.; Jiménez-Bremont, Juan F.

2015-01-01

The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization. PMID:26442018

CCHCR1 interacts with EDC4, suggesting its localization in P-bodies

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

Ling, Y.H.; Wong, C.C.; Li, K.W.

2014-09-10

Coiled‐coil alpha‐helical rod protein 1 (CCHCR1) is suggested as a candidate biomarker for psoriasis for more than a decade but its function remains poorly understood because of the inconsistent findings in the literature. CCHCR1 protein is suggested to be localized in the cytoplasm, nucleus, mitochondria, or centrosome and to regulate various cellular functions, including steroidogenesis, proliferation, differentiation, and cytoskeleton organization. In this study, we attempted to find a consensus between these findings by identifying the interaction partners of CCHCR1 using co-immunoprecipiation with a stable cell line expressing EGFP-tagged CCHCR1. Out of more than 100 co-immunoprecipitants identified by liquid chromatography-tandem massmore » spectrometry (LC-MS/MS), the enhancer of mRNA-decapping protein 4 (EDC4), which is a processing body (P-body) component, was particularly found to be the major interacting partner of CCHCR1. Confocal imaging confirmed the localization of CCHCR1 in P-bodies and its N-terminus is required for this subcellular localization, suggesting that CCHCR1 is a novel P-body component. As P-bodies are the site for mRNA metabolism, our findings provide a molecular basis for the function of CCHCR1, any disruption of which may affect the transcriptome of the cell, and causing abnormal cell functions. - Highlights: • We identified CCHCR1 as a novel P-body component. • We identified EDC4 as the major interacting partner of CCHCR1. • N-terminus of CCHCR1 protein is required for its P-bodies localization.« less

Tissue dielectric constant (TDC) as an index of localized arm skin water: differences between measuring probes and genders.

PubMed

Mayrovitz, H N; Weingrad, D N; Brlit, F; Lopez, L B; Desfor, R

2015-03-01

An easily measured, non-invasive, quantitative estimate of local skin tissue water is useful to assess local lymphedema and its change. One method uses skin tissue dielectric constant (TDC) values that at 300 MHz TDC depend on free and bound water within the measurement volume. In practice such measurements have been done with a research-type multi-probe, but recently a hand-held compact-probe has become available that may be more clinically convenient. Because most available published data is based on multiprobe measurements it is important to characterize possible differences between devices that unless known might lead to ambiguous quantitative comparisons between TDC values. Thus, our purpose was to evaluate potential differences in measured TDC values between multi-probe and compact-probe devices with respect to probe effective sampling depth, anatomical site, and gender and also to compare compact-probe TDC values measured on women with and without breast cancer (BC). TDC was measured bilaterally on forearms and biceps of 32 male and 32 female volunteers and on 12 female patients awaiting surgery for breast cancer. Results show that 1) TDC values at 2.5 mm depth were significantly less than at 1.5 mm; 2) Female TDC values were significantly less than male values; 3) TDC values were not different between females with and without BC; and 4) dominant/non-dominant arm TDC ratios were not significantly different for any probe among genders or arm anatomical site. These findings indicate that probe type differences in absolute TDC values are present and should be taken into account when TDC values are compared. However, comparisons based on inter-arm TDC ratios are not statistically different among probes with respect to gender or anatomical location.

Localization of Usher syndrome type II to chromosome 1q.

PubMed

Kimberling, W J; Weston, M D; Möller, C; Davenport, S L; Shugart, Y Y; Priluck, I A; Martini, A; Milani, M; Smith, R J

1990-06-01

Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.