A role for E2-2 at the DN3 stage of early thymopoiesis

DEFF Research Database (Denmark)

Wikström, Ingela; Forssell, Johan; Penha-Goncalves, Mario N

2008-01-01

Roles for the E-proteins E2A and HEB during T lymphocyte development have been well established. Based on our previous observations of counter selection against T cells lacking E2-2, it seemed reasonable to assume that there would be a function also for E2-2 in thymocyte development. Aiming...... proteins, Id2 displayed a prominent expression exclusively in DN1, whereas Id3 showed some expression in DN1, followed by a down regulation and then a prominent induction, peaking in the DP stage. E2-2 was expressed during the DN stages, as well as in the DP stage, suggesting that E2-2 operates in concert...

RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

Science.gov (United States)

Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

2015-12-01

The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

Functional characterization of DnSIZ1, a SIZ/PIAS-type SUMO E3 ligase from Dendrobium.

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Liu, Feng; Wang, Xiao; Su, Mengying; Yu, Mengyuan; Zhang, Shengchun; Lai, Jianbin; Yang, Chengwei; Wang, Yaqin

2015-09-17

SUMOylation is an important post-translational modification of eukaryotic proteins that involves the reversible conjugation of a small ubiquitin-related modifier (SUMO) polypeptide to its specific protein substrates, thereby regulating numerous complex cellular processes. The PIAS (protein inhibitor of activated signal transducers and activators of transcription [STAT]) and SIZ (scaffold attachment factor A/B/acinus/PIAS [SAP] and MIZ) proteins are SUMO E3 ligases that modulate SUMO conjugation. The characteristic features and SUMOylation mechanisms of SIZ1 protein in monocotyledon are poorly understood. Here, we examined the functions of a homolog of Arabidopsis SIZ1, a functional SIZ/PIAS-type SUMO E3 ligase from Dendrobium. In Dendrobium, the predicted DnSIZ1 protein has domains that are highly conserved among SIZ/PIAS-type proteins. DnSIZ1 is widely expressed in Dendrobium organs and has a up-regulated trend by treatment with cold, high temperature and wounding. The DnSIZ1 protein localizes to the nucleus and shows SUMO E3 ligase activity when expressed in an Escherichia coli reconstitution system. Moreover, ectopic expression of DnSIZ1 in the Arabidopsis siz1-2 mutant partially complements several phenotypes and results in enhanced levels of SUMO conjugates in plants exposed to heat shock conditions. We observed that DnSIZ1 acts as a negative regulator of flowering transition which may be via a vernalization-induced pathway. In addition, ABA-hypersensitivity of siz1-2 seed germination can be partially suppressed by DnSIZ1. Our results suggest that DnSIZ1 is a functional homolog of the Arabidopsis SIZ1 with SUMO E3 ligase activity and may play an important role in the regulation of Dendrobium stress responses, flowering and development.

RETRACTED: Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population.

Science.gov (United States)

Zhong, Weiqiang; Jiang, Zongpei; Zhou, Tian-Biao

2015-12-01

This article has been included in a multiple retraction: Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10

Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

Science.gov (United States)

López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

2016-01-01

Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

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Mervi E. Hyvönen

2015-01-01

Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

Quasirecognition by prime graph of finite simple groups ${}^2D_n(3$

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Behrooz Khosravi

2014-12-01

Full Text Available Let $G$ be a finite group. In [Ghasemabadi et al., characterizations of the simple group ${}^2D_n(3$ by prime graph and spectrum, Monatsh Math., 2011] it is proved that if $n$ is odd, then ${}^2D _n(3$ is recognizable by prime graph and also by element orders. In this paper we prove that if $n$ is even, then $D={}^2D_{n}(3$ is quasirecognizable by prime graph, i.e. every finite group $G$ with $Gamma(G=Gamma(D$ has a unique nonabelian composition factor and this factor is isomorphic to $D$.

DN2 Thymocytes Activate a Specific Robust DNA Damage Response to Ionizing Radiation-Induced DNA Double-Strand Breaks

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Irene Calvo-Asensio

2018-06-01

Full Text Available For successful bone marrow transplantation (BMT, a preconditioning regime involving chemo and radiotherapy is used that results in DNA damage to both hematopoietic and stromal elements. Following radiation exposure, it is well recognized that a single wave of host-derived thymocytes reconstitutes the irradiated thymus, with donor-derived thymocytes appearing about 7 days post BMT. Our previous studies have demonstrated that, in the presence of donor hematopoietic cells lacking T lineage potential, these host-derived thymocytes are able to generate a polyclonal cohort of functionally mature peripheral T cells numerically comprising ~25% of the peripheral T cell pool of euthymic mice. Importantly, we demonstrated that radioresistant CD44+ CD25+ CD117+ DN2 progenitors were responsible for this thymic auto-reconstitution. Until recently, the mechanisms underlying the radioresistance of DN2 progenitors were unknown. Herein, we have used the in vitro “Plastic Thymus” culture system to perform a detailed investigation of the mechanisms responsible for the high radioresistance of DN2 cells compared with radiosensitive hematopoietic stem cells. Our results indicate that several aspects of DN2 biology, such as (i rapid DNA damage response (DDR activation in response to ionizing radiation-induced DNA damage, (ii efficient repair of DNA double-strand breaks, and (iii induction of a protective G1/S checkpoint contribute to promoting DN2 cell survival post-irradiation. We have previously shown that hypoxia increases the radioresistance of bone marrow stromal cells in vitro, at least in part by enhancing their DNA double-strand break (DNA DSB repair capacity. Since the thymus is also a hypoxic environment, we investigated the potential effects of hypoxia on the DDR of DN2 thymocytes. Finally, we demonstrate for the first time that de novo DN2 thymocytes are able to rapidly repair DNA DSBs following thymic irradiation in vivo.

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome.

Science.gov (United States)

Powers, Brian E; Velazquez, Ramon; Kelley, Christy M; Ash, Jessica A; Strawderman, Myla S; Alldred, Melissa J; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2016-12-01

Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs.

Um suplemento entre dois mundos: Causas e consequências da transição papel/digital do DN Jovem

OpenAIRE

Freitas, Helena de Sousa

2012-01-01

The DN Jovem, a supplement that the Portuguese newspaper Diário de Notícias (DN) began publishing in May 1983, quickly became a showcase for new prose writers, poets, photographers and illustrators. In June 1996, when access to the Internet didn’t even reach one percent of Portuguese homes, its contents migrated from print to online. The transition, determined by the Administration of DN within a newspaper’s restructuring, announced the death of a supplement that was, according to Portuguese ...

Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks.

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Wang, Yingying; Chang, Jianhui; Shao, Lijian; Feng, Wei; Luo, Yi; Chow, Marie; Du, Wei; Meng, Aimin; Zhou, Daohong

2016-06-01

Down syndrome (DS) is a genetic disorder caused by the presence of an extra partial or whole copy of chromosome 21. In addition to musculoskeletal and neurodevelopmental abnormalities, children with DS exhibit various hematologic disorders and have an increased risk of developing acute lymphoblastic leukemia and acute megakaryocytic leukemia. Using the Ts65Dn mouse model, we investigated bone marrow defects caused by trisomy for 132 orthologs of the genes on human chromosome 21. The results showed that, although the total bone marrow cellularity as well as the frequency of hematopoietic progenitor cells (HPCs) was comparable between Ts65Dn mice and their age-matched euploid wild-type (WT) control littermates, human chromosome 21 trisomy led to a significant reduction in hematopoietic stem cell (HSC) numbers and clonogenic function in Ts65Dn mice. We also found that spontaneous DNA double-strand breaks (DSBs) were significantly increased in HSCs from the Ts65Dn mice, which was correlated with the significant reduction in HSC clonogenic activity compared to those from WT controls. Moreover, analysis of the repair kinetics of radiation-induced DSBs revealed that HSCs from Ts65Dn mice were less proficient in DSB repair than the cells from WT controls. This deficiency was associated with a higher sensitivity of Ts65Dn HSCs to radiation-induced suppression of HSC clonogenic activity than that of euploid HSCs. These findings suggest that an additional copy of genes on human chromosome 21 may selectively impair the ability of HSCs to repair DSBs, which may contribute to DS-associated hematological abnormalities and malignancies.

Modulation of gut microbiota and increase in fecal water content in mice induced by administration of Lactobacillus kefiranofaciens DN1.

Science.gov (United States)

Jeong, Dana; Kim, Dong-Hyeon; Kang, Il-Byeong; Kim, Hyunsook; Song, Kwang-Young; Kim, Hong-Seok; Seo, Kun-Ho

2017-02-22

Lactobacillus kefiranofaciens is the key probiotic bacterium in kefir. In this study, we investigated the effects of oral consumption of L. kefiranofaciens on the fecal quality and intestinal microbiota of mice. Four-week-old Balb/c mice were divided into two groups (n = 8 each) and administered 0.2 mL of saline (control group) or saline containing 2 × 10 8 cfu L. kefiranofaciens DN1 (LKF_DN1 group) for two weeks. At the end of the experiment, their fecal samples were collected and the fecal quality and microbiota were assessed. The LKF_DN1 group exhibited higher total fecal weight and fecal weight per stool sample than the control group (p kefiranofaciens DN1 administration could alleviate constipation and improve gut microbiota.

H-mode transition physics close to DN on MAST and its applications to other tokamaks

International Nuclear Information System (INIS)

Meyer, H.

2004-01-01

Full text: ELMy H-mode is the base-line operating scenario for the next step fusion device ITER. To improve active and passive pedestal control a deeper understanding of H- mode physics is desirable. MAST contributes towards this understanding with good edge diagnostics, and by accessing extreme parameter regimes. The first inter-machine comparisons with respect to the influence of the magnetic topology on the power threshold with ASDEX-Upgrade and NSTX reveal a reduction of the power threshold in true double null (C-DN) configuration opening new operation regimes in both devices. The 30% reduction in threshold power close to C-DN observed on ASDEX-Upgrade, though significant, is less than the factor of two or more observed in both large spherical tokamaks, MAST and NSTX. This points towards the importance of field line curvature for this effect. The power thresholds measured in C-DN on MAST and NSTX are very similar. Despite this strong effect on the power threshold, changes in most edge parameters in L-mode due to the different magnetic configurations are small. However, significant changes are seen in the toroidal impurity flow velocity, related to the radial electric field, and in the scrape-off-layer temperature decay length at the high field side. The statistical comparison of MAST data with various H-mode theories suggests that different instabilities need to be stabilised at different spatial positions in the region where the pedestal forms to access H-mode. Pedestal temperatures observed on MAST are two to five times lower than in MAST equivalent discharges at ASDEX-Upgrade. However, the pedestal densities are similar. The differences in L-mode are less significant. The usual DN operating regime with co current NBI in MAST has been extended to include single null (SN) configurations, to provide more direct comparisons with conventional tokamaks. The plasma edge in SN on MAST is more stable to ELMs and the typical type-III ELMs, often observed in C-DN, are

Um suplemento entre dois mundos : Causas e consequências da transição papel/digital do DN Jovem

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Helena de Sousa Freitas

2012-01-01

Full Text Available The DN Jovem, a supplement that the Portuguese newspaper Diário de Notícias (DN began publishing in May 1983, quickly became a showcase for new prose writers, poets, photographers and illustrators. In June 1996, when access to the Internet didn’t even reach one percent of Portuguese homes, its contents migrated from print to online. The transition, determined by the Administration of DN within a newspaper’s restructuring, announced the death of a supplement that was, according to Portuguese writer José Jorge Letria, “the most important spot for the revelation and affirmation of new literary values” in democratic Portugal.

Possible measurements of the spin one observables in elastic dN, dd collisions at the NICA deuteron beams

International Nuclear Information System (INIS)

Sharov, V I

2016-01-01

The report shows the possibilities of studying the spin one observables in the elastic dN and dd interactions at the NICA collider of the VBLHEP JINR. The use of the colliding deuteron beams would allow us to carry out the measurements of the differential cross sections I 0 (dN, dd) of the elastic scattering of unpolarized deuterons and the differential cross sections I pol (dN,dd) and the vector A y (Ed,θ) and tensor A yy (Ed,θ) and A xx (E d .θ) analyzing powers in elastic collisions of the vector and tensor polarized deuterons. The planned luminosity of the colliding polarized deuteron beams will provide sufficiently high elastic events counting rate. The use of the colliding beams of the polarized deuterons for the spin one >dN and dd observables research has a number of significant advantages in comparison with the experiments with the “fixed” target. The angular acceptance of the collider detector covers the full solid angle 4π radians while the wide ranges of the energies of the dN, dd interactions and the 4-momentum transfer squared are available. (paper)

Časopis "Módní svět" a "Lada" v kulturním kontextu

OpenAIRE

Šrolová, Kristýna

2010-01-01

The thesis discusses tbe fashion magazine Módní svět (Fashion World) and its enclosure Lada, which it implants into their cultural and historica1 context. The magazine Módní svět (Fashion World) was puhli,hed from 1875 to 1935 and thi, a1,o deline, lhe time circmnscription of tbe themes in tbe thesis. It contextua11y deals with tbe women society during tbe tum of 19th to 20th century, with women's emancipatory movement, with tbe beginning of publishing of rn.agazines for women and fashion mag...

Protein dynamics associated with failed and rescued learning in the Ts65Dn mouse model of Down syndrome.

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Md Mahiuddin Ahmed

Full Text Available Down syndrome (DS is caused by an extra copy of human chromosome 21 (Hsa21. Although it is the most common genetic cause of intellectual disability (ID, there are, as yet, no effective pharmacotherapies. The Ts65Dn mouse model of DS is trisomic for orthologs of ∼55% of Hsa21 classical protein coding genes. These mice display many features relevant to those seen in DS, including deficits in learning and memory (L/M tasks requiring a functional hippocampus. Recently, the N-methyl-D-aspartate (NMDA receptor antagonist, memantine, was shown to rescue performance of the Ts65Dn in several L/M tasks. These studies, however, have not been accompanied by molecular analyses. In previous work, we described changes in protein expression induced in hippocampus and cortex in control mice after exposure to context fear conditioning (CFC, with and without memantine treatment. Here, we extend this analysis to Ts65Dn mice, measuring levels of 85 proteins/protein modifications, including components of MAP kinase and MTOR pathways, and subunits of NMDA receptors, in cortex and hippocampus of Ts65Dn mice after failed learning in CFC and after learning was rescued by memantine. We show that, compared with wild type littermate controls, (i of the dynamic responses seen in control mice in normal learning, >40% also occur in Ts65Dn in failed learning or are compensated by baseline abnormalities, and thus are considered necessary but not sufficient for successful learning, and (ii treatment with memantine does not in general normalize the initial protein levels but instead induces direct and indirect responses in approximately half the proteins measured and results in normalization of the endpoint protein levels. Together, these datasets provide a first view of the complexities associated with pharmacological rescue of learning in the Ts65Dn. Extending such studies to additional drugs and mouse models of DS will aid in identifying pharmacotherapies for effective

The integrable quantum group invariant A2n-1(2) and Dn+1(2) open spin chains

Science.gov (United States)

Nepomechie, Rafael I.; Pimenta, Rodrigo A.; Retore, Ana L.

2017-11-01

A family of A2n(2) integrable open spin chains with Uq (Cn) symmetry was recently identified in arxiv:arXiv:1702.01482. We identify here in a similar way a family of A2n-1(2) integrable open spin chains with Uq (Dn) symmetry, and two families of Dn+1(2) integrable open spin chains with Uq (Bn) symmetry. We discuss the consequences of these symmetries for the degeneracies and multiplicities of the spectrum. We propose Bethe ansatz solutions for two of these models, whose completeness we check numerically for small values of n and chain length N. We find formulas for the Dynkin labels in terms of the numbers of Bethe roots of each type, which are useful for determining the corresponding degeneracies. In an appendix, we briefly consider Dn+1(2) chains with other integrable boundary conditions, which do not have quantum group symmetry.

The integrable quantum group invariant A2n−1(2 and Dn+1(2 open spin chains

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Rafael I. Nepomechie

2017-11-01

Full Text Available A family of A2n(2 integrable open spin chains with Uq(Cn symmetry was recently identified in arXiv:1702.01482. We identify here in a similar way a family of A2n−1(2 integrable open spin chains with Uq(Dn symmetry, and two families of Dn+1(2 integrable open spin chains with Uq(Bn symmetry. We discuss the consequences of these symmetries for the degeneracies and multiplicities of the spectrum. We propose Bethe ansatz solutions for two of these models, whose completeness we check numerically for small values of n and chain length N. We find formulas for the Dynkin labels in terms of the numbers of Bethe roots of each type, which are useful for determining the corresponding degeneracies. In an appendix, we briefly consider Dn+1(2 chains with other integrable boundary conditions, which do not have quantum group symmetry.

Λ{sub b} → π{sup -}(D{sub s}{sup -})Λ{sub c}(2595), π{sup -}(D{sub s}{sup -})Λ{sub c}(2625) decays and DN, D*N molecular components

Energy Technology Data Exchange (ETDEWEB)

Liang, Wei-Hong [Guangxi Normal University, Department of Physics, Guilin (China); Centro Mixto Universidad de Valencia-CSIC Institutos de Investigacion de Paterna, Departamento de Fisica Teorica y IFIC, Valencia (Spain); Bayar, Melahat [Kocaeli University, Department of Physics, Izmit (Turkey); Oset, Eulogio [Centro Mixto Universidad de Valencia-CSIC Institutos de Investigacion de Paterna, Departamento de Fisica Teorica y IFIC, Valencia (Spain)

2017-01-15

From the perspective that Λ{sub c}(2595) and Λ{sub c}(2625) are dynamically generated resonances from the DN, D*N interaction and coupled channels, we have evaluated the rates for Λ{sub b} → π{sup -}Λ{sub c}(2595) and Λ{sub b} → π{sup -}Λ{sub c}(2625) up to a global unknown factor that allows us to calculate the ratio of rates and compare with experiment, where good agreement is found. Similarly, we can also make predictions for the ratio of rates of the, yet unknown, decays of Λ{sub b} → D{sub s}{sup -}Λ{sub c}(2595) and Λ{sub b} → D{sub s}{sup -}Λ{sub c}(2625) and make estimates for their individual branching fractions. (orig.)

Assessment of reproductive and developmental effects of DINP, DnHP and DCHP using quantitative weight of evidence.

Science.gov (United States)

Dekant, Wolfgang; Bridges, James

2016-11-01

Quantitative weight of evidence (QWoE) methodology utilizes detailed scoring sheets to assess the quality/reliability of each publication on toxicity of a chemical and gives numerical scores for quality and observed toxicity. This QWoE-methodology was applied to the reproductive toxicity data on diisononylphthalate (DINP), di-n-hexylphthalate (DnHP), and dicyclohexylphthalate (DCHP) to determine if the scientific evidence for adverse effects meets the requirements for classification as reproductive toxicants. The scores for DINP were compared to those when applying the methodology DCHP and DnHP that have harmonized classifications. Based on the quality/reliability scores, application of the QWoE shows that the three databases are of similar quality; but effect scores differ widely. Application of QWoE to DINP studies resulted in an overall score well below the benchmark required to trigger classification. For DCHP, the QWoE also results in low scores. The high scores from the application of the QWoE methodology to the toxicological data for DnHP represent clear evidence for adverse effects and justify a classification of DnHP as category 1B for both development and fertility. The conclusions on classification based on the QWoE are well supported using a narrative assessment of consistency and biological plausibility. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Condensation pool experiments with steam using DN200 blowdown pipe

International Nuclear Information System (INIS)

Laine, J.; Puustinen, M.

2005-08-01

This report summarizes the results of the condensation pool experiments with steam using a DN200 blowdown pipe. Altogether five experiment series, each consisting of several steam blows, were carried out in December 2004 with a scaled-down test facility designed and constructed at Lappeenranta University of Technology. The main purpose of the experiments was to increase the understanding of different phenomena in the condensation pool during steam discharge. (au)

Overexpression of an orchid (Dendrobium nobile SOC1/TM3-like ortholog, DnAGL19, in Arabidopsis regulates HOS1-FT expression

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Xiao-ru eLiu

2016-02-01

Full Text Available Flowering in the appropriate season is critical for successful reproduction in angiosperms. The orchid species, Dendrobium nobile, requires vernalization to achieve flowering in the spring, but the underlying regulatory network has not been identified to date. The MADS-box transcription factor DnAGL19 was previously identified in a study of low-temperature treated D. nobile buds and was suggested to regulate vernalization-induced flowering. In this study, phylogenetic analysis of DnAGL9 and the MADS-box containing proteins showed that DnAGL19 is phylogenetically closely related to the SOC1-like protein from orchid Dendrobium Chao Parya Smile, DOSOC1. The orchid clade closed to but is not included into the SOC1-1/TM3 clades associated with either eudicots or monocots, suggesting that DnAGL19 is an SOC1-1/TM3-like ortholog. DnAGL19 was found to be highly expressed in pseudobulbs, leaves, roots and axillary buds but rarely in flowers, and to be substantially upregulated in axillary buds by prolonged low-temperature treatments. Overexpression of DnAGL19 in Arabidopsis thaliana resulted in a small but significantly reduced time to bolting, suggesting that flowering time was slightly accelerated under normal growth conditions. Consistent with this, the A. thaliana APETELA1 (AP1 gene was expressed at an earlier stage in transgenic lines than in wild type plants, while the FLOWERING LOCUS T (FT gene was suppressed, suggesting that altered regulations on these transcription factors caused the weak promotion of flowering. HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1 was slightly activated under the same conditions, suggesting that the HOS1-FT module may be involved in the DnAGL19-related network. Under vernalization conditions, FT expression was significantly upregulated, whereas HOS1 expression in the transgenic A. thaliana has a level similar to that in wild type. Taken together, these results suggest that DnAGL19 controls the action of the

Utility of DN4 questionnaire in assessment of neuropathic pain and its clinical correlations in Turkish patients with diabetes mellitus.

Science.gov (United States)

Celik, S; Yenidunya, G; Temel, E; Purisa, S; Uzum, A Kubat; Gul, N; Cinkil, G; Dinccag, N; Satman, I

2016-08-01

We aimed to assess the utility of DN4 questionnaire (Douleur Neuropathique en 4 questions) to define the frequency and severity of neuropathic pain (NP) and also its clinical correlation to daily clinical practice. We included 1357 patients with diabetes (56.5% women, 90.4% type 2 diabetes) who were followed up in our diabetes outpatient clinic. Presence of NP was evaluated by performing simultaneous DN4 questionnaires and physical examination. Those who had a DN4 score ≥4 were considered to have NP. The mean age was 58.2±12.1 years, mean duration was 12.5±7.5; (min-max: 1-45) years, mean HbA1c level was 7.8±1.6% (min-max: 5-16.2%), (61.7±6.0mmol/mol; min-max: 31.1-153.6mmol/mol). Three hundred thirteen patients (23%) were diagnosed with NP using the DN4 tool. Male gender (p=0.01), receiving antihypertensive treatment (p=0.01), presence of retinopathy (pdiabetes duration (pdiabetes duration (OR: 1.02, 95% CI: 1.00-1.04, p=0.007), elevated HbA1c levels (1.11, 1.02-1.21, 0.015), presence of retinopathy (1.41, 1.20-1.64, diet only-regimens) were significantly associated with NP. Utilization of DN4 questionnaire in daily clinical practice is an effective tool in the identification of pain related with peripheral diabetic polyneuropathy. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome.

Science.gov (United States)

de Souza, Fabio M Simoes; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N; Restrepo, Diego

2011-01-01

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities.

Rational quantum integrable systems of DN type with polarized spin reversal operators

Directory of Open Access Journals (Sweden)

B. Basu-Mallick

2015-09-01

Full Text Available We study the spin Calogero model of DN type with polarized spin reversal operators, as well as its associated spin chain of Haldane–Shastry type, both in the antiferromagnetic and ferromagnetic cases. We compute the spectrum and the partition function of the former model in closed form, from which we derive an exact formula for the chain's partition function in terms of products of partition functions of Polychronakos–Frahm spin chains of type A. Using a recursion relation for the latter partition functions that we derive in the paper, we are able to numerically evaluate the partition function, and thus the spectrum, of the DN-type spin chain for relatively high values of the number of spins N. We analyze several global properties of the chain's spectrum, such as the asymptotic level density, the distribution of consecutive spacings of the unfolded spectrum, and the average degeneracy. In particular, our results suggest that this chain is invariant under a suitable Yangian group, and that its spectrum coincides with that of a Yangian-invariant vertex model with linear energy function and dispersion relation.

DN/DG Screening of Environmental Swipe Samples: FY2016 Report

Energy Technology Data Exchange (ETDEWEB)

Glasgow, David C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Croft, Stephen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Venkataraman, Ramkumar [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McElroy, Robert Dennis [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Knowles, Justin R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-02-01

The Delayed Neutron Delayed Gamma (DNDG) technique provides a new analytical capability to the International Atomic Energy Agency (IAEA) for detecting undeclared nuclear activities. IAEA’s Long Term R&D (LTRD) plan has a stated high urgency need to develop elemental and isotopic signatures of nuclear fuel cycle activities and processes (LTRD 2.2). The new DNDG capability is used to co-detect both uranium and plutonium as an extension of a DN only method that is already being utilized by the IAEA for the analysis of swipes to inform on undeclared nuclear activities. Analytical method involving irradiation of swipe samples potentially containing trace quantities of fissile material in a thermal neutron field, followed by the counting of delayed neutrons, is a well-known technique in the field of safeguards and nonproliferation. It is used for detecting the presence of microscopic amounts of fissile material, (typically a linear combination of ²³³U, ²³⁵U, ²³⁹Pu, and ²⁴¹Pu)and quantifying it in terms of the equivalent mass of 235U. The delayed neutron (DN) technique is very sensitive and is been routinely employed at the High Flux Isotope Reactor (HFIR) facility at Oak Ridge National Laboratory (ORNL). Both uranium and plutonium are of high safeguards value. However, the DN technique is not well suited for distinguishing between U and Pu isotopes since the decay curves overlap closely. The delayed gamma (DG) technique will help detect the presence of 239Pu in a mixture of U and Pu. Thus the DNDG approach combines the best of both worlds; the sensitivity of DN counting and the isotopic specificity of DG counting. The present work seeks to build on the delayed neutron and delayed gamma methods that have been developed at ORNL. It is recognized that the distribution profile of heavy fission products remains fairly invariant for the fissile nuclides whereas the distribution of light fission products varies from one isotope to

Las quinoproteínas alcohol deshidrogenasas en los sistemas bacterianos: distribución, clasificación, estructura y función

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Saúl Gómez-Manzo

2005-01-01

Full Text Available Existe una gran diversidad de alcohol deshidrogenasas (ADHs microbianas; las cuales son divididas en tres grandes grupos: (a Las que son dependientes de las coenzimas NAD o NADP, (b Las que son independientes de estas coenzimas; sin embargo, utilizan pirroloquinolina quinona (PQQ y hemo tipo C como grupo prostético y (c Las oxidasas dependientes de FAD que catalizan la reacción irreversible de alcoholes. Las ADHs que utilizan el PQQ, se encuentran a su vez divididas en tres tipos. Las ADHs tipo I que contienen sólo PQQ como grupo prostético y se les conoce como quinoproteínas; mientras que las ADHs tipo II y tipo III además del PQQ contienen hemo tipo C y se les conoce como quinohemoproteínas. Las ADHs tipo II son enzimas solubles que se encuentran en el espacio periplásmico y están presentes en proteobacterias como Pseudomonas putida, Ralstonia eutropha y Comamonas testosteroni. Las ADHs tipo III son enzimas que se encuentran ancladas a la membrana y trabajan orientadas hacia el espacio periplásmico. Se les ha identificado y caracterizado únicamente en bacterias ácido acéticas. Las ADH tipo III, por lo general contienen tres subunidades. El transporte intramolecular de electrones en las ADHs tipo II y IIII se propone que es del PQQ al hemo C de la primera subunidad y de ahí, de hemo en hemo en la segunda subunidad hasta llegar a la quinona endógena. Los tres tipos de PQQ-ADHs son discutidas en esta revisión.

Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome

Directory of Open Access Journals (Sweden)

Markus Heinen

2012-01-01

Full Text Available Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAA receptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAA receptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome.

Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

Science.gov (United States)

Stringer, Megan; Abeysekera, Irushi; Thomas, Jared; LaCombe, Jonathan; Stancombe, Kailey; Stewart, Robert J; Dria, Karl J; Wallace, Joseph M; Goodlett, Charles R; Roper, Randall J

2017-08-01

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis

Precision Measurement of the Neutron Twist-3 Matrix Element dn2: Probing Color Forces

Energy Technology Data Exchange (ETDEWEB)

Posik, Matthew; Flay, David; Parno, Diana; Allada, Kalyan; Armstrong, Whitney; Averett, Todd; Benmokhtar, Fatiha; Bertozzi, William; Camsonne, Alexandre; Canan, Mustafa; Cates, Gordon; Chen, Chunhua; Chen, Jian-Ping; Choi, Seonho; Chudakov, Eugene; Cusanno, Francesco; Dalton, Mark; Deconinck, Wouter; De Jager, Cornelis; Deng, Xiaoyan; Deur, Alexandre; Dutta, Chiranjib; El Fassi, Lamiaa; Franklin, Gregg; Friend, Megan; Gao, Haiyan; Garibaldi, Franco; Gilad, Shalev; Gilman, Ronald; Glamazdin, Oleksandr; Golge, Serkan; Gomez, Javier; Guo, Lei; Hansen, Jens-Ole; Higinbotham, Douglas; Holmstrom, Timothy; Huang, J; Hyde, Charles; Ibrahim Abdalla, Hassan; Jiang, Xiaodong; Jin, Ge; Katich, Joseph; Kelleher, Aidan; Kolarkar, Ameya; Korsch, Wolfgang; Kumbartzki, Gerfried; LeRose, John; Lindgren, Richard; Liyanage, Nilanga; Long, Elena; Lukhanin, Oleksandr; Mamyan, Vahe; McNulty, Dustin; Meziani, Zein-Eddine; Michaels, Robert; Mihovilovic, Miha; Moffit, Bryan; Muangma, Navaphon; Nanda, Sirish; Narayan, Amrendra; Nelyubin, Vladimir; Norum, Blaine; Nuruzzaman, nfn; Oh, Yongseok; Peng, Jen-chieh; Qian, Xin; Qiang, Yi; Rakhman, Abdurahim; Riordan, Seamus; Saha, Arunava; Sawatzky, Bradley; Hashemi Shabestari, Mitra; Shahinyan, Albert; Sirca, Simon; Solvignon-Slifer, Patricia; Subedi, Ramesh; Sulkosky, Vincent; Tobias, William; Troth, Wolfgang; Wang, Diancheng; Wang, Y; Wojtsekhowski, Bogdan; Yan, X; Yao, Huan; Ye, Yunxiu; Ye, Zhihong; Yuan, Lulin; Zhan, X; Zhang, Y; Zhang, Y -W; Zhao, Bo; Zheng, Xiaochao

2014-07-01

Double-spin asymmetries and absolute cross sections were measured at large Bjorken x (0.25 lte x lte 0.90), in both the deep-inelastic and resonance regions, by scattering longitudinally polarized electrons at beam energies of 4.7 and 5.9 GeV from a transversely and longitudinally polarized 3He target. In this dedicated experiment, the spin structure function g2 on 3He was determined with precision at large x, and the neutron twist-three matrix element dn2 was measured at ?Q2? of 3.21 and 4.32 GeV2/c2, with an absolute precision of about 10?5. Our results are found to be in agreement with lattice QCD calculations and resolve the disagreement found with previous data at ?Q2?= 5 GeV2/c2. Combining dn2 and a newly extracted twist-four matrix element, fn2, the average neutron color electric and magnetic forces were extracted and found to be of opposite sign and about 60 MeV/fm in magnitude.

Um suplemento entre dois mundos: Causas e consequências da transição papel/digital do DN Jovem

OpenAIRE

Freitas, Helena de Sousa

2012-01-01

O DN Jovem, suplemento que o Diário de Notícias começou a publicar em maio de 1983, rapidamente se tornou uma montra para novos prosadores, poetas, fotógrafos e ilustradores. Em junho de 1996, ano em que o acesso à Internet nos lares portugueses não atingia sequer um por cento, os seus conteúdos migraram do suporte impresso para o online. A transição, decidida pela Administração do DN no âmbito de uma reestruturação do jornal, anunciou a morte daquele que, segundo o escritor José Jorge Letria...

Purification and Characterization of a Novel Anti-Campylobacter Bacteriocin Produced by Lactobacillus curvatus DN317.

Science.gov (United States)

Zommiti, Mohamed; Almohammed, Hamdan; Ferchichi, Mounir

2016-12-01

The lactic acid bacteria (LAB) microbiota of Saudi chicken ceca was determined. From 60 samples, 204 isolates of lactic acid bacteria were obtained. Three isolates produced antimicrobial activities against Campylobacter jejuni, Listeria monocytogenes, and Bacillus subtilis. The isolate DN317, which had the highest activity against Campylobacter jejuni ATCC 33560, was identified as Lactobacillus curvatus (GenBank accession numbers: KX353849 and KX353850). Full inhibitory activity was observed after a 2-h incubation with the supernatant at pH values between 4 and 8. Only 16% of the activity was conserved after a treatment at 121 °C for 15 min. The use of proteinase K, pepsin, chymotrypsin, trypsin, papain, and lysozyme drastically reduced the antimicrobial activity. However, lipase, catalase, and lysozyme had no effect on this activity. The active peptide produced by Lactobacillus curvatus DN317 was purified by precipitation with an 80% saturated ammonium sulfate solution, and two steps of reversed phase HPLC on a C18 column. The molecular weight of this peptide was 4448 Da as determined by MALDI-ToF. N-terminal sequence analysis using Edman degradation revealed 47 amino acid residues (UniProt Knowledgebase accession number C0HK82) revealing homology with the amino acid sequences of sakacin P and curvaticin L442. The antimicrobial activity of the bacteriocin, namely curvaticin DN317, was found to be bacteriostatic against Campylobacter jejuni ATCC 33560. The use of microbial antagonism by LAB is one of the best ways to control microorganisms safely in foods. This result constitutes a reasonable advance in the antimicrobial field because of its potential applications in food technology.

Rupture of DN 500 - design basic accident at units 3 and 4 of Kozloduy NPP

International Nuclear Information System (INIS)

Uruchev, V.; Vassilev, P.; Ivanova, A.; Sartmadjiev, A.

2005-01-01

The original design of Kozloduy NPP Units 3 and 4 assumes as Design Basis Accident (DBA) the rupture of DN 32 mm primary pipeline, while an initial event of double-sided guillotine break of primary pipeline with maximal diameter is not considered. In the course of units modernization it have been demonstrated once and again that both the emergency core cooling systems and the localization systems can cope with larger and larger primary circuit leaks. After the installation of a Jet-Vortex Condenser (JVC) at Units 3 and 4 it was substantiated that, the integrity of the hermetic rooms is ensured even in case of double-sided guillotine break of a primary circuit pipeline with maximal diameter (DEGB). The technical justification of the jet-vortex condenser, elaborated by VNIAEC, contains calculations determining both the source term and the doses obtained outside the NPP site after LOCA DN 500. LOCA DN 500 is considered in these analyses as a beyond design basis accident and it is so included in the SAR and approved by the Nuclear Regulatory Agency (NRA). The thermo-hydraulic calculations performed later on show that the emergency core cooling systems can cope with this initial event at conservative assumptions. In order to classify this initiating event as a design basis accident it is necessary to demonstrate that the core cooling criteria are fulfilled and the internal and external doses outside the NPP site are within the permissible limits fixed for design basis accident by the Bulgarian regulatory body (NRA), when using conservative assumptions. For this purpose two consecutive studies were performed - evaluation of the DEGB probability and categorization of the initial event according to the contemporary regulations acting in Republic of Bulgaria. The presented report summarizes the results of the performed conservative analyses of double-sided guillotine break accident of main circulation line taking into account the probability of rupture of large diameter

Long-term effect of neonatal inhibition of APP gamma-secretase on hippocampal development in the Ts65Dn mouse model of Down syndrome.

Science.gov (United States)

Stagni, Fiorenza; Raspanti, Alessandra; Giacomini, Andrea; Guidi, Sandra; Emili, Marco; Ciani, Elisabetta; Giuliani, Alessandro; Bighinati, Andrea; Calzà, Laura; Magistretti, Jacopo; Bartesaghi, Renata

2017-07-01

Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed. Previous evidence showed that neonatal treatment with ELND006, an inhibitor of gamma-secretase, reinstates the Shh pathway and fully restores neurogenesis in Ts65Dn pups. In the framework of potential therapies for DS, it is extremely important to establish whether the positive effects of early intervention are retained after treatment cessation. Therefore, the goal of the current study was to establish whether early treatment with ELND006 leaves an enduring trace in the brain of Ts65Dn mice. Ts65Dn and euploid pups were treated with ELND006 in the postnatal period P3-P15 and the outcome of treatment was examined at ~one month after treatment cessation. We found that in treated Ts65Dn mice the pool of proliferating cells in the hippocampal dentate gyrus (DG) and total number of granule neurons were still restored as was the number of pre- and postsynaptic terminals in the stratum lucidum of CA3, the site of termination of the mossy fibers from the DG. Accordingly, patch-clamp recording from field CA3 showed functional normalization of the input to CA3. Unlike in field CA3, the number of pre- and postsynaptic terminals in the DG of treated Ts65Dn mice was no longer fully restored. The finding that many of the positive effects of neonatal treatment were retained after treatment cessation provides proof of principle demonstration of the efficacy of early

Effect of a fermented milk containing Bifidobacterium lactis DN-173010 on Chinese constipated women.

Science.gov (United States)

Yang, Yue-Xin; He, Mei; Hu, Gang; Wei, Jie; Pages, Philippe; Yang, Xian-Hua; Bourdu-Naturel, Sophie

2008-10-28

To investigate the effect of a fermented milk containing Bifidobacterium lactis DN-173010 and yogurt strains (BIO(R)) on adult women with constipation in Beijing. A total of 135 adult females with constipation were randomly allocated to consume for 2 wk either 100 g of the test fermented milk or 100 g of an acidified milk containing non-living bacteria (control). Stool frequency, defecation condition scores, stool consistency and food intake were recorded at baseline and after 1 and 2 wk in an intention-to-treat population of 126 subjects. In parallel, safety evaluation parameters were performed. At baseline, no differences were found between groups. Following consumption of test product, stool frequency was significantly increased after 1 wk (3.5 +/- 1.5 vs 2.4 +/- 0.6, P food intake did not change between the two groups, and safety parameters of the subjects were within normal ranges. This study suggests a beneficial effect of a fermented milk containing B. lactis DN-173010 on stool frequency, defecation condition and stool consistency in adult women with constipation constipated women after 1 and 2 wk of consumption.

Fermented Milk Containing Bifidobacterium lactis DN-173 010 in Childhood Constipation: A Randomized, Double-Blind, Controlled Trial

NARCIS (Netherlands)

Tabbers, Merit M.; Chmielewska, Ania; Roseboom, Maaike G.; Crastes, Nolwenn; Perrin, Catherine; Reitsma, Johannes B.; Norbruis, Obbe; Szajewska, Hania; Benninga, Marc A.

2011-01-01

BACKGROUND: Constipation is a frustrating symptom affecting 3% of children worldwide. A fermented dairy product containing Bifidobacterium lactis strain DN-173 010 was effective in increasing stool frequency in constipated women. Our aim was to assess the effects of this product in constipated

V. kongres světové literárněvědné bohemistiky

Czech Academy of Sciences Publication Activity Database

Holanová, Markéta; Jareš, Michal; Pišna, Jan; Segi, Stefan; Soukupová, K.

2015-01-01

Roč. 63, č. 5 (2015), s. 793-807 ISSN 0009-0468. [V. kongres světové literárněvědné bohemistiky: Válka a konflikt v české literatuře. Praha, 29.06.2015-04.07.2015] Institutional support: RVO:68378068 Keywords : Czech literature * war and conflict * congress * literary studies Subject RIV: AJ - Letters, Mass-media, Audiovision

Touchscreen learning deficits in Ube3a, Ts65Dn and Mecp2 mouse models of neurodevelopmental disorders with intellectual disabilities.

Science.gov (United States)

Leach, P T; Crawley, J N

2017-12-20

Mutant mouse models of neurodevelopmental disorders with intellectual disabilities provide useful translational research tools, especially in cases where robust cognitive deficits are reproducibly detected. However, motor, sensory and/or health issues consequent to the mutation may introduce artifacts that preclude testing in some standard cognitive assays. Touchscreen learning and memory tasks in small operant chambers have the potential to circumvent these confounds. Here we use touchscreen visual discrimination learning to evaluate performance in the maternally derived Ube3a mouse model of Angelman syndrome, the Ts65Dn trisomy mouse model of Down syndrome, and the Mecp2 Bird mouse model of Rett syndrome. Significant deficits in acquisition of a 2-choice visual discrimination task were detected in both Ube3a and Ts65Dn mice. Procedural control measures showed no genotype differences during pretraining phases or during acquisition. Mecp2 males did not survive long enough for touchscreen training, consistent with previous reports. Most Mecp2 females failed on pretraining criteria. Significant impairments on Morris water maze spatial learning were detected in both Ube3a and Ts65Dn, replicating previous findings. Abnormalities on rotarod in Ube3a, and on open field in Ts65Dn, replicating previous findings, may have contributed to the observed acquisition deficits and swim speed abnormalities during water maze performance. In contrast, these motor phenotypes do not appear to have affected touchscreen procedural abilities during pretraining or visual discrimination training. Our findings of slower touchscreen learning in 2 mouse models of neurodevelopmental disorders with intellectual disabilities indicate that operant tasks offer promising outcome measures for the preclinical discovery of effective pharmacological therapeutics. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice.

Science.gov (United States)

Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S; Reeves, Roger H; Richtsmeier, Joan T

2014-08-01

Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. © 2014 Wiley Periodicals, Inc.

Efecto de la aplicación de vinazas en las propiedades físicas y la actividad de deshidrogenasas en suelos cultivados con maíz dulce (Zea mays L. Effect of vinasse application on physical properties and dehydrogenases activity in soils under sweet corn (Zea mays L. cultivation

Directory of Open Access Journals (Sweden)

Magda Narváez Castillo

2010-04-01

Full Text Available Se evaluó el efecto de la aplicación de vinazas en algunas propiedades físicas y en la actividad de las deshidrogenasas en un Entic dystropept y en un Fluventic haplustoll del Valle de Cauca, Colombia. Para suplir los requerimientos de K+ del cultivo de maíz dulce (Zea mays L. se utilizaron seis tratamientos (T1 = 100% de K+ como vinaza, T2 = 100% de K+ con KCl; T3 = 50% de K+ como vinaza y KCl, T4 = 75% de K+ con vinaza y 25% de K+ como KCl, T5 = testigo absoluto sin planta, T6 = testigo más planta que fueron dispuestos en un diseño completamente al azar con cinco repeticiones. En el Entic dystropept la densidad aparente disminuyó y en consecuencia la porosidad total aumentó, mientras que en el Fluventic haplustoll sucedió lo contrario. La actividad de las deshidrogenasas fue significativamente mayor (P The effect of vinasse application was assessed on physical properties and dehydrogenases activity in Entic Dystropept and Fluventic Haplustoll of Valle del Cauca, Colombia. To meet the requirements of K+ in sweet corn (Zea mays L. six treatments were used (T1 = 100% of K+ as vinasse; T2 = 100% of K+ with KCl; T3 = 50% of K+ as vinasse and KCl; T4 = 75% of K+ with vinasse and 25% of K+ as KCl; T5 = absolute control without plants; T6 = control plus plants arranged in a completely randomized design with five replications. In Dystropept Entic bulk density decreased and consequently the total porosity increased, while the opposite happened in Haplustoll Fluventic. The dehydrogenase activity was significantly higher (P <0.05 in the Dystropept Entic than in Haplustoll Fluventic presenting low values. The results showed that the changes that are generated as a result of the application of vinasse are different for each type of soil.

Study on the reactions dp → dpπ+π- and dp → dnπ+ at 33 GeV/c in the hydrogen bubble chamber

International Nuclear Information System (INIS)

Aladashvili, B.S.; Glagolev, V.V.; Gorbunov, A.N.; Khairetdinov, K.U.; Lebedev, R.M.; Nioradze, M.S.; Saitov, I.S.; Streltsov, V.N.

1975-01-01

A narrow singularity is observed in the effective mass spectrum in the dp → dpπ + π - and dp → dnπ + reactions at the incident deutron momentum of 3.3 GeV/c. The position and width of the singularity are (2,151+0.005) GeV and (13+6) MeV, respectively. The signal in the distribution of dπ + -mass at (2.294+0.005)GeV with the width of (47+13) MeV in reaction dp → dnπ + is identified as a kinematic effect

Tableau Formulas for One-Row Macdonald Polynomials of Types C_n and D_n

Science.gov (United States)

Feigin, Boris; Hoshino, Ayumu; Noumi, Masatoshi; Shibahara, Jun; Shiraishi, Jun'ichi

2015-12-01

We present explicit formulas for the Macdonald polynomials of types C_n and D_n in the one-row case. In view of the combinatorial structure, we call them ''tableau formulas''. For the construction of the tableau formulas, we apply some transformation formulas for the basic hypergeometric series involving very well-poised balanced {}_{12}W_{11} series. We remark that the correlation functions of the deformed W algebra generators automatically give rise to the tableau formulas when we principally specialize the coordinate variables.

Disruption of Inhibitory Function in the Ts65Dn Mouse Hippocampus Through Overexpression of GIRK2

Science.gov (United States)

2007-10-24

embryological and developmental or a result of later problems. Delays in prenatal growth of the Ts65Dn cerebral cortex and hippocampus due to longer...cultured from both DS patients and model animals are also reportedly more vulnerable to apoptosis (Sawa, 1999). A majority of research investigating cell...death in DS has been limited to several apoptosis -related genes, including those related to oxidative stress, and transcription factors overexpressed

Study of deuteron break-up at low energies in the reactions D(d,pn)d and D(d,dn)p

International Nuclear Information System (INIS)

Cocu, Francis; Ambrosino, Georges; Guerreau, Daniel.

1977-06-01

Quasi-free scattering in the reactions d+D=n+p+d has been studied at incident energies between 7 and 12 MeV by steps of 1 MeV. In a kinematically complete experiment, the cross sections were measured for the coincidences (p,n) and for the coincidences (d,n). The energy of the charged particle was also enregistered. The detector of the charged particles was put at an angle thetasub(p)=thetasub(d)=19 0 5 counted from the incident axis, the detector of neutrons at thetasub(n)=-30 0 . The geometry was coplanar. Pure gaseous target gives an excellent signal/back-ground ratio. The measure of the time-of-flight of the neutron allows indirectly the discrimination of the nature of the detected charged particle. Absolute cross sections are compared with the results of the complete Born approximation. The nucleon-nucleon potential is spin-dependant. The shape of the measured (d,n) spectra is fairly well reproduced but not its intensity. The (p,n) spectra is not so well reproduced but the distortion diminishes on increasing the incident energy [fr

Role of deuteron NN*-components in processes pd → dp and pd → dN*

International Nuclear Information System (INIS)

Uzikov, Yu.N.

1996-01-01

The contribution of nucleon isobar N * exchanges to backward elastic pd-scattering is calculated on the basis of deuteron 6q-model and found to be negligible in comparison with neutron exchange. It is shown that the pole amplitude of neutron pickup from the deuteron nN * -component is favoured in the reaction pd → dN * for backward going N * (1440) and N* (1710) at kinetic energy of incident proton of 1.5-2 GeV whereas the triangular diagram with subprocess pp → dπ + related to the usual pn-component of deuteron considerably suppressed. 19 refs., 3 figs

Load tests with a pipe bend DN 425, applying slowly changing bending loads up to occurrence of leak

International Nuclear Information System (INIS)

Uhlmann, D.; Hunger, H.

1990-01-01

The experimental program deals with the formation of incipient cracks and subsequent crack growth of axially oriented cracks at a pipe bend with a nominal width of DN 425. The pipe bend consists of the ferritic material 20MnMoNi55. The numerical experiments by means of 3 D-FE analyses concentrate on determining the influence of the asymmetric crack depths at the two bend halves, and of the multiple crack fields, on the effective crack strain. (DG) [de

Effects of Probiotic Lactobacillus Casei DN-114 001 in Prevention of Radiation-Induced Diarrhea: Results From Multicenter, Randomized, Placebo-Controlled Nutritional Trial

International Nuclear Information System (INIS)

Giralt, Jordi; Regadera, Jose Perez; Verges, Ramona; Romero, Jesus; Fuente, Isabel de la; Biete, Albert; Villoria, Jesus; Cobo, Jose Maria; Guarner, Francisco

2008-01-01

Purpose: To determine whether a probiotic drink containing Lactobacillus casei DN-114 001 reduces the incidence of radiation-induced diarrhea in patients with gynecologic cancer. Methods and Materials: Patients who were undergoing pelvic radiotherapy (45-50 Gy, conventional fractionation) for either cervical carcinoma (radiotherapy and weekly cisplatin) or endometrial adenocarcinoma (postoperative radiotherapy) were randomly assigned to a probiotic drink or placebo, in a double-blind fashion. The probiotic drink consisted of liquid yogurt containing L. casei DN-114 001 at 10 8 CFU/g. The patients recorded the daily the number of bowel movements and scored the stool consistency using the Bristol scale. Diarrhea was graded weekly according the Common Toxicity Criteria system. The primary endpoint was to reduce the incidence of diarrhea, defined by a Common Toxicity Criteria Grade of 2 or greater or the need for loperamide. Results: A total of 85 patients were enrolled. Grade 2 or greater diarrhea and/or the use of loperamide was observed in 24 of 41 patients in the placebo group and 30 of 44 in the probiotic group (p = 0.568). No differences were found in the median time to the presentation of the primary endpoint. Probiotic intervention had a significant effect on stool consistency (p = 0.04). The median time for patients to present with Bristol scale stools of Type 6 or greater was 14 days for patients receiving the probiotic drink vs. 10 days for those receiving placebo. Conclusion: Nutritional intervention with the probiotic drink containing L. casei DN-114 001 does not reduce the incidence of radiation-induced diarrhea as defined by a Common Toxicity Criteria Grade 2 or greater. However, it had a significant effect on stool consistency as measured by the Bristol scale

Maitrise de la fermentation alcoolique sous stress éthanolique, thermique et osmotique de la souche Saccharomyces cerevisiae YS-DN1 en vue de la préparation du vinaigre de fruits

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Majid MOUNIR

2016-07-01

Full Text Available The purpose of the present study is to isolate, identify and characterize new yeast species of industrial interest. A total of 54 strains were isolated and identified from agricultural raw products and from by-products of the food industry. Among these, four strains were selected, purified and tested for their ability to perform efficient fermentation on Bouslikhène date juice. After the sequencing of the 18S gene of the ribosomal DNA, the two strains YS-DN1 and YS-M isolated respectively from dates and molasses have been identified belonging to Saccharomyces cerevisiae species. In addition, the other two strains, YS-OMP and YS-G isolated from olives and grapes belonged to Kluyveromyces marxianus (78% homology and Candida utilis (89% homology species, respectively. In addition, YS-DN1 strain showed the highest performance in terms of ethanol production in comparison with two other industrial reference strains. YS-DN1 strain was the only one that was able to grow at a temperature ranged from 35 to 40°C in the presence of a high alcoholic concentration and aggressive osmotic pressure condition. Finally, production of the cellular biomass of YS-DN1 strain was improved by optimization of temperature, Brix and pH fixed respectively at 29.75°C, 15.7% and 4.15. These values allowed to obtain a maximum of cells of about 8.4x10 8 UFC/ml. It was concluded that this strain is well suited for fruit vinegar production at a large-scale.

Riccardin D-N induces lysosomal membrane permeabilization by inhibiting acid sphingomyelinase and interfering with sphingomyelin metabolism in vivo

Energy Technology Data Exchange (ETDEWEB)

Li, Lin [Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan 250012 (China); Niu, Huanmin [Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012 (China); Sun, Bin [Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan 250012 (China); Xiao, Yanan [School of Pharmaceutical Science, Shandong University, Jinan 250012 (China); Li, Wei [Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan 250012 (China); Yuan, Huiqing [Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012 (China); Lou, Hongxiang, E-mail: louhongxiang@sdu.edu.cn [Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan 250012 (China)

2016-11-01

Lysosomes are important targets for anticancer drug discovery. Our previous study showed that Riccardin D-N (RD-N), a natural macrocylic bisbibenzyl derivative produced by Mannich reaction, induced cell death by accumulating in lysosomes. Experiments were performed on human lung squamous cell carcinoma tissue from left inferior lobar bronchus of patient xenografts and H460 cells. RD-N was administrated for 25 days. The specimens of xenografts in Balb/c athymic (nu +/nu +) male mice were removed for immunohistochemistry, subcellular fractionation, enzyme activities and Western blotting analysis. mRFP-GFP-LC3 reporter was used to examine autophagy in H460 cells. Sphingomyelin assay was evaluated by thin-layer chromatography and assay kit. Lysosomal membrane permeabilization (LMP) caused by acid sphingomyelinase (ASM) inhibition and subsequent changes of sphingomyelin (SM) metabolism selectively destabilized the cancer cell lysosomes in RD-N-treated H460 cells in vitro and tumor xenograft model in vivo. The destabilized lysosomes induced the release of cathepsins from the lysosomes into the cytosol and further triggered cell death. These results explain the underlying mechanism of RD-N induced LMP. It can be concluded that a more lysosomotropic derivative was synthesized by introduction of an amine group, which could have more potential applications in cancer therapy. - Highlights: • Riccardin D-N (RD-N) significantly downregulated LAMP1 expressions. • RD-N inhibited the acid sphingomyelinase activity. • RD-N induced lysosomal membrane permeabilization in vivo. • RD-N induced SM accumulation in the lysosomal membranes. • RD-N also induced the release of cathepsins from destabilized lysosomes.

Riccardin D-N induces lysosomal membrane permeabilization by inhibiting acid sphingomyelinase and interfering with sphingomyelin metabolism in vivo

International Nuclear Information System (INIS)

Li, Lin; Niu, Huanmin; Sun, Bin; Xiao, Yanan; Li, Wei; Yuan, Huiqing; Lou, Hongxiang

2016-01-01

Lysosomes are important targets for anticancer drug discovery. Our previous study showed that Riccardin D-N (RD-N), a natural macrocylic bisbibenzyl derivative produced by Mannich reaction, induced cell death by accumulating in lysosomes. Experiments were performed on human lung squamous cell carcinoma tissue from left inferior lobar bronchus of patient xenografts and H460 cells. RD-N was administrated for 25 days. The specimens of xenografts in Balb/c athymic (nu +/nu +) male mice were removed for immunohistochemistry, subcellular fractionation, enzyme activities and Western blotting analysis. mRFP-GFP-LC3 reporter was used to examine autophagy in H460 cells. Sphingomyelin assay was evaluated by thin-layer chromatography and assay kit. Lysosomal membrane permeabilization (LMP) caused by acid sphingomyelinase (ASM) inhibition and subsequent changes of sphingomyelin (SM) metabolism selectively destabilized the cancer cell lysosomes in RD-N-treated H460 cells in vitro and tumor xenograft model in vivo. The destabilized lysosomes induced the release of cathepsins from the lysosomes into the cytosol and further triggered cell death. These results explain the underlying mechanism of RD-N induced LMP. It can be concluded that a more lysosomotropic derivative was synthesized by introduction of an amine group, which could have more potential applications in cancer therapy. - Highlights: • Riccardin D-N (RD-N) significantly downregulated LAMP1 expressions. • RD-N inhibited the acid sphingomyelinase activity. • RD-N induced lysosomal membrane permeabilization in vivo. • RD-N induced SM accumulation in the lysosomal membranes. • RD-N also induced the release of cathepsins from destabilized lysosomes.

The structural innovative design of DN400 experimental facility with inversed U-shaped twin tower for uranium ion exchange

International Nuclear Information System (INIS)

Li Geng; Lei Ze'nan; Liu Qing

2012-01-01

A DN400 experimental facility with inversed U-shaped twin towers for uranium ion exchange is designed and developed to solve the existing problems in ion exchange equipment, such as easy agglomeration on the upper layer of resin bed, much resin abrasion, high sensitiveness for mud and sand, and difficulty in producing ideal plug flow in back-wash process. The facility combined with the valve control principle, cross flow type sieve plate and the unique inlet and outlet structures can solve the above problems, and the efficiency of uranium extraction can be improved significantly. (authors)

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571).

Science.gov (United States)

Tabbers, Merit M; Chmielewska, Ania; Roseboom, Maaike G; Boudet, Claire; Perrin, Catherine; Szajewska, Hania; Benninga, Marc A

2009-03-18

Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30-50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency fermented dairy product is effective in the treatment of constipated children with a defecation frequency fermented dairy product containing Bifidobacterium lactis DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5-10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as > or = 3 bowel movements per week and or = 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary) will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated. This study is aimed to show that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency after 3 weeks of product consumption in children with functional constipation and a defecation

Experience-dependent reduction of soluble β-amyloid oligomers and rescue of cognitive abilities in middle-age Ts65Dn mice, a model of Down syndrome.

Science.gov (United States)

Sansevero, Gabriele; Begenisic, Tatjana; Mainardi, Marco; Sale, Alessandro

2016-09-01

Down syndrome (DS) is the most diffused genetic cause of intellectual disability and, after the age of forty, is invariantly associated with Alzheimer's disease (AD). In the last years, the prolongation of life expectancy in people with DS renders the need for intervention paradigms aimed at improving mental disability and counteracting AD pathology particularly urgent. At present, however, there are no effective therapeutic strategies for DS and concomitant AD in mid-life people. The most intensively studied mouse model of DS is the Ts65Dn line, which summarizes the main hallmarks of the DS phenotype, included severe learning and memory deficits and age-dependent AD-like pathology. Here we report for the first time that middle-age Ts65Dn mice display a marked increase in soluble Aβ oligomer levels in their hippocampus. Moreover, we found that long-term exposure to environmental enrichment (EE), a widely used paradigm that increases sensory-motor stimulation, reduces Aβ oligomers and rescues spatial memory abilities in trisomic mice. Our findings underscore the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes in DS subjects. Copyright © 2016 Elsevier Inc. All rights reserved.

Systematic study of (d,n) reactions at Ed = 16 MeV using a deuterated scintillator array

International Nuclear Information System (INIS)

Febbraro, M.; Becchetti, F.D.; Torres-Isea, R.O.; Riggins, A.; Lawrence, C.; Howard, A.M.; Kolata, J.J.

2014-01-01

We have developed a multi-element deuterated liquid scintillator array for the study of reactions involving neutrons utilizing high-speed digital signal processing. The liquid organic scintillators exhibit good digital pulse shape discrimination (DPSD). Typical configuration involves the detectors fixed to adjustable aluminium mounts, secured to an 80/20 aluminium frame. This allows for quick and adaptable configurations to be made for varying experimental conditions including measurements over a large angular range. A systematic study of (d,n) reactions at E d = 16 MeV on 9 Be, 11 B, 13 C, 14 N, 15 N, and 19 F has been conducted from 10 to 160 degrees (lab). In addition to previously unmeasured back-angle cross sections, this data can complement existing and future ( 3 He,d) measurements as an analog to (p,γ) for astrophysics applications

Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome.

Science.gov (United States)

Stagni, Fiorenza; Giacomini, Andrea; Emili, Marco; Trazzi, Stefania; Guidi, Sandra; Sassi, Martina; Ciani, Elisabetta; Rimondini, Roberto; Bartesaghi, Renata

2016-10-01

Cognitive disability is an unavoidable feature of Down syndrome (DS), a genetic disorder due to the triplication of human chromosome 21. DS is associated with alterations of neurogenesis, neuron maturation and connectivity that are already present at prenatal life stages. Recent evidence shows that pharmacotherapies can have a large impact on the trisomic brain provided that they are administered perinatally. Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, performs many actions in the brain, including inhibition of DYRK1A, a kinase that is over-expressed in the DS brain and contributes to the DS phenotype. Young adults with DS treated with EGCG exhibit some cognitive benefits, although these effects disappear with time. We deemed it extremely important, however, to establish whether treatment with EGCG at the initial stages of brain development leads to plastic changes that outlast treatment cessation. In the current study, we exploited the Ts65Dn mouse model of DS in order to establish whether pharmacotherapy with EGCG during peak of neurogenesis in the hippocampal dentate gyrus (DG) enduringly restores hippocampal development and memory performance. Euploid and Ts65Dn mice were treated with EGCG from postnatal day 3 (P3) to P15. The effects of treatment were examined at its cessation (at P15) or after one month (at P45). We found that at P15 treated trisomic pups exhibited restoration of neurogenesis, total hippocampal granule cell number and levels of pre- and postsynaptic proteins in the DG, hippocampus and neocortex. However, at P45 none of these effects were still present, nor did treated Ts65Dn mice exhibit any improvement in hippocampus-dependent tasks. These findings show that treatment with EGCG carried out in the neonatal period rescues numerous trisomy-linked brain alterations. However, even during this, the most critical time window for hippocampal development, EGCG does not elicit enduring effects on the hippocampal physiology

AAV-dominant negative tumor necrosis factor (DN-TNF gene transfer to the striatum does not rescue medium spiny neurons in the YAC128 mouse model of Huntington's disease.

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Laura Taylor Alto

Full Text Available CNS inflammation is a hallmark of neurodegenerative disease, and recent studies suggest that the inflammatory response may contribute to neuronal demise. In particular, increased tumor necrosis factor (TNF signaling is implicated in the pathology of both Parkinson's disease (PD and Alzheimer's disease (AD. We have previously shown that localized gene delivery of dominant negative TNF to the degenerating brain region can limit pathology in animal models of PD and AD. TNF is upregulated in Huntington's disease (HD, like in PD and AD, but it is unknown whether TNF signaling contributes to neuronal degeneration in HD. We used in vivo gene delivery to test whether selective reduction of soluble TNF signaling could attenuate medium spiny neuron (MSN degeneration in the YAC128 transgenic (TG mouse model of Huntington's disease (HD. AAV vectors encoding cDNA for dominant-negative tumor necrosis factor (DN-TNF or GFP (control were injected into the striatum of young adult wild type WT and YAC128 TG mice and achieved 30-50% target coverage. Expression of dominant negative TNF protein was confirmed immunohistologically and biochemically and was maintained as mice aged to one year, but declined significantly over time. However, the extent of striatal DN-TNF gene transfer achieved in our studies was not sufficient to achieve robust effects on neuroinflammation, rescue degenerating MSNs or improve motor function in treated mice. Our findings suggest that alternative drug delivery strategies should be explored to determine whether greater target coverage by DN-TNF protein might afford some level of neuroprotection against HD-like pathology and/or that soluble TNF signaling may not be the primary driver of striatal neuroinflammation and MSN loss in YAC128 TG mice.

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571

Directory of Open Access Journals (Sweden)

Perrin Catherine

2009-03-01

Full Text Available Abstract Background Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30–50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency Methods/design It is a two nation (The Netherlands and Poland double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3–16 years with a defecation frequency Bifidobacterium lactis DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5–10 minutes after each meal (3 times a day and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence, adverse effects (nausea, diarrhoea, bad taste and intake of rescue medication (Bisacodyl. Rate of success and rate of responders are also evaluated, with success defined as ≥ 3 bowel movements per week and ≤1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency ≥ 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated. Conclusion This

Rationale, Design, and Baseline Characteristics of ARTS-DN : A Randomized Study to Assess the Safety and Efficacy of Finerenone in Patients with Type 2 Diabetes Mellitus and a Clinical Diagnosis of Diabetic Nephropathy

NARCIS (Netherlands)

Ruilope, Luis M.; Agarwal, Rajiv; Chan, Juliana C.; Cooper, Mark E.; Gansevoort, Ron T.; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E.; Nowack, Christina; Ferreira, Anna C.; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Bakris, George L.

2014-01-01

Background/Aims: Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter,

Nitrate reductase and nitrous oxide production by Fusarium oxysporum 11dn1 under aerobic and anaerobic conditions.

Science.gov (United States)

Kurakov, A V; Nosikov, A N; Skrynnikova, E V; L'vov, N P

2000-08-01

The fungus Fusarium oxysporum 11dn1 was found to be able to grow and produce nitrous oxide on nitrate-containing medium in anaerobic conditions. The rate of nitrous oxide formation was three to six orders of magnitude lower than the rates of molecular nitrogen production by common denitrifying bacteria. Acetylene and ammonia did not affect the release of nitrous oxide release. It was shown that under anaerobic conditions fast increase of nitrate reductase activity occurred, caused by the synthesis of enzyme de novo and protein dephosphorylation. Reverse transfer of the mycelium to aerobic conditions led to a decline in nitrate reductase activity and stopped nitrous oxide production. The presence of two nitrate reductases was shown, which differed in molecular mass, location, temperature optima, and activity in nitrate- and ammonium-containing media. Two enzymes represent assimilatory and dissimilatory nitrate reductases, which are active in aerobic and anaerobic conditions, respectively.

A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS.

Science.gov (United States)

Stagni, Fiorenza; Giacomini, Andrea; Guidi, Sandra; Emili, Marco; Uguagliati, Beatrice; Salvalai, Maria Elisa; Bortolotto, Valeria; Grilli, Mariagrazia; Rimondini, Roberto; Bartesaghi, Renata

2017-12-01

Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB). Systemic BDNF administration is impracticable because BDNF has a poor blood-brain barrier penetration. Recent screening of a chemical library has identified a flavone derivative, 7,8-dihydroxyflavone (7,8-DHF), a small-molecule that crosses the blood-brain barrier and binds with high affinity and specificity to the TrkB receptor. The therapeutic potential of TrkB agonists for neurogenesis improvement in DS has never been examined. The goal of our study was to establish whether it is possible to restore brain development in the Ts65Dn mouse model of DS by targeting the TrkB receptor with 7,8-DHF. Ts65Dn mice subcutaneously injected with 7,8-DHF in the neonatal period P3-P15 exhibited a large increase in the number of neural precursor cells in the dentate gyrus and restoration of granule cell number, density of dendritic spines and levels of the presynaptic protein synaptophysin. In order to establish the functional outcome of treatment, mice were treated with 7,8-DHF from P3 to adolescence (P45-50) and were tested with the Morris Water Maze. Treated Ts65Dn mice exhibited improvement of learning and memory, indicating that the recovery of the hippocampal anatomy translated into a functional rescue. Our study in a mouse model of DS provides novel evidence that treatment with 7,8-DHF during the early postnatal period restores the major trisomy-linked neurodevelopmental defects, suggesting that therapy with 7,8-DHF may represent a

Conciderações sobre a oxidação lipíca e seus limitações: o possível papel do fracionamento de carboidratos

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André de Camargo Smolarek

2012-05-01

Full Text Available Os ácidos graxos estocados principalmente na forma de triacilglicerois no tecido adiposo ou em reduzidas quantidades no tecido muscular representam uma fundamental via energética em exercícios de intensidade leve a moderada. Caracterizam-se pela alta disponibilidade de trifosfato de adenosina (ATP possuindo relevância em termos quantitativos nos exercícios de longa duração (aeróbios. De forma simplificada, a oxidação lipídica divide-se em mobilização e transporte dos ácidos graxos, β-oxidação e formação de acetil-CoA para então ser metabolizado no ciclo de Krebs. Nesse trabalho levantaremos a hipótese de que a contínua metabolização dos ácidos graxos depende em parte do fracionamento dos carboidratos (CHO. Após a glicólise, com a formação de piruvato, há formação de oxaloacetato através da enzima piruvato carboxilase. O ciclo de Krebs inicia-se com a condensação de acetil-CoA e oxaloacetato. Quando há restrição nutricional ou período extenso de atividade física (AF, há um decréscimo na quantidade de glicogênio gerando uma queda na formação de piruvato. A oxidação dos AG no ciclo de Krebs depende da acessibilidade adequada de oxaloacetato para condensar-se com o acetil-CoA. Uma queda na quantidade de CHO incitará uma diminuição conseqüente na produção de oxaloacetato o que resultará em diminuição oxidativa dos ácidos graxos. Sendo assim, o objetivo do presente estudo foi verificar, através da revisão bibliográfica, considerações sobre a oxidação lipídica e suas limitações visando o possível papel do fracionamento dos CHO.

Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial.

Science.gov (United States)

Guillemard, E; Tondu, F; Lacoin, F; Schrezenmeir, J

2010-01-01

Common infectious diseases (CID) of the airways and the gastrointestinal tract are still a considerable cause of morbidity and mortality in elderly. The present study examined the beneficial effect of a dairy product containing the probiotic strain Lactobacillus casei DN-114 001 (fermented product) on the resistance of free-living elderly to CID. The study was multicentric, double blind and controlled, involving 1072 volunteers (median age = 76.0 years) randomised for consumption of either 200 g/d of fermented (n 537) or control (non-fermented) dairy product (n 535) for 3 months, followed by an additional 1 month's follow-up. The results showed that, when considering all CID, the fermented product significantly reduced the average duration per episode of CID (6.5 v. 8 d in control group; P = 0.008) and the cumulative duration of CID (7 v. 8 d in control group; P = 0.009). Reduction in both episode and cumulative durations was also significant for all upper respiratory tract infections (URTI; P fermented product consumption (2-3.8 x 107 equivalents of colony-forming unit/g of stools, P fermented product was safe and well tolerated. In conclusion, consumption of a fermented dairy product containing the probiotic strain L. casei DN-114 001 in elderly was associated with a decreased duration of CID in comparison with the control group, especially for URTI such as rhinopharyngitis.

Alteraciones bioquímicas de los lípidos en los alimentos vegetales. II. Metabolismo de los hidroperóxidos lipídicos

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Zamora, R.

1991-06-01

Full Text Available The enzymes of the lipoxygenase pathway in plant foods are reviewed. This part analyzes the enzymes related to the descomposition or transformation of the lipidic hydroperoxides. Lipoxygenase, hydroperoxide lyase, enal isomerase, alcohol dehydrogenase, aldehyde dehydrogenase, hydroperoxide dehydrase, alene oxide ciclase and 12-Oxo-phytodienoic acid reductase in plants are described. Posible control mechanisms of the lipoxygenase pathway are also considered.

Los enzimas responsables de la degradación enzimática de los lípidos en los alimentos vegetales son examinados en este trabajo. Esta parte describe la descomposición o transformación de los hidroperóxidos lipídicos producida por la lipoxigenasa, hidroperóxido liasa, enal isomerasa, alcohol deshidrogenasa, aldehído deshidrogenasa, hidroperóxido dehidrasa, óxido de aleño ciclasa y ácido 12-Oxofitodienoico reductasa, así como los distintos mecanismos de control de la ruta.

High-resolution measurements of the exited states (n,pn), (n,dn) C-12 cross sections

Science.gov (United States)

Pillon, M.; Angelone, M.; Belloni, F.; Geerts, W.; Loreti, S.; Milocco, A.; Plompen, A. J. M.

2017-09-01

Measurements of C12 cross sections for the excited states (n,p0) up to (n,p4) and (n,d0), (n,d1) have been carried out. The Van de Graaff neutron generator of the EC-JRC-IRMM laboratory has been used for these measurements. A very thin tritiated target (263 μg/cm2) was employed with deuteron beams energies impinging on the target in the range 2.5-4.0 MeV. Neutrons in the range 18.9-20.7 MeV were produced with an intrinsic energy spread of 0.2-0.25% FWHM. With such narrow neutron energy spread, using a high energy resolution device such as a single crystal diamond detector, several peaks from the outgoing charged particles produced by the (n,pn), (n,dn) and also (n,α0) reactions appear in the pulse height spectrum. The peaks can be identified using the reaction Q-values. The diamond detector used for these measurements has shown an intrinsic energy resolution lower than 0.9% FWHM. The analysis of the peaks has permitted to derive the partial carbon reaction cross sections for several excited states. The results are presented in this paper with the associated uncertainties and they are compared with different versions of TENDL compilation when these data are available (e.g. versions 2009, 2010, 2011 and 2015) and also with experimental results available in the EXFOR database.

High-resolution measurements of the exited states (n,pn, (n,dn C-12 cross sections

Directory of Open Access Journals (Sweden)

Pillon M.

2017-01-01

Full Text Available Measurements of C12 cross sections for the excited states (n,p0 up to (n,p4 and (n,d0, (n,d1 have been carried out. The Van de Graaff neutron generator of the EC-JRC-IRMM laboratory has been used for these measurements. A very thin tritiated target (263 μg/cm2 was employed with deuteron beams energies impinging on the target in the range 2.5–4.0 MeV. Neutrons in the range 18.9–20.7 MeV were produced with an intrinsic energy spread of 0.2–0.25% FWHM. With such narrow neutron energy spread, using a high energy resolution device such as a single crystal diamond detector, several peaks from the outgoing charged particles produced by the (n,pn, (n,dn and also (n,α0 reactions appear in the pulse height spectrum. The peaks can be identified using the reaction Q-values. The diamond detector used for these measurements has shown an intrinsic energy resolution lower than 0.9% FWHM. The analysis of the peaks has permitted to derive the partial carbon reaction cross sections for several excited states. The results are presented in this paper with the associated uncertainties and they are compared with different versions of TENDL compilation when these data are available (e.g. versions 2009, 2010, 2011 and 2015 and also with experimental results available in the EXFOR database.

Initiation of protein synthesis by a labeled derivative of the Lactobacillus casei DN-114 001 strain during transit from the stomach to the cecum in mice harboring human microbiota.

Science.gov (United States)

Oozeer, R; Mater, D D G; Goupil-Feuillerat, N; Corthier, G

2004-12-01

Although studies on the survival of bacteria in the digestive tract have been reported in the literature, little data are available on the physiological adaptation of probiotics to the digestive environment. In previous work, a transcriptional fusion system (i.e., luciferase genes under the control of a deregulated promoter) was used to demonstrate that a derivative of the Lactobacillus casei DN-114 001 strain, ingested in a fermented milk and thus exhibiting initially a very weak metabolic activity, synthesized proteins de novo after its transit in the digestive tract of mice harboring human microbiota (known as human-microbiota-associated mice). With the same genetic system and animal model, we here investigate for the first time the ability of L. casei to reinitiate synthesis in the different digestive tract compartments. In this study, most ingested L. casei cells transited from the stomach to the duodenum-jejunum within 1 h postingestion. No luciferase activity was observed in these digestive tract compartments after the first hour. At later times, the bulk of bacteria had transited to the ileum and the cecum. Luciferase synthesis was detected between 1.5 and 2.0 h postingestion at the ileal level and from 1.5 h to at least 6.0 h postingestion in the cecum, where the activity remained at a maximum level. These results demonstrate that ingested L. casei (derivative of the DN-114 001 strain) administered via a fermented milk has already reinitiated protein synthesis when it reaches the ileal and cecal compartments.

Structural dynamics and fracture mechanics calculations of the behaviour of a DN 425 test piping system subjected to transient loading by water hammer

International Nuclear Information System (INIS)

Kussmaul, K.; Kobes, E.; Diem, H.; Schrammel, D.; Brosi, S.

1994-01-01

Within the scope of the German HDR safety programme, several tests were carried out to investigate transient pipe loading initiated by a simulated double-ended guillotine break event, and subsequent closure of a feedwater check valve (water hammer, blow-down). Numerical analyses by means of finite element programmes were performed in parallel to the experiments. Using water hammer tests of a DN 425 piping system with predamaged components, the procedure of such analyses will be demonstrated. The results are presented, beginning with structural dynamic calculations of the undamaged piping; followed by coupling of structural dynamics and fracture mechanics computations with simple flaw elements (line spring); and finishing with costly three-dimensional fracture mechanics analyses. A good description of the real piping behaviour can be made by the numerical methods, even in the case of high plastification processes. ((orig.))

Ornitina alfa-cetoglutarato na isquemia-reperfusÃo intestinal em ratos

OpenAIRE

Eduardo Silvio Gouveia GonÃalves

2009-01-01

Objetivo: Avaliar os efeito da ornitina α-cetoglutarato (OKG) no sangue e tecido intestinal de ratos submetidos à isquemia/reperfusÃo intestinal atravÃs da determinaÃÃo das concentraÃÃes in vivo no sangue e no tecido do intestino delgado, submetido a isquemia/reperfusÃo, de glicose, G 6 PDH, piruvato, acetoacetato, lactato, 3 HBDH, glutationa, T-Bars, mieloperoxidase, CPK e LDH. MÃtodo: Sessenta ratos (Rattus norvergicus albinus, Rodentia Mammalia) foram distribuÃdos aleatoriamente em ci...

Use of a fermented dairy probiotic drink containing Lactobacillus casei (DN-114 001) to decrease the rate of illness in kids: the DRINK study. A patient-oriented, double-blind, cluster-randomized, placebo-controlled, clinical trial.

Science.gov (United States)

Merenstein, D; Murphy, M; Fokar, A; Hernandez, R K; Park, H; Nsouli, H; Sanders, M E; Davis, B A; Niborski, V; Tondu, F; Shara, N M

2010-07-01

To evaluate whether a fermented dairy drink containing the probiotic strain Lactobacillus casei DN-114 001 could reduce the incidence of common infectious diseases (CIDs) and the change of behavior because of illness in children. We conducted a double-blinded, randomized, placebo-controlled allocation concealment clinical trial in the Washington, DC metropolitan area. Participants were 638 children 3-6 years old in daycare/schools. The intervention was a fermented dairy drink containing a specific probiotic strain or matching placebo with no live cultures for 90 consecutive days. Two primary outcomes were assessed: incidence of CIDs and change of behavior because of illness (both assessed by parental report). The rate of change of behavior because of illness was similar among active and control groups. However, the incidence rate for CIDs in the active group (0.0782) is 19% lower than that of the control group (0.0986) (incidence rate ratio=0.81, 95% CI: 0.65, 099) P=0.046. Daily intake of a fermented dairy drink containing the probiotic strain L. casei DN-114 001 showed some promise in reducing overall incidence of illness, but was primarily driven by gastrointestinal infections and there were no differences in change of behavior.

Brno: genius loci. 47. mezinárodní hudebněvědné kolokvium, konané při Mezinárodním festivalu Janáček Brno 2012, Brno, 19.-21. listopadu 2012

Czech Academy of Sciences Publication Activity Database

Bajgarová, Jitka

2013-01-01

Roč. 50, č. 1-2 (2013), s. 190-192 ISSN 0018-7003. [Brno: genius loci. 47. mezinárodní hudebněvědné kolokvium, konané při Mezinárodním festival u Janáček Brno 2012. Brno, 19.11.2012-21.11.2012] Institutional support: RVO:68378076 Keywords : musicological conference * Brno * genius loci Subject RIV: AL - Art, Architecture, Cultural Heritage

Parameters of DEMO DN and JET DN

International Nuclear Information System (INIS)

Anon.

1987-01-01

The paper is an appendix to a study of the reactor relevance of the NET design concept. The latter study examines whether the technologies and design principles proposed for NET can be directly extrapolated to a demonstration (DEMO) reactor. The appendix presents the parameters of the DEMO and NET under the topic headings: power, geometry, plasma, toroidal and poloidal magnetic field coils, first wall engineering, divertor physics, divertor engineering, and blanket. (U.K.)

Effects of consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114 001 on common respiratory and gastrointestinal infections in shift workers in a randomized controlled trial.

Science.gov (United States)

Guillemard, Eric; Tanguy, Jérôme; Flavigny, Ann'Laure; de la Motte, Stephan; Schrezenmeir, Juergen

2010-10-01

The risk of infection may be increased in people under stress such as shift workers. This study examined the effect of a fermented dairy product containing the probiotic Lactobacillus casei DN-114 001 (verum) on the incidence of respiratory and gastrointestinal common infectious diseases (CIDs) and on immune functions in healthy shift workers. The study was single-center, randomized, double-blind, and controlled. Volunteers received 200 g/day of verum (n = 500) or control product (n = 500) for 3 months; 1-month follow-up was carried out. The cumulated number of CIDs (primary outcome) was not significantly different between groups. Because the Poisson distribution of the primary parameter did not fully fit the observed data, a post hoc categorical analysis was applied and showed a significantly lower cumulated number of CIDs in the verum group during the product consumption phase (odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.59-0.95, p = 0.017). Verum also reduced the proportion of volunteers experiencing at least 1 CID (43% vs. 51%, p = 0.005), increased the time to the first occurrence of CID (p = 0.017) in the whole population, and reduced the cumulated number of CIDs in the subgroup of smokers (p = 0.033). In the course of CID, cumulated duration of fever was lower in the verum group (in the whole study phase) (p = 0.022), and an increase in leukocyte, neutrophil, and natural killer (NK) cell counts and activity (p = 0.047 to p fermented dairy product containing Lactobacillus casei DN-114 001 could reduce the risk of common infections in stressed individuals such as shift workers.

Deficiencia de glucosa 6-fostato deshidrogenasa en hombres sanos y en pacientes maláricos; Turbo (Antioquia, Colombia Deficiency of glucose-6-phosphate dehydrogenase in healthy men and malaria patients; Turbo (Antioquia, Colombia

Directory of Open Access Journals (Sweden)

Jaime Carmona-Fonseca

2008-06-01

Full Text Available INTRODUCCIÓN: En América Latina la deficiencia de glucosa 6-fosfato deshidrogenasa (d-G6PD ha sido poco estudiada y en Colombia solo conocemos tres publicaciones antiguas. Urge conocer más la prevalencia de d-G6PD, sobre todo ahora que el tratamiento de la malaria vivax plantea aumentar la dosis diaria o total de primaquina. OBJETIVO: Medir la prevalencia de d-G6PD en poblaciones masculina sana y de enfermos con malaria por Plasmodium vivax, en Turbo (Urabá, departamento de Antioquia, Colombia. METODOLOGÍA: Encuestas de prevalencia, para evaluar la G6PD en dos poblaciones de Turbo (Antioquia: hombres sanos; hombres y mujeres con malaria vivax. Se trabajó con muestras diseñadas con criterios estadístico-epidemiológicos. La actividad enzimática se midió con el método normalizado de Beutler para valorar la G6PD en hemolizados. RESULTADOS: Entre los hombres sanos (n = 508, el intervalo de confianza 95% para el promedio (IC95% estuvo entre 4,15 y 4,51 UI/g hemoglobina y 14,8% presentaron valores por debajo del "límite normal" de INTRODUCTION: Glucose-6-phosphate dehydrogenase (G6PD deficiency in Latin America has not been fully studied and in Colombia only three outdated publications are known. Recent information on the prevalence of G6PD deficiency is required now, because the recommended treatment of vivax malaria requires higher daily or total doses of primaquine. OBJECTIVE: To measure the prevalence of G6PD in a healthy male population and in a Plasmodium vivax infected population in Turbo (Urabá, Antioquia Department, Colombia. METHOD: Prevalence survey to evaluate G6PD in two populations of Turbo (Antioquia: healthy male; male and female with vivax malaria. The work was carried out on population samples selected using statistical and epidemiological criteria. Enzyme activity was measured using Beutler's normalized method to evaluate G6PD after hemolysis. RESULTS: For the healthy male group (n = 508, and with a 95% confidence

Methylobacterium populi sp. nov., a novel aerobic, pink-pigmented, facultatively methylotrophic, methane-utilizing bacterium isolated from poplar trees (Populus deltoides x nigra DN34).

Science.gov (United States)

Van Aken, Benoit; Peres, Caroline M; Doty, Sharon Lafferty; Yoon, Jong Moon; Schnoor, Jerald L

2004-07-01

A pink-pigmented, aerobic, facultatively methylotrophic bacterium, strain BJ001T, was isolated from internal poplar tissues (Populus deltoidesxnigra DN34) and identified as a member of the genus Methylobacterium. Phylogenetic analyses showed that strain BJ001T is related to Methylobacterium thiocyanatum, Methylobacterium extorquens, Methylobacterium zatmanii and Methylobacterium rhodesianum. However, strain BJ001T differed from these species in its carbon-source utilization pattern, particularly its use of methane as the sole source of carbon and energy, an ability that is shared with only one other member of the genus, Methylobacterium organophilum. In addition, strain BJ001T is the only member of the genus Methylobacterium to be described as an endophyte of poplar trees. On the basis of its physiological, genotypic and ecological properties, the isolate is proposed as a member of a novel species of the genus Methylobacterium, Methylobacterium populi sp. nov. (type strain, BJ001T=ATCC BAA-705T=NCIMB 13946T).

First in situ determination of gas transport coefficients (DO2, DAr and DN2) from bulk gas concentration measurements (O2, N2, Ar) in natural sea ice

DEFF Research Database (Denmark)

Crabeck, O.; Delille, B.; Rysgaard, Søren

2014-01-01

We report bulk gas concentrations of O2, N2, and Ar, as well as their transport coefficients, in natural landfast subarctic sea ice in southwest Greenland. The observed bulk ice gas composition was 27.5% O2, 71.4% N2, and 1.09% Ar. Most previous studies suggest that convective transport is the main...... driver of gas displacement in sea ice and have neglected diffusion processes. According to our data, brines were stratified within the ice, so that no convective transport could occur within the brine system. There- fore, diffusive transport was the main driver of gas migration. By analyzing the temporal...... evolution of an internal gas peak within the ice, we deduced the bulk gas transport coefficients for oxygen (DO2), argon (DAr), and nitrogen (DN2). The values fit to the few existing estimates from experimental work, and are close to the diffusivity values in water (1025 cm2 s21). We suggest that gas...

Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses.

Science.gov (United States)

Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

2017-05-04

Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs , including DnARF1 , DnARF4 , and DnARF6 , were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1 , DnARF4 , and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale . To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment.

Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy.

Science.gov (United States)

Sun, Guang-dong; Li, Chao-yuan; Cui, Wen-peng; Guo, Qiao-yan; Dong, Chang-qing; Zou, Hong-bin; Liu, Shu-jun; Dong, Wen-peng; Miao, Li-ning

2016-01-01

Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20-40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN.

Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity

Science.gov (United States)

House, M.L.; Kim, C.H.; Reno, P.W.

1998-01-01

Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

Releasing dentate nucleus cells from Purkinje cell inhibition generates output from the cerebrocerebellum.

Directory of Open Access Journals (Sweden)

Takahiro Ishikawa

Full Text Available The cerebellum generates its vast amount of output to the cerebral cortex through the dentate nucleus (DN that is essential for precise limb movements in primates. Nuclear cells in DN generate burst activity prior to limb movement, and inactivation of DN results in cerebellar ataxia. The question is how DN cells become active under intensive inhibitory drive from Purkinje cells (PCs. There are two excitatory inputs to DN, mossy fiber and climbing fiber collaterals, but neither of them appears to have sufficient strength for generation of burst activity in DN. Therefore, we can assume two possible mechanisms: post-inhibitory rebound excitation and disinhibition. If rebound excitation works, phasic excitation of PCs and a concomitant inhibition of DN cells should precede the excitation of DN cells. On the other hand, if disinhibition plays a primary role, phasic suppression of PCs and activation of DN cells should be observed at the same timing. To examine these two hypotheses, we compared the activity patterns of PCs in the cerebrocerebellum and DN cells during step-tracking wrist movements in three Japanese monkeys. As a result, we found that the majority of wrist-movement-related PCs were suppressed prior to movement onset and the majority of wrist-movement-related DN cells showed concurrent burst activity without prior suppression. In a minority of PCs and DN cells, movement-related increases and decreases in activity, respectively, developed later. These activity patterns suggest that the initial burst activity in DN cells is generated by reduced inhibition from PCs, i.e., by disinhibition. Our results indicate that suppression of PCs, which has been considered secondary to facilitation, plays the primary role in generating outputs from DN. Our findings provide a new perspective on the mechanisms used by PCs to influence limb motor control and on the plastic changes that underlie motor learning in the cerebrocerebellum.

Polymorphism of angiotensin-converting enzyme (rs4340 and diabetic nephropathy in Caucasians with type 2 diabetes mellitus

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Šeruga M

2016-12-01

Full Text Available Diabetic nephropathy (DN is the leading cause of endstage renal disease (ESRD in developed countries. Several environmental and genetic factors predict the development and progression of DN. The renin-angiotensin system was demonstrated to be involved in the development of DN. We evaluated the association between rs4340 of the angiotensin-converting enzyme (ACE gene and DN in Caucasians with type 2 diabetes mellitus (T2DM in 276 Slovenian patients with T2DM who had DN, and 375 patients without clinical signs of DN. Genetic analysis was performed with either standard polymerase chain reaction (PCR (for rs4340. Results were analyzed using the χ2 test and multivariate logistic regression analyses. We found no association between rs4340 and DN. Cystatin C was significantly higher in the DN+ group (p <0.001 than in the DN group. Cystatin C was a better marker for the estimation of renal function than estimated glomerular filtration rate (eGFR according to the modification diet in renal disease (MDRD equation mL/ min. We concluded that there was no association between the rs4340 of the ACE gene and DN in Caucasian patients who have T2DM.

Hydroxyapatite-coated double network hydrogel directly bondable to the bone: Biological and biomechanical evaluations of the bonding property in an osteochondral defect.

Science.gov (United States)

Wada, Susumu; Kitamura, Nobuto; Nonoyama, Takayuki; Kiyama, Ryuji; Kurokawa, Takayuki; Gong, Jian Ping; Yasuda, Kazunori

2016-10-15

We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2weeks, and the osteoid tissue was mineralized at 4weeks. The push-out load of the HAp/DN gel averaged 37.54N and 42.15N at 4 and 12weeks, respectively, while the push-out load of the DN gel averaged less than 5N. The bonding area of the HAp/DN gel to the bone was above 80% by 4weeks, and above 90% at 12weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A retrospective study on the impact of comorbid depression or anxiety on healthcare resource use and costs among diabetic neuropathy patients

Directory of Open Access Journals (Sweden)

Bao Yanjun

2009-06-01

Full Text Available Abstract Background Diabetic neuropathy (DN is a common complication of diabetes that has significant economic burden, especially for patients with comorbid depression or anxiety. This study examines and quantifies factors associated with healthcare costs among patients diagnosed with diabetic neuropathy (DN with or without a comorbid diagnosis of depression or anxiety (DA using retrospective administrative claims data. No study has examined the differences in economic outcomes depending on the presence of comorbid DA disorders. Methods Over-age-18 individuals with 1+ diagnosis of DN in 2005 were selected. The first observed DN claim was considered the "index date." All individuals had a 12-month pre-index and follow-up period. For both under-age-65 commercially insured and over-age-65 individuals with employer-sponsored Medicare supplemental insurance, we constructed 2 subgroups for individuals with DA (DN-DA or without (DN-only. Patients' clinical characteristics over pre-index period were compared. Multivariate regressions were performed to assess whether DN-DA patients had higher utilization of healthcare resources and costs than DN-only patients, controlling for demographic and clinical characteristics. Results We identified 16,831 DN-only and 1,699 DN-DA patients in the Medicare supplemental cohort, as well as 17,205 and 3,105 in the commercially insured. DN-DA patients had higher prevalence of diabetes-related comorbidities for cardiovascular disease, cerebrovascular/peripheral vascular disease, nephropathy, obesity, and hypoglycemic events than DN-only patients (all p Conclusion These findings indicate that the healthcare costs were significantly higher for DN patients with depression or anxiety relative to those without such comorbid disorders.

Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Guang-dong Sun

2016-01-01

Full Text Available Diabetic nephropathy (DN is the most serious chronic complications of diabetes; 20–40% of diabetic patients develop into end stage renal disease (ESRD. However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN.

The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy.

Science.gov (United States)

Andeen, Nicole K; Nguyen, Tri Q; Steegh, Floor; Hudkins, Kelly L; Najafian, Behzad; Alpers, Charles E

2015-11-01

Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman's capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman's capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.

[Financing Regional Dementia Networks in Germany: Determinants of Sustainable Healthcare Networks].

Science.gov (United States)

Michalowsky, B; Wübbeler, M; Thyrian, J R; Holle, B; Gräske, J; Schäfer-Walkmann, S; Fleßa, S; Hoffmann, W

2017-12-01

Analysis of practice-based financing concepts in German dementia networks (DN); Provision of sustainable financing structures and their determinants in DN. Qualitative expert interviews with leaders of 13 DN were conducted. A semi-structured interview guide was used to analyse four main topics: Finance-related organization, cost, sources of funding and financial sustainability. DN were primarily financed by membership fees, earnings of services provided, public funds and payments by municipalities or health care providers. 63% of the DN reported a financial sustainability. Funds to support the interpersonal expanding, a mix of internal and external financing sources and investments of the municipality were determinants of a sustainable financing. Overall, DN in rural areas seemed to be disadvantaged due to a lack of potential linkable service providers. DN in urban regions are more likely able to gather sustainable funding resources. A minimum funding of 50.000 €/year for human resources coordinating the DN, seems to be a threshold for a sustainable DN. © Georg Thieme Verlag KG Stuttgart · New York.

Características metabólicas del músculoGluteus medius de equinos mestizos con aptitud de tiro

OpenAIRE

MERINO, V.; ISLAS, A.; LOPEZ-RIVERO, J.; MORA, G.; QUEZADA, M.; LOPEZ, J.; REYES, J.

1998-01-01

De 16 equinos mestizos de tiro, de ambos sexos, clínicamente sanos, se obtuvieron biopsias del músculo Gluteus medius a 3, 6 y 9 cm de profundidad, con el objetivo de evaluar su metabolismo anaeróbico y aeróbico, determinando las actividades de las enzimas creatinquinasa (CK), deshidrogenasa láctica (LDH) y citrato sintetasa (CS) en animales inactivos y trabajando en faenas agrícolas. El tejido muscular se homogeneizó, sonicó y centrifugó; posteriormente en el sobrenadante se determinaron la...

Características metabólicas del músculoGluteus medius de equinos mestizos con aptitud de tiro Metabolic characteristics of the Gluteus medius musclein crossbreed draft horses

OpenAIRE

V. MERINO; A. ISLAS; J. LOPEZ-RIVERO; G. MORA; M. QUEZADA; J. LOPEZ; J. REYES

1998-01-01

De 16 equinos mestizos de tiro, de ambos sexos, clínicamente sanos, se obtuvieron biopsias del músculo Gluteus medius a 3, 6 y 9 cm de profundidad, con el objetivo de evaluar su metabolismo anaeróbico y aeróbico, determinando las actividades de las enzimas creatinquinasa (CK), deshidrogenasa láctica (LDH) y citrato sintetasa (CS) en animales inactivos y trabajando en faenas agrícolas. El tejido muscular se homogeneizó, sonicó y centrifugó; posteriormente en el sobrenadante se determinaron las...

Estudio de la expresión de enzimas del metabolismo de aminoácidos en lactococcus lactis

OpenAIRE

García Cayuela, Tomás

2011-01-01

Los aminoácidos son fundamentales para la supervivencia y el desarrollo de bacterias. Son las principales fuentes de nitrógeno y están implicados en la producción de energía, el control del pH intracelular y la regeneración de cofactores. Además, son los precursores de una larga variedad de compuestos volátiles en Lactococcus lactis y, por ello, diversas enzimas son consideradas clave para su formación, como aminotransferasas, deshidrogenasas, liasas y decarboxilasas, entre otras. Estas enzim...

Evaluación genética de los salmónidos asturianos como recurso natural

OpenAIRE

Abad García, David

2012-01-01

En este proyecto se analiza la estructura genética de los stocks utilizados para la repoblación de trucha común en el Principado de Asturias, pertenecientes a dos piscifactorías diferentes, con el fin de establecer si los repobladores cumplen con la normativa vigente sobre la liberación de individuos no autóctonos al medio natural, que está actualmente prohibida. Para ello se utiliza como marcador genético el gen del enzima lactato deshidrogenasa LDH-C, que permite diferenciar las poblaciones...

Incidence and Factors Associated with De Novo DSA After BK Viremia in Renal Transplant Recipients.

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Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Graviss, Edward A; Nguyen, Duc; Gaber, A Osama

2016-01-01

BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted. Copyright© 2017 by the Terasaki Research Institute.

Development of a face-to-face injunctive norms brief motivational intervention for college drinkers and preliminary outcomes.

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Prince, Mark A; Maisto, Stephen A; Rice, Samara L; Carey, Kate B

2015-12-01

Findings are presented from the first randomized clinical trial that compared changes in alcohol consumption and alcohol-related consequences among college student drinkers from baseline to follow-up across 4 conditions: (a) a new single component injunctive norms brief motivational intervention (IN-BMI) condition; (b) a single component descriptive norms brief motivational intervention (DN-BMI); (c) a combined IN and DN brief motivational intervention (Combined-BMI); and (d) assessment-only control. DN-BMI focused on the juxtaposition of personal, perceived, and actual alcohol use by typical same-sex students at your university. IN-BMI focused on the juxtaposition of personal, perceived, and actual attitudes about alcohol-related consequences by the typical same-sex student at your university. Exploratory analyses assessed the effect of IN-BMI and DN-BMI on matched (e.g., the effect of DN-BMI on perceived DN) and mismatched norms (e.g., the effect of DN-BMI on perceived IN). IN-BMI resulted in greater decreases in alcohol use and consequences when delivered alone and in conjunction with DN-BMI compared with the control condition. Further, the Combined-BMI condition reported greater reductions in alcohol use but not consequences compared to the DN condition. Receiving IN-BMI either alone or in combination with DN-BMI produced greater changes in IN perceptions than were produced in the control group. Grounded in norms theory, this study examined how college student problem drinking is affected by both IN-BMI and DN-BMI alone and in combination. We conclude that IN-BMI alone or in combination with DN-BMI is able to modify alcohol use and reduce alcohol-related consequences. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

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Jingsong Shi

2016-01-01

Full Text Available Objective. To investigate potential drugs for diabetic nephropathy (DN using whole-genome expression profiles and the Connectivity Map (CMAP. Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1 A total of 1065 DEGs (FDR 1.5 were found in late stage DN patients compared with early stage DN patients. (2 Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2, vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs, PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

Enhanced tolerance against early and late apoptotic oxidative stress in mammalian neurons through nicotinamidase and sirtuin mediated pathways.

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Chong, Zhao Zhong; Maiese, Kenneth

2008-08-01

Focus upon therapeutic strategies that intersect between pathways that govern cellular metabolism and cellular survival may offer the greatest impact for the treatment of a number of neurodegenerative and metabolic disorders, such as diabetes mellitus. In this regard, we investigated the role of a Drosophila nicotinamidase (DN) in mammalian SH-SY5Y neuronal cells during oxidative stress. We demonstrate that during free radical exposure to nitric oxide generators DN neuronal expression significantly increased cell survival and blocked cellular membrane injury. Furthermore, DN neuronal expression prevented both apoptotic late DNA degradation and early phosphatidylserine exposure that may serve to modulate inflammatory cell activation in vivo. Nicotinamidase activity that limited nicotinamide cellular concentrations appeared to be necessary for DN neuroprotection, since application of progressive nicotinamide concentrations could abrogate the benefits of DN expression during oxidative stress. Pathways that involved sirtuin activation and SIRT1 were suggested to be vital, at least in part, for DN to confer protection through a series of studies. First, application of resveratrol increased cell survival during oxidative stress either alone or in conjunction with the expression of DN to a similar degree, suggesting that DN may rely upon SIRT1 activation to foster neuronal protection. Second, the overexpression of either SIRT1 or DN in neurons prevented apoptotic injury specifically in neurons expressing these proteins during oxidative stress, advancing the premise that DN and SIRT1 may employ similar pathways for neuronal protection. Third, inhibition of sirtuin activity with sirtinol was detrimental to neuronal survival during oxidative stress and prevented neuronal protection during overexpression of DN or SIRT1, further supporting that SIRT1 activity may be necessary for DN neuroprotection during oxidative stress. Implementation of further work to elucidate the

Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial.

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Guyonnet, D; Chassany, O; Ducrotte, P; Picard, C; Mouret, M; Mercier, C-H; Matuchansky, C

2007-08-01

Health-related quality of life (HRQoL) has been rarely evaluated as a primary endpoint in the assessment of the effect of probiotics on the irritable bowel syndrome (IBS). To study the effects of fermented milk containing Bifidobacterium animalis DN-173 010 and yoghurt strains on the IBS in a multicentre, double-blind, controlled trial. A total of 274 primary care adults with constipation-predominant IBS (Rome II) were randomized to consume for 6 weeks either the test fermented milk or a heat-treated yoghurt (control). HRQoL and digestive symptoms were assessed after 3 and 6 weeks on an intention-to-treat population of 267 subjects. The HRQoL discomfort score, the primary endpoint, improved (P food on discomfort HRQoL score and bloating in constipation-predominant IBS, and on stool frequency in subjects with <3 stools/week.

Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group.

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de Wit, P E; van't Hof-Grootenboer, B; Ruiter, D J; Bondi, R; Bröcker, E B; Cesarini, J P; Hastrup, N; Hou-Jensen, K; MacKie, R M; Scheffer, E

1993-01-01

Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN. Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low. The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non-DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively. On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN.

Study on Association of Pentraxin 3 and Diabetic Nephropathy in a Rat Model

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Xuehai Chen

2018-01-01

Full Text Available Diabetic nephropathy (DN is a serious microvascular complication of diabetes. Compared with other therapies for diabetic patients, islet transplantation can effectively prevent and reverse diabetes-induced microvascular disease, such as diabetic retinopathy and nephropathy. PTX3 is the only long pentraxin that can be detected in renal tissue. In this study, we investigated the expression of PTX3 when early DN was reversed after islet transplantation. Methods. Diabetes was induced in rats by injecting streptozotocin (STZ. Twelve weeks later, the diabetic rats were divided into 2 groups: the islet transplantation group (IT and the diabetic nephropathy group (DN. Renal injury, renal function, and the expression of PTX3 in the plasma and the kidneys were assessed with urinalysis, immunohistochemical staining, and Western blot, respectively. Results. The expression of PTX3 in the kidney was significantly decreased in the DN group but increased in the IT group because of the reversal of DN. Conclusions. Our data showed that the level of PTX3 in renal tissue is closely related to renal injury in DN. This may be used to quantify the extent of renal injury in DN, provide a potential early indicator of renal tubular injury in early DN patients, and assess DN clinical progression.

Subcellular distribution and uptake mechanism of di-n-butyl phthalate in roots of pumpkin (Cucurbita moschata) seedlings.

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Lin, Qingqi; Yang, Xiuhong; Huang, Xiongfei; Wang, Shizhong; Chao, Yuanqing; Qiu, Rongliang

2016-01-01

Phthalate acid esters (PAEs) are of particular concern due to their potential environmental risk to human and nonhuman organisms. Although uptake of PAEs by plants has been reported by several researchers, information about the intracellular distribution and uptake mechanisms of PAEs is still lacking. In this study, a series of hydroponic experiments using intact pumpkin (Cucurbita moschata) seedlings was conducted to investigate how di-n-butyl phthalate (DnBP), one of the most frequently identified PAEs in the environment, enters and is distributed in roots. DnBP was transported into subcellular tissues rapidly in the initial uptake period (<12 h). More than 80% of DnBP was detected in the cell walls and organelles, which suggests that DnBP is primarily accumulated in these two fractions due to their high affinity to DnBP. The kinetics of DnBP uptake were fitted well with the Michaelis-Menten equation, suggesting that a carrier-mediated process was involved. The application of 2,4-dinitrophenol and sodium vanadate reduced the uptake of DnBP by 37 and 26%, respectively, while aquaporin inhibitors, silver and glycerol, had no effect on DnBP uptake. These data demonstrated that the uptake of DnBP included a carrier-mediated and energy-dependent process without the participation of aquaporins.

Aerodynamic parameters of across-wind self-limiting vibration for square sections after lock-in in smooth flow

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Wu, Jong-Cheng; Chang, Feng-Jung

2011-08-01

The paper aims to identify the across-wind aerodynamic parameters of two-dimensional square section structures after the lock-in stage from the response measurements of wind tunnel tests under smooth wind flow conditions. Firstly, a conceivable self-limiting model was selected from the existent literature and the revisit of the analytical solution shows that the aerodynamic parameters (linear and nonlinear aerodynamic dampings Y1 and ɛ, and aerodynamic stiffness Y2) are not only functions of the section shape and reduced wind velocity but also dependent on both the mass ratio ( mr) and structural damping ratio ( ξ) independently, rather than on the Scruton number as a whole. Secondly, the growth-to-resonance (GTR) method was adopted for identifying the aerodynamic parameters of four different square section models (DN1, DN2, DN3 and DN4) by varying the density ranging from 226 to 409 kg/m 3. To improve the accuracy of the results, numerical optimization of the curve-fitting for experimental and analytical response in time domain was performed to finalize the results. The experimental results of the across-wind self-limiting steady-state amplitudes after lock-in stage versus the reduced wind velocity show that, except the tail part of the DN1 case slightly decreases indicating a pure vortex-induced lock-in persists, the DN2, DN3 and DN4 cases have a trend of monotonically increasing with the reduced wind velocity, which shows an asymptotic combination with the galloping behavior. Due to such a combination effect, all three aerodynamic parameters decrease as the reduced wind velocity increases and asymptotically approaches to a constant at the high branch. In the DN1 case, the parameters Y1 and Y2 decrease as the reduced wind velocity increases while the parameter ɛ slightly reverses in the tail part. The 3-dimensional surface plot of the Y1, ɛ and Y2 curves further show that, excluding the DN1 case, the parameters in the DN2, DN3 and DN4 cases almost follow a

Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy.

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Liu, Jingping; Wang, Chengshi; Liu, Fang; Lu, Yanrong; Cheng, Jingqiu

2015-03-01

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by (1)H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN.

Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria

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Jauregui, Alexandra; Mintz, Daniel H; Mundel, Peter; Fornoni, Alessia

2010-01-01

Purpose of review In diabetic nephropathy (DN), insulin resistance and hyperinsulinemia correlate with the development of albuminuria. The possibility that altered insulin signaling in glomerular cells and particularly podocytes contributes to the development of DN will be discussed. Recent findings While normal podocytes uptake glucose in response to insulin, diabetic podocytes become insulin resistant in experimental DN prior to the development of significant albuminuria. Both clinical and experimental data suggest that insulin sensitizers may be renoprotective independently of their systemic effects on the metabolic control of diabetes. Summary We will review the clinical and experimental evidence that altered insulin signaling correlates with the development of DN in both type 1 and type 2 diabetes, and that insulin sensitizers may be superior to other hypoglycemic agents in the prevention of DN. We will then review potential mechanisms by which altered podocyte insulin signaling may contribute to the development of DN. Understanding the role of podocyte in glucose metabolism is important because it may lead to the discovery of novel pathogenetic mechanisms of DN, it may affect current strategies for prevention and treatment of DN, and it may allow for the identification of novel therapeutic targets. PMID:19724224

Dental neglect among college going adolescents in Virajpet, India

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Sunil Lingaraj Ajagannanavar

2014-01-01

Full Text Available Introduction: Dental neglect (DN has been defined as behavior and attitudes which are likely to have detrimental consequences for the individual′s oral health, or more specifically as failure to take precautions to maintain oral health, failure to obtain needed dental care, and physical neglect of the oral cavity. Aim: The aim was to assess the association of DN with dental caries and oral hygiene among adolescents in Virajpet, India. Materials and Methods: A total of six hundred adolescents aged 15-18 years were selected. DN was recorded using self-administered questionnaire. Oral health status was clinically assessed using simplified oral hygiene index (OHI-S and dental caries through dentition status as per WHO criteria. Results: The mean DN score for this population was 10.18. Sociodemographic variables and Dental Attendance pattern were significantly associated with DN. Mean decayed missing filled value and OHI-S values were also significantly associated with DN. Conclusion: The present study revealed that variations in DN exist in relation to sociodemographic characteristics and pattern of dental attendance. In addition, oral health status was significantly associated with DN among adolescents.

The Search for Molecular Prognostic Markers of Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

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V. M. Ibragimov

2016-03-01

Full Text Available The purpose of this study was to search for molecular prognostic markers of diabetic nephropathy (DN in patients with type 2 diabetes mellitus (T2DM. The study included 205 patients with T2DM and DN (stages 1 to 4. All patients were stratified by the MDRD equation. The control group included 30 healthy individuals. All T2DM patients were divided into 4 groups depending on the DN stages. Group 1 included 42 patients with DN-Stage 1 (prenephropathy, Group 2 included 48 patients with DN-Stage 2 (incipient nephropathy; Group 3 included 65 patients with DN-Stage 3 (overt nephropathy, and Group 4 included 50 patients with DN-Stage 4 (kidney failure. Molecular phenotyping of urine was processed with methods of proteomics: the prefractionation, the separation of proteins with standard sets (MB-HIC C8 Kit, MB-IMAC Cu, MB-Wax Kit, «Bruker», USA, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS/MS, Ultraflex II, «Bruker», USA. The data of the molecular interactions and functional features of proteins were received with STRING 10.0 database. Potentially new molecular markers of DN development were identified. The research into signaling pathways and the molecules that are involved in ECM formation may help in developing strategies to prevent DN.

The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

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Zhuang, Langen; Li, Ming; Yu, Changhua; Li, Can; Zhao, Mingming; Lu, Ming; Zheng, Taishan; Zhang, Rong; Zhao, Weijing; Bao, Yuqian; Xiang, Kunsan; Jia, Weiping; Wang, Niansong; Liu, Limei

2014-02-01

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus

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Gu Harvest F

2010-07-01

Full Text Available Abstract Background MCF2L2, ADIPOQ and SOX2 genes are located in chromosome 3q26-27, which is linked to diabetic nephropathy (DN. ADIPOQ and SOX2 genetic polymorphisms are found to be associated with DN. In the present study, we first investigated the association between MCF2L2 and DN, and then evaluated effects of these three genes on the development of DN. Methods A total of 1177 type 1 diabetes patients with and without DN from the GoKinD study were genotyped with TaqMan allelic discrimination. All subjects were of European descent. Results Leu359Ile T/G variant in the MCF2L2 gene was found to be associated with DN in female subjects (P = 0.017, OR = 0.701, 95%CI 0.524-0.938 but not in males. The GG genotype carriers among female patients with DN had tendency decreased creatinine and cystatin levels compared to the carriers with either TT or TG genotypes. This polymorphism MCF2L2-rs7639705 together with SNPs of ADIPOQ-rs266729 and SOX2-rs11915160 had combined effects on decreased risk of DN in females (P = 0.001. Conclusion The present study provides evidence that MCF2L2, ADIPOQ and SOX2 genetic polymorphisms have effects on the resistance of DN in female T1D patients, and suggests that the linkage with DN in chromosome 3q may be explained by the cumulated genetic effects.

Clinical value of proton magnetic resonance spectroscopy for differentiating recurrent or residual brain tumor from delayed cerebral necrosis

International Nuclear Information System (INIS)

Taylor, June S.; Langston, James W.; Reddick, Wilburn E.; Kingsley, Peter B.; Ogg, Robert J.; Pui, Margaret H.; Kun, Larry E.; Jenkins, Jesse J.; Gang, Chen; Ochs, Judith J.; Sanford, Robert A.; Heideman, Richard L.

1996-01-01

Purpose: Delayed cerebral necrosis (DN) is a significant risk for brain tumor patients treated with high-dose irradiation. Although differentiating DN from tumor progression is an important clinical question, the distinction cannot be made reliably by conventional imaging techniques. We undertook a pilot study to assess the ability of proton magnetic resonance spectroscopy ( 1 H MRS) to differentiate prospectively between DN or recurrent/residual tumor in a series of children treated for primary brain tumors with high-dose irradiation. Methods and Materials: Twelve children (ages 3-16 years), who had clinical and MR imaging (MRI) changes that suggested a diagnosis of either DN or progressive/recurrent brain tumor, underwent localized 1 H MRS prior to planned biopsy, resection, or other confirmatory histological procedure. Prospective 1 H MRS interpretations were based on comparison of spectral peak patterns and quantitative peak area values from normalized spectra: a marked depression of the intracellular metabolite peaks from choline, creatine, and N-acetyl compounds was hypothesized to indicate DN, and median-to-high choline with easily visible creatine metabolite peaks was labeled progressive/recurrent tumor. Subsequent histological studies identified the brain lesion as DN or recurrent/residual tumor. Results: The patient series included five cases of DN and seven recurrent/residual tumor cases, based on histology. The MRS criteria prospectively identified five out of seven patients with active tumor, and four out of five patients with histologically proven DN correctly. Discriminant analysis suggested that the primary diagnostic information for differentiating DN from tumor lay in the normalized MRS peak areas for choline and creatine compounds. Conclusions: Magnetic resonance spectroscopy shows promising sensitivity and selectivity for differentiating DN from recurrent/progressive brain tumor. A novel diagnostic index based on peak areas for choline and

Leadership in non governmental sports organisations in Slovenia [Vůdcovská role v nevládních sportovních organizacích ve Slovinsku

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Jakob Bednarik

2010-12-01

& Bednarik, 2006. Řízení tak významného zdroje je proto významným úkolem vedení slovinského sportu. CÍLE: Účelem této studie bylo odhalit stávající charakteristiky vůdcovské role dobrovolníků ve slovinských nevládních sportovních organizacích. METODIKA: Výzkum se prováděl na stratifikovaném vzorku 190 vedoucích nevládních sportovních organizací, kteří pracují v různých segmentech slovinského sportu. Měření různých stylů vedení bylo provedeno za pomoci dotazníku o způsobech vedení, zpracovaného na základě situačního modelu vedení Herseyho a Blancharda. VÝSLEDKY: Studie odhalila, že vedoucí sportovních organizací nejčastěji využívají koučování (selling – 42 % případů a podporování (participating – 37 %, zatímco přikazování (telling – 12 % a delegování (delegating – 9 % se používá mnohem méně. Vedoucí přizpůsobují styl vedení aktuálním okolnostem; ovšem nepoužívají vhodný styl vedení vzhledem k úrovni připravenosti svých svěřenců a okolností. Styl vedení nemá přímý dopad na měřené indikátory úspěšnosti sportovních organizací. Zjištění vedou k závěru, že vedoucí slovinských nevládních sportovních organizací obecně přehlížejí význam vůdcovství v tomto kontextu. ZÁVĚRY: Vzhledem k výše uvedeným průměrným výsledkům slovinského sportu lze vyvozovat, že dobrovolná práce ve sportovních organizacích představuje jednu z konkurenčních výhod v naší společnosti. Je proto nezbytné věnovat zvláštní pozornost jejímu rozvojovému potenciálu. Zjištění studie vedou k závěru, že by bylo vhodné ustavit národní strategii dobrovolné práce ve sportu.

The application of neuropathic pain questionnaires in burning mouth syndrome patients.

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Heo, Jun-Young; Ok, Soo-Min; Ahn, Yong-Woo; Ko, Myung-Yun; Jeong, Sung-Hee

2015-01-01

To evaluate and compare the validity of the PainDETECT, DN4, and abbreviated DN4 (DN4i) neuropathic pain questionnaires for primary burning mouth syndrome (BMS), which is a burning sensation in the oral mucosa in the absence of any identifiable organic etiology. Eighty-one patients (42 with primary BMS and 39 with nociceptive pain) complaining of a burning sensation and pain in their oral mucosa were enrolled in this study. All of the patients completed the neuropathic pain questionnaires. The sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic (ROC) curve were estimated. Then the relationship between pain intensity and total neuropathic pain score was investigated. Data were analyzed with the chi-square test and independent t test for subjects' baseline characteristic differences, and with Pearson correlation coefficients for the relationship of variables. The mean area under the ROC curves (AUCs) for PainDETECT, DN4, and DN4i were 0.81, 0.79, and 0.81, respectively. There was no statistically significant difference in the AUCs among the questionnaires. PainDETECT, DN4, and DN4i had a lower sensitivity and specificity for BMS compared to previous validation studies. The total scores for PainDETECT, DN4, and DN4i in the primary BMS group were significantly associated with pain intensity. Although the results of this study suggest that neuropathic pain questionnaires, such as PainDETECT and DN4, are not ideal principal screening tools for BMS patients, a substantial proportion of neuropathic symptoms in primary BMS patients were identified.

Protein S Protects against Podocyte Injury in Diabetic Nephropathy.

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Zhong, Fang; Chen, Haibing; Xie, Yifan; Azeloglu, Evren U; Wei, Chengguo; Zhang, Weijia; Li, Zhengzhe; Chuang, Peter Y; Jim, Belinda; Li, Hong; Elmastour, Firas; Riyad, Jalish M; Weber, Thomas; Chen, Hongyu; Wang, Yongjun; Zhang, Aihua; Jia, Weiping; Lee, Kyung; He, John C

2018-05-01

Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN. Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose-induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose- and TNF- α -induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice. Conclusions Our results support a protective role of PS against glomerular injury in DN progression. Copyright © 2018 by the American Society of Nephrology.

The Role of Endoplasmic Reticulum Stress in Diabetic Nephropathy.

Science.gov (United States)

Fan, Ying; Lee, Kyung; Wang, Niansong; He, John Cijiang

2017-03-01

Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a major role in the development and progression of DN. Recent findings suggested that many attributes of DN, such as hyperglycemia, proteinuria, and increased advanced glycation end products and free fatty acids, can all trigger unfolded protein response (UPR) in kidney cells. Herein, we review the current knowledge on the role of ER stress in the setting of kidney injury with a specific emphasis on DN. As maladaptive ER stress response caused by excessively prolonged UPR will eventually cause cell death and increase kidney injury, several ER stress inhibitors have been shown to improve DN in animal models, albeit blocking both adaptive and maladaptive UPR. More recently, reticulon-1A (RTN1A), an ER-associated protein, was shown to be increased in both human and mouse diabetic kidneys. Its expression correlates with the progression of DN, and its polymorphisms are associated with kidney disease in people with diabetes. Increased RTN1A expression heightened the ER stress response and renal cell apoptosis, and conversely reduced RTN1A in renal cells decreased apoptosis and ameliorated kidney injury and DN progression, suggesting that RTN1A may be a novel target to specifically restrain the maladaptive UPR. These findings suggest that ER stress response in renal cells is a key driver of progression of DN and that the inhibition of the unchecked ER stress response in DN, such as by inhibition of RTN1A function, may be a promising therapeutic approach against DN.

Immediate and short-term effects of the combination of dry needling and percutaneous TENS on post-needling soreness in patients with chronic myofascial neck pain

Science.gov (United States)

León-Hernández, Jose V.; Martín-Pintado-Zugasti, Aitor; Frutos, Laura G.; Alguacil-Diego, Isabel M.; de la Llave-Rincón, Ana I.; Fernandez-Carnero, Josue

2016-01-01

ABSTRACT Background Dry needling (DN) and percutaneous electrical nerve stimulation (PENS) are widely used techniques in the treatment of myofascial pain. Objective To investigate the immediate and short-term effects of the combination of DN and PENS compared to DN alone on the upper trapezius muscle. Method This is a 72-hour follow-up single-blinded randomized controlled trial. Sixty-two volunteer patients with chronic myofascial neck pain with active Myofascial Trigger Points (MTrPs) in the upper trapezius muscle were recruited. Randomization was performed, and 31 patients received DN treatment (DN group) and 31 received DN and PENS (DN+PENS group). The primary outcomes were neck disability index (NDI) and visual analog scale for pain for both post-needling soreness (PNS) and neck pain intensity (NPI). Pressure pain threshold (PPT) and cervical range of motion (CROM) were the secondary outcomes. Results We detected between-group differences in NPI and PNS in favor of the DN+PENS group immediately after treatment. No between-group differences in NDI were observed. Conclusion PENS application after dry needling treatment is more effective than dry needling alone for decreasing soreness in the short term and improving neck pain intensity immediately in patients with myofascial chronic neck pain. PMID:27410163

Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

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Temesgen Fiseha

2016-01-01

Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

New susceptibility loci associated with kidney disease in type 1 diabetes

DEFF Research Database (Denmark)

Sandholm, Niina; Salem, Rany M; McKnight, Amy Jayne

2012-01-01

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion...... mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2...... SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN....

Clinical Characteristics of Patients with Diabetic Nephropathy on Maintenance Hemodialysis: A Multicenter Cross-sectional Survey in Anhui Province, Eastern China

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Hu Chen

2016-01-01

Conclusions: DN patients on MHD in Anhui province exhibited different clinical characteristics compared to non-DN hemodialysis patients. They presented higher percentage in TCC use and cardiovascular complication, lower serum albumin and iPTH levels than those in non-DN patients.

Renal pathological implications in type 2 diabetes mellitus patients with renal involvement.

Science.gov (United States)

Li, Li; Zhang, Xiuhui; Li, Zhicheng; Zhang, Rui; Guo, Ruikun; Yin, Qinghua; Yang, Lichuan; Yue, Rongzheng; Su, Baihai; Huang, Songmin; Xu, Huan; He, Cijiang; Liu, Fang

2017-01-01

To investigate the renal pathological implications in type 2 diabetes mellitus patients with renal involvement. A total of 328 type 2 diabetes mellitus (T2DM) patients with renal involvement who underwent a renal biopsy and received follow-up for at least one year were recruited in our study. The patients were divided into the diabetic nephropathy (DN), non-diabetic renal disease (NDRD), and NDRD superimposed on DN groups based on the pathological diagnosis. Renal outcomes were defined by the initiation of renal replacement therapy or doubling of the serum creatinine. Kaplan-Meier analysis was used to compare renal survival, and Cox proportional hazard analysis was used to determine the predictors of renal outcomes in the DN group. Renal biopsy findings revealed that 188 patients (57.32%) had pure DN, 121 patients (36.89%) had NDRD alone, and 19 patients (5.79%) had NDRD superimposed on DN. The most frequent subclassification of NDRD was membranous nephropathy (MN). Compared with the NDRD and NDRD superimposed on DN groups, patients with pure DN had poorer renal function and lower renal survival rates. In the DN group, the five-year renal survival rates of glomerular classes of I, IIa, IIb, III and IV were 100%, 84.62%, 60%, 47.5% and 33.33%, respectively. Multivariate Cox proportional hazard analysis showed that the glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes, while interstitial fibrosis/inflammation and arteriolar hyalinosis were not independently associated with renal outcomes in the DN group. Making an accurate pathologic diagnosis by renal biopsy is crucial for diabetes mellitus (DM) patients with renal involvement. The findings of our present study indicated that patients with pure DN had poorer renal outcomes than patients with NDRD or NDRD superimposed on DN. The classification of glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes in the DN group

The CNDP1 (CTG)(5) Polymorphism Is Associated with Biopsy-Proven Diabetic Nephropathy, Time on Hemodialysis, and Diabetes Duration

NARCIS (Netherlands)

Albrecht, Thomas; Zhang, Shiqi; Braun, Jana D.; Xia, Zuo Li; Rodriquez, Angelica; Qiu, Jiedong; Peters, Verena; Schmitt, Claus P.; van den Born, Jacob; Bakker, Stephan J. L.; Lammert, Alexander; Koeppel, Hannes; Schnuelle, Peter; Kraemer, Bernhard K.; Yard, Benito A.; Hauske, Sibylle J.

2017-01-01

Considering that the homozygous CNDP1 (CTG)(5) genotype affords protection against diabetic nephropathy (DN) in female patients with type 2 diabetes, this study assessed if this association remains gender-specific when applying clinical inclusion criteria (CIC-DN) or biopsy proof (BP-DN).

New susceptibility loci associated with kidney disease in type 1 diabetes.

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Niina Sandholm

2012-09-01

Full Text Available Diabetic kidney disease, or diabetic nephropathy (DN, is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D. Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8 and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9. Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1 pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7, a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

NARCIS (Netherlands)

Siwy, Justyna; Schanstra, Joost P.; Argiles, Angel; Bakker, Stephan J. L.; Beige, Joachim; Boucek, Petr; Brand, Korbinian; Delles, Christian; Duranton, Flore; Fernandez-Fernandez, Beatriz; Jankowski, Marie-Luise; Al Khatib, Mohammad; Kunt, Thomas; Lajer, Maria; Lichtinghagen, Ralf; Lindhardt, Morten; Maahs, David M.; Mischak, Harald; Mullen, William; Navis, Gerarda; Noutsou, Marina; Ortiz, Alberto; Persson, Frederik; Petrie, John R.; Roob, Johannes M.; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L.; Snell-Bergeon, Janet; Spasovski, Goce; Stojceva-Taneva, Olivera; Trillini, Matias; von der Leyen, Heiko; Winklhofer-Roob, Brigitte M.; Zuerbig, Petra; Jankowski, Joachim

Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system

The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy

NARCIS (Netherlands)

Andeen, Nicole K; Nguyen, Tri Q; Steegh, Floor; Hudkins, Kelly L; Najafian, Behzad; Alpers, Charles E

2015-01-01

Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells

A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells

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Joey Z. Liu

2009-01-01

Full Text Available PPARγ ligands have been shown to have antiproliferative effects on many cell types. We herein report that a synthetic dominant-negative (DN PPARγ mutant functions like a growth factor to promote cell cycle progression and cell proliferation in human coronary artery smooth muscle cells (CASMCs. In quiescent CASMCs, adenovirus-expressed DN-PPARγ promoted G1→S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation. DN-PPARγ expression also markedly enhanced positive regulators of the cell cycle, increasing Rb and CDC2 phosphorylation and the expression of cyclin A, B1, D1, and MCM7. Conversely, overexpression of wild-type (WT or constitutively-active (CA PPARγ inhibited cell cycle progression and the activity and expression of positive regulators of the cell cycle. DN-PPARγ expression, however, did not up-regulate positive cell cycle regulators in PPARγ-deficient cells, strongly suggesting that DN-PPARγ effects on cell cycle result from blocking the function of endogenous wild-type PPARγ. DN-PPARγ expression enhanced phosphorylation of ERK MAPKs. Furthermore, the ERK specific-inhibitor PD98059 blocked DN-PPARγ-induced phosphorylation of Rb and expression of cyclin A and MCM7. Our data thus suggest that DN-PPARγ promotes cell cycle progression and cell growth in CASMCs by modulating fundamental cell cycle regulatory proteins and MAPK mitogenic signaling pathways in vascular smooth muscle cells (VSMCs.

Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model.

Science.gov (United States)

Stringer, Megan; Abeysekera, Irushi; Dria, Karl J; Roper, Randall J; Goodlett, Charles R

2015-11-01

Down syndrome (DS) or Trisomy 21 causes intellectual disabilities in humans and the Ts65Dn DS mouse model is deficient in learning and memory tasks. DYRK1A is triplicated in DS and Ts65Dn mice. Ts65Dn mice were given up to ~20mg/kg/day epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, or water beginning on postnatal day 24 and continuing for three or seven weeks, and were tested on a series of behavioral and learning tasks, including a novel balance beam test. Ts65Dn as compared to control mice exhibited higher locomotor activity, impaired novel object recognition, impaired balance beam and decreased spatial learning and memory. Neither EGCG treatment improved performance of the Ts65Dn mice on these tasks. Ts65Dn mice had a non-significant increase in Dyrk1a activity in the hippocampus and cerebellum. Given the translational value of the Ts65Dn mouse model, further studies will be needed to identify the EGCG doses (and mechanisms) that may improve cognitive function. Copyright © 2015 Elsevier Inc. All rights reserved.

Diamond Nanoparticles Modify Curcumin Activity: In Vitro Studies on Cancer and Normal Cells and In Ovo Studies on Chicken Embryo Model.

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Barbara Strojny

Full Text Available Curcumin has been studied broadly for its wide range of biological activities, including anticancer properties. The major problem with curcumin is its poor bioavailability, which can be improved by the addition of carriers, such as diamond nanoparticles (DN. They are carbon allotropes, and are therefore biocompatible and easily taken up by cells. DN are non-toxic and have antiangiogenic properties with potential applications in cancer therapy. Their large surface makes them promising compounds in a drug delivery system for bioactive agents, as DN create bio-complexes in a fast and simple process of self-organisation. We investigated the cytotoxicity of such bio-complexes against liver cancer cells and normal fibroblasts, revealing that conjugation of curcumin with DN significantly improves its activity. The experiment performed in a chicken embryo model demonstrated that neither curcumin nor DN nor bio-complexes affect embryo development, even though DN can form deposits in tissues. Preliminary results confirmed the applicability of DN as an efficient carrier of curcumin, which improves its performance against cancer cells in vitro, yet is not toxic to an organism, which makes the bio-complex a promising anticancer agent.

Diabetic nephropathy and antioxidants.

Science.gov (United States)

Tavafi, Majid

2013-01-01

Oxidative stress has crucial role in pathogenesis of diabetic nephropathy (DN). Despite satisfactory results from antioxidant therapy in rodent, antioxidant therapy showed conflicting results in combat with DN in diabetic patients. Directory of Open Access Journals (DOAJ), Google Scholar,Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Treatment of DN in human are insufficient with rennin angiotensin system (RAS) blockers, so additional agent ought to combine with this management. Meanwhile based on DN pathogenesis and evidences in experimental and human researches, the antioxidants are the best candidate. New multi-property antioxidants may be improved human DN that show high power antioxidant capacity, long half-life time, high permeability to mitochondrion, improve body antioxidants enzymes activity and anti-inflammatory effects. Based on this review and our studies on diabetic rats, rosmarinic acid a multi-property antioxidant may be useful in DN patients, but of course, needs to be proven in clinical trials studies.

Analyses of (0.5part>)-1dNch/dη distributions of PHOBOS and BRAHMS collaborations by means of a stochastic process

International Nuclear Information System (INIS)

Biyajima, M.; Ide, M.; Mizoguchi, T.; Suzuki, N.

2002-01-01

Recently interesting data on dN ch /dη in Au-Au collisions (η=-ln tan(θ/2)) with the centrality cuts have been reported by PHOBOS and BRAHMS Collaborations. Their data are usually divided by the number of participants (nucleons) in collisions. Instead of this way, using the total multiplicity N ch =∫(dN ch /dη)dη, we find that there are scaling phenomena among (N ch ) -1 dN ch /dη=dn/dη with different centrality cuts at √s NN = 130 GeV and 200 GeV, respectively. To explain these scaling behaviors of dn/dη, we consider the stochastic approach named Ornstein-Uhlenbeck process with two sources. The Langevin equation is adopted for the present explanation. Among dn/dη at 130 GeV and 200 GeV, no significant difference has been found. Possible detection method of the quark-gluon plasma (QGP) through dN ch /dη is presented. (author)

CHANGES IN EDGE AND SCRAPE-OFF LAYER PLASMA BEHAVIOE DUE TO VAARIATION IN MAGNETIC BALANCE IN DIII-D

International Nuclear Information System (INIS)

PETRIE, T.W.; WATKINS, J.G.; BAYLOR, L.R.; BROOKS, N.H.; FENSTERMACHER, M.E.; HYATT, A.W.; JACKSON, G.L.; LASNIER, C.J.; LEONARD, A.W.; PIGAROV, A.YU.; RENSINK, M.E.; ROGNLIEN, T.D.; SCHAFFER, M.J.; WOLF, N.S.

2002-01-01

Changes in the divertor magnetic balance in DIII-D H-mode plasmas affects core, edge, and divertor plasma behavior. Both the pedestal density n e,PED and plasma stored energy W T were sensitive to changes in magnetic balance near the double-null (DN) configuration, e.g., both decreased 20%-30% when the DN shifted to a slightly unbalanced DN, where the B x (del)B drift direction pointed away from the main X-point. Recycling at each of the four divertor targets was sensitive to changes in magnetic balance and the B x (del)B drift direction. The poloidal distribution of the recycling in DN is in qualitative agreement with the predictions of UEDGE modeling with particle drifts included. The particle flux at the inner divertor target is shown to be much more sensitive to magnetic balance than the particle flux at the outer divertor target near the DN shape. These results suggest possible advantages and drawbacks for balanced DN operation

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats Efeitos do pré-tratamento em curto prazo com ornitina alfa-cetoglutarato na isquemia-reperfusão intestinal em ratos

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Eduardo Silvio Gouveia Gonçalves

2011-01-01

grupo G5 foi submetido à reperfusão por 30 minutos. Amostras de sangue foram coletadas no final da laparotomia (G1, após 30 minutos (G2, G4 e 60 minutos (G3, G5 para determinação das concentrações de metabolitos (piruvato, lactato, creatinofosfoquinase (CPK, substâncias reativas ao ácido tiobarbitúrico (TBARS e glutationa (GSH. RESULTADOS: Observou-se redução significante (p<0,05 das concentrações de piruvato e lactato, teciduais e CPK plasmático em ratos tratados com OKG, no final do período de reperfusão. Não houve alteração significante nos níveis plasmáticos e teciduais de GSH. Entretanto os níveis de TBARS aumentaram significativamente (p<0,05 em amostras de tecido de ratos tratados com OKG submetido à isquemia por 30 minutos. CONCLUSÃO: o pré-tratamento em curto prazo com OKG antes da indução da I/R diminui a lesão tecidual, aumenta a utilização de piruvato para produção de energia no ciclo de Krebs, mas não atenua o estresse oxidativo neste modelo animal.

La expresión del promotor del gen ahybadh4 en plantas transgénicas de Arabidopsis thaliana es específica en la raíz

OpenAIRE

Onofre, J; Legaria, J.P.; Avonce, Nelson; Iturriaga, G.

2003-01-01

La glicina betaína es uno de los solutos compatibles con el metabolismo más eficiente. En las plantas, la biosíntesis de la glicina betaína se lleva a cabo en dos pasos enzimáticos. Primero se oxida el sustrato colina a betaína aldehído por medio de la colina monooxigenasa (CMO); el segundo paso es catalizado por una betaína aldehído deshidrogenasa (BADH) que convierte la betaína aldehído a glicina betaína. Estudios previos mostraron que la transcripción del gen ahybadh17, que codifica para l...

The relationship between hemoglobin level and the type 1 diabetic nephropathy in Anhui Han's patients.

Science.gov (United States)

Jiang, Jun; Lei, Lan; Zhou, Xiaowan; Li, Peng; Wei, Ren

2018-02-20

Recent studies have shown that low hemoglobin (Hb) level promote the progression of chronic kidney disease. This study assessed the relationship between Hb level and type 1 diabetic nephropathy (DN) in Anhui Han's patients. There were a total of 236 patients diagnosed with type 1 diabetes mellitus and (T1DM) seen between January 2014 and December 2016 in our centre. Hemoglobin levels in patients with DN were compared with those without DN. The relationship between Hb level and the urinary albumin-creatinine ratio (ACR) was examined by Spearman's correlational analysis and multiple stepwise regression analysis. The binary logistic multivariate regression analysis was performed to analyze the correlated factors for type 1 DN, calculate the Odds Ratio (OR) and 95%confidence interval (CI). The predicting value of Hb level for DN was evaluated by area under receiver operation characteristic curve (AUROC) for discrimination and Hosmer-Lemeshow goodness-of-fit test for calibration. The average Hb levels in the DN group (116.1 ± 20.8 g/L) were significantly lower than the non-DN group (131.9 ± 14.4 g/L) , P levels were independently correlated with the urinary ACR in multiple stepwise regression analysis. The logistic multivariate regression analysis showed that the Hb level (OR: 0.936, 95% CI: 0.910 to 0.963, P level (Hb level for DN. The value of P was 0.593 in Hosmer-Lemeshow goodness-of-fit test. In Anhui Han's patients with T1DM, the Hb level is inversely correlated with urinary ACR and DN. This article is protected by copyright. All rights reserved.

OCTANOL/WATER PARTITION COEFFICIENTS AND WATER SOLUBILITIES OF PHTHALATE ESTERS

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Measurements of the octanol/water partition coefficients (K-ow) and water solubilities of di-n-octyl phthalate (DnOP) and di-n-decyl phthalate (DnDP) by the slow-stirring method are reported. The water solubility was also measured for di-n-hexyl phthalate (DnHP). The log K-ow val...

The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Science.gov (United States)

Timar, Bogdan; Timar, Romulus; Gaiță, Laura; Oancea, Cristian; Levai, Codrina; Lungeanu, Diana

2016-01-01

Diabetic neuropathy (DN) is a prevalent complication of Type 2 Diabetes Mellitus (T2DM) with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN's three major components: sensitive (lack of motion associated sensory), motor (impairments in movement coordination) and autonomic (the presence of postural hypotension), the presence of DN may impair the balance in the affected patients. Our study's main aim is to evaluate the possible association between the presence and severity of DN and both the balance impairment and the risk of falls in patients with T2DM. In this cross-sectional study we enrolled, according to a consecutive-case population-based setting 198 patients with T2DM. The presence and severity of DN was evaluated using the Michigan Neuropathy Screening Instrument, a tool which allows both diagnosing and severity staging of DN. The balance impairment and the risk of falls were evaluated using four validated and standardized tools: Berg Balance Scale (BBS), Timed-up and Go test (TUG), Single Leg Stand test (SLS) and Fall Efficacy Scale (FES-I). The presence of DN was associated with significant decreases in the BBS score (40.5 vs. 43.7 points; prisk of falls in patients with T2DM. The presence of DN in patients with DM is associated with impaired balance and with a consecutively increase in the risk of falls.

Charmed meson rescattering in the reaction anti pd→ anti DDN

International Nuclear Information System (INIS)

Haidenbauer, J.; Krein, G.; Meissner, U.G.; Sibirtsev, A.

2008-01-01

We examine the possibility to extract information about the DN and anti DN interactions from the anti pd→D 0 D - p reaction. We utilize the notion that the open-charm mesons are first produced in the annihilation of the antiproton on one nucleon in the deuteron and subsequently rescatter on the other (the spectator) nucleon. The latter process is then exploited for investigating the DN and anti DN interactions. We study different methods for isolating the contributions from the D 0 p and D - p rescattering terms. (orig.)

Improving Protein Fold Recognition by Deep Learning Networks

Science.gov (United States)

Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

2015-12-01

For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl’s benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

Improving Protein Fold Recognition by Deep Learning Networks.

Science.gov (United States)

Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

2015-12-04

For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl's benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

The App-Runx1 region is critical for birth defects and electrocardiographic dysfunctions observed in a Down syndrome mouse model.

Directory of Open Access Journals (Sweden)

Matthieu Raveau

2012-05-01

Full Text Available Down syndrome (DS leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1. In addition cardiac connexins (Cx40, Cx43 and sodium channel sub-units (Scn5a, Scn1b, Scn10a were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people.

EFECTO DE NIVELES CRECIENTES DE NITRÓGENO NO PROTÉICO DIETARIO SOBRE LA CONCENTRACIÓN DE PRECURSORES GLUCONEOGÉNICOS EN HÍGADO BOVINO EFFECT OF INCREASING LEVELS OF DIETARY NONPROTEIN NITROGEN ON GLUCONEOGENIC PRECURSORS CONCENTRATION IN BOVINE LIVER

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Rubén Darío Galvis Goez

2010-06-01

Full Text Available Con el fin de evaluar el efecto de niveles crecientes de proteína degradable en rumen (PDR sobre las concentraciones de amonio y piruvato en hígado, se utilizaron 15 vacas Holstein que cursaban los primeros cien días posparto. Estas se asignaron aleatoriamente a tres tratamientos experimentales que consistieron en el suministro de un suplemento alimenticio comercial al que se le adicionó urea de tal manera que se incrementará el consumo de PDR en aproximadamente 0 (T0, 10 (T1 y 15% (T2 respecto a los requerimientos. A estas vacas se les determinaron las concentraciones hepáticas de amonio (Ahep y piruvato (Pihep. Se realizó un balance nutricional de energía neta de lactancia (ENL, proteína metabolizable (PM, PDR y proteína no degradable en rumen (PNDR donde se encontraron diferencias significativas entre los tratamientos (PIn order to test the effect of growing levels of diet rumen degradable protein on hepatic concentrations of ammonia and piruvate, fifteen cows Holstein in their first one hundred post calving days were used. They were assigned at random to three different experimental treatments, which consisted on the supply of a commercial feeding supplement without any addition of urea as a source of NNP (T0; the second treatment (T1 consisted on the supply of the same supplement with an addition of urea, so that the supply of PDR was increased 10% approximately to the requirements;finally, in the third treatment, (T2 the cows were given the same supplement which was added with enough urea so that the supply of PDR was increased 15% approximately to the requirements. In these cows were determined hepatic concentrations of ammonia (Ahep and pyruvate (Pyhep. The concentrations of Ahep were different among treatments, whereas the concentrations of Pihep were similar. Negative relations between Ahep and ENL, Ahep and PNDR, Ahep, and PM, were found it; while Pihep was positively related with Ahep. These results suggest the

Caracterização da mitocôndria isolada de fígado de tilápia-do-nilo (Oreochromis niloticus e alterações da bioenergética mitocondrial causadas pela exposição herbicida oxifluorfena Characterization of liver mitochondria from Nile tilapia (Oreochromis niloticus and mitochondrial bioenergetics alterations caused by exposure to oxyfluorfen herbicide

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F.P. Peixoto

2009-04-01

Full Text Available Descreve-se um método de isolamento de mitocôndrias acopladas de tilápia-do-nilo Oreochromis niloticus, isoladas de células hepáticas de peixes adultos. As mitocôndrias estavam metabolicamente ativas, sendo capazes de realizarem fosforilação oxidativa, de acordo com os valores do quociente de controle respiratório. Os valores de controle respiratório obtidos com malato/piruvato (complexo I e com succinato (complexo II foram de 5,8±0,8 e 3,38±0,4, respectivamente. O potencial de membrana exibiu o valor de 197±4mV, quer se utilizasse malato/piruvato ou succinato como substrato. O procedimento de isolamento de mitocôndrias de O. niloticus permite o estudo do efeito de xenobióticos na bioenergética mitocondrial, tendo sido avaliada a ação da oxifluorfena (0,6mgL-1 na bioenergética mitocondrial. Os resultados demonstram que o tratamento com oxifluorfena influencia a capacidade fosforilativa dos peixes, interferindo na sua carga energética, o que poderá levar à sua morte.A method for isolation of coupled mitochondria isolated from the liver of adult Nile tilapia Oreochromis niloticus is described for the first time. They were metabolically active, able to sustain oxidative phosphorylation, as shown by respiratory control ratio values, which were about 5.8±0.8 and 3.3±0.4 when respiring on malate/piruvate (complex I or succinate (complex II, respectively, as substrate. Membrane potential exhibited a value of approximately 197±4mV for malate/piruvate or succinate. The procedure now described for the isolation of O. niloticus mitochondria is an important new tool, allowing the study about the effect of xenobiotics on mitochondrial bioenergetic, being evaluated the effect of oxyfluorfen (0.6mgL-1 in the liver mitocondrial bioenergetic. These results showed that phosphorylation was significantly affected by oxyfluorfen which contributed to the decrease on the liver cell energy charge and consequently led to the fish dead.

The rate of second electron transfer to QB(-) in bacterial reaction center of impaired proton delivery shows hydrogen-isotope effect.

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Maróti, Ágnes; Wraight, Colin A; Maróti, Péter

2015-02-01

The 2nd electron transfer in reaction center of photosynthetic bacterium Rhodobacter sphaeroides is a two step process in which protonation of QB(-) precedes interquinone electron transfer. The thermal activation and pH dependence of the overall rate constants of different RC variants were measured and compared in solvents of water (H2O) and heavy water (D2O). The electron transfer variants where the electron transfer is rate limiting (wild type and M17DN, L210DN and H173EQ mutants) do not show solvent isotope effect and the significant decrease of the rate constant of the second electron transfer in these mutants is due to lowering the operational pKa of QB(-)/QBH: 4.5 (native), 3.9 (L210DN), 3.7 (M17DN) and 3.1 (H173EQ) at pH7. On the other hand, the proton transfer variants where the proton transfer is rate limiting demonstrate solvent isotope effect of pH-independent moderate magnitude (2.11±0.26 (WT+Ni(2+)), 2.16±0.35 (WT+Cd(2+)) and 2.34±0.44 (L210DN/M17DN)) or pH-dependent large magnitude (5.7 at pH4 (L213DN)). Upon deuteration, the free energy and the enthalpy of activation increase in all proton transfer variants by about 1 kcal/mol and the entropy of activation becomes negligible in L210DN/M17DN mutant. The results are interpreted as manifestation of equilibrium and kinetic solvent isotope effects and the structural, energetic and kinetic possibility of alternate proton delivery pathways are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel susceptibility locus at 22q11 for diabetic nephropathy in type 1 diabetes

DEFF Research Database (Denmark)

Wessman, Maija; Forsblom, Carol; Kaunisto, Mari A

2011-01-01

Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21-q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loci...

Development of low-cost, high-performance non-evaporable getter (NEG) pumps

Energy Technology Data Exchange (ETDEWEB)

Mase, Kazuhiko, E-mail: mase@post.kek.jp [Institute of Materials Structure Science, KEK, 1-1 Oho, Tsukuba 305-0801 (Japan); SOKENDAI (The Graduate University for Advanced Studies), 1-1 Oho, Tsukuba 305-0801 (Japan); Tanaka, Masato [Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku 263-8522 (Japan); Ida, Naoya [Faculty of Science and Technology, Hirosaki University, 1 Bunkyocho, Hirosaki 036-8560 (Japan); Kodama, Hiraku [Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501 (Japan); Kikuchi, Takashi [Institute of Materials Structure Science, KEK, 1-1 Oho, Tsukuba 305-0801 (Japan)

2016-07-27

Low-cost, high-performance non-evaporable getter (NEG) pumps were constructed using commercial NEG pills comprising 70 wt% Zr, 24.6 wt% V, and 5.4 wt% Fe, a conflat flange with an outer diameter of 70, 152, or 203 mm (DN 40 CF, DN 100 CF, and DN 160 CF, respectively), and a tantalum heater. After activation at 400 °C for 30 min, the pumping speeds of a DN 40 CF NEG pump measured with the orifice method were 47–40, 8–6, 24–17, and 19–15 L/s for H{sub 2}, N{sub 2}, CO, and CO{sub 2} gasses, respectively. NEG pumps using DN 100 CF and DN 160 CF were also developed, and their pumping speeds are estimated. These NEG pumps are favorable alternatives to sputtering ion pumps in VSX beamlines because they do not produce hydrocarbons except during the activation period. The NEG pumps can also be used for accelerators, front ends, end stations, and differential pumping systems.

Associations between clinical characteristics and angiotensin-converting enzyme gene insertion/deletion polymorphism in Moroccan population with Type-2 diabetic nephropathy

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Maria Mansouri

2017-01-01

Full Text Available Diabetic nephropathy (DN is one of the severe complications of Type-2 diabetes mellitus (T2DM and a major cause of end-stage renal disease in these patients. Results from published studies on the relationship between angiotensin-converting enzyme (ACE insertion/ deletion (I/D gene polymorphism and patients with DN are still conflicting. We compared the clinical characteristics and the genotype frequencies of ACE polymorphism in 130 T2DM Moroccan patients with DN and 85 T2DM Moroccan patients without DN (controls using specific primers in a polymerase chain reaction. The degenerative complications of diabetes were significantly higher in the group with nephropathy. The distribution of the I/D genotypes was in Hardy–Weinberg equilibrium. The D allele was the most frequent allele in the Moroccan population in both groups studied (P = 0.68, however, there was no significant difference between the genotypes in T2DM patients with or without DN (P = 0.78. The ACE gene I/D polymorphism was not associated with an increased risk of DN in the Moroccan population.

Peripheral neuropathy in children with type 1 diabetes.

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Louraki, M; Karayianni, C; Kanaka-Gantenbein, C; Katsalouli, M; Karavanaki, K

2012-10-01

Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The diagnosis value of endothelin, calcitonin gene-related peptide and the ratio in diabetic nephropathy

International Nuclear Information System (INIS)

Li Lusheng; Zhao Xin; Chi Liuying; Yang Xixiu; Mao Hongyu

2007-01-01

Objective: To evaluate the diagnosis value of Endothelin (ET), Calcitonin gene-related peptide(CGRP) and theratio in diabetic nephropathy(DN). Methods: To choose 54 healthy as the control group and 124 patients with diabetes or DN as test group. According to urinary albumin excretion rate (uAER), the test group was divided into three groups, which were diabetes group of normalalbuminmia (group A), early DN (group B) and clinical DN and renal failure group( group C ). Plasma concentration of ET and CGRP were measured with radioimmunossay for those in the Control group and patients with diabetes or DN. Results: The level of ET was significantly higher in diabetic nephropathy than that in the control group (P<0.01), and there was positive correlation between ET and uAER(r=0.591, P<0.01). The plasma level of CGRP was significantly lower in diabetic nephropathy than that in the control group (P<0.01), and there was negative correlation between CGRP and uAER(r-0.389, P<0.05). The level of ET, CGRP and ET/CGRP ratio have evidently changed with the uAER rised. Conclusion: (1)The level of ET, CGRP and type 2 diabetic nephropathy are closely related, and which probably plays a role in the development of DN. (2)ET/CGRP ratio, as a new way for diagnosis, can even more reflecte the seriousness of DN. (3)This experiment provide us a new way for the prevention and treatment of DN with extrinsic CGRP. (authors)

Odpovědný management a odpovědné podnikání

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Dytrt Zdenek

2009-12-01

Full Text Available Dynamika vývoje nových poznatků v technice, medicíně a v poslední době i farmacií vyvolávají potřebu inovovat i filozofii a obsah managementu a jeho úlohu v podnikatelském prostředí. Aktuálně na potřebu inovovat management upozorňuje současná celosvětová finanční a ekonomické krize. Její průběh vyžaduje analyzovat příčiny a nově definovat filo-zofii, obsah a cíle managementu, aby odpovídaly potřebám globalizace a 21. století. Sou-časná teorie managementu vznikla více než před sto léty a její modernizace se soustředila hlavně na automatizaci a zpracování dat kvantitativního vývoje podnikových a společenských jevů. Nové směry a cíle managementu by se měly více orientovat na odpovědnost, etické rozhodování a zvyšování pracovní motivace a kreativní plnění strategických cílů společnosti a podnikatelských aktivit.The dynamics of the development of new knowledge in technology, medicine and, more recently, pharmacy invokes the need to innovate the philosophy as well as management content and its role in the business environment. As it stands now, the need to innovate management is highlighted by the current global financial and economic crisis. Its course requires analyzing the causes and redefining the philosophy, content and objectives of management, to meet the needs of globalization and of the 21st century. The present theory of management was established more than a hundred years ago, and its modernization has focused mainly on the automation of processing the data of quantitative development of corporate and social phenomena. New directions and objectives of management should focus more on accountability, ethical decision-making and increasing the working motivation and creative fulfilment of strategic objectives and business activities.

Preliminary condensation pool experiments with steam using DN80 and DN100 blowdown pipes

International Nuclear Information System (INIS)

Laine, J.; Puustinen, M.

2004-03-01

The report summarizes the results of the preliminary steam blowdown experiments. Altogether eight experiment series, each consisting of several steam blows, were carried out in autumn 2003 with a scaled-down condensation pool test rig designed and constructed at Lappeenranta University of Technology. The main purpose of the experiments was to evaluate the capabilities of the test rig and the needs for measurement and visualization devices. The experiments showed that a high-speed video camera is essential for visual observation due to the rapid condensation of steam bubbles. Furthermore, the maximum measurement frequency of the current combination of instrumentation and data acquisition system is inadequate for the actual steam tests in 2004. (au)

Benazepril hydrochloride improves diabetic nephropathy and decreases proteinuria by decreasing ANGPTL-4 expression.

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Xue, Lingyu; Feng, Xiaoqing; Wang, Chuanhai; Zhang, Xuebin; Sun, Wenqiang; Yu, Kebo

2017-10-04

This study aimed to investigate the effects of benazepril hydrochloride (BH) on proteinuria and ANGPTL-4 expression in a diabetic nephropathy (DN) rat model. A total of 72 Wistar male rats were randomly divided into three groups: normal control (NC), DN group and BH treatment (BH) groups. The DN model was induced by streptozotocin (STZ). Weight, glucose, proteinuria, biochemical indicators and the kidney weight index were examined at 8, 12 and 16 weeks. In addition, ANGPTL-4 protein and mRNA expressions were assessed by immunohistochemistry and qRT-PCR, respectively. Relationships between ANGPTL-4 and biochemical indicators were investigated using Spearman analysis. Weight was significantly lower but glucose levels were significantly higher in both the DN and BH groups than in the NC group (P Benazepril hydrochloride improves DN and decreases proteinuria by decreasing ANGPTL-4 expression.

Histone Lysine Methylation in Diabetic Nephropathy

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Guang-dong Sun

2014-01-01

Full Text Available Diabetic nephropathy (DN belongs to debilitating microvascular complications of diabetes and is the leading cause of end-stage renal diseases worldwide. Furthermore, outcomes from the DCCT/EDIC study showed that DN often persists and progresses despite intensive glucose control in many diabetes patients, possibly as a result of prior episode of hyperglycemia, which is called “metabolic memory.” The underlying mechanisms responsible for the development and progression of DN remain poorly understood. Activation of multiple signaling pathways and key transcription factors can lead to aberrant expression of DN-related pathologic genes in target renal cells. Increasing evidence suggests that epigenetic mechanisms in chromatin such as DNA methylation, histone acetylation, and methylation can influence the pathophysiology of DN and metabolic memory. Exciting researches from cell culture and experimental animals have shown that key histone methylation patterns and the related histone methyltransferases and histone demethylases can play important roles in the regulation of inflammatory and profibrotic genes in renal cells under diabetic conditions. Because histone methylation is dynamic and potentially reversible, it can provide a window of opportunity for the development of much-needed novel therapeutic potential for DN in the future. In this minireview, we discuss recent advances in the field of histone methylation and its roles in the pathogenesis and progression of DN.

Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

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Kouki Nakagawa

2017-01-01

Full Text Available The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON, denervation (DN, and denervation with direct ES (DN + ES. Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA, and capillary-to-fiber (C/F ratio of the tibialis anterior (TA muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs.

Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

Science.gov (United States)

Nakagawa, Kouki; Hayao, Keishi; Yotani, Kengo; Ogita, Futoshi; Yamamoto, Noriaki; Onishi, Hideaki

2017-01-01

The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES) on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP) immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON), denervation (DN), and denervation with direct ES (DN + ES). Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA), and capillary-to-fiber (C/F) ratio of the tibialis anterior (TA) muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs. PMID:28497057

The Ikaros transcription factor regulates responsiveness to IL-12 and expression of IL-2 receptor alpha in mature, activated CD8 T cells.

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Eric T Clambey

Full Text Available The Ikaros family of transcription factors is critical for normal T cell development while limiting malignant transformation. Mature CD8 T cells express multiple Ikaros family members, yet little is known about their function in this context. To test the functions of this gene family, we used retroviral transduction to express a naturally occurring, dominant negative (DN isoform of Ikaros in activated CD8 T cells. Notably, expression of DN Ikaros profoundly enhanced the competitive advantage of activated CD8 T cells cultured in IL-12, such that by 6 days of culture, DN Ikaros-transduced cells were 100-fold more abundant than control cells. Expression of a DN isoform of Helios, a related Ikaros-family transcription factor, conferred a similar advantage to transduced cells in IL-12. While DN Ikaros-transduced cells had higher expression of the IL-2 receptor alpha chain, DN Ikaros-transduced cells achieved their competitive advantage through an IL-2 independent mechanism. Finally, the competitive advantage of DN Ikaros-transduced cells was manifested in vivo, following adoptive transfer of transduced cells. These data identify the Ikaros family of transcription factors as regulators of cytokine responsiveness in activated CD8 T cells, and suggest a role for this family in influencing effector and memory CD8 T cell differentiation.

Free Triiodothyronine Levels Are Associated with Diabetic Nephropathy in Euthyroid Patients with Type 2 Diabetes

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Jingcheng Wu

2015-01-01

Full Text Available Objective. To investigate the association of thyroid function and diabetic nephropathy (DN in euthyroid patients with type 2 diabetes. Methods. A total of 421 patients were included in this cross-sectional study. The following parameters were assessed: anthropometric measurements, fast plasma glucose, serum creatinine, lipid profile, HbA1c, free triiodothyronine (FT3, free thyroxine, thyroid-stimulating hormone levels, and urinary albumin-to-creatinine ratio (UACR. Patients with UACR of ≥30 mg/g were defined as those suffering from DN. Results. Of the 421 patients, 203 (48.2% suffered from DN, and no difference was found between males and females. The patients with DN yielded significantly lower FT3 levels than those without DN (P<0.01. The prevalence of DN showed a significantly decreasing trend across the three tertiles based on FT3 levels (59.6%, 46.4%, and 38.6%, P<0.01. After adjustment for gender and age, FT3 levels were found to correlate positively with estimated glomerular filtration rate (P=0.03 and negatively with UACR (P<0.01. Multiple linear regression analysis showed that FT3 level was independently associated with UACR (β=-0.18, t=-3.70, and P<0.01. Conclusion. Serum FT3 levels are inversely associated with DN in euthyroid patients with type 2 diabetes, independent of traditional risk factors.

Genotipos de Giardia duodenalis en muestras de niños de las guarderías del Instituto Colombiano de Bienestar Familiar y de perros en Ibagué, Colombia

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Victoria Rodríguez

2014-06-01

Full Text Available Introducción. Se han descrito ocho genotipos de Giardia duodenalis, del A al H. Los genotipos A y B se han aislado de humanos y de una gran variedad de mamíferos; sin embargo, los genotipos del C al H han mostrado mayor especificidad de huésped. Objetivo. Identificar los genotipos de G. duodenalis a partir de quistes obtenidos en heces de niños de las guarderías del Instituto Colombiano de Bienestar Familiar (ICBF y de perros en Ibagué, mediante PCR-RFLP de los genes de la beta giardina y la glutamato deshidrogenasa. Materiales y métodos. Los quistes de las muestras positivas para G. duodenalis fueron sometidos a concentración; se extrajo su ADN y se efectuó el análisis de PCR-RFLP de los genes de la beta giardina y de la glutamato deshidrogenasa. Como control positivo se utilizó la cepa MHOM/CO/04/G40 procedente del Grupo de Parasitología del Instituto Nacional de Salud. Resultados. De las muestras tomadas de niños, 11/23 (48 % correspondieron al genotipo A y, 12/23 (52 %, al genotipo B. Cuatro muestras de perros presentaron los genotipos C y D, específicos de este huésped. Conclusiones. En los niños solamente se encontraron los genotipos asociados a infecciones humanas (AII, BIII y BIV y en los perros, los genotipos específicos para este huésped (C y D. Debido al reducido tamaño de las muestras analizadas provenientes de perros, y dado que estos no estuvieron en contacto con los niños de las guarderías del ICBF, no fue posible determinar una interacción entre el ciclo de transmisión de los humanos y el de los animales.

Benefit of magnesium-25 carrying porphyrin-fullerene nanoparticles in experimental diabetic neuropathy

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Hosseini, Asieh; Sharifzadeh, Mohammad; Rezayat, Seyed Mahdi; Hassanzadeh, Gholamreza; Hassani, Shokoufeh; Baeeri, Maryam; Shetab-Bushehri, Vahid; Kuznetsov, Dmitry A; Abdollahi, Mohammad

2010-01-01

Diabetic neuropathy (DN) is a debilitating disorder occurring in most diabetic patients without a viable treatment yet. The present work examined the protective effect of 25Mg-PMC16 nanoparticle (porphyrin adducts of cyclohexil fullerene-C60) in a rat model of streptozotocin (STZ)-induced DN. 25Mg-PMC16 (0.5 lethal dose50 [LD50]) was administered intravenously in two consecutive days before intraperitoneal injection of STZ (45 mg/kg). 24Mg-PMC16 and MgCl2 were used as controls. Blood 2,3-diphosphoglycerate (2,3-DPG), oxidative stress biomarkers, adenosine triphosphate (ATP) level in dorsal root ganglion (DRG) neurons were determined as biomarkers of DN. Results indicated that 2,3-DPG and ATP decreased whereas oxidative stress increased by induction of DN which all were improved in 25Mg-PMC16-treated animals. No significant changes were observed by administration of 24Mg-PMC16 or MgCl2 in DN rats. It is concluded that in DN, oxidative stress initiates injuries to DRG neurons that finally results in death of neurons whereas administration of 25Mg-PMC16 by release of Mg and increasing ATP acts protectively. PMID:20957114

Occurrence and risk assessment of phthalate esters (PAEs) in vegetables and soils of suburban plastic film greenhouses.

Science.gov (United States)

Wang, Jun; Chen, Gangcai; Christie, Peter; Zhang, Manyun; Luo, Yongming; Teng, Ying

2015-08-01

Phthalate esters (PAEs) are suspected of having adverse effects on human health and have been frequently detected in soils and vegetables. The present study investigated their occurrence and composition in plastic film greenhouse soil-vegetable systems and assessed their potential health risks to farmers exposed to these widespread pollutants. Six priority control phthalates, namely dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP), were determined in 44 plastic film greenhouse vegetables and corresponding soils. Total PAEs ranged from 0.51 to 7.16mgkg(-1) in vegetables and 0.40 to 6.20mgkg(-1) in soils with average concentrations of 2.56 and 2.23mgkg(-1), respectively. DnBP, DEHP and DnOP contributed more than 90% of the total PAEs in both vegetables and soils but the proportions of DnBP and DnOP in vegetables were significantly (p3.00mgkg(-1) but were plastic film greenhouses. Health risks were mainly by exposure through vegetable consumption and soil ingestion. Copyright © 2015 Elsevier B.V. All rights reserved.

Pseudorapidity distributions of charged particles produced in bar pp interactions at √s =630 and 1800 GeV

International Nuclear Information System (INIS)

Abe, F.; Amidei, D.; Apollinari, G.; Ascoli, G.; Atac, M.; Auchincloss, P.; Baden, A.R.; Barbaro-Galtieri, A.; Barnes, V.E.; Bedeschi, F.; Belforte, S.; Bellettini, G.; Bellinger, J.; Bensinger, J.; Beretvas, A.; Berge, P.; Bertolucci, S.; Bhadra, S.; Binkley, M.; Blair, R.; Blocker, C.; Bofill, J.; Booth, A.W.; Brandenburg, G.; Brown, D.; Byon, A.; Byrum, K.L.; Campbell, M.; Carey, R.; Carithers, W.; Carlsmith, D.; Carroll, J.T.; Cashmore, R.; Cervelli, F.; Chadwick, K.; Chapin, T.; Chiarelli, G.; Chinowsky, W.; Cihangir, S.; Cline, D.; Connor, D.; Contreras, M.; Cooper, J.; Cordelli, M.; Curatolo, M.; Day, C.; DelFabbro, R.; Dell'Orso, M.; DeMortier, L.; Devlin, T.; DiBitonto, D.; Diebold, R.; Dittus, F.; DiVirgilio, A.; Elias, J.E.; Ely, R.; Errede, S.; Esposito, B.; Flaugher, B.; Focardi, E.; Foster, G.W.; Franklin, M.; Freeman, J.; Frisch, H.; Fukui, Y.; Garfinkel, A.F.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Gold, M.; Goulianos, K.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Handler, R.; Harris, R.M.; Hauser, J.; Hessing, T.; Hollebeek, R.; Hu, P.; Hubbard, B.; Hurst, P.; Huth, J.; Jensen, H.; Johnson, R.P.; Joshi, U.; Kadel, R.W.; Kamon, T.; Kanda, S.; Kardelis, D.A.; Karliner, I.; Kearns, E.; Kephart, R.; Kesten, P.; Keutelian, H.; Kim, S.; Kirsch, L.; Kondo, K.; Kruse, U.; Kuhlmann, S.E.; Laasanen, A.T.; Li, W.; Liss, T.; Lockyer, N.; Marchetto, F.; Markeloff, R.; Markosky, L.A.; McIntyre, P.; Menzione, A.; Meyer, T.; Mikamo, S.; Miller, M.; Mimashi, T.; Miscetti, S.; Mishina, M.; Miyashita, S.; Mondal, N.; Mori, S.; Morita, Y.; Mukherjee, A.; Newman-Holmes, C.; Nodulman, L.; Paoletti, R.; Para, A.; Patrick, J.; Phillips, T.J.; Piekarz, H.; Plunkett, P.; Pondrom, L.; Proudfoot, J.; Punzi, G.; Quarrie, D.; Ragan, K.; Redlinger, G.; Rhoades, J.; Rimondi, F.; Ristori, L.; Rohaly, T.; Roodman, A.; Sansoni, A.; Sard, R.; Scarpine, V.; Schlabach, P.; Schmidt, E.E.; Schoessow, P.; Schub, M.H.; Schwitters, R.; Scribano, A.; Segler, S.

1990-01-01

We present measurements of the pseudorapidity (η) distribution of charged particles (dN ch /dη) produced with |η|≤3.5 in proton-antiproton collisions at √s of 630 and 1800 GeV. We measure dN ch /dη at η=0 to be 3.18±0.06(stat)±0.10(syst) at 630 GeV, and 3.95±0.03(stat)±0.13(syst) at 1800 GeV. Many systematic errors in the ratio of dN ch /dη at the two energies cancel, and we measure 1.26±0.01±0.04 for the ratio of dN ch /dη at 1800 GeV to that at 630 GeV within |η|≤3. Comparing to lower-energy data, we observe an increase faster than ln(s) in dN ch /dη at η=0

Development of a methodology for analysis of delayed-neutron signals

International Nuclear Information System (INIS)

Gross, K.C.; Strain, R.V.; Fryer, R.M.

1980-02-01

Experimental and analytical techniques have been developed for analysis and characterization of delayed-neutron (DN) signals that can provide diagnostic information to augment data from cover-gas analyses in the detection and identification of breached elements in an LMFBR. Eleven flow-reduction tests have been run in EBR-II to provide base data support for predicting DN signal characteristics during exposed-fuel operation. Results from the tests demonstrate the feasibility and practicability of response-analysis techniques for determining (a) the transit time, T/sub tr/, for DN emitters traveling from the core to the detector and (b) the isotropic holdup time, T/sub h/, of DN precursors in the fuel element

Impact polarization and alignment creation parameters via stepwise excitation processes

International Nuclear Information System (INIS)

Csanak, G.; Cartwright, D.C.; Kazantsev, S.A.; Bray, I.

1998-01-01

W report here results from first order many body theory, distorted wave approximation, and converged close coupling calculations for polarization fractions and alignment creation parameters in the case of 2 1 S → n 1 P(n 3 - 5), 2 3 S → n 1 P(n = 2 - 5), 2 1 S → n 1 D(n = 3 - 5), 2 3 S → n 1 D(n = 3 - 5), 2 3 S → n 3 D(n = 3 - 5), and 2 1 S → n 3 D(n = 3 - 5) excitations in helium for electron impact energies from threshold to several hundred eV. (author)

Child dental neglect: is it a neglected area in the UK?

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Sarri, G; Marcenes, W

2012-08-01

This commentary focuses on the condition of dental neglect (DN) in children in the UK. It is divided into three sections: the first section defines DN in children and its consequences, the second section discusses who may be responsible for dental diseases in children as a result of neglect and the third section proposes a holistic approach to address DN in children in the UK.

The Prevalence and Management of Diabetic Nephropathy in Asia

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Tomino, Yasuhiko; Gohda, Tomohito

2015-01-01

Background Diabetic nephropathy (DN), especially type 2 diabetes, is now increasing rapidly worldwide, also in Asian countries, and is one of the major long-term vascular complications. The pathogenesis of DN involves both genetic and environmental factors. Around 30-40% of type 2 diabetic patients develop DN despite strict blood glucose and/or blood pressure control. Although it is considered that the genetic background may influence the initiation and progression of DN, the candidate genes are still obscure. Summary To search for genes that are involved in the susceptibility of DN, a candidate gene approach was taken in the beginning before the development of genome-wide association studies. Although a candidate gene approach can detect rare genetic variants, in advance we need known or presumed pathophysiological knowledge of the specific gene. Investigations using spontaneous animal models are important to determine the pathogenesis and treatment of DN patients. There are many spontaneous animal models, such as the NOD and Akita mice for type 1 diabetes and the Ob/Ob, db/db, Tsumura Suzuki Obese Diabetics, and KK-Ay mice for type 2 diabetes. Furthermore, the toxicity of persistent hyperglycemia, the activation of reactive oxygen species, systemic and/or glomerular hypertension, microinflammation, dyslipidemia, and other factors are considered to play important roles. Diabetic patients with normoalbuminuria and normal renal function showed typical histological patterns of DN. The discovery of a specific and reliable diagnostic and prognostic biomarker other than albuminuria is urgently needed and indispensable. Since large clinical trials of oral hypoglycemic drugs in renal failure are lacking, these recommendations will need to be regularly updated after results of larger randomized trials with longer follow-up durations are available. Key Message It is necessary to summarize the basic and clinical features of DN patients in Asia and to use these for the

SPECTROSCOPIC STUDY OF INTERACTION OF SODIUM DOLUTEGRAVIR WITH HUMAN SERUM ALBUMIN

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A. V. Yegorova

2017-11-01

Full Text Available Drug-protein binding has become an important research field in life sciences, chemistry and clinical medicine. Under physiological conditions, in vitro interaction between the antiviral drug 2 Sodium (4R, 12aS-9-{[(2,4-difluorophenylmethyl]carbamoyl}-4-methyl-6,8-dioxo3,4,6,8, 12,12a-hexahydro-2H-pyrido[1’,2’:4,5]pyrazino[2, 1-b][1,3]oxazin-7 –olate (dolutegravir sodium, DN and human serum albumin (HSA was investigated at excitation wavelength 280 nm and at different temperatures (298 K and 313 K by fluorescence emission spectroscopy. The emission of HSA was characterized by a broad emission band at 346 nm. The results of the experiment showed that DN quench the intrinsic fluorescence of the protein as a result of static interaction in the HSA -DN system, which is confirmed by shifts in the difference UV spectra of the HSA -DN and the reduction of the binding constant for the HSA -DN system with increasing temperature. The constant (KA =9,82· 103 L·mol-1 at 298 K and the number of binding sites of the HSA –DN system are established. The negative values of enthalpy change (ΔHº and entropy change (ΔSº can be attributed in part to van der Waals forces and in part to the formation of hydrogen bonds. A value of 2,14 nm for the average distance r between DN (acceptor and tryptophan residues of HSA (donor was derived from the fluorescence resonance energy transfer. The overlap of the absorbance spectrum of DN with the fluorescence emission spectrum of HAS has been shown. Since, the pharmaceutical firms need standardized screens for protein binding in the first step of new drug design, this kind of study of interaction between HSA with DN would be useful in pharmaceutical industry and clinical medicine.

The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

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Bogdan Timar

Full Text Available Diabetic neuropathy (DN is a prevalent complication of Type 2 Diabetes Mellitus (T2DM with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN's three major components: sensitive (lack of motion associated sensory, motor (impairments in movement coordination and autonomic (the presence of postural hypotension, the presence of DN may impair the balance in the affected patients. Our study's main aim is to evaluate the possible association between the presence and severity of DN and both the balance impairment and the risk of falls in patients with T2DM.In this cross-sectional study we enrolled, according to a consecutive-case population-based setting 198 patients with T2DM. The presence and severity of DN was evaluated using the Michigan Neuropathy Screening Instrument, a tool which allows both diagnosing and severity staging of DN. The balance impairment and the risk of falls were evaluated using four validated and standardized tools: Berg Balance Scale (BBS, Timed-up and Go test (TUG, Single Leg Stand test (SLS and Fall Efficacy Scale (FES-I.The presence of DN was associated with significant decreases in the BBS score (40.5 vs. 43.7 points; p<0.001 and SLS time (9.3 vs. 10.3 seconds; p = 0.003 respectively increases in TUG time (8.9 vs. 7.6 seconds; p = 0.002 and FES-I score (38 vs. 33 points; p = 0.034. The MNSI score was reverse and significantly correlated with both BBS score (Spearman's r = -0.479; p<0.001 and SLS time (Spearman's r = -0.169; p = 0.017. In the multivariate regression model, we observed that patient's age, DN severity and depression's symptoms acted as independent, significant predictors for the risk of falls in patients with T2DM.The presence of DN in patients with DM is associated with impaired balance and with a consecutively increase in the risk of falls.

Nondiabetic renal disease in patients with type 2 diabetes

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Ikram Mami

2017-01-01

Full Text Available Diabetic nephropathy (DN is one of the major complications of type 2 diabetes mellitus (T2DM. The diagnosis of DN is mostly clinical. Kidney biopsy is indicated only if nondiabetic renal disease (NDRD is suspected. This study is aimed to assess the prevalence of NDRD and to determine predictor and prognostic factors of DN, NDRD. It was a retrospective analytic study including T2DM patients in whom renal biopsies were performed at our department from 1988 to 2014. Seventy-five patients were included. Mean age was 52.7 years with sex ratio at 1.56. Renal biopsy findings were isolated NDRD in 33 cases, NDRD superimposed on DN in 24 cases, and isolated DN in 18 cases. Most common NDRD found were focal segmental glomerulosclerosis (21% and membranous nephropathy (19%. Multivariate analysis showed that the absence of ischemic heart disease [odds ratio (OR = 0.178, 95% confidence interval (CI = 0.041–0.762], absence of peripheral vascular disease (OR = 0.173, 95% CI = 0.045–0.669, and presence of hematuria (OR = 7.200, 95%CI = 0.886–58.531 were independent predictors of NDRD. 24 patients reached end-stage renal disease 55% in DN group, 16% in DN associated to NDRD group, and 30% in NDRD group. The prevalence of NDRD found in our study confirmed usefulness of renal biopsy in patients with T2DM, especially in those without degenerative complications, hypertension, and insulin therapy.

MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

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Marcelo E Ezquer

2012-01-01

Full Text Available Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN, a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs. The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.

In vivo dentate nucleus MRI relaxometry correlates with previous administration of Gadolinium-based contrast agents

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Tedeschi, Enrico; Canna, Antonietta; Cocozza, Sirio; Russo, Carmela; Angelini, Valentina; Brunetti, Arturo [University ' ' Federico II' ' , Neuroradiology, Department of Advanced Biomedical Sciences, Naples (Italy); Palma, Giuseppe; Quarantelli, Mario [National Research Council, Institute of Biostructure and Bioimaging, Naples (Italy); Borrelli, Pasquale; Salvatore, Marco [IRCCS SDN, Naples (Italy); Lanzillo, Roberta; Postiglione, Emanuela; Morra, Vincenzo Brescia [University ' ' Federico II' ' , Department of Neurosciences, Reproductive and Odontostomatological Sciences, Naples (Italy)

2016-12-15

To evaluate changes in T1 and T2* relaxometry of dentate nuclei (DN) with respect to the number of previous administrations of Gadolinium-based contrast agents (GBCA). In 74 relapsing-remitting multiple sclerosis (RR-MS) patients with variable disease duration (9.8±6.8 years) and severity (Expanded Disability Status Scale scores:3.1±0.9), the DN R1 (1/T1) and R2* (1/T2*) relaxation rates were measured using two unenhanced 3D Dual-Echo spoiled Gradient-Echo sequences with different flip angles. Correlations of the number of previous GBCA administrations with DN R1 and R2* relaxation rates were tested, including gender and age effect, in a multivariate regression analysis. The DN R1 (normalized by brainstem) significantly correlated with the number of GBCA administrations (p<0.001), maintaining the same significance even when including MS-related factors. Instead, the DN R2* values correlated only with age (p=0.003), and not with GBCA administrations (p=0.67). In a subgroup of 35 patients for whom the administered GBCA subtype was known, the effect of GBCA on DN R1 appeared mainly related to linear GBCA. In RR-MS patients, the number of previous GBCA administrations correlates with R1 relaxation rates of DN, while R2* values remain unaffected, suggesting that T1-shortening in these patients is related to the amount of Gadolinium given. (orig.)

MHC class II restricted innate-like double negative T cells contribute to optimal primary and secondary immunity to Leishmania major.

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Mou, Zhirong; Liu, Dong; Okwor, Ifeoma; Jia, Ping; Orihara, Kanami; Uzonna, Jude Ezeh

2014-09-01

Although it is generally believed that CD4(+) T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3(+)CD4(-)CD8(-) (double negative, DN) T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17) and granzyme B (GrzB) in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95%) alpha-beta T cell receptor (αβ TCR), are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis.

Adiposity Impacts Intrarenal Hemodynamic Function in Adults With Long-standing Type 1 Diabetes With and Without Diabetic Nephropathy: Results From the Canadian Study of Longevity in Type 1 Diabetes.

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Bjornstad, Petter; Lovshin, Julie A; Lytvyn, Yuliya; Boulet, Genevieve; Lovblom, Leif E; Alhuzaim, Omar N; Farooqi, Mohammed A; Lai, Vesta; Tse, Josephine; Cham, Leslie; Orszag, Andrej; Scarr, Daniel; Weisman, Alanna; Keenan, Hillary A; Brent, Michael H; Paul, Narinder; Bril, Vera; Perkins, Bruce A; Cherney, David Z I

2018-04-01

Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN). Patients with type 1 diabetes ( n = 66, duration ≥50 years) and age-/sex-matched control subjects ( n = 73) were studied. The cohort was stratified into 44 DN Resistors (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m 2 and inulin [GFR INULIN ], effective renal plasma flow for p -aminohippuric acid [ERPF PAH ]) was measured. Afferent arteriolar resistance, efferent arteriolar resistance, renal blood flow, renal vascular resistance [RVR], filtration fraction, and glomerular pressure were derived from the Gomez equations. Fat and lean mass were quantified by DXA. Whereas measures of adiposity did not associate with GFR INULIN or ERPF PAH in healthy control subjects, trunk fat mass inversely correlated with GFR INULIN ( r = -0.46, P INULIN values in DN and DN Resistors, but the relationships between central adiposity and ERPF PAH and RVR were attenuated and/or reversed in patients with DN compared with DN Resistors. The adiposity-intrarenal hemodynamic function relationship may be modified by the presence of type 1 diabetes and DN, requiring further study of the mechanisms by which adiposity influences renal hemodynamic function. © 2018 by the American Diabetes Association.

The Arabidopsis Rho of Plants GTPase AtROP6 Functions in Developmental and Pathogen Response Pathways1[C][W][OA

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Poraty-Gavra, Limor; Zimmermann, Philip; Haigis, Sabine; Bednarek, Paweł; Hazak, Ora; Stelmakh, Oksana Rogovoy; Sadot, Einat; Schulze-Lefert, Paul; Gruissem, Wilhelm; Yalovsky, Shaul

2013-01-01

How plants coordinate developmental processes and environmental stress responses is a pressing question. Here, we show that Arabidopsis (Arabidopsis thaliana) Rho of Plants6 (AtROP6) integrates developmental and pathogen response signaling. AtROP6 expression is induced by auxin and detected in the root meristem, lateral root initials, and leaf hydathodes. Plants expressing a dominant negative AtROP6 (rop6DN) under the regulation of its endogenous promoter are small and have multiple inflorescence stems, twisted leaves, deformed leaf epidermis pavement cells, and differentially organized cytoskeleton. Microarray analyses of rop6DN plants revealed that major changes in gene expression are associated with constitutive salicylic acid (SA)-mediated defense responses. In agreement, their free and total SA levels resembled those of wild-type plants inoculated with a virulent powdery mildew pathogen. The constitutive SA-associated response in rop6DN was suppressed in mutant backgrounds defective in SA signaling (nonexpresser of PR genes1 [npr1]) or biosynthesis (salicylic acid induction deficient2 [sid2]). However, the rop6DN npr1 and rop6DN sid2 double mutants retained the aberrant developmental phenotypes, indicating that the constitutive SA response can be uncoupled from ROP function(s) in development. rop6DN plants exhibited enhanced preinvasive defense responses to a host-adapted virulent powdery mildew fungus but were impaired in preinvasive defenses upon inoculation with a nonadapted powdery mildew. The host-adapted powdery mildew had a reduced reproductive fitness on rop6DN plants, which was retained in mutant backgrounds defective in SA biosynthesis or signaling. Our findings indicate that both the morphological aberrations and altered sensitivity to powdery mildews of rop6DN plants result from perturbations that are independent from the SA-associated response. These perturbations uncouple SA-dependent defense signaling from disease resistance execution. PMID

Comparison of del Nido and St Thomas Cardioplegia Solutions in Pediatric Patients: A Prospective Randomized Clinical Trial.

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Talwar, Sachin; Bhoje, Amolkumar; Sreenivas, Vishnubhatla; Makhija, Neeti; Aarav, Sudheer; Choudhary, Shiv Kumar; Airan, Balram

2017-01-01

We conducted a prospective randomized trial to compare del Nido (DN) cardioplegia with conventional cold blood cardioplegia (St Thomas [STH]) in pediatric patients. We randomized 100 pediatric patients aged ≤12 years undergoing elective repair of ventricular septal defects and tetralogy of Fallot to the DN and the STH groups. In the DN group, a 20 mL/kg single dose was administered. In the STH group, a 30 mL/kg dose was administered, followed by repeated doses at 25- to 30-minute intervals. The primary outcome was cardiac index that was measured 4 times intra- and postoperatively. Troponin-I, interleukin-6, and tissue necrosis factor-alpha were measured. Myocardial biopsy was obtained to assess electron-microscopic ultrastructural changes. Cardiac indices were significantly higher in the DN group than in the STH group 2 hours after termination of cardiopulmonary bypass (P = 0.0006), after 6 hours (P = 0.0006), and after 24 hours (P ≤ 0.0001). On repeated measure regression analysis, the cardiac index was on an average 0.50 L/min/m 2 higher in the DN group than in the STH group at any time point (P = 0.002). Duration of mechanical ventilation (P = 0.01), intensive care unit stay (P = 0.01), and hospital stay (P = 0.0007) was significantly lower in the DN group. Patients in the DN group exhibited lower troponin-I release 24 hours following cardiopulmonary bypass (P = 0.021). Electron microscopic studies showed more myofibrillar disarray in the STH group (P = 0.02). Use of long-acting DN cardioplegia solution was associated with better preservation of cardiac index, lesser troponin-I release, and decreased morbidity. Ultrastructural changes showed better preservation of myofibrillar architecture. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Temperature on Chronic Trapezius Myofascial Pain Syndrome during Dry Needling Therapy

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Gang Wang

2014-01-01

Full Text Available The purpose of this study was to investigate the effects of temperature on chronic trapezius myofascial pain syndrome during dry needling therapy. Sixty patients were randomized into two groups of dry needling (DN alone (group A and DN combined with heat therapy group (group B. Each patient was treated once and the therapeutic effect was assessed by the visual analogue scale (VAS, pressure pain threshold (PPT, and the 36-item short form health survey (SF-36 at seven days, one month, and three months after treatment. Evaluation based on VAS and PPT showed that the pain of patients in groups A and B was significantly (P<0.05 relieved at seven days, one month, and three months after treatment Compared to before treatment. There was significantly (P<0.05 less pain in group B than group A at one and three months after treatment. The SF-36 evaluation demonstrated that the physical condition of patients in both groups showed significant (P<0.05 improvement at one month and three months after treatment than before treatment. Our study suggests that both DN and DN heating therapy were effective in the treatment of trapezius MPS, and that DN heating therapy had better long-term effects than DN therapy.

Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

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Asieh Hosseini

2013-01-01

Full Text Available Diabetic neuropathy (DN is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin, aldose reductase inhibitors (fidarestat, epalrestat, ranirestat, advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine, the hexosamine pathway inhibitor (benfotiamine, inhibitor of poly ADP-ribose polymerase (nicotinamide, and angiotensin-converting enzyme inhibitor (trandolapril. The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.

Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

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Hosseini, Asieh; Abdollahi, Mohammad

2013-01-01

Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat

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Jianan Geng

2018-01-01

Full Text Available Diabetic nephropathy (DN is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2 and the expression of tissue transglutaminase (tTG, which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.

Emotional and cognitive stimuli differentially engage the default network during inductive reasoning.

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Eldaief, Mark C; Deckersbach, Thilo; Carlson, Lindsay E; Beucke, Jan C; Dougherty, Darin D

2012-04-01

The brain's default network (DN) is comprised of several cortical regions demonstrating robust intrinsic connectivity at rest. The authors sought to examine the differential effects of emotional reasoning and reasoning under certainty upon the DN through the employment of an event-related fMRI design in healthy participants. Participants were presented with syllogistic arguments which were organized into a 2 × 2 factorial design in which the first factor was emotional salience and the second factor was certainty/uncertainty. We demonstrate that regions of the DN were activated both during reasoning that is emotionally salient and during reasoning which is more certain, suggesting that these processes are neurally instantiated on a network level. In addition, we present evidence that emotional reasoning preferentially activates the dorsomedial (dMPFC) subsystem of the DN, whereas reasoning in the context of certainty activates areas specific to the DN's medial temporal (MTL) subsystem. We postulate that emotional reasoning mobilizes the dMPFC subsystem of the DN because this type of reasoning relies upon the recruitment of introspective and self-relevant data such as personal bias and temperament. In contrast, activation of the MTL subsystem during certainty argues that this form of reasoning involves the recruitment of mnemonic and semantic associations to derive conclusions.

The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy

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Ruichao Yu

2016-02-01

Full Text Available Background/Aims: There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN. The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4 is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17 pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. Methods: Streptozotocin (STZ-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6; and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6 and a control group (Control, n =6. Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. Results: Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. Conclusions: Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through

The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis.

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Shao, Weijuan; Xiong, Xiaoquan; Ip, Wilfred; Xu, Fenghao; Song, Zhuolun; Zeng, Kejing; Hernandez, Marcela; Liang, Tao; Weng, Jianping; Gaisano, Herbert; Nostro, M Cristina; Jin, Tianru

2015-04-01

Disruption of TCF7L2 in mouse pancreatic β-cells has generated different outcomes in several investigations. Here we aim to clarify role of β-cell TCF7L2 and Wnt signaling using a functional-knockdown approach. Adenovirus-mediated dominant negative TCF7L2 (TCF7L2DN) expression was conducted in Ins-1 cells. The fusion gene in which TCF7L2DN expression is driven by P TRE3G was utilized to generate the transgenic mouse line TCF7L2DN Tet . The double transgenic line was created by mating TCF7L2DN Tet with Ins2-rtTA, designated as βTCFDN. β-cell specific TCF7L2DN expression was induced in βTCFDN by doxycycline feeding. TCF7L2DN expression in Ins-1 cells reduced GSIS, cell proliferation and expression of a battery of genes including incretin receptors and β-cell transcription factors. Inducing TCF7L2DN expression in βTCFDN during adulthood or immediately after weaning generated no or very modest metabolic defect, while its expression during embryonic development by doxycycline feeding in pregnant mothers resulted in significant glucose intolerance associated with altered β-cell gene expression and reduced β-cell mass. Our observations support a cell autonomous role for TCF7L2 in pancreatic β-cells suggested by most, though not all, investigations. βTCFDN is a novel model for further exploring the role of TCF7L2 in β-cell genesis and metabolic homeostasis.

What if? Neural activity underlying semantic and episodic counterfactual thinking.

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Parikh, Natasha; Ruzic, Luka; Stewart, Gregory W; Spreng, R Nathan; De Brigard, Felipe

2018-05-25

Counterfactual thinking (CFT) is the process of mentally simulating alternative versions of known facts. In the past decade, cognitive neuroscientists have begun to uncover the neural underpinnings of CFT, particularly episodic CFT (eCFT), which activates regions in the default network (DN) also activated by episodic memory (eM) recall. However, the engagement of DN regions is different for distinct kinds of eCFT. More plausible counterfactuals and counterfactuals about oneself show stronger activity in DN regions compared to implausible and other- or object-focused counterfactuals. The current study sought to identify a source for this difference in DN activity. Specifically, self-focused counterfactuals may also be more plausible, suggesting that DN core regions are sensitive to the plausibility of a simulation. On the other hand, plausible and self-focused counterfactuals may involve more episodic information than implausible and other-focused counterfactuals, which would imply DN sensitivity to episodic information. In the current study, we compared episodic and semantic counterfactuals generated to be plausible or implausible against episodic and semantic memory reactivation using fMRI. Taking multivariate and univariate approaches, we found that the DN is engaged more during episodic simulations, including eM and all eCFT, than during semantic simulations. Semantic simulations engaged more inferior temporal and lateral occipital regions. The only region that showed strong plausibility effects was the hippocampus, which was significantly engaged for implausible CFT but not for plausible CFT, suggestive of binding more disparate information. Consequences of these findings for the cognitive neuroscience of mental simulation are discussed. Published by Elsevier Inc.

The role of novel biomarkers in predicting diabetic nephropathy: a review

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Uwaezuoke SN

2017-08-01

Full Text Available Samuel N Uwaezuoke Pediatric Nephrology Firm, Department of Pediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria Abstract: Diabetic nephropathy (DN is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM, and occasionally from type 2 diabetes mellitus (T2DM. Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN. Keywords: type 1 diabetes mellitus, renal microvascular complication, microalbuminuria, end-stage kidney disease, biomarker panel

The co-optimization of floral display and nectar reward

Indian Academy of Sciences (India)

Prakash

H d R. dD d R. dN d R. dDdN. = −. 2. 2. 2. 2. 2. 2 d R. dD. 2. 2. dR. dD. aA a A D A. N p p p. = + ×. +. −. +1. 2. 1. (. ) (. ) ,. dR. dN. apA N a A D A. N p p p p. = + ×. +. −. −1. 2. 1. (. )( ) ,. dR. dD and. dR. dN. = = 0. 0 d R. dD. aA a A D A. N p p p. 2. 2. 2. 3. 2. 0. = −. + ×. +. <. +. (. ) (. ) d R. dN. apA N. A p. N p a A D A. N d R. dDdN a p.

A pilot trial assessing urinary gene expression profiling with an mRNA array for diabetic nephropathy.

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Min Zheng

Full Text Available BACKGROUND: The initiation and progression of diabetic nephropathy (DN is complex. Quantification of mRNA expression in urinary sediment has emerged as a novel strategy for studying renal diseases. Considering the numerous molecules involved in DN development, a high-throughput platform with parallel detection of multiple mRNAs is needed. In this study, we constructed a self-assembling mRNA array to analyze urinary mRNAs in DN patients with aims to reveal its potential in searching novel biomarkers. METHODS: mRNA array containing 88 genes were fabricated and its performance was evaluated. A pilot study with 9 subjects including 6 DN patients and 3 normal controls were studied with the array. DN patients were assigned into two groups according to their estimate glomerular rate (eGFR: DNI group (eGFR>60 ml/min/1.73 m(2, n = 3 and DNII group (eGFR<60 ml/min/1.73 m(2, n = 3. Urinary cell pellet was collected from each study participant. Relative abundance of these target mRNAs from urinary pellet was quantified with the array. RESULTS: The array we fabricated displayed high sensitivity and specificity. Moreover, the Cts of Positive PCR Controls in our experiments were 24±0.5 which indicated high repeatability of the array. A total of 29 mRNAs were significantly increased in DN patients compared with controls (p<0.05. Among these genes, α-actinin4, CDH2, ACE, FAT1, synaptopodin, COL4α, twist, NOTCH3 mRNA expression were 15-fold higher than those in normal controls. In contrast, urinary TIMP-1 mRNA was significantly decreased in DN patients (p<0.05. It was shown that CTGF, MCP-1, PAI-1, ACE, CDH1, CDH2 mRNA varied significantly among the 3 study groups, and their mRNA levels increased with DN progression (p<0.05. CONCLUSION: Our pilot study demonstrated that mRNA array might serve as a high-throughput and sensitive tool for detecting mRNA expression in urinary sediment. Thus, this primary study indicated that mRNA array probably could be a

The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

OpenAIRE

Timar, Bogdan; Timar, Romulus; Gai??, Laura; Oancea, Cristian; Levai, Codrina; Lungeanu, Diana

2016-01-01

Introduction Diabetic neuropathy (DN) is a prevalent complication of Type 2 Diabetes Mellitus (T2DM) with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN?s three major components: sensitive (lack of motion associated sensory), motor (impairments in movement coordination) and autonomic (the presence of postural hypotension), the presence of DN may impair the balance in the affected patients. Our study?s main aim i...

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

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Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

2014-09-01

Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

Application of the ReNuMa model in the Sha He river watershed: tools for watershed environmental management.

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Sha, Jian; Liu, Min; Wang, Dong; Swaney, Dennis P; Wang, Yuqiu

2013-07-30

Models and related analytical methods are critical tools for use in modern watershed management. A modeling approach for quantifying the source apportionment of dissolved nitrogen (DN) and associated tools for examining the sensitivity and uncertainty of the model estimates were assessed for the Sha He River (SHR) watershed in China. The Regional Nutrient Management model (ReNuMa) was used to infer the primary sources of DN in the SHR watershed. This model is based on the Generalized Watershed Loading Functions (GWLF) and the Net Anthropogenic Nutrient Input (NANI) framework, modified to improve the characterization of subsurface hydrology and septic system loads. Hydrochemical processes of the SHR watershed, including streamflow, DN load fluxes, and corresponding DN concentration responses, were simulated following calibrations against observations of streamflow and DN fluxes. Uncertainty analyses were conducted with a Monte Carlo analysis to vary model parameters for assessing the associated variations in model outputs. The model performed accurately at the watershed scale and provided estimates of monthly streamflows and nutrient loads as well as DN source apportionments. The simulations identified the dominant contribution of agricultural land use and significant monthly variations. These results provide valuable support for science-based watershed management decisions and indicate the utility of ReNuMa for such applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

XbaI GLUT1 Gene Polymorphism and the Risk of Type 2 Diabetes with Nephropathy

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Ioannis Stefanidis

2009-01-01

Full Text Available Altered expression of the facilitated glucose transporter GLUT1 affects pathways implicated in the pathogenesis of diabetic nephropathy. There is indication that variation of GLUT1 gene (SLC2A1 contributes to development of microangiopathy in diabetes mellitus type 2 (DM patients. A genetic association study involving Caucasians was carried out to investigate the role of XbαI polymorphism in the GLUT1 gene in diabetic nephropathy (DN. Study population (n = 240 consisted of 148 unrelated patients with DM (92 cases with diabetic nephropathy (DN, and of 92 matched healthy control subjects. Diabetic nephropathy was defined as persistent albuminuria (> 300 mg/24 h and/or renal failure, in the absence of non-diabetes induced renal disease. The analysis showed that the risk of developing DM and DN in XbaI(− carriers, when healthy individuals were considered as controls, was two-fold: odds ratio (OR 2.08 [95% confidence interval (1.14–3.79]. However, there was no evidence of association between XbaI(− and DN when patients with DM and without DN were considered as controls: OR = 1.12 (0.55–2.26. Thus, the GLUT1 XbaI(− allele is associated with DM, and possibly with a more severe form of the disease that can lead to development of DN.

Honey Quality as Affected by Handling, Processing and Marketing Channels in Uganda

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Nabakabya, D.

2008-01-01

Full Text Available The factors that affect honey quality in Uganda were surveyed in 120 beekeeping households. Honey was sampled from supermarkets, hawkers and stall markets along four transects across Kampala, the capital. Honey quality parameters assessed were diastase number (DN, free acidity (FA, moisture content (MC, hydroxymethylfurfural (HMF, and water insoluble solids (WIS. Honey was mostly harvested from basket and grass hives. Pressing, boiling and straining were popular honey processing methods. Honey quality was mainly compromised by harvesting immature honey, bad extraction methods and contamination by extraneous materials. Constraints to beekeeping were lack of appropriate equipment (52%, inadequate farmer skills, bad weather and vermin. Honey brands differed (P< 0.05 in DN, most failed the Uganda and Codex Alimentarius standards, and 20% met European Union HMF and DN standards. Correlation was observed between HMF vs. DN (r= 0.94; MC vs. FA (r= 0.56. Supermarket honey (4.65 was more superior (P< 0.05 in DN than stall markets (1.93, and hawkers (2.3. Similarly, WIS levels differed (P< 0.05 between honeys from supermarkets (0.08, stall markets (3.0 and hawkers (3.15. All honeys met MC standards, while DN and WIS were major shortcomings. Farmer training and extension in proper honey harvesting, handling and processing should be strengthened. Quality monitoring at all levels should be emphasized.

Clinical value of the joint measurement of serum concentrations of type IV collagen and laminin in patients with diabetic nephropathy

International Nuclear Information System (INIS)

Wang Lu; Wang Ping; Li Yongpei

2004-01-01

Objective: To study clinical value of the joint measurement of serum concentrations of type IV collagen (IV C) and laminin (LN) in patients with diabetic nephropathy (DN) by radioimmunoassay (RIA). Methods: Serum concentrations of IV C, LN were measured by RIA in 35 diabetic patients with normalbuminuria (group A), 28 cases of microalbuminuria (group B), 15 cases of macroalbuminuria (group C) and 30 normal subjects as control . Results: The serum concentrations of IV C, LN in total 78 diabetic patients [(97.6 ± 19.2), (132.4 ± 31.5) μg/L] were higher than that of the controls [(77.4 ± 8.2), (101.5 ± 17.6) μg/L, P<0.05], especially in group B and C, it was remarkably higher compared with the controls (P<0.05, P<0.01). There was significant positive correlation of serum IV C, LN to diabetic duration and the levels of blood urea nitrogen (BUN), creatinine (Cr), urinary albumin excretion rate (UAER). Conclusions: The results suggest that the joint measurement of serum levels of IV C, LN and UAER in DN patients might better evaluate the development process of DN, and be of help for early diagnosis and treatment of DN. Serum levels of IV C, LN and UAER in DN patients may become the reliable clinical markers for assessing the severity and predicting the prognosis of DN

Delayed Treatment with a Small Pigment Epithelium Derived Factor (PEDF Peptide Prevents the Progression of Diabetic Renal Injury.

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Alaa S Awad

Full Text Available Our recent publication showed that a small bioactive pigment epithelium derived factor (PEDF peptide (P78-PEDF prevents the development of diabetic nephropathy (DN. However, its effects on the progression of established DN were not clear. Therefore, the purpose of this study was to determine the effect of P78-PEDF in the progression of DN and to compare the effects of P78-PEDF and an ACE inhibitor (ACEi, a standard of care in DN. Experiments were conducted in Ins2(Akita mice treated with P78-PEDF or captopril starting at 6 wks of age for 12 wks (early treatment or starting at 12 wks of age for 6 wks (late treatment. We first established the optimal dose of the P78-PEDF peptide to ameliorate DN in Ins2(Akita mouse for a 6 wk study period and found that the peptide was effective at 0.1- 0.5 µg/g/day. We next showed that early or late treatment with P78-PEDF resulted in protection from DN as indicated by reduced albuminuria, kidney macrophage recruitment, histological changes, inflammatory cytokines and fibrotic markers (kidney TNF-α, fibronectin, VEGFA and EGFR, and restored nephrin expression compared with vehicle-treated Ins2(Akita mice. Interestingly, only early but not late treatment with captopril was as effective as P78-PEDF in reducing most DN complications, despite its lack of effect on nephrin, VEGFA and EGFR expression. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in both the development and progression of diabetic renal injury.

Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice

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Patrick M. Cowley

2017-10-01

Full Text Available Down syndrome (DS is a genetic condition caused by the triplication of chromosome 21. Persons with DS exhibit pronounced muscle weakness, which also occurs in the Ts65Dn mouse model of DS. Oxidative stress is thought to be an underlying factor in the development of DS-related pathologies including muscle dysfunction. High-levels of oxidative stress have been attributed to triplication and elevated expression of superoxide dismutase 1 (SOD1; a gene located on chromosome 21. The elevated expression of SOD1 is postulated to increase production of hydrogen peroxide and cause oxidative injury and cell death. However, it is unknown whether SOD1 protein expression is associated with greater oxidant production in skeletal muscle from Ts65Dn mice. Thus, our objective was to assess levels of SOD1 expression and oxidant production in skeletal myofibers from the flexor digitorum brevis obtained from Ts65Dn and control mice. Measurements of oxidant production were obtained from myofibers loaded with 2′,7′-dichlorodihydrofluorescein diacetate (DCFH2-DA in the basal state and following 15 min of stimulated unloaded contraction. Ts65Dn myofibers exhibited a significant decrease in basal DCF emissions (p 0.05. Myofibers from Ts65Dn mice tended to be smaller and myonuclear domain was lower (p < 0.05. In summary, myofibers from Ts65Dn mice exhibited decreased basal DCF emissions that were coupled with elevated protein expression of SOD1. Stimulated contraction in isolated myofibers did not affect DCF emissions in either group. These findings suggest the skeletal muscle dysfunction in the adult Ts65Dn mouse is not associated with skeletal muscle oxidative stress.

Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

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Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

2011-06-01

A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

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Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

2014-04-01

Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

Fatigue, insomnia and nervousness: gender disparities and roles of individual characteristics and lifestyle factors among economically active people.

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Peretti-Watel, Patrick; Legleye, Stéphane; Baumann, Michèle; Choquet, Marie; Falissard, Bruno; Chau, Nearkasen

2009-09-01

Individuals with certain personal, family and job characteristics are at elevated risk of poor mental health. Yet, the respective role of obesity, smoking, alcohol abuse, low education, income, living and family conditions, and socio-occupational category in fatigue/insomnia (FI), nervousness (N) and frequent drug use for those disorders (DFI and DN) among men and women and in gender disparities are not well known. We studied gender differences in FI, N, DFI, DN, and in their correlated, and whether the gender differences were mediated by individual and lifestyle factors among 3,450 active subjects aged 18-64, randomly selected from North-eastern France. Subjects completed a post-mailed questionnaire. Data were analyzed via adjusted odds ratio (ORa) computed with the logistic regression model. Women were more affected than men for FI (21.3 vs. 13.1%, OR adjusted for age ORa 1.80, 95% CI 1.50-2.16), DFI (11.6 vs. 7.1%, ORa 1.74, 1.38-2.21), N (14.7 vs. 9.9%, ORa 1.58, 1.28-1.94), and for DN (12.1 vs. 5.7%, ORa 2.29, 1.79-2.94). These differences were not mediated by the individual characteristics studied. Multivariate analysis showed that the risk patterns varied between the two sexes. Smoking was related to N in men as well as in women; alcohol abuse to DFI in men only; lack of family support to all outcome variables in men and women; low educational level to DFI in men only; low income to FI, N and DN in men and to FI and DN in women; being unmarried to DN in men; being divorced/separated to N and DN in women; being a manual worker to FI and being a farmer to DFI in men; and being a manual worker to DN and being an employee to FI in women (1.50 roles among men and women but they did not explain the gender disparities.

Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning.

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Cortez, IbDanelo; Bulavin, Dmitry V; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

2017-03-30

A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α AF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α AF/+ ) and kinase activity. As a result, aged DN-p38α AF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer's disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual's relative risk. In the present study, we evaluated aged DN-p38α AF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38α AF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38α AF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38α AF/+ , we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38α AF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. Copyright © 2016 Elsevier B.V. All rights reserved.

Immune pressure analysis of protease and reverse transcriptase ...

African Journals Online (AJOL)

/dn) were analyzed for 33 HIV-1 subtype C protease (PR) and reverse transcriptase (RT) nucleotide sequences each from antiretroviral naïve South African chronically infected individuals. The ds/dn ratios were calculated using the ...

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

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Corrales, Andrea; Parisotto, Eduardo B; Vidal, Verónica; García-Cerro, Susana; Lantigua, Sara; Diego, Marian; Wilhem Filho, Danilo; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

2017-09-15

Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity. Copyright © 2017 Elsevier B.V. All rights reserved.

Preliminary condensation pool experiments with steam using DN80 and DN100 blowdown pipes[VIDEO CAMERAS

Energy Technology Data Exchange (ETDEWEB)

Laine, J.; Puustinen, M. [Lappeenranta University of Technology (Finland)

2004-03-01

The report summarizes the results of the preliminary steam blowdown experiments. Altogether eight experiment series, each consisting of several steam blows, were carried out in autumn 2003 with a scaled-down condensation pool test rig designed and constructed at Lappeenranta University of Technology. The main purpose of the experiments was to evaluate the capabilities of the test rig and the needs for measurement and visualization devices. The experiments showed that a high-speed video camera is essential for visual observation due to the rapid condensation of steam bubbles. Furthermore, the maximum measurement frequency of the current combination of instrumentation and data acquisition system is inadequate for the actual steam tests in 2004. (au)

Relationship between fibrillin-1 genotype and severity of cardiovascular involvement in Marfan syndrome.

Science.gov (United States)

Franken, Romy; Teixido-Tura, Gisela; Brion, Maria; Forteza, Alberto; Rodriguez-Palomares, Jose; Gutierrez, Laura; Garcia Dorado, David; Pals, Gerard; Mulder, Barbara Jm; Evangelista, Artur

2017-11-01

The effect of FBN1 mutation type on the severity of cardiovascular manifestations in patients with Marfan syndrome (MFS) has been reported with disparity results. This study aims to determine the impact of the FBN1 mutation type on aortic diameters, aortic dilation rates and on cardiovascular events (ie, aortic dissection and cardiovascular mortality). MFS patients with a pathogenic FBN1 mutation followed at two specialised units were included. FBN1 mutations were classified as being dominant negative (DN; incorporation of non-mutated and mutated fibrillin-1 in the extracellular matrix) or having haploinsufficiency (HI; only incorporation of non-mutated fibrillin-1, thus a decreased amount of fibrillin-1 protein). Aortic diameters and the aortic dilation rate at the level of the aortic root, ascending aorta, arch, descending thoracic aorta and abdominal aorta by echocardiography and clinical endpoints comprising dissection and death were compared between HI and DN patients. Two hundred and ninety patients with MFS were included: 113 (39%) with an HI- FBN1 mutation and 177 (61%) with a DN- FBN1 . At baseline, patients with HI- FBN1 had a larger aortic root diameter than patients with DN- FBN1 (HI: 39.3±7.2 mm vs DN: 37.3±6.8 mm, p=0.022), with no differences in age or body surface area. After a mean follow-up of 4.9±2.0 years, aortic root and ascending dilation rates were increased in patients with HI- FBN1 (HI: 0.57±0.8 vs DN: 0.28±0.5 mm/year, p=0.004 and HI: 0.59±0.9 vs DN: 0.30±0.7 mm/year, p=0.032, respectively). Furthermore, patients with HI- FBN1 tended to be at increased risk for the combined endpoint of dissection and death compared with patients with DN- FBN1 (HR: 3.3, 95% CI 1.0 to 11.4, p=0.060). Patients with an HI mutation had a more severely affected aortic phenotype, with larger aortic root diameters and a more rapid dilation rate, and tended to have an increased risk of death and dissections compared with patients with a DN

Neural Responses to Heartbeats in the Default Network Encode the Self in Spontaneous Thoughts

Science.gov (United States)

Babo-Rebelo, Mariana; Richter, Craig G.

2016-01-01

The default network (DN) has been consistently associated with self-related cognition, but also to bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the first-person perspective subject or agent in the thought (“I”), and on another scale to what degree they were thinking about themselves (“Me”). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the “I” and the “Me” dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN. SIGNIFICANCE STATEMENT The default network (DN) has been consistently associated with self-processing but also with autonomic regulation. We hypothesized that these two functions could be functionally coupled in the DN, inspired by

Dose-response relationship of neutrons and γ rays to leukemia incidence among atomic bomb survivors in Hiroshima and Nagasaki by type of leukemia, 1950--1971

International Nuclear Information System (INIS)

Ishimaru, T.; Otake, M.; Ichimaru, M.

1979-01-01

The incidence of leukemia during 1950 to 1971 in a fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki was analyzed as a function of neutron and γ kerma and marrow doses. Two dose-response models were tested for acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that the leukemia incidence depends upon the sum of separate risks imposed by γ and neutron doses. In Model I the risk from both types of radiation is assumed to be directly proportional to the respective doses, while Model II assumes that whereas the risk from neutrons is directly proportional to the dose, the risk from γ rays is proportional to dose-squared. The analysis demonstrated that the dose-response of the two types of leukemia differed by type of radiation. The data suggested that the response of acute leukemia was best explained by Model II, while the response of chronic granulocytic leukemia depended almost linearly upon neutron dose alone, because the regression coefficients associated with γ radiation for both Models I and II were not significant. The relative biological effectiveness (RBE) of neutrons in relation to γ rays for incidence of acute leukemia was estimated to be approximately 30/(Dn)/sup 1/2/ [95% confidence limits; 17/(Dn)/sup 1/2/ approx. 54/(Dn)/sup 1/2/] for kerma and 32/(Dn)/sup 1/2/ [95% confidence limits; 18/(Dn)/sup 1/2/ approx. 58/(Dn)/sup 1/2/] for marrow dose (Dn = neutron dose). If acute and chronic granulocytic leukemias are considered together as all types of leukemia, Model II appears to fit the data slightly better than Model I, but neither model is statistically rejected by the data

Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT.

Science.gov (United States)

London, Barry; Baker, Linda C; Petkova-Kirova, Polina; Nerbonne, Jeanne M; Choi, Bum-Rak; Salama, Guy

2007-01-01

Enhanced dispersion of repolarization (DR) and refractoriness may be a unifying mechanism central to arrhythmia genesis in the long QT (LQT) syndrome. The role of DR in promoting arrhythmias was investigated in several strains of molecularly engineered mice: (a) Kv4.2 dominant negative transgenic (Kv4.2DN) that lacks the fast component of the transient outward current, I(to,f), have action potential (AP) and QT prolongation, but no spontaneous arrhythmias, (b) Kv1.4 targeted mice (Kv1.4-/-) that lack the slow component of I(to) (I(to,s)), have no QT prolongation and no spontaneous arrhythmias, and (c) double transgenic (Kv4.2DN x Kv1.4-/-) mice that lack both I(to,f) and I(to,s), have AP and QT prolongation, and spontaneous ventricular tachyarrhythmias. Hearts were perfused, stained with di-4-ANEPPS and optically mapped. Activation patterns and conduction velocities were similar between the strains but AP duration at 75% recovery (APD75) was longer in Kv4.2DN (28.0 +/- 2.5 ms, P mice than controls (20.3 +/- 1.0 ms, n = 5). Dispersion of refractoriness between apex and base was markedly reduced in Kv4.2DN (0.3 +/- 0.5 ms, n = 6, P mice compared with controls (10 +/- 2 ms, n = 5). A premature pulse elicited ventricular tachycardia (VT) in Kv1.4-/- (n = 4/5) and Kv4.2DN x Kv1.4-/- hearts (n = 5/5) but not Kv4.2DN hearts (n = 0/6). Voltage-clamp recordings showed that I(to,f) was 30% greater in myocytes from the apex than base which may account for the absence of DR in Kv4.2DN mice. Thus, dispersion of repolarization (DR) appears to be an important determinant of arrhythmia vulnerability.

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

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Igo, Robert P.; Iyengar, Sudha K.; Nicholas, Susanne B.; Goddard, Katrina A.B.; Langefeld, Carl D.; Hanson, Robert L.; Duggirala, Ravindranath; Divers, Jasmin; Abboud, Hanna; Adler, Sharon G.; Arar, Nedal H.; Horvath, Amanda; Elston, Robert C.; Bowden, Donald W.; Guo, Xiuqing; Ipp, Eli; Kao, W.H. Linda; Kimmel, Paul L.; Knowler, William C.; Meoni, Lucy A.; Molineros, Julio; Nelson, Robert G.; Pahl, Madeline V.; Parekh, Rulan S.; Rasooly, Rebekah S.; Schelling, Jeffrey R.; Shah, Vallabh O.; Smith, Michael W.; Winkler, Cheryl A.; Zager, Philip G.; Sedor, John R.; Freedman, Barry I.

2011-01-01

Background Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. Methods A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Results Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10−5, LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. Conclusion These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. PMID:21454968

A Comparison of Screening Tools for the Early Detection of Peripheral Neuropathy in Adults with and without Type 2 Diabetes

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Jennifer J. Brown

2017-01-01

Full Text Available Objective. Examine the effectiveness of the 128 Hz tuning fork, two monofilaments, and Norfolk Quality of Life Diabetic Neuropathy (QOL-DN questionnaire as tools for the early detection of diabetic peripheral neuropathy (DPN in overweight, obese, and inactive (OOI adults or those who have prediabetes (PD or type 2 diabetes (T2D. Research Design and Methods. Thirty-four adults (mean age 58.4 years ± 12.1 were divided by glycemia (10 OOI normoglycemic, 13 PD, and 11 T2D. Sural nerves were tested bilaterally with the NC-stat DPNCheck to determine sural nerve amplitude potential (SNAP and sural nerve conduction velocity (SNCV. All other testing results were compared to SNAP and SNCV. Results. Total 1 g monofilament scores significantly correlated with SNAP values and yielded the highest sensitivity and specificity combinations of tested measures. Total QOL-DN scores negatively correlated with SNAP values, as did QOL-DN symptoms. QOL-DN activities of daily living correlated with the right SNAP, and the QOL-DN small fiber subscore correlated with SNCV. Conclusions. The 1 g monofilament and total QOL-DN are effective, low-cost tools for the early detection of DPN in OOI, PD, and T2D adults. The 128 Hz tuning fork and 10 g monofilament may assist DPN screening as a tandem, but not primary, early DPN detection screening tools.

Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal Endothelial Injury with Diabetic Nephropathy

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Yang Liu

2014-01-01

Full Text Available Background. The purpose of the present study was to assess the feasibility of using miR-126 in the urine as a biomarker for diabetic nephropathy. Methods. miRNAs were extracted from the urine samples of T2DM patients with diabetic nephropathy (DN; n=92, T2DM without DN (n=86, and 85 healthy volunteers using quantitative reverse transcriptase polymerase chain reaction (real-time polymerase chain reaction analysis. Stability of urinary miR-126 and factors that affected the stability were assessed. A subgroup analysis was also carried out to compare the urinary miR-126 level in T2DM patients well controlled by the treatment versus those who were not well controlled. Results. Urinary miR-126 was stable when the urine samples were kept at room temperature for extended period of time, 4°C, −20°C, and −80°C for up to 12 hours or subjected to 10 freeze-and-thaw cycle. Urinary miR-126 was significantly higher in T2DM patients with DN (5.76±0.33 versus 3.25±0.45 in T2DM patients without DN. Successful treatment significantly reduced urinary miR-126 in T2DM patients with DN to 3.89±0.52 (P<0.05. Conclusion. miR-126 in the urine is stable and it could be used as a biomarker of DN and to monitor the treatment response.

The Protective Effects of Oral Low-dose Quercetin on Diabetic Nephropathy in Hypercholesterolemic Mice

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Isabele Beserra Santos Gomes

2015-09-01

Full Text Available Aims: Diabetic nephropathy (DN is one of the major causes of end-stage renal disease, and the incidence of DN is increasing worldwide. Considering our previous report indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg demonstrated renoprotective, anti-oxidative and anti-apoptotic effects in the C57BL/6J model of diabetic nephropathy, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE-/-. Methods: DN was induced by streptozotocin (100 mg/kg/day, for 3 days in adult apoE-/-mice. Six weeks later, the mice were divided into the following groups: diabetic apoE-/- mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks, diabetic ApoE-/- mice treated with vehicle (DV and non-treated non-diabetic (ND mice.Results: Quercetin treatment caused a reduction in polyuria (~30%, glycemia (~25%, abolished the hypertriglyceridemia and had significant effects on renal function, including decreased proteinuria (~15% and creatininemia (~30%, which were accompanied by beneficial effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight.Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical and morphological modifications. Thus, this translational study highlights the importance of quercetin as a potential nutraceutical for the management of DN, including in diabetes associated with dyslipidemia.

Superposition of elliptic functions as solutions for a large number of nonlinear equations

International Nuclear Information System (INIS)

Khare, Avinash; Saxena, Avadh

2014-01-01

For a large number of nonlinear equations, both discrete and continuum, we demonstrate a kind of linear superposition. We show that whenever a nonlinear equation admits solutions in terms of both Jacobi elliptic functions cn(x, m) and dn(x, m) with modulus m, then it also admits solutions in terms of their sum as well as difference. We have checked this in the case of several nonlinear equations such as the nonlinear Schrödinger equation, MKdV, a mixed KdV-MKdV system, a mixed quadratic-cubic nonlinear Schrödinger equation, the Ablowitz-Ladik equation, the saturable nonlinear Schrödinger equation, λϕ 4 , the discrete MKdV as well as for several coupled field equations. Further, for a large number of nonlinear equations, we show that whenever a nonlinear equation admits a periodic solution in terms of dn 2 (x, m), it also admits solutions in terms of dn 2 (x,m)±√(m) cn (x,m) dn (x,m), even though cn(x, m)dn(x, m) is not a solution of these nonlinear equations. Finally, we also obtain superposed solutions of various forms for several coupled nonlinear equations

Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants.

Science.gov (United States)

de Jong, Jan; Skee, Donna; Murphy, Joe; Sukbuntherng, Juthamas; Hellemans, Peter; Smit, Johan; de Vries, Ronald; Jiao, Juhui James; Snoeys, Jan; Mannaert, Erik

2015-08-01

Ibrutinib (PCI-32765), a potent covalent inhibitor of Bruton's tyrosine kinase, has shown efficacy against a variety of B-cell malignancies. Given the prominent role of CYP3A in ibrutinib metabolism, effect of coadministration of CYP3A perpetrators with ibrutinib was evaluated in healthy adults. Ibrutinib (120 mg [Study 1, fasted], 560 mg [studies 2 (fasted), and 3 (nonfasted)]) was given alone and with ketoconazole [Study 1; 400 mg q.d.], rifampin [Study 2; 600 mg q.d.], and grapefruit juice [GFJ, Study 3]. Lower doses of ibrutinib were used together with CYP3A inhibitors [Study 1: 40 mg; Study 3: 140 mg], as safety precaution. Under fasted condition, ketoconazole increased ibrutinib dose-normalized (DN) exposure [DN-AUClast: 24-fold; DN-C max: 29-fold], rifampin decreased ibrutinib exposure [C max: 13-fold; AUClast: 10-fold]. Under nonfasted condition, GFJ caused a moderate increase [DN-C max: 3.5-fold; DN-AUC: 2.2-fold], most likely through inhibition of intestinal CYP3A. Half-life was not affected by CYP perpetrators indicating the interaction was mainly on first-pass extraction. All treatments were well-tolerated.

Bubble growth as a means to measure dissolved nitrogen concentration in aerated water

Science.gov (United States)

Ando, Keita; Yamashita, Tatsuya

2017-11-01

Controlling the amount of dissolved gases in water is important, for example, to food processing; it is essential to quantitatively evaluate dissolved gas concentration. The concentration of dissolved oxygen (DO) can be measured by commercial DO meters, but that of dissolved nitrogen (DN) cannot be obtained easily. Here, we propose a means to measure DN concentration based on Epstein-Plesset-type analysis of bubble growth under dissolved gas supersaturation. DO supersaturation in water is produced by oxygen microbubble aeration. The diffusion-driven growth of bubbles nucleated at glass surfaces in contact with the aerated water is first observed. The observed growth is then compared to the extended Epstein-Plesset theory that considers Fick's mass transfer of both DO and DN across bubble interfaces; in this comparison, the unknown DN concentration is treated as a fitting parameter. Comparisons between the experiment and the theory suggest, as expected, that DN can be effectively purged by oxygen microbubble aeration. This study was supported in part by the Mizuho Foundation for the Promotion of Science and by a MEXT Grant-in-Aid for the Program for Leading Graduate Schools.

Nucleon electric dipole moments and the isovector parity- and time-reversal-odd pion–nucleon coupling

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Chien-Yeah Seng

2014-09-01

Full Text Available The isovector time-reversal- and parity-violating pion–nucleon coupling g¯π(1 is uniquely sensitive to dimension-six interactions between right-handed light quarks and the Standard Model Higgs doublet that naturally arises in left-right symmetric models. Recent work has used the g¯π(1-induced one-loop contribution to the neutron electric dipole moment dn, together with the present experimental dn bound, to constrain the CP-violating parameters of the left-right symmetric model. We show that this and related analyses are based on an earlier meson theory dn computation that is not consistent with the power-counting appropriate for an effective field theory. We repeat the one-loop calculation using heavy baryon chiral perturbation theory and find that the resulting dn sensitivity to g¯π(1 is suppressed, implying more relaxed constraints on the parameter space of the left-right symmetric model. Assuming no cancellations between this loop contribution and other contributions, such as the leading order EDM low-energy constant, the present limit on dn implies |g¯π(1|≲1.1×10−10.

Synthesis and characterization of a novel double cross-linked hydrogel based on Diels-Alder click reaction and coordination bonding.

Science.gov (United States)

Li, Shubin; Wang, Lu; Yu, Xuemei; Wang, Chengli; Wang, Zhenyu

2018-01-01

Hydrogels, promising biological materials, need to have both strong mechanical properties and also inherent self-healing properties. In this work a double cross-linked network (DN) hydrogel was designed and prepared by combining a Diels-Alder click reaction and coordination effects. This DN hydrogel had good thermodynamic properties, anti-EDTA performance and self-healing properties. In addition, the mechanical properties, swelling properties and surface morphology of DN hydrogels can be controlled by adjusting the ratio of Fe 3+ -catechol. The adjustment of pH value can change the color, crosslinking mode and mechanical properties of the DN hydrogel. This smart hydrogel created from DA click chemistry and coordination effects has significance for guiding the design of new hydrogels with good mechanical properties, self-healing properties and controlled cross-link density. Copyright © 2017. Published by Elsevier B.V.

Biotransformation of Dioscorea nipponica by Rat Intestinal Microflora and Cardioprotective Effects of Diosgenin

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Jia-Fu Feng

2017-01-01

Full Text Available Studying the biotransformation of natural products by intestinal microflora is an important approach to understanding how and why some medicines—particularly natural medicines—work. In many cases, the active components are generated by metabolic activation. This is critical for drug research and development. As a means to explore the therapeutic mechanism of Dioscorea nipponica (DN, a medicinal plant used to treat myocardial ischemia (MI, metabolites generated by intestinal microflora from DN were identified, and the cardioprotective efficacy of these metabolites was evaluated. Our results demonstrate that diosgenin is the main metabolite produced by rat intestinal microflora from DN. Further, our results show that diosgenin protects the myocardium against ischemic insult through increasing enzymatic and nonenzymatic antioxidant levels in vivo and by decreasing oxidative stress damage. These mechanisms explain the clinical efficacy of DN as an anti-MI drug.

Lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes with diabetic nephropathy depending on the stage of chronic kidney disease

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2012-06-01

Full Text Available Aim: to study the role and relationship of lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes mellitus (DM2 with diabetic nephropathy (DN, depending on the stage of chronic kidney disease (CKD. Materials and Methods: a total of 240 patients with type 2 diabetes in the early stages of DN and CKD were studied. Results: in patients with type 2 diabetes development of DN was associated with an increased level of proinflammatory cytokines and lipid abnormalities (hypertriglyceridemia. We found a negative correlation between the level of triglycerides (TG and glomerular filtration rate (GFR (r = -0,43 and a direct correlation between the level of IL-6 and TG (r = 0,48. Conclusions: increased levels of proinflammatory cytokines and triglycerides increase the risk of development and progression of DN and CKD.

Endothelial progenitor cells in long-standing asymptomatic type 1 diabetic patients with or without diabetic nephropathy

DEFF Research Database (Denmark)

Reinhard, Henrik; Jacobsen, Peter Karl; Lajer, Maria

2011-01-01

with or without DN and to study the effect of CVD and medication on EPC numbers. Methods: We examined EPC numbers in 37 type 1 diabetic patients with DN and 35 type 1 diabetic patients with long-standing normoalbuminuria. Patients were without symptoms of CVD and the prevalence of CVD was previously shown......A decrease in the number and dysfunction of endothelial progenitor cells (EPC) may increase the risk for progression of cardiovascular disease (CVD) in type 1 diabetic patients with diabetic nephropathy (DN). Our aim was to evaluate EPC numbers in asymptomatic CVD type 1 diabetic patients...... with CVD (p > 0.05). Conventional risk factors were significantly higher in patients with DN and they received more CVD-preventive treatment. All patients receiving simvastatin or calcium-channel blockers had higher numbers of EPC compared to patients not treated with these drugs. Conclusions: Asymptomatic...

Construction of Injectable Double-Network Hydrogels for Cell Delivery.

Science.gov (United States)

Yan, Yan; Li, Mengnan; Yang, Di; Wang, Qian; Liang, Fuxin; Qu, Xiaozhong; Qiu, Dong; Yang, Zhenzhong

2017-07-10

Herein we present a unique method of using dynamic cross-links, which are dynamic covalent bonding and ionic interaction, for the construction of injectable double-network (DN) hydrogels, with the objective of cell delivery for cartilage repair. Glycol chitosan and dibenzaldhyde capped poly(ethylene oxide) formed the first network, while calcium alginate formed the second one, and in the resultant DN hydrogel, either of the networks could be selectively removed. The moduli of the DN hydrogel were significantly improved compared to that of the parent single-network hydrogels and were tunable by changing the chemical components. In situ 3D cell encapsulation could be easily performed by mixing cell suspension to the polymer solutions and transferred through a syringe needle before sol-gel transition. Cell proliferation and mediated differentiation of mouse chondrogenic cells were achieved in the DN hydrogel extracellular matrix.

Phenotypical and functional characterization of double-negative (CD4-CD8-) alpha beta T-cell receptor positive cells from an immunodeficient patient

DEFF Research Database (Denmark)

Illum, N; Ralfkiaer, E; Pallesen, G

1991-01-01

We have characterized CD4-CD8- double-negative (DN) alpha beta TCR+ T cells from a patient with immunodeficiency, lymphocytosis, lymphadenopathy, and hepatosplenomegaly. The majority of peripheral blood lymphocytes were DN alpha beta TCR+ T cells as evaluated by FACS and biochemical analysis...... (MoAbs) indicated a polyclonal T-cell expansion. Thymic biopsy showed normal histology, whereas lymph node biopsy samples showed altered histological and immunohistological patterns with markedly expanded paracortical areas containing the DN T cells of the same phenotype as found in peripheral blood T...

Estrategias bioinformáticas y moleculares para aislar genes con potencial biotecnológico a partir de especies huérfanas de la ciencia

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Juan Castro Gómez

2013-12-01

Full Text Available La amazonía peruana es megabiodiversa y posee millones de genes con potencial biotecnológico que debemos descubrir. Para identificarlos, aislarlos y poder aprovecharlos tenemos que secuenciar los genomas y transcriptomas de las especies más importantes. Sin embargo, hasta concretar este tipo de proyectos, combinando estrategias bioinformáticas y moleculares podemos aislar genes con potencial biotecnológico. El objetivo fue aislar genes involucrados en la biosíntesis de vitamina C en Myrciaria dubia. De acuerdo a las relaciones filogenéticas de M. dubia con otras especies, se buscaron secuencias homólogas en el banco de genes del gen que codifica L-galactono-1,4-lactona deshidrogenasa (L-GalLDH. En base al alineamiento múltiple obtenido, se construyó un filograma consenso y de los clados formados se diseñaron cebadores degenerados. Los frutos fueron obtenidos de una colección de germoplasma y el ARN total se purificó, el ADNc se sintetizó y amplificó con cebadores degenerados. El amplicón sintetizado se clonó y secuenció con técnicas estándares. Con las aproximaciones empleadas se logró aislar, clonar y secuenciar un segmento de 921 pb del gen L-GalLDH de M. dubia. En conclusión, con las estrategias bioinformáticas y moleculares descritas se aisló el segmento de un gen que codifica la enzima L-galactono-1,4-lactona deshidrogenasa de la vía biosintética de vitamina C en M. dubia, especie de la que no se disponía de secuencias génicas. Con estas mismas aproximaciones será posible aislar genes de interés biotecnológico de esta y otras especies amazónicas que aún no cuentan con bases de datos de secuencias nucleotídicas.

Toward improved target conformity for two spot scanning proton therapy delivery systems using dynamic collimation

Science.gov (United States)

Moignier, Alexandra; Gelover, Edgar; Smith, Blake R.; Wang, Dongxu; Flynn, Ryan T.; Kirk, Maura L.; Lin, Liyong; Solberg, Timothy D.; Lin, Alexander; Hyer, Daniel E.

2016-01-01

Purpose: To quantify improvement in target conformity in brain and head and neck tumor treatments resulting from the use of a dynamic collimation system (DCS) with two spot scanning proton therapy delivery systems (universal nozzle, UN, and dedicated nozzle, DN) with median spot sizes of 5.2 and 3.2 mm over a range of energies from 100 to 230 MeV. Methods: Uncollimated and collimated plans were calculated with both UN and DN beam models implemented within our in-house treatment planning system for five brain and ten head and neck datasets in patients previously treated with spot scanning proton therapy. The prescription dose and beam angles from the clinical plans were used for both the UN and DN plans. The average reduction of the mean dose to the 10-mm ring surrounding the target between the uncollimated and collimated plans was calculated for the UN and the DN. Target conformity was analyzed using the mean dose to 1-mm thickness rings surrounding the target at increasing distances ranging from 1 to 10 mm. Results: The average reductions of the 10-mm ring mean dose for the UN and DN plans were 13.7% (95% CI: 11.6%–15.7%; p < 0.0001) and 11.5% (95% CI: 9.5%–13.5%; p < 0.0001) across all brain cases and 7.1% (95% CI: 4.4%–9.8%; p < 0.001) and 6.3% (95% CI: 3.7%–9.0%; p < 0.001), respectively, across all head and neck cases. The collimated UN plans were either more conformal (all brain cases and 60% of the head and neck cases) than or equivalent (40% of the head and neck cases) to the uncollimated DN plans. The collimated DN plans offered the highest conformity. Conclusions: The DCS added either to the UN or DN improved the target conformity. The DCS may be of particular interest for sites with UN systems looking for a more economical solution than upgrading the nozzle to improve the target conformity of their spot scanning proton therapy system. PMID:26936726

77 FR 14423 - Certain Food Containers, Cups, Plates, Cutlery, and Related Items, and Packaging Thereof; Notice...

Science.gov (United States)

2012-03-09

... INTERNATIONAL TRADE COMMISSION [DN 2883] Certain Food Containers, Cups, Plates, Cutlery, and... Containers, Cups, Plates, Cutlery, and Related Items, and Packaging Thereof, DN 2883; the Commission is... importation of certain food containers, cups, plates, cutlery, and related items, and packaging thereof. The...

Theory of charge transport in diffusive normal metal conventional superconductor point contacts

NARCIS (Netherlands)

Tanaka, Y.; Golubov, Alexandre Avraamovitch; Kashiwaya, S.

2003-01-01

Tunneling conductance in diffusive normal (DN) metal/insulator/s-wave superconductor junctions is calculated for various situations by changing the magnitudes of the resistance and Thouless energy in DN and the transparency of the insulating barrier. The generalized boundary condition introduced by

Oxidative Stress, Cytotoxicity and Genotoxicity in Earthworm Eisenia fetida at Different Di-n-Butyl Phthalate Exposure Levels.

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Tingting Ma

Full Text Available Recognized as ubiquitous contaminants in soil, the environmental risk of phthalic acid esters (PAEs is of great concern recently. Effects of di-n-butyl phthalate (DnBP, an extensively used PAE compound to Eisenia fetida have been investigated in spiked natural brown yellow soil (Alfisol for soil contact test. The toxicity of DnBP to E. fetida on the activity of superoxide dismutase (SOD activity, peroxidase (POD, reactive oxygen species (ROS content, and the apoptosis of coelomocytes and DNA damage at the 7th, 14th, 21st and 28th day of the incubation have been paid close attention to. In general, SOD activity and ROS content were significantly induced, opposite to total protein content and POD activity, during the toxicity test of 28 days especially under concentrations higher than 2.5 mg kg-1. The reduction in neutral red retention (NRR time along with the increase of dead coelomocytes as the increasing of DnBP concentrations, indicating severe damage to cell viability under varying pollutant stress during cultivation, which could also be proved by comet assay results for exerting evident DNA damage in coelomocytes. DnBP in spiked natural soil could indeed cause damage to tissues, coelomocytes and the nucleus of E. fetida. The key point of the apparent change in different indices presented around 2.5 mg DnBP kg-1 soil, which could be recommended as the threshold of DnBP soil contamination, so that further investigation on threshold values to other soil animals or microorganisms could be discussed.

Design study and comparative evaluation of JSFR failed fuel detection system

Energy Technology Data Exchange (ETDEWEB)

Aizawa, K.; Chikazawa, Y.; Ishikawa, N. [Japan Atomic Energy Agency JAEA, 4002 Narita, Oarai, Higashi-ibaraki-gun, Ibaraki 311-1393 (Japan); Kubo, S. [Japan Atomic Power Company JAPC (Japan); Okazaki, H.; Mito, M. [Mitsubishi FBR Systems, Inc. MFBR (Japan); Tozawa, K. [Fuji Electric Co., Ltd. (Japan); Hayashi, M. [MitsubishiElectric Corporation (Japan)

2012-07-01

A conceptual design study of an advanced sodium-cooled fast reactor JSFR has progressed in the 'Fast Reactor Cycle Technology Development (FaCT) 'project in Japan. JSFR has two failed fuel detection systems in the core. One is a failed fuel detection (FFD) system which continuously monitors a fission product from failed fuel subassembly. The other is a failed fuel detection and location (FFDL) system which locates when it receives signals from FFD. The FFD system consists of a FFD-DN which detects delayed neutron (DN) in sodium and a FFD-CG which detects fission products in the cover gas of the reactor vessel. In this study, requirements to the FFD-DN and the FFD-DN design to meet the requirements were investigated for the commercial and demonstration JSFR. In the commercial JSFR, a sampling type FFD which collects sodium from the reactor vessel by sampling lines for DN detectors was adopted. The performances have been investigated and confirmed by a fluid analysis in the reactor upper plenum. In the demonstration JSFR, the performance of DN detectors installed on the primary cold-leg piping has been confirmed. For the FFDL systems, experiences in the previous fast reactors and the R and D of FFDL system for JSFR were investigated. This study focuses on the Selector-Valve and the Tagging-Gas FFDL systems. Operation experiences of the Selector-valve FFDL system were accumulated in PFR and Phenix. Tagging-gas system experiences were accumulated in EBR-II and FFTF. The feasibility of both FFDL systems for JSFR was evaluated. (authors)

Neuroscience education in addition to trigger point dry needling for the management of patients with mechanical chronic low back pain: A preliminary clinical trial.

Science.gov (United States)

Téllez-García, Mario; de-la-Llave-Rincón, Ana I; Salom-Moreno, Jaime; Palacios-Ceña, Maria; Ortega-Santiago, Ricardo; Fernández-de-Las-Peñas, César

2015-07-01

The objective of the current study was to determine the short-term effects of trigger point dry needling (TrP-DN) alone or combined with neuroscience education on pain, disability, kinesiophobia and widespread pressure sensitivity in patients with mechanical low back pain (LBP). Twelve patients with LBP were randomly assigned to receive either TrP-DN (TrP-DN) or TrP-DN plus neuroscience education (TrP-DN + EDU). Pain intensity (Numerical Pain Rating Scale, 0-10), disability (Roland-Morris Disability Questionnaire-RMQ-, Oswestry Low Back Pain Disability Index-ODI), kinesiophobia (Tampa Scale of Kinesiophobia-TSK), and pressure pain thresholds (PPT) over the C5-C6 zygapophyseal joint, transverse process of L3 vertebra, second metacarpal, and tibialis anterior muscle were collected at baseline and 1-week after the intervention. Patients treated with TrP-DN + EDU experienced a significantly greater reduction of kinesiophobia (P = 0.008) and greater increases in PPT over the transverse process of L3 (P = 0.049) than those patients treated only with TrP-DN. Both groups experienced similar decreases in pain, ODI and RMQ, and similar increases in PPT over the C5/C6 joint, second metacarpal, and tibialis anterior after the intervention (all, P > 0.05). The results suggest that TrP-DN was effective for improving pain, disability, kinesiophobia and widespread pressure sensitivity in patients with mechanical LBP at short-term. The inclusion of a neuroscience educational program resulted in a greater improvement in kinesiophobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Significance of Hemostatic Parameters in the Prediction for Type 2 Diabetes Mellitus and Diabetic Nephropathy

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Lianlian Pan

2018-01-01

Full Text Available It would be important to predict type 2 diabetes mellitus (T2DM and diabetic nephropathy (DN. This study was aimed at evaluating the predicting significance of hemostatic parameters for T2DM and DN. Plasma coagulation and hematologic parameters before treatment were measured in 297 T2DM patients. The risk factors and their predicting power were evaluated. T2DM patients without complications exhibited significantly different activated partial thromboplastin time (aPTT, platelet (PLT, and D-dimer (D-D levels compared with controls (P<0.01. Fibrinogen (FIB, PLT, and D-D increased in DN patients compared with those without complications (P<0.001. Both aPTT and PLT were the independent risk factors for T2DM (OR: 1.320 and 1.211, P<0.01, resp., and FIB and PLT were the independent risk factors for DN (OR: 1.611 and 1.194, P<0.01, resp.. The area under ROC curve (AUC of aPTT and PLT was 0.592 and 0.647, respectively, with low sensitivity in predicting T2DM. AUC of FIB was 0.874 with high sensitivity (85% and specificity (76% for DN, and that of PLT was 0.564, with sensitivity (60% and specificity (89% based on the cutoff values of 3.15 g/L and 245 × 109/L, respectively. This study suggests that hemostatic parameters have a low predicting value for T2DM, whereas fibrinogen is a powerful predictor for DN.

Iron-based magnetic molecular imprinted polymers and their application in removal and determination of di-n-pentyl phthalate in aqueous media.

Science.gov (United States)

Li, Jing; Zhou, Qingxiang; Yuan, Yongyong; Wu, Yalin

2017-08-01

Iron-based magnetic molecular imprinted polymers (Fe@SiO 2 @MIP) were synthesized for highly selective removal and recognition of di- n -pentyl phthalate (DnPP) from water. Well-defined core-shell Fe@SiO 2 nanoparticles (less than 70 nm) were decorated on MIPs reticular layers to endow DnPP-MIPs with magnetic property for the first time. Five other phthalic acid esters including dimethyl phthalate, diethyl phthalate, dipropyl phthalate, di- n -butyl phthalate and di-iso-octyl phthalate were used to investigate the adsorptive selectivity to DnPP. The designed experiments were carried out to explore the adsorption kinetics, isotherms and thermodynamics and the results demonstrated that the adsorption was a spontaneous, exothermal and physical adsorption process. The materials were proved to be excellent adsorbents in removal of DnPP with an adsorption capacity as high as 194.15 mg g -1 in optimal condition. Furthermore, a magnetic solid phase extraction with Fe@SiO 2 @MIP coupled to high-performance liquid chromatography method was successfully developed for the determination of DnPP, and the proposed method achieved a good linear range of 0.5-250 µg l -1 with a correlation coefficient ( R 2 ) of 0.999 and low limit of detection (LOD) of 0.31 µg l -1 . These materials exhibited excellent capacity in removal and highly sensitive identification of DnPP from aqueous environment samples, and opened a valuable direction for developing new adsorbents for the removal and enrichment of important pollutants.

Changes of platelet GMP-140 in diabetic nephropathy and its multi-factor regression analysis

International Nuclear Information System (INIS)

Wang Zizheng; Du Tongxin; Wang Shukui

2001-01-01

The relation of platelet GMP-140 and its related factors with diabetic nephropathy was studied. 144 patients of diabetic mellitus without nephropathy (group without DN, mean suffering duration of 25.5 +- 18.6 months); 80 with diabetic nephropathy (group DN, mean suffering duration of 58.7 +- 31.6 months) and 50 normal controls were chosen in the research. Platelet GMP-140, plasma α 1 -MG, β 2 -MG, and 24 hour urine albumin (ALB), IgG, α 1 -MG, β 2 -MG were detected by RIA, while HBA 1 C via chromatographic separation and FBG, PBG, Ch, TG, HDL, FG via biochemical methods. All the data had been processed with software on computer with t-test and linear regression, and multi-factor analysis were done also. The levels of platelet GMP-140, FG, DBP, TG, HBA 1 C and PBG in group DN were significantly higher than those of group without DN and normal control (P 0.05), while they were higher than those of normal controls. Multi-factor analysis of platelet GMP-140 with TG, DBP and HBA 1 C were performed in 80 patients with DN (P 1 C are the independent factors enhancing the activation of platelets. The disturbance of lipid metabolism in type II diabetic mellitus may also enhance the activation of platelets. Elevation of blood pressure may accelerate the initiation and deterioration of DN in which change of platelet GMP-140 is an independent factor. Elevation of HBA 1 C and blood glucose are related closely to the diabetic nephropathy

Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities

NARCIS (Netherlands)

Reijmer, Y. D.; Schultz, A. P.; Leemans, A.; O'Sullivan, M. J.; Gurol, M. E.; Sperling, R.; Greenberg, S. M.; Viswanathan, A.; Hedden, T.

2015-01-01

Age-related impairments in the default network (DN) have been related to disruptions in connecting white matter tracts. We hypothesized that the local correlation between DN structural and functional connectivity is negatively affected in the presence of global white matter injury. In 125 clinically

77 FR 17093 - Certain Food Waste Disposers and Components and Packaging Thereof: Notice of Receipt of Complaint...

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2012-03-23

... INTERNATIONAL TRADE COMMISSION [DN 2886] Certain Food Waste Disposers and Components and Packaging.... International Trade Commission has received a complaint entitled Certain Food Waste Disposers and Components and Packaging Thereof, DN 2886; the Commission is soliciting comments on any public interest issues raised by...

Quasiparticle Green's function theory of the Josephson effect in chiral p-wave superconductor/diffusive normal metal/chiral p-wave superconductor junctions

NARCIS (Netherlands)

Sawa, Y.; Yokoyama, T.; Tanaka, Y.; Golubov, Alexandre Avraamovitch

2007-01-01

We study the Josephson effect in chiral p-wave superconductor/diffusive normal metal (DN)/chiral p-wave superconductor (CP/DN/CP) junctions using quasiclassical Green's function formalism with proper boundary conditions. The px+ipy-wave symmetry of superconducting order parameter is chosen which is

Theory of Josephson effect in Sr2RuO4/diffusive normal metal/Sr2RuO4 junctions

NARCIS (Netherlands)

Sawa, Y.; Yokoyama, T.; Tanaka, Y.; Golubov, Alexandre Avraamovitch

2007-01-01

We derive a generalized Nazarov’s boundary condition for diffusive normal metal (DN)/chiral p-wave superconductor (CP) interface including the macroscopic phase of the superconductor. The Josephson effect is studied in CP/DN/CP junctions solving the Usadel equations under the above boundary

The role of coagulation and inflammation in the development of diabetic nephropathy in patients withdiabetes mellitus type 2

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Yulia Valer'evna Khasanova

2012-03-01

Full Text Available Aim. To reveal the role of inflammatory markers (homocystein (HC, interleukin-6 (IL-6, components of hemostatic mechanism ofcoagulation in the development of diabetic nephropathy (DN in patients with type 2 diabetes mellitus (T2DM. Materials and methods. A total of 240 patients with T2DM and DN were examined. Results. Negative correlation between HC level and glomerular filtration rate (GFR (r= -0,38 and positive correlation between IL-6and fibrinogen (r=0,55 were observed. Conclusion. Inflammation and changes in mechanism of coagulation have influence on development and progression of DN in patientswith T2DM.

A comparative profile of methanol extracts of Allium cepa and Allium sativum in diabetic neuropathy in mice

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Bhanot, Abhishek; Shri, Richa

2010-01-01

Introduction: Diabetic Neuropathy (DN) is a major microvascular complication of uncontrolled diabetes. This may result from increased oxidative stress that accompanies diabetes. Hence plants with antioxidant action play an important role in management of diabetes and its complications. Materials and Methods: This study was designed to evaluate preventive as well as curative effect of methanol extracts of outer scales and edible portions of two plants with established antioxidant action - Allium cepa and Allium sativum, in induced DN in albino mice. Mice were divided into control, diabetic and test extracts treated groups. Test extracts were administered daily at a dose of 200 mg/kg p.o. for 21 days, in the preventive group prior to onset of DN, and in the curative group after the onset of DN. Hyperalgesia and oxidative stress markers were assessed. STZ-diabetic mice showed a significant thermal hyperalgesia (as assessed by the tail-flick test), indicating development of DN. Results: Treatment with test extracts prevented loss in body weight, decreased plasma glucose level, and significantly ameliorated the hyperalgesia, TBARS, serum nitrite and GSH levels in diabetic mice. Conclusion: Methanol extract of outer scales of onion has shown most significant improvement; may be due to higher content of phenolic compounds in outer scales of A. cepa. PMID:21713142

Variation of particle exhaust with changes in divertor magnetic balance

International Nuclear Information System (INIS)

Petrie, T.W.; Allen, S.L.; Brooks, N.H.

2006-01-01

Recent experiments on DIII-D point to the importance of two factors in determining how effectively the deuterium particle inventory in a tokamak plasma can be controlled through pumping at the divertor target(s): (1) the divertor magnetic balance, i.e. the degree to which the divertor topology is single-null or double-null (DN) and (2) the direction of the of B x ∇B ion drift with respect to the X-point(s). Changes in divertor magnetic balance near the DN shape have a much stronger effect on the particle exhaust rate at the inner divertor target(s) than on the particle exhaust rate at the outer divertor target(s). The particle exhaust rate for the DN shape is strongest at the outer strike point opposite the B x ∇B ion particle drift direction. Our data suggests that the presence of B x ∇B and E x B ion particle drifts in the scrape-off layer and divertor(s) play an important role in the particle exhaust rates of DN and near-DN plasmas. Particle exhaust rates are shown to depend strongly on the edge (pedestal) density. These results have implications for particle control in ITER and other future tokamaks

Tiaolipiwei Acupuncture Reduces Albuminuria by Alleviating Podocyte Lesions in a Rat Model of Diabetic Nephropathy

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Zhilong Zhang

2018-01-01

Full Text Available Background. Diabetic nephropathy is a common and serious complication of diabetes and a major cause of end-stage renal disease. Tiaolipiwei acupuncture is a safe treatment approach that may be effective for lowering albuminuria in diabetic nephropathy. Yet, the exact mechanisms of this therapeutic effect are unclear. Methods. A rodent model of type 2 diabetic nephropathy (T2DN was induced by a high-fat diet combined with low-dose streptozotocin. T2DN rats were treated with Tiaolipiwei acupuncture (ACU for 4, 8, or 12 weeks. At the end of treatment, urinary and blood samples were collected for analysis. Transmission electron microscopy was used to observe morphological changes, and protein expression levels of nephrin, CD2AP, podocalyxin, and desmin were quantified in renal tissue. Results. Compared to the T2DN groups, the T2DN + ACU groups showed significant improvements in 24-hour urinary protein, serum urea, cholesterol, and triglycerides at all time points. ACU treatment also improved the density of slit diaphragms. Simultaneously, ACU promoted the renal expression of nephrin, CD2AP, and podocalyxin and decreased the expression of desmin. Conclusion. Our study suggests that Tiaolipiwei acupuncture ameliorates podocyte lesions to reduce albuminuria and prevent the progression of T2DN in a rat model.

IL-6 signaling in diabetic nephropathy: From pathophysiology to therapeutic perspectives.

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Feigerlová, Eva; Battaglia-Hsu, Shyue-Fang

2017-10-01

Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated. Both IL-6 classical signaling pathway via receptor IL-6R (IL-6R) and IL-6 trans-signaling pathway via soluble IL-6R (sIL-6R) were shown to participate in the pathogenesis and progression of DN, and IL-6 appears to influence renal cells also in an autocrine manner. To date, evidence is limited. The goal of this review is to provide an overview of our current understanding on the role of IL-6 signaling in DN and to delineate challenges for future research. Putative sequential events related to IL-6 secretion by different cell populations in diabetic conditions are outlined. Further, we discuss potential applications of anti-IL-6 therapy in the context of DN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

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Alejandra Guillermina Miranda-Díaz

2016-01-01

Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

MAML1 regulates cell viability via the NF-κB pathway in cervical cancer cell lines

International Nuclear Information System (INIS)

Kuncharin, Yanin; Sangphech, Naunpun; Kueanjinda, Patipark; Bhattarakosol, Parvapan; Palaga, Tanapat

2011-01-01

The Notch signaling pathway plays important roles in tumorigenesis in a context-dependent manner. In human cervical cancer, alterations in Notch signaling have been reported, and both tumor-suppressing and tumor-promoting roles of Notch signaling have been proposed; however, the precise molecular mechanisms governing these roles in cervical cancer remain controversial. MAML is a transcriptional co-activator originally identified by its role in Notch signaling. Recent evidence suggests that it also plays a role in other signaling pathways, such as the p53 and β-catenin pathways. MAML is required for stable formation of Notch transcriptional complexes at the promoters of Notch target genes. Chromosomal translocations affecting MAML have been shown to promote tumorigenesis. In this study, we used a truncated dominant-negative MAML1 (DN-MAML) to investigate the role of MAML in HPV-positive cervical cancer cell lines. Three human cervical cancer cell lines (HeLa, SiHa and CaSki) expressed all Notch receptors and the Notch target genes Hes1 and MAML1. Among these 3 cell lines, constitutive appearance of cleaved Notch1 was found only in CaSki cells, which suggests that Notch1 is constitutively activated in this cell line. Gamma secretase inhibitor (GSI) treatment, which suppresses Notch receptor activation, completely abrogated this form of Notch1 but had no effect on cell viability. Overexpression of DN-MAML by retroviral transduction in CaSki cells resulted in significant decreases in the mRNA levels of Hes1 and Notch1 but had no effects on the levels of MAML1, p53 or HPV E6/E7. DN-MAML expression induced increased viability of CaSki cells without any effect on cell cycle progression or cell proliferation. In addition, clonogenic assay experiments revealed that overexpression of DN-MAML resulted in increased colony formation compared to the overexpression of the control vector. When the status of the NF-κB pathway was investigated, CaSki cells overexpressing DN

Identification, prevalence, and treatment of painful diabetic neuropathy in patients from a rural area in South Carolina

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Pruitt III J

2017-04-01

Full Text Available Jimmy Pruitt III,1 Carolina Moracho-Vilrriales,1,2 Tiffaney Threatt,3 Sarah Wagner,3 Jun Wu,1 E Alfonso Romero-Sandoval1 1Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA; 2Department of Biochemistry and Biotechnology, University of Alcalá de Henares, Madrid, Spain; 3Department of Pharmacy Practice, Presbyterian College School of Pharmacy, Clinton, SC, USA Abstract: Diabetic peripheral neuropathy (DPN represents significant burdens to many patients and the public health-care system. Patients with diabetes in rural areas have higher risk of developing complications and having less access to proper treatment. We studied a rural population of patients with diabetes who attended a pharmacist-led free clinic for a diabetic education program. Our objectives were to 1 determine the prevalence of DPN and painful diabetic neuropathy (p-DN in patients with type 2 diabetes; 2 assess the proportion of patients with DPN and p-DN left undocumented upon physician referral to a pharmacist-led free clinic; and 3 determine the appropriateness of pain medication regimen. We performed a retrospective analysis of clinical records of patients from the Presbyterian College School of Pharmacy (PCSP Wellness Center located in Clinton, SC. Diagnoses of DPN and/or p-DN were obtained from referral notes in the clinical records and compared with results from foot examinations performed in the free clinic and clinical features. Medication regimens were also obtained and compared using American Academy of Neurology (AAN treatment guidelines. Within our study population (n=111, the prevalence of DPN was 62.2% (national average of 28%–45% and that of p-DN was 23.4% (national average of 11%–24%. In p-DN patients (n=26, 53.8% (n=14 had a documented diagnosis of p-DN by the referring physician, and 46.2% (n=12 were identified by the pharmacists. A total of 95% (19 of 20 of the patients treated for p-DN

MAML1 regulates cell viability via the NF-{kappa}B pathway in cervical cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Kuncharin, Yanin [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Sangphech, Naunpun [Biotechnology Program, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Kueanjinda, Patipark [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Bhattarakosol, Parvapan [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Palaga, Tanapat, E-mail: tanapat.p@chula.ac.th [Department of Microbiology, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand)

2011-08-01

The Notch signaling pathway plays important roles in tumorigenesis in a context-dependent manner. In human cervical cancer, alterations in Notch signaling have been reported, and both tumor-suppressing and tumor-promoting roles of Notch signaling have been proposed; however, the precise molecular mechanisms governing these roles in cervical cancer remain controversial. MAML is a transcriptional co-activator originally identified by its role in Notch signaling. Recent evidence suggests that it also plays a role in other signaling pathways, such as the p53 and {beta}-catenin pathways. MAML is required for stable formation of Notch transcriptional complexes at the promoters of Notch target genes. Chromosomal translocations affecting MAML have been shown to promote tumorigenesis. In this study, we used a truncated dominant-negative MAML1 (DN-MAML) to investigate the role of MAML in HPV-positive cervical cancer cell lines. Three human cervical cancer cell lines (HeLa, SiHa and CaSki) expressed all Notch receptors and the Notch target genes Hes1 and MAML1. Among these 3 cell lines, constitutive appearance of cleaved Notch1 was found only in CaSki cells, which suggests that Notch1 is constitutively activated in this cell line. Gamma secretase inhibitor (GSI) treatment, which suppresses Notch receptor activation, completely abrogated this form of Notch1 but had no effect on cell viability. Overexpression of DN-MAML by retroviral transduction in CaSki cells resulted in significant decreases in the mRNA levels of Hes1 and Notch1 but had no effects on the levels of MAML1, p53 or HPV E6/E7. DN-MAML expression induced increased viability of CaSki cells without any effect on cell cycle progression or cell proliferation. In addition, clonogenic assay experiments revealed that overexpression of DN-MAML resulted in increased colony formation compared to the overexpression of the control vector. When the status of the NF-{kappa}B pathway was investigated, CaSki cells overexpressing

Uric acid as a mediator of diabetic nephropathy

DEFF Research Database (Denmark)

Jalal, Diana I; Maahs, David M; Hovind, Peter

2011-01-01

Despite advances in the management of patients with diabetes, diabetic nephropathy (DN) remains the most common cause of end-stage renal disease in the United States and worldwide. Inflammation and endothelial dysfunction appear to play a central role in the onset and the progression of DN. Recen...

Influence of magnetic impurities on charge transport in diffusive-normal-metal/superconductor junctions

NARCIS (Netherlands)

Yokoyama, T.; Tanaka, Y.; Golubov, Alexandre Avraamovitch; Inoue, J.; Asano, Y.

2005-01-01

Charge transport in the diffusive normal metal (DN)/insulator/s- and d-wave superconductor junctions is studied in the presence of magnetic impurities in DN in the framework of the quasiclassical Usadel equations with the generalized boundary conditions. The cases of s- and d-wave superconducting

Activins and inhibins: Novel regulators of thymocyte development

International Nuclear Information System (INIS)

Licona-Limon, Paula; Aleman-Muench, German; Chimal-Monroy, Jesus; Macias-Silva, Marina; Garcia-Zepeda, Eduardo A.; Matzuk, Martin M.; Fortoul, Teresa I.; Soldevila, Gloria

2009-01-01

Activins and inhibins are members of the transforming growth factor-β superfamily that act on different cell types and regulate a broad range of cellular processes including proliferation, differentiation, and apoptosis. Here, we provide the first evidence that activins and inhibins regulate specific checkpoints during thymocyte development. We demonstrate that both activin A and inhibin A promote the DN3-DN4 transition in vitro, although they differentially control the transition to the DP stage. Whereas activin A induces the accumulation of a CD8 + CD24 hi TCRβ lo intermediate subpopulation, inhibin A promotes the differentiation of DN4 to DP. In addition, both activin A and inhibin A appear to promote CD8 + SP differentiation. Moreover, inhibin α null mice have delayed in vitro T cell development, showing both a decrease in the DN-DP transition and reduced thymocyte numbers, further supporting a role for inhibins in the control of developmental signals taking place during T cell differentiation in vivo.

Discovery of 1-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one, an orally active multi-target agent for the treatment of diabetic nephropathy.

Science.gov (United States)

Chen, Jun; Peng, Zhangzhe; Lu, Miaomiao; Xiong, Xuan; Chen, Zhuo; Li, Qianbin; Cheng, Zeneng; Jiang, Dejian; Tao, Lijian; Hu, Gaoyun

2018-01-15

Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC 50 of 90μM in NIH3T3 cell lines, t 1/2 of 4.89±1.33h in male rats and LD 50 >2000mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distinct and overlapping effector functions of expanded human CD4+, CD8α+ and CD4-CD8α- invariant natural killer T cells.

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Vincent O'Reilly

Full Text Available CD1d-restricted invariant natural killer T (iNKT cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. Activation of iNKT cells can protect against multiple diseases in mice but clinical trials in humans have had limited impact. Clinical studies to date have targeted polyclonal mixtures of iNKT cells and we proposed that their subset compositions will influence therapeutic outcomes. We sorted and expanded iNKT cells from healthy donors and compared the phenotypes, cytotoxic activities and cytokine profiles of the CD4(+, CD8α(+ and CD4(-CD8α(- double-negative (DN subsets. CD4(+ iNKT cells expanded more readily than CD8α(+ and DN iNKT cells upon mitogen stimulation. CD8α(+ and DN iNKT cells most frequently expressed CD56, CD161 and NKG2D and most potently killed CD1d(+ cell lines and primary leukemia cells. All iNKT subsets released Th1 (IFN-γ and TNF-α and Th2 (IL-4, IL-5 and IL-13 cytokines. Relative amounts followed a CD8α>DN>CD4 pattern for Th1 and CD4>DN>CD8α for Th2. All iNKT subsets could simultaneously produce IFN-γ and IL-4, but single-positivity for IFN-γ or IL-4 was strikingly rare in CD4(+ and CD8α(+ fractions, respectively. Only CD4(+ iNKT cells produced IL-9 and IL-10; DN cells released IL-17; and none produced IL-22. All iNKT subsets upregulated CD40L upon glycolipid stimulation and induced IL-10 and IL-12 secretion by dendritic cells. Thus, subset composition of iNKT cells is a major determinant of function. Use of enriched CD8α(+, DN or CD4(+ iNKT cells may optimally harness the immunoregulatory properties of iNKT cells for treatment of disease.

The Philosophy of Science and Technology in China: Political and Ideological Influences

Science.gov (United States)

Guo, Yuanlin

2014-01-01

In China, the philosophy of science and technology (PST) is derived from "Dialectics of Nature" (DN), which is based on Engels' unfinished book "Dialektik der Natur." DN as a political ideology provides political guidance for scientists and engineers. Therefore, since 1981, "Introduction to Dialectics of Nature" (IDN)…

Nonmonotonic temperature dependence of critical current in diffusive d-wave junctions

NARCIS (Netherlands)

Yokoyama, T.; Tanaka, Y.; Golubov, Alexandre Avraamovitch; Asano, Y.

2006-01-01

We study the Josephson effect in D/I/DN/I/D junctions, where I, DN, and D denote an insulator, a diffusive normal metal, and a d-wave superconductor, respectively. The Josephson current is calculated based on the quasiclassical Green's function theory with a general boundary condition for

The eschatological opponent of Daniel and the Antichrist of the Syriac Apocalypse of Daniel

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Sara Daiane Silva José

2014-12-01

Full Text Available The Syriac Apocalypse of Daniel (Syr Apoc Dan, a Christian apocalypse from the seventh century of Common Era, is clearly tributary to the canonical book of Daniel (Dn. In its turn, Dn provided the figure of an eschatological opponent who was re-signified in Christianity: the Antichrist. The cosmic dimensions of the malevolent character of oppressive tyrant of Dn – his arrogance against the gods, the abomination of desolation, military conquests and persecutions of the saints, the change of the cosmic order, the time of the reign and death of the tyrant – are considered in this work compared with the Antichrist of the Syr Apoc Dan.

Fatigue 󈨛. Volume 1,

Science.gov (United States)

1987-06-01

277 FATIGUE 87 da/dn (m/ ciclo ) 10 - 07 10 - 08 10 - 0 9 R=0.5 S* • -Long Crack 10-10 e Smax = 195 MPa *Smax = 205 MPa 1Smax = 225 MPa 0.5 1 5 10 AK...MPa/m) Figure 1 Crack growth rate vs stress intensity factor range 10 . da/dn (m/ ciclo ) i0 - ° 09 i0-o -Long crack 10 . ° Smax = 10 Pa 10 Smax...120 NPa Smax = 145 NlPa 0.5 I 10 AKN~~)50 Figure 2 Crack growth rate vs stress intensity factor range 278 FATIGUE 87 da/dn (m/ ciclo ) 10- 10- 0 7 % 10

Electric Dipole Moment of the Neutron from 2+1 Flavor Lattice QCD.

Science.gov (United States)

Guo, F-K; Horsley, R; Meissner, U-G; Nakamura, Y; Perlt, H; Rakow, P E L; Schierholz, G; Schiller, A; Zanotti, J M

2015-08-07

We compute the electric dipole moment d(n) of the neutron from a fully dynamical simulation of lattice QCD with 2+1 flavors of clover fermions and nonvanishing θ term. The latter is rotated into a pseudoscalar density in the fermionic action using the axial anomaly. To make the action real, the vacuum angle θ is taken to be purely imaginary. The physical value of dd(n) is obtained by analytic continuation. We find d(n)=-3.9(2)(9)×10(-16) θ  e cm, which, when combined with the experimental limit on d(n), leads to the upper bound |θ|≲7.4×10(-11).

Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

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Wu S

2014-12-01

Full Text Available Shengzheng Wu,1 Lu Li,1 Gong Wang,1 Weiwei Shen,2 Yali Xu,1 Zheng Liu,1 Zhongxiong Zhuo,1 Hongmei Xia,1 Yunhua Gao,1 Kaibin Tan1 1Department of Ultrasound, 2Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Mesenchymal stem cell (MSC therapy has been considered a promising strategy to cure diabetic nephropathy (DN. However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1 plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MBSDF-1 via covalent conjugation. The characterization and bioactivity of MBSDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MBSDF-1. The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 µg/mL. MBSDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with

Finding diabetic nephropathy biomarkers in the plasma peptidome by high-throughput magnetic bead processing and MALDI-TOF-MS analysis

DEFF Research Database (Denmark)

Hansen, Henning G; Overgaard, Julie; Lajer, Maria

2010-01-01

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease and improved biomarkers would help identify high-risk individuals. The aim of this study was to discover candidate biomarkers for DN in the plasma peptidome in an in-house cross-sectional cohort (n=122) of type 1 diabet...

Activity-Dependent Excitability Changes Suggest Na[superscript +]/K[superscript +] Pump Dysfunction in Diabetic Neuropathy

Science.gov (United States)

Krishnan, Arun V.; Lin, Cindy S.-Y.; Kiernan, Matthew C.

2008-01-01

The present study was undertaken to evaluate the role of Na[superscript +]/K[superscript +] pump dysfunction in the development of diabetic neuropathy (DN). Nerve excitability techniques, which provide information about membrane potential and axonal ion channel function, were undertaken in 15 patients with established DN and in 10 patients with…

Maintaining Arc Consistency in Non-Binary Dynamic CSPs using Simple Tabular Reduction

DEFF Research Database (Denmark)

Queva, Matthieu Stéphane Benoit; Probst, Christian W.; Ricci, Laurent

2010-01-01

CSPs use filtering techniques such as arc consistency, which also have been adapted to handle DCSPs with binary constraints. However, there exists only one algorithm targeting non-binary DCSPs (DnGAC4). In this paper we present a new algorithm DnSTR for maintaining arc consistency in DCSPs with non-binary...

Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

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Pan Shiow-Lin

2009-05-01

Full Text Available Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1 in denbinobin-induced apoptosis in human lung adenocarcinoma (A549 cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN, two antioxidants (N-acetyl-L-cysteine (NAC and glutathione (GSH, a c-Jun N-terminal kinase (JNK inhibitor (SP600125, and an activator protein-1 (AP-1 inhibitor (curcumin. Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

Internal structure analysis of particle-double network gels used in a gel organ replica

Science.gov (United States)

Abe, Mei; Arai, Masanori; Saito, Azusa; Sakai, Kazuyuki; Kawakami, Masaru; Furukawa, Hidemitsu

2016-04-01

In recent years, the fabrication of patient organ replicas using 3D printers has been attracting a great deal of attention in medical fields. However, the cost of these organ replicas is very high as it is necessary to employ very expensive 3D printers and printing materials. Here we present a new gel organ replica, of human kidney, fabricated with a conventional molding technique, using a particle-double network hydrogel (P-DN gel). The replica is transparent and has the feel of a real kidney. It is expected that gel organ replicas produced this way will be a useful tool for the education of trainee surgeons and clinical ultrasonography technologists. In addition to developing a gel organ replica, the internal structure of the P-DN gel used is also discussed. Because the P-DN gel has a complex structure comprised of two different types of network, it has not been possible to investigate them internally in detail. Gels have an inhomogeneous network structure. If it is able to get a more uniform structure, it is considered that this would lead to higher strength in the gel. In the present study we investigate the structure of P-DN gel, using the gel organ replica. We investigated the internal structure of P-DN gel using Scanning Microscopic Light Scattering (SMILS), a non-contacting and non-destructive.

Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated renal oxidative stress and inflammation via Akt/NF-κB pathway.

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Ji, Xiaoqian; Li, Changzheng; Ou, Yitao; Li, Ning; Yuan, Kai; Yang, Guizhi; Chen, Xiaoyan; Yang, Zhicheng; Liu, Bing; Cheung, Wai W; Wang, Lijing; Huang, Ren; Lan, Tian

2016-12-05

Diabetic nephropathy (DN) is characterized by proliferation of mesangial cells, mesangial hypertrophy and extracellular matrix (ECM) accumulation. Our recent study found that andrographolide inhibited high glucose-induced mesangial cell proliferation and fibronectin expression through inhibition of AP-1 pathway. However, whether andrographolide has reno-protective roles in DN has not been fully elucidated. Here, we studied the pharmacological effects of andrographolide against the progression of DN and high glucose-induced mesangial dysfunction. Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). After 1 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Diabetic mice were intraperitoneal injected with andrographolide (2 mg/kg, twice a week). After 8 weeks, functional and histological analyses were carried out. Parallel experiments uncovering the molecular mechanism by which andrographolide prevents from DN was performed in mesangial cells. Andrographolide inhibited the increases in fasting blood glucose, triglyceride, kidney/body weight ratio, blood urea nitrogen, serum creatinine and 24-h albuminuria in diabetic mice. Andrographolide also prevented renal hypertrophy and ECM accumulation. Furthermore, andrographolide markedly attenuated NOX1 expression, ROS production and pro-inflammatory cytokines as well. Additionally, andrographolide inhibited Akt/NF-κB signaling pathway. These results demonstrate that andrographolide is protective against the progression of experimental DN by inhibiting renal oxidative stress, inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rogue periodic waves of the modified KdV equation

Science.gov (United States)

Chen, Jinbing; Pelinovsky, Dmitry E.

2018-05-01

Rogue periodic waves stand for rogue waves on a periodic background. Two families of travelling periodic waves of the modified Korteweg–de Vries (mKdV) equation in the focusing case are expressed by the Jacobian elliptic functions dn and cn. By using one-fold and two-fold Darboux transformations of the travelling periodic waves, we construct new explicit solutions for the mKdV equation. Since the dn-periodic wave is modulationally stable with respect to long-wave perturbations, the new solution constructed from the dn-periodic wave is a nonlinear superposition of an algebraically decaying soliton and the dn-periodic wave. On the other hand, since the cn-periodic wave is modulationally unstable with respect to long-wave perturbations, the new solution constructed from the cn-periodic wave is a rogue wave on the cn-periodic background, which generalizes the classical rogue wave (the so-called Peregrine’s breather) of the nonlinear Schrödinger equation. We compute the magnification factor for the rogue cn-periodic wave of the mKdV equation and show that it remains constant for all amplitudes. As a by-product of our work, we find explicit expressions for the periodic eigenfunctions of the spectral problem associated with the dn and cn periodic waves of the mKdV equation.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study

Energy Technology Data Exchange (ETDEWEB)

Conte, Giorgio; Minotti, Marta; De Piano, Francesca [Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Preda, Lorenzo [Universita degli Studi di Pavia, Department of Clinical-Surgical Diagnostic and Pediatric Sciences, Pavia (Italy); National Center of Oncological Hadrontherapy (CNAO Foundation), Division of Radiology, Pavia (Italy); Cocorocchio, Emilia; Ferrucci, Pier Francesco [European Institute of Oncology, Melanoma and Sarcoma Medical Oncology Division, Milan (Italy); Raimondi, Sara [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Giannitto, Caterina; Petralia, Giuseppe [European Institute of Oncology, Division of Radiology, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Division of Radiology, Milan (Italy); Universita degli Studi di Milano, Oncology and Haematology/Oncology Department, Milan (Italy)

2017-10-15

To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. We retrospectively included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. (orig.)

Resistance to Wheat Curl Mite in Arthropod-Resistant Rye-Wheat Translocation Lines

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Lina Maria Aguirre-Rojas

2017-11-01

Full Text Available The wheat curl mite, Aceria toschiella (Keifer, and a complex of viruses vectored by A. toschiella substantially reduce wheat yields in every wheat-producing continent in the world. The development of A. toschiella-resistant wheat cultivars is a proven economically and ecologically viable method of controlling this pest. This study assessed A. toschiella resistance in wheat genotypes containing the H13, H21, H25, H26, H18 and Hdic genes for resistance to the Hessian fly, Mayetiola destructor (Say and in 94M370 wheat, which contains the Dn7 gene for resistance to the Russian wheat aphid, Diuraphis noxia (Kurdjumov. A. toschiella populations produced on plants containing Dn7 and H21 were significantly lower than those on plants of the susceptible control and no different than those on the resistant control. Dn7 resistance to D. noxia and H21 resistance to M. destructor resulted from translocations of chromatin from rye into wheat (H21—2BS/2RL, Dn7—1BL/1RS. These results provide new wheat pest management information, indicating that Dn7 and H21 constitute resources that can be used to reduce yield losses caused by A. toschiella, M. destructor, D. noxia, and wheat streak mosaic virus infection by transferring multi-pest resistance to single sources of germplasm.

Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.

Science.gov (United States)

Aida, Yasuko; Shibata, Yoko; Abe, Shuichi; Inoue, Sumito; Kimura, Tomomi; Igarashi, Akira; Yamauchi, Keiko; Nunomiya, Keiko; Kishi, Hiroyuki; Nemoto, Takako; Sato, Masamichi; Sato-Nishiwaki, Michiko; Nakano, Hiroshi; Sato, Kento; Kubota, Isao

2014-01-01

Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.

Prevalence of nephropathy in type 1 diabetes in the Arab world: A systematic review and meta-analysis.

Science.gov (United States)

Abdel-Motal, Ussama M; G, Akila; Abdelalim, Essam M; Ponnuraja, Chinnaiyan; Iken, Khadija; Jahromi, Mohamed; Doss, George Priya; El Bekay, Rajaa; Zayed, Hatem

2018-05-17

The aim of this study was to conduct a systematic review and meta-analysis and determine the prevalence of diabetic nephropathy (DN) among Arab patients with T1D. A systematic literature search was conducted using 4 different literature databases (PubMed, ScienceDirect, Web of Science, and Embase) to capture all relevant data about Arab patients with T1D that had DN. Meta-analysis and systematic review were performed using the random effect model, and the heterogeneity of the studies was assessed using the Q-test, I2, and Tau-squared statistics. Publication bias was assessed using the funnel-plot test. Our search strategy captured 372 studies in only 10 out of the 22 Arab countries in a period of 48 years (1969-2017); of which, 41 met our inclusion criteria for full article analysis, of those, 15 were eligible for meta-analysis. We estimated the prevalence of DN among Arab people with T1D to be 18.2% (95% confidence interval 13.1%-24.8%). In conclusion, DN prevalence is underexplored among Arab patients with T1D and represents a significant risk for the well-being of Arab patients with T1D. Therefore, there is an urgent need for comprehensive epidemiological studies for DN among Arab patients with T1D. Copyright © 2018 John Wiley & Sons, Ltd.

Interactive effects of genotype x environment on the live weight of GIFT Nile tilapias.

Science.gov (United States)

Oliveira, Sheila N DE; Ribeiro, Ricardo P; Oliveira, Carlos A L DE; Alexandre, Luiz; Oliveira, Aline M S; Lopera-Barrero, Nelson M; Santander, Victor F A; Santana, Renan A C

2017-01-01

In this paper, the existence of a genotype x environment interaction for the average daily weight in GIFT Nile tilapia (Oreochromis niloticus) in different regions in the state of Paraná (Brazil) was analyzed. The heritability results were high in the uni-characteristic analysis: 0.71, 0.72 and 0.67 for the cities of Palotina (PL), Floriano (FL) and Diamond North (DN), respectively. Genetic correlations estimated in bivariate analyzes were weak with values between 0.12 for PL-FL, 0.06 for PL and 0.23 for DN-FL-DN. The Spearman correlation values were low, which indicated a change in ranking in the selection of animals in different environments in the study. There was heterogeneity in the phenotypic variance among the three regions and heterogeneity in the residual variance between PL and DN. The direct genetic gain was greater for the region with a DN value gain of 198.24 g/generation, followed by FL (98.73 g/generation) and finally PL (98.73 g/generation). The indirect genetic gains were lower than 0.37 and greater than 0.02 g/generation. The evidence of the genotype x environment interaction was verified, which indicated the phenotypic heterogeneity of the variances among the three regions, weak genetic correlation and modified rankings in the different environments.

A dominant negative zebrafish Ahr2 partially protects developing zebrafish from dioxin toxicity.

Directory of Open Access Journals (Sweden)

Kevin A Lanham

Full Text Available The toxicity by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD is thought to be caused by activation of the aryl hydrocarbon receptor (AHR. However, our understanding of how AHR activation by TCDD leads to toxic effects is poor. Ideally we would like to manipulate AHR activity in specific tissues and at specific times. One route to this is expressing dominant negative AHRs (dnAHRs. This work describes the construction and characterization of dominant negative forms of the zebrafish Ahr2 in which the C-terminal transactivation domain was either removed, or replaced with the inhibitory domain from the Drosophila engrailed repressor protein. One of these dnAhr2s was selected for expression from the ubiquitously active e2fα promoter in transgenic zebrafish. We found that these transgenic zebrafish expressing dnAhr2 had reduced TCDD induction of the Ahr2 target gene cyp1a, as measured by 7-ethoxyresorufin-O-deethylase activity. Furthermore, the cardiotoxicity produced by TCDD, pericardial edema, heart malformation, and reduced blood flow, were all mitigated in the zebrafish expressing the dnAhr2. These results provide in vivo proof-of-principle results demonstrating the effectiveness of dnAHRs in manipulating AHR activity in vivo, and demonstrating that this approach can be a means for blocking TCDD toxicity.

Prevention of Infections Associated with Combat-Related Burn Injuries

Science.gov (United States)

2011-08-01

microbial flora and wound colonization in burned patients. Burns. 2004;30:357–361. 20. Barret JP, Herndron DN. Effects of burn wound excision on bacterial...Biobrane versus 1% silver sulfadiazine. Ann Emerg Med. 1990;19:121–124. 57. Barret JP, Dziewulski P, Ramzy PI, Wolf SE, Desai MH, Herndon DN

The Li-7((d)over-right-arrow, n(0))Be-8 and Li-7((d)over-right-arrow, n(1))Be-8 reactions below 160 keV

NARCIS (Netherlands)

Sabourov, A.; Ahmed, M. W.; Blackston, M. A.; Crowell, A. S.; Howell, C. R.; Joshi, K.; Nelson, S. O.; Perdue, B. A.; Sabourov, K.; Tonchev, A.; Weller, H. R.; Prior, R. M.; Spraker, M. C.; Braizinha, B.; Kalantar-Nayestanaki, N.

2006-01-01

The polarization observables have been determined for the Li-7(d,n(0))Be-8 and Li-7(d,n(1))Be-8 reactions at beam energies between 80 and 160 keV. A Transition Matrix Element (TME) analysis revealed unique, dominant p-wave solutions for both neutron channels. The polarization observables were

On conjugacy of MASAs and the outer automorphism group of the Cuntz algebra

DEFF Research Database (Denmark)

Conti, Roberto; Hong, Jeong Hee; Szymanski, Wojciech

2015-01-01

We investigate the structure of the outer automorphism group of the Cuntz algebra and the closely related problem of conjugacy of MASAs in O_n. In particular, we exhibit an uncountable family of MASAs, conugate to the standard MASA D_n via Bogolubov automorphisms, that are not inner conjugate to D_n....

78 FR 958 - Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof Notice of Receipt...

Science.gov (United States)

2013-01-07

... INTERNATIONAL TRADE COMMISSION [DN 2929] Certain Wireless Devices With 3G and/or 4G Capabilities... with 3G and/or 4G Capabilities and Components Thereof, DN 2929; the Commission is soliciting comments... importation of certain wireless devices with 3g and/or 4g capabilities and components thereof. The complaint...

Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis.

Science.gov (United States)

Ray, Jessica L; Kopec, Anna K; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H; Williams, Kurt J; Leung, Patrick S; Gershwin, M Eric; Luyendyk, James P

2017-04-01

Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL+/+ mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The structural basis of the dominant negative phenotype of the Gαi1β1γ2 G203A/A326S heterotrimer

Science.gov (United States)

Liu, Ping; Jia, Ming-zhu; Zhou, X Edward; De Waal, Parker W; Dickson, Bradley M; Liu, Bo; Hou, Li; Yin, Yan-ting; Kang, Yan-yong; Shi, Yi; Melcher, Karsten; Xu, H Eric; Jiang, Yi

2016-01-01

Aim: Dominant negative mutant G proteins have provided critical insight into the mechanisms of G protein-coupled receptor (GPCR) signaling, but the mechanisms underlying the dominant negative characteristics are not completely understood. The aim of this study was to determine the structure of the dominant negative Gαi1β1γ2 G203A/A326S complex (Gi-DN) and to reveal the structural basis of the mutation-induced phenotype of Gαi1β1γ2. Methods: The three subunits of the Gi-DN complex were co-expressed with a baculovirus expression system. The Gi-DN heterotrimer was purified, and the structure of its complex with GDP was determined through X-ray crystallography. Results: The Gi-DN heterotrimer structure revealed a dual mechanism underlying the dominant negative characteristics. The mutations weakened the hydrogen bonding network between GDP/GTP and the binding pocket residues, and increased the interactions in the Gα-Gβγ interface. Concomitantly, the Gi-DN heterotrimer adopted a conformation, in which the C-terminus of Gαi and the N-termini of both the Gβ and Gγ subunits were more similar to the GPCR-bound state compared with the wild type complex. From these structural observations, two additional mutations (T48F and D272F) were designed that completely abolish the GDP binding of the Gi-DN heterotrimer. Conclusion: Overall, the results suggest that the mutations impede guanine nucleotide binding and Gα-Gβγ protein dissociation and favor the formation of the G protein/GPCR complex, thus blocking signal propagation. In addition, the structure provides a rationale for the design of other mutations that cause dominant negative effects in the G protein, as exemplified by the T48F and D272F mutations. PMID:27498775

Response surface methodology based optimization of diesel–n-butanol –cotton oil ternary blend ratios to improve engine performance and exhaust emission characteristics

International Nuclear Information System (INIS)

Atmanlı, Alpaslan; Yüksel, Bedri; İleri, Erol; Deniz Karaoglan, A.

2015-01-01

Highlights: • RSM based optimization for optimum blend ratio of diesel fuel, n-butanol and cotton oil was done. • 65.5 vol.% diesel fuel, 23.1 vol.% n-butanol and 11.4 vol.% cotton oil (DnBC) was determined. • DnBC decreased brake torque, brake power, BTE and BMEP, while increased BSFC. • DnBC decreased NO x , CO and HC emissions. - Abstract: Many studies declare that 20% biodiesel is the optimum concentration for biodiesel–diesel fuel blends to improve performance. The present work focuses on finding diesel fuel, n-butanol, and cotton oil optimum blend ratios for diesel engine applications by using the response surface method (RSM). Experimental test fuels were prepared by choosing 7 different concentrations, where phase decomposition did not occur in the phase diagram of −10 °C. Experiments were carried out at full load conditions and the constant speed (2200 rpm) of maximum brake torque to determine engine performance and emission parameters. According to the test results of the engine, optimization was done by using RSM considering engine performance and exhaust emissions parameters, to identify the rates of concentrations of components in the optimum blend of three. Confirmation tests were employed to compare the output values of concentrations that were identified by optimization. The real experiment results and the R 2 actual values that show the relation between the outputs from the optimizations and real experiments were determined in high accordance. The optimum component concentration was determined as 65.5 vol.% diesel, 23.1 vol.% n-butanol and 11.4 vol.% cotton oil (DnBC). According to engine performance tests brake torque, brake power, BTE and BMEP of DnBC decreased while BSFC increased compared to those of diesel fuel. NO x , CO and HC emissions of DnBC drastically decreased as 11.33%, 45.17% and 81.45%, respectively

Inhibition of Thrombopoietin/Mpl Signaling in Adult Hematopoiesis Identifies New Candidates for Hematopoietic Stem Cell Maintenance.

Science.gov (United States)

Kohlscheen, Saskia; Wintterle, Sabine; Schwarzer, Adrian; Kamp, Christel; Brugman, Martijn H; Breuer, Daniel C; Büsche, Guntram; Baum, Christopher; Modlich, Ute

2015-01-01

Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl-signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl). The transplantation of bone marrow cells retrovirally transduced to express dnMpl into wildtype mice induced thrombocytopenia, and a progressive loss of HSC. The aplastic BM allowed the engraftment of a second BM transplant without further conditioning. Functional analysis of the truncated Mpl in vitro and in vivo demonstrated no internalization after Thpo binding and the inhibition of Thpo/Mpl-signaling in wildtype cells due to dominant-negative (dn) effects by receptor competition with wildtype Mpl for Thpo binding. Intracellular inhibition of Mpl could be excluded as the major mechanism by the use of a constitutive-dimerized dnMpl. To further elucidate the molecular changes induced by Thpo/Mpl-inhibition on the HSC-enriched cell population in the BM, we performed gene expression analysis of Lin-Sca1+cKit+ (LSK) cells isolated from mice transplanted with dnMpl transduced BM cells. The gene expression profile supported the exhaustion of HSC due to increased cell cycle progression and identified new and known downstream effectors of Thpo/Mpl-signaling in HSC (namely TIE2, ESAM1 and EPCR detected on the HSC-enriched LSK cell population). We further compared gene expression profiles in LSK cells of dnMpl mice with human CD34+ cells of aplastic anemia patients and identified similar deregulations of important stemness genes in both cell populations. In summary, we established a novel way of Thpo/Mpl inhibition in the adult mouse and performed in depth analysis of the phenotype including gene expression profiling.

TREATMENT OF SUBACUTE POSTERIOR KNEE PAIN IN AN ADOLESCENT BALLET DANCER UTILIZING TRIGGER POINT DRY NEEDLING: A CASE REPORT

Science.gov (United States)

Tansey, Kimberly A.; Westrick, Richard B.

2014-01-01

Study Design: Case Report. Background and Purpose: Dry needling (DN) is an increasingly popular intervention used by clinicians as a treatment of regional neuromusculoskeletal pain. DN is an invasive procedure that involves insertion of a thin monofilament needle directly into a muscle trigger point (MTP) with the intent of stimulating a local twitch response. Current evidence is somewhat limited, but recent literature supports the use of this intervention in specific neuromusculoskeletal conditions. The purpose of this case report is to present the outcomes of DN as a primary treatment intervention in an adolescent subject with subacute posterior knee pain. Case Description: The subject was a 16‐year‐old female competitive ballet dancer referred to physical therapy with a two month history of right posterior knee pain. Palpation identified MTPs which reproduced the patient’s primary symptoms. In addition to an exercise program promoting lower extremity flexibility and hip stability, the subject was treated with DN to the right gastrocnemius, soleus, and popliteus muscles. Outcomes: The subject reported being pain free on the Numerical Pain Scale and a +7 improvement in perceived change in recovery on the Global Rating of Change at final follow‐up. Physical examination demonstrated no observed impairments or functional limitations, including normal mobility, full strength, and unrestricted execution of dance maneuvers. Discussion: The patient was able to return to high level dance training and competition without physical limitations and resumed pre‐injury dynamic movement activities including dancing, running, jumping, and pivoting without pain. DN can be an effective and efficient intervention to assist patients in decreasing pain and returning to high intensity physical activity. Additional research is needed to determine if DN is effective for other body regions and has long‐term positive outcomes. Level of Evidence: Level 4 PMID:24567862

RasGRP1, but not RasGRP3, is required for efficient thymic β-selection and ERK activation downstream of CXCR4.

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Dominic P Golec

Full Text Available T cell development is a highly dynamic process that is driven by interactions between developing thymocytes and the thymic microenvironment. Upon entering the thymus, the earliest thymic progenitors, called CD4(-CD8(- 'double negative' (DN thymocytes, pass through a checkpoint termed "β-selection" before maturing into CD4(+CD8(+ 'double positive' (DP thymocytes. β-selection is an important developmental checkpoint during thymopoiesis where developing DN thymocytes that successfully express the pre-T cell receptor (TCR undergo extensive proliferation and differentiation towards the DP stage. Signals transduced through the pre-TCR, chemokine receptor CXCR4 and Notch are thought to drive β-selection. Additionally, it has long been known that ERK is activated during β-selection; however the pathways regulating ERK activation remain unknown. Here, we performed a detailed analysis of the β-selection events in mice lacking RasGRP1, RasGRP3 and RasGRP1 and 3. We report that RasGRP1 KO and RasGRP1/3 DKO deficient thymi show a partial developmental block at the early DN3 stage of development. Furthermore, DN3 thymocytes from RasGRP1 and RasGRP1/3 double knock-out thymi show significantly reduced proliferation, despite expression of the TCRβ chain. As a result of impaired β-selection, the pool of TCRβ(+ DN4 is significantly diminished, resulting in inefficient DN to DP development. Also, we report that RasGRP1 is required for ERK activation downstream of CXCR4 signaling, which we hypothesize represents a potential mechanism of RasGRP1 regulation of β-selection. Our results demonstrate that RasGRP1 is an important regulator of proliferation and differentiation at the β-selection checkpoint and functions downstream of CXCR4 to activate the Ras/MAPK pathway.

The requirement for pre-TCR during thymic differentiation enforces a developmental pause that is essential for V-DJβ rearrangement.

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Karen S Hathcock

Full Text Available T cell development occurs in the thymus and is critically dependent on productive TCRβ rearrangement and pre-TCR expression in DN3 cells. The requirement for pre-TCR expression results in the arrest of thymocytes at the DN3 stage (β checkpoint, which is uniquely permissive for V-DJβ recombination; only cells expressing pre-TCR survive and develop beyond the DN3 stage. In addition, the requirement for TCRβ rearrangement and pre-TCR expression enforces suppression of TCRβ rearrangement on a second allele, allelic exclusion, thus ensuring that each T cell expresses only a single TCRβ product. However, it is not known whether pre-TCR expression is essential for allelic exclusion or alternatively if allelic exclusion is enforced by developmental changes that can occur in the absence of pre-TCR. We asked if thymocytes that were differentiated without pre-TCR expression, and therefore without pause at the β checkpoint, would suppress all V-DJβ rearrangement. We previously reported that premature CD28 signaling in murine CD4(-CD8(- (DN thymocytes supports differentiation of CD4(+CD8(+ (DP cells in the absence of pre-TCR expression. The present study uses this model to define requirements for TCRβ rearrangement and allelic exclusion. We demonstrate that if cells exit the DN3 developmental stage before TCRβ rearrangement occurs, V-DJβ rearrangement never occurs, even in DP cells that are permissive for D-Jβ and TCRα rearrangement. These results demonstrate that pre-TCR expression is not essential for thymic differentiation to DP cells or for V-DJβ suppression. However, the requirement for pre-TCR signals and the exclusion of alternative stimuli such as CD28 enforce a developmental "pause" in early DN3 cells that is essential for productive TCRβ rearrangement to occur.

Improved elucidation of biological processes linked to diabetic nephropathy by single probe-based microarray data analysis.

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Clemens D Cohen

Full Text Available BACKGROUND: Diabetic nephropathy (DN is a complex and chronic metabolic disease that evolves into a progressive fibrosing renal disorder. Effective transcriptomic profiling of slowly evolving disease processes such as DN can be problematic. The changes that occur are often subtle and can escape detection by conventional oligonucleotide DNA array analyses. METHODOLOGY/PRINCIPAL FINDINGS: We examined microdissected human renal tissue with or without DN using Affymetrix oligonucleotide microarrays (HG-U133A by standard Robust Multi-array Analysis (RMA. Subsequent gene ontology analysis by Database for Annotation, Visualization and Integrated Discovery (DAVID showed limited detection of biological processes previously identified as central mechanisms in the development of DN (e.g. inflammation and angiogenesis. This apparent lack of sensitivity may be associated with the gene-oriented averaging of oligonucleotide probe signals, as this includes signals from cross-hybridizing probes and gene annotation that is based on out of date genomic data. We then examined the same CEL file data using a different methodology to determine how well it could correlate transcriptomic data with observed biology. ChipInspector (CI is based on single probe analysis and de novo gene annotation that bypasses probe set definitions. Both methods, RMA and CI, used at default settings yielded comparable numbers of differentially regulated genes. However, when verified by RT-PCR, the single probe based analysis demonstrated reduced background noise with enhanced sensitivity and fewer false positives. CONCLUSIONS/SIGNIFICANCE: Using a single probe based analysis approach with de novo gene annotation allowed an improved representation of the biological processes linked to the development and progression of DN. The improved analysis was exemplified by the detection of Wnt signaling pathway activation in DN, a process not previously reported to be involved in this disease.

Journal of Earth System Science | Indian Academy of Sciences

Indian Academy of Sciences (India)

The reflectances of different sediments are represented in digital format by different DN values from 0 –255 within the radiometric ranges of '8 bit 'data. Density slicing has been chosen as the method of microstructure mapping in this research.This study shows that lower DN values normally present dark coloured coarser ...

The Hilbert-Schmidt method in the three-particle problem and determination of the vertex parts tdn and td*n

International Nuclear Information System (INIS)

Baryshnikov, A.G.; Blokhintsev, L.D.; Narodetsky, I.M.

1974-01-01

Vertex constants for virtual decays t → dn and t → d*n are calculated using the resonance expansion technique for the three-particle amplitude suggested recently. In the model with a spin-dependent separable NN-potential values Gsub(tdn)sup(2) = 1.92 fm, Gsub(td*n)sup(2) = -0.38 fm are obtained

Variation in Primary Radioclimatic Variables, And Its Effects on ...

African Journals Online (AJOL)

The result shows that refractive index decrease with an increase in height and thus, refractivity gradient also decrease from normal – 40 dN / Kilo meter to – 127 dN / Kilo meter for eleven months, thereby resulting to super- refraction propagation condition, while in one month the refractivity gradient increases from normal ...

Regulatory role of neuron-restrictive silencing factor in expression of TRPC1

International Nuclear Information System (INIS)

Ohba, Takayoshi; Watanabe, Hiroyuki; Takahashi, Yoichiro; Suzuki, Takashi; Miyoshi, Ichiro; Nakayama, Shinnsuke; Satoh, Eisaku; Iino, Kenji; Sasano, Hironobu; Mori, Yasuo; Kuromitsu, Sadao; Imagawa, Keiichi; Saito, Yoshihiko; Iijima, Toshihiko; Ito, Hiroshi; Murakami, Manabu

2006-01-01

Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca 2+ channel (SOCC)-mediated Ca 2+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT activation. Our findings strongly suggest that NRSF regulates TRP1 gene expression and causes changes in the levels of calcium entry through SOCCs

Climate variability and extremes, interacting with nitrogen storage, amplify eutrophication risk

Science.gov (United States)

Lee, Minjin; Shevliakova, Elena; Malyshev, Sergey; Milly, P.C.D.; Jaffe, Peter R.

2016-01-01

Despite 30 years of basin-wide nutrient-reduction efforts, severe hypoxia continues to be observed in the Chesapeake Bay. Here we demonstrate the critical influence of climate variability, interacting with accumulated nitrogen (N) over multidecades, on Susquehanna River dissolved nitrogen (DN) loads, known precursors of the hypoxia in the Bay. We used the process model LM3-TAN (Terrestrial and Aquatic Nitrogen), which is capable of capturing both seasonal and decadal-to-century changes in vegetation-soil-river N storage, and produced nine scenarios of DN-load distributions under different short-term scenarios of climate variability and extremes. We illustrate that after 1 to 3 yearlong dry spells, the likelihood of exceeding a threshold DN load (56 kt yr−1) increases by 40 to 65% due to flushing of N accumulated throughout the dry spells and altered microbial processes. Our analyses suggest that possible future increases in climate variability/extremes—specifically, high precipitation occurring after multiyear dry spells—could likely lead to high DN-load anomalies and hypoxia.

The Phoenix TECP Relative Humidity Sensor: Revised Results

Science.gov (United States)

Zent, Aaron

2014-01-01

The original calibration function of the RH sensor on the Phoenix mission's Thermal and Electrical Conductivity Sensor (TECP), has been revised to correct the erroneously-published original calibration equation, to demonstrate the value of this unique data set, and to improve characterization of H2O exchange between the martian regolith and atmosphere. TECP returned two data streams, the temperature of the electronics analog board (Tb) and the digital 12-bit output of the RH sensor (DN), both of which are required to uniquely specify the H2O abundance. Because the original flight instrument calibration was performed against a pair of hygrometers that measured frost point (Tf), the revised calibration equation is also cast in terms of frost point. The choice of functional form for the calibration function is minimally constrained. A series of profiles across the calibration data cloud at constant DN and Tb does not reveal any evidence of a complex functional form. Therefore, a series of polynomials in both DN and Tb was investigated, along with several non-linear functions of DN and Tb.

A pilot study on genetic variation in purine-rich elements in the nephrin gene promoter in type 2 diabetic patients

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RODRIGO GONZÁLEZ

2007-01-01

Full Text Available Diabetic nephropathy (DN is one of the major complications of type 2 diabetes and is associated with coronary disease. Nephrin, a protein mainly expressed in glomeruli, is decreased in DN and other kidney diseases. Since insulin levels are misregulated in type 2 diabetes, a possible connection between DN and its decreased nephrin expression could be the presence of regulatory elements responsive to insulin in the nephrin gene (NPHS1 promoter region. In this work, using bioinformatic tools, we identified a purine-rich GAGA element in the nephrin gene promoter and conducted a genomic study in search of the presence of polymorphisms in this element and its possible association with DN in type 2 diabetic patients. We amplified and sequenced a 514 bp promoter region of 100 individuals and found no genetic variants in the purine-rich GAGA-box of the nephrin gene promoter between groups of patients with diabetes type 2 with and without renal and coronary complications, control patients without diabetes and healthy controls

Effect of homocysteinemia on the development of diabetic nephro- and retinopathy in adolescents

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Zh V Shutskaya

2009-03-01

Full Text Available Aim. To consider homocysteinemia in children and adolescents with diabetes mellitus (DM1 as an independent risk factor of diabetic nephro- and retinopathy (DN and DR. Materials and methods. Twenty nine adolescents (19 girls and 10 boys with DM1 were examined. DN and DR were diagnosed in conformity with medical aid standards for DM1patients. Plasma homocysteine level was measured by IEA. Results. Plasma homocysteine level in DN patients was higher (6.4?1.6, n=10 than in DR group (5.3?1.7, n=9 and controls (5.6?1.8, n=10. Patients of all study groups werecomparable in terms of age, DM duration, and HbA1c level. Conclusion. Plasma homocysteine level in DN patients was higher than in DR and control groups. It gives reason to consider this parameter as an independent risk factor alongwith some others in pathogenesis of diabetic microangiopathies (in the first place, nephropathy. Adolescents with DM1 and elevated plasma homocysteine level need additionalcorrection by specific medicines.

Long-range ordering of III-V semiconductor nanostructures by shallowly buried dislocation networks

International Nuclear Information System (INIS)

Coelho, J; Patriarche, G; Glas, F; Saint-Girons, G; Sagnes, I

2004-01-01

We account for lateral orderings of III-V nanostructures resulting from a GaAs/InAs/InGaAs/GaAs sequence grown on GaAs by metallorganic vapour phase epitaxy at two different temperatures. For both samples, the ordering is induced by the stress field of a periodic dislocation network (DN) shallowly buried and parallel to the surface. This DN is a grain boundary (GB) that forms, between a thin GaAs layer (on which growth was performed) and a GaAs substrate joined together by wafer bonding, in order to accommodate a tilt and a twist between these two crystals; both these misorientations are imposed in a controlled manner. This GB is composed of a one-dimensional network of mixed dislocations and of a one-dimensional network of screw dislocations. For both samples, the nanostructures observed by transmission electron microscopy (TEM) and atomic force microscopy are ordered by the underlying DN observed by TEM since they have same dimensions and orientations as the cells of the DN

Electroluminescent properties of an electrochemically cross-linkable carbazole peripheral poly(benzyl ether) dendrimer.

Science.gov (United States)

Park, Jin Young; Kim, Dong-Eun; Ponnapati, Ramakrishna; Kim, Jong-Min; Kwon, Young-Soo; Advincula, Rigoberto C

2011-04-04

The electroluminescent (EL) properties of a cross-linkable carbazole-terminated poly(benzyl ether) dendrimer, G(3)-cbz DN, doped into a PVK:PBD host matrix with a double-layer device configuration are investigated. Different concentrations of the guest material can control device efficiency, related to chromaticity of white emission and the origin of excited-state complexes occurring between hole-transporting carbazole units (PVK or G(3)-cbz DN) and electron-transporting oxadiazole (PBD). Two excited states (exciplex and electroplex) generated at the interfaces of PVK/G(3)-cbz DN and PBD result in competitive emission, exhibiting a broad band in the EL spectra. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Uncovering the roots of paranoid suicidal plants

DEFF Research Database (Denmark)

Lolle, Signe

is that forms of plant autoimmunity are due to inappropriate NLR activation. We show here that NLR triggered immunity in pat1 can be prevented by the expression of a dominant negative (DN) allele of the NLR SUMM2. We further find that this DN approach is faster than crossing in knock-outs, and has the advantage...

Cardiovascular alcification in diabetic nephropathy patients in uremic stage and analysis on its risk factors

International Nuclear Information System (INIS)

Xue Yang; Lin Shan; Jia Junya; Yan Tiekun

2010-01-01

Objective: To investigate the prevalence of arterial vascular calcification (VC) in uremic patients undergoing diabetic nephropathy (DN) and explore its risk factors. Methods: Demographic and clinical data were collected in the patients latest diagnosed as uremia and not received dialysis treatment. The uremic patients were divided into DN group and non-diabetic nephropathy (NDN) group. And 20 healthy subjects were chosen as control group from the Physical Examination Room. The patients'sex and ages were similar in the 3 groups. VC was semi-quantitatively evaluated by plain radiographic films from abdomen, pelvis and hands. The clinical and laboratorial parameters related to VC were detected and analyzed. Results: 1)The present study included 20 (51.28%) DN uremic patients and 19 (48.72%) NDN uremic patients. The average diabetic duration in the DN patients was (8.11 ± 7.39) years. 2)Among the 39 uremic patients, VC was found on radiographic films in 29 cases (74.36%), including 23 cases (58.97%) with the con-score 1-3 and 6 cases (15.38%) with 3-6 scores. And VC was not detected in control group. Bone density analysis showed that osteopenia occupied 14 cases (35.90%) in all and the T-score was-0.81 ± 0.87. 3)Linear correlation analysis revealed that VC was correlated with serum calcium and phosphate (r=0.026, P 0.05). VC score was significantly correlated with the diabetic duration (r=0.790, P<0.001). Logistic regression revealed that the diabetes duration was the independent risk factors (P<0.05) for VC. The reflections of serum calcium and phosphate were rejected. 4)The prevalence of VC in DN group (95.0%) was higher than that in NDN group (42.1%, P<0.05). And the VC score in DN group(3.18 ± 1.77) was higher than that in NDN group (1.56 ± 0.97, P<0.05). Conclusion: There is a higher VC prevalence rate and more VC severity in DN uremic patients than in NDN patients. Diabetes duration is an independent risk factor for VC. Preventing from the high serum glucose

Early diagnostic predictors: useful in treatment and progression of diabetes associated nephropathy

International Nuclear Information System (INIS)

Nawab, S.N.; Shahid, S.M.; Azhar, A.; Ahmed, N.

2013-01-01

Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes mellitus (T2DM) characterized by frequent microalbuminuria, elevated arterial blood pressure, persistent decline in glomerular filtration rate and high risk of morbidity and mortality. It encompasses long-term duration of diabetes, which has an effect on the minute blood vessels of kidney. The biochemical parameters play a key role in the prediction of nephropathy in T2DM patients. Therefore, the present study was conducted to investigate the role of biochemical markers in the prediction of DN in T2DM patients. The aim of this study was addressed in case-control setting, 230 T2DM, 200 DN patients and 110 non diabetic healthy individuals were included in order to assess the biochemical parameters and risk of DN. Patients were recruited according to WHO's criteria from various hospitals of Karachi, Pakistan. After getting informed consent from patients and control subjects, clinical data was recorded. Five hundred and forty (n=540) samples were studied for their serum blood glucose, blood pressure, glycosylated hemoglobin (HbAlc), serum creatinine, serum urea, lipid profile and urinary albumin levels. The analysis showed that incidence and the progression of the DN increased with hyperglycemia, longer duration of diabetes, dyslipidemia, elevated level of serum urea, creatinine and urinary albumin levels in patients with T2DM. Therefore, these biochemical predictors can anticipate the occurrence of nephropathy in later stages of diabetes. (author)

Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus.

Science.gov (United States)

Marques, T; Patente, T A; Monteiro, M B; Cavaleiro, A M; Queiroz, M S; Nery, M; de Azevedo, M J; Canani, L H; Parisi, M C; Moura-Neto, A; Passarelli, M; Giannella-Neto, D; Machado, U F; Corrêa-Giannella, M L

2015-04-15

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 ± 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 - 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control. Copyright © 2015 Elsevier B.V. All rights reserved.

Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

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Keisuke Ishizawa

Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

Variation of Particle Control with Changes in Divertor Geometry

International Nuclear Information System (INIS)

Petrie, T W; Allen, S L; Brooks, N H; Fenstermacher, M E; Ferron, J R; Greenfield, C M; Groth, M; Hyatt, A W; Leonard, A W; Luce, T C; Mahdavi, M A; Murakami, M; Porter, G D; Rensink, M E; Schaffer, M J; Wade, M R; Watkins, J G; West, W P; Wolf, N S

2004-01-01

Recent experiments on DIII-D point to the importance of two factors in determining how effectively the deuterium particle inventory in a tokamak plasma can be controlled through pumping at the divertor target(s): (1) the divertor magnetic balance, i.e., the degree to which the divertor topology is single-null (SN) or double-null (DN), and (2) the direction of the of Bx(divergent)B ion drift with respect to the X-point(s). Changes in divertor magnetic balance near the DN shape have a much stronger effect on the particle exhaust rate at the inner divertor target(s) than on the particle exhaust rate at the outer divertor target(s). The particle exhaust rate for the DN shape is strongest at the outer strike point opposite the Bx(divergent)B ion particle drift direction. Our data suggests that the presence of Bx(divergent)B and ExB ion particle drifts in the scrapeoff layer (SOL) and divertors play an important role in the particle exhaust rates of DN and near-DN plasmas. Particle exhaust rates are shown to depend strongly on the edge (pedestal) density n e,PED . In the lower range of densities considered in this study, i.e., n e,PED / n GREENWALD <0.4, particle exhaust rates are also found to be approximately proportional to the deuterium recycling intensity in front of the respective plenum entrance. Our results are shown to have implications for particle control in ITER and other future tokamaks

Variation of particle control with changes in divertor geometry

International Nuclear Information System (INIS)

Petrie, T.W.; Allen, S.L.; Brooks, N.H.; Fenstermacher, M.E.; Groth, M.; Porter, G.D.; Rensink, M.E.; Wolf, N.S.; Ferron, J.R.; Greenfield, C.M.; Hyatt, A.W.; Leonard, A.W.; Luce, T.C.; Mahdavi, M.A.; Schaffer, M.J.; West, W.P.; Murakami, M.; Wade, M.R.; Watkins, J.G.

2005-01-01

Recent experiments on DIII-D point to the importance of two factors in determining how effectively the deuterium particle inventory in a tokamak plasma can be controlled through pumping at the divertor target(s): (1) the divertor magnetic balance, i.e., the degree to which the divertor topology is single-null (SN) or double-null (DN), and (2) the direction of the of Bx∇B ion drift with respect to the X-point(s). Changes in divertor magnetic balance near the DN shape have a much stronger effect on the particle exhaust rate at the inner divertor target(s) than on the particle exhaust rate at the outer divertor target(s). The particle exhaust rate for the DN shape is strongest at the outer strike point opposite the Bx∇B ion particle drift direction. Our data suggests that the presence of Bx∇B and ExB ion particle drifts in the scrapeoff layer (SOL) and divertors play an important role in the particle exhaust rates of DN and near-DN plasmas. Particle exhaust rates are shown to depend strongly on the edge (pedestal) density n e,PED . In the lower range of densities considered in this study, i.e., n e,PED /n GREENWALD <0.4, particle exhaust rates are also found to be approximately proportional to the deuterium recycling intensity in front of the respective plenum entrance. Our results are shown to have implications for particle control in ITER and other future tokamaks. (author)

Comparison of renal function following donor nephrectomy versus radical nephrectomy for renal tumor

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Mohamed Etafy

2015-01-01

Full Text Available In this study, we compared renal function in patients after donor nephrectomy (DN and radical nephrectomy (RN. We retrospectively reviewed 68 patients (mean follow-up 15 months, including 30 patients who had undergone DN and 38 patients who had undergone RN. The study was performed between April 2006 and July 2010 at a single institute. Patients were matched for age and co-morbidities (hypertension and diabetes mellitus. We calculated the estimated glomerular filtration rate (eGFR using the Modification of Diet in Renal Disease study group equation. Parameters studied included GFR (≥60 to 2.0 mg/dL, metabolic acidosis (serum bicarbonate 30 mg. There were no significant demographic differences between the two study groups. After a mean follow-up of 15 months, low eGFR (<60 mL/min/1.73 m 2 was seen in 28% and 6.7% of patients in the RN and DN groups, respectively (P = 0.03. Similarly, proteinuria was seen in 21% vs 0%, P = 0.007, and de novo elevated creatinine was seen in 13% vs 0%, respectively P = 0.04; thus the changes were greater in the RN group. Our study shows that undergoing RN had a significantly greater risk of developing renal insufficiency and proteinuria compared with age-and co-morbidity-matched patients undergoing DN. We concluded that patients undergoing RN show a significantly greater risk of developing renal insufficiency and proteinuria compared with the patients undergoing DN.

H-mode transition physics close to double null on MAST and its applications to other tokamaks

International Nuclear Information System (INIS)

Meyer, H.; Carolan, P.G.; Cunningham, G.; Kirk, A.; Lloyd, B.; Saarelma, S.; Wilson, H.R.; Conway, G.D.; Horton, L.D.; Ryter, F.; Schirmer, J.; Suttrop, W.; Maingi, R.

2005-01-01

By accessing extreme parameter regimes combined with well diagnosed edge MAST data contribute towards the understanding of H-mode physics. The first inter-machine comparisons with respect to the influence of the magnetic topology on the power threshold with ASDEX Upgrade and NSTX reveal a reduction of the power threshold in true double null (C-DN) configuration opening new operation regimes in both devices. In L-mode, the negative radial electric field close to the separatrix was found to be more negative in C-DN than in single null (SN), whilst most of the other edge parameters are similar. Pedestal temperatures in MAST are lower than in ASDEX Upgrade in MAST-equivalent discharges, whereas the pedestal densities can be similar, although in long inter ELM periods the MAST density pedestal is higher than on ASDEX Upgrade. In order to test four leading H-mode theories MAST data are compared statistically to their H-mode access criteria. The usual DN operating regime with co current NBI in MAST has been extended to include single null (SN) configurations, to provide more direct comparisons with conventional tokamaks. The plasma edge in SN on MAST is more stable to ELMs and the typical type-III ELMs, often observed in C-DN, are absent, despite input powers close to the H-mode threshold power. In this respect, the stability of measured plasma edge profiles in SN and DN against ideal peeling-ballooning modes will be discussed. (author)

Improving the reversibility of thermal denaturation and catalytic efficiency of Bacillus licheniformis α-amylase through stabilizing a long loop in domain B.

Directory of Open Access Journals (Sweden)

Zhu Li

Full Text Available The reversibility of thermal denaturation and catalytic efficiency of Bacillus licheniformis α-amylase were improved through site-directed mutagenesis. By using multiple sequence alignment and PoPMuSiC algorithm, Ser187 and Asn188, which located within a long loop in Domain B of Bacillus licheniformis α-amylase, were selected for mutation. In addition, Ala269, which is adjacent to Ser187 and Asn188, was also investigated. Seven mutants carrying the mutations S187D, N188T, N188S, A269K, A269K/S187D, S187D/N188T, and A269K/S187D/N188T were generated and characterized. The most thermostable mutant, A269K/S187D/N188T, exhibited a 9-fold improvement in half-life at 95°C and pH 5.5, compared with that of the wild-type enzyme. Mutant A269K/S187D/N188T also exhibited improved catalytic efficiency. The catalytic efficiency of mutant A269K/S187D/N188T reached 5.87×103±0.17 g·L-1·s-1 at pH 5.5, which is 1.84-fold larger than the corresponding value determined for the wild-type enzyme. Furthermore, the structure analysis showed that immobilization of the loop containing Ser187 and Asn188 plays a significant role in developing the properties of Bacillus licheniformis α-amylase.

Improving the reversibility of thermal denaturation and catalytic efficiency of Bacillus licheniformis α-amylase through stabilizing a long loop in domain B.

Science.gov (United States)

Li, Zhu; Duan, Xuguo; Chen, Sheng; Wu, Jing

2017-01-01

The reversibility of thermal denaturation and catalytic efficiency of Bacillus licheniformis α-amylase were improved through site-directed mutagenesis. By using multiple sequence alignment and PoPMuSiC algorithm, Ser187 and Asn188, which located within a long loop in Domain B of Bacillus licheniformis α-amylase, were selected for mutation. In addition, Ala269, which is adjacent to Ser187 and Asn188, was also investigated. Seven mutants carrying the mutations S187D, N188T, N188S, A269K, A269K/S187D, S187D/N188T, and A269K/S187D/N188T were generated and characterized. The most thermostable mutant, A269K/S187D/N188T, exhibited a 9-fold improvement in half-life at 95°C and pH 5.5, compared with that of the wild-type enzyme. Mutant A269K/S187D/N188T also exhibited improved catalytic efficiency. The catalytic efficiency of mutant A269K/S187D/N188T reached 5.87×103±0.17 g·L-1·s-1 at pH 5.5, which is 1.84-fold larger than the corresponding value determined for the wild-type enzyme. Furthermore, the structure analysis showed that immobilization of the loop containing Ser187 and Asn188 plays a significant role in developing the properties of Bacillus licheniformis α-amylase.

Social Norm, Family Communication, and HBV Screening among Asian Americans.

Science.gov (United States)

Juon, Hee-Soon; Rimal, Rajiv N; Klassen, Ann; Lee, Sunmin

2017-12-01

Individuals' behaviors are influenced by those of others in their social environment (i.e., descriptive norms), as well as by how individuals perceive they should behave in that environment (e.g., injunctive norms). Although social norms are thought to play an important role in hepatitis B virus (HBV) screening, limited theoretical or empirical guidance exists on how the underlying process works. In addition, norms are social phenomena that are spread through family discussion about the importance of getting HBV screening. Using the theory of normative social behavior (TNSB), this study examined the roles of injunctive norms (IN), descriptive norms (DN), and family discussion in HBV screening behavior among Asian Americans. Data from a survey of Asian Americans in the Baltimore Washington metropolitan area (N = 877) were used to test underlying theoretical propositions. DN and family discussion emerged as key factors in HBV screening behavior among all Asian Americans. IN were associated with HBV screening among Chinese and Korean Americans, but not for Vietnamese Americans. Family discussion moderated the influence of DN on behavior among Chinese and Vietnamese Americans. However, the main effect of DN on screening behavior was not modified by IN (no interactions between DN and IN). The results indicate that family discussion and social norms are integral in enabling Asian Americans to undergo HBV screening and warrant sensitivity in the design and implementation of a liver cancer prevention program in this high-risk group of Asian Americans.

Early diagnostic predictors: useful in treatment and progression of diabetes associated nephropathy

Energy Technology Data Exchange (ETDEWEB)

Nawab, S. N.; Shahid, S. M.; Azhar, A. [University of Karachi, Karachi (Pakistan). Dept. of Biotechnology and Genetic Engineering; Ahmed, N. [University of Karachi, Karachi (Pakistan). Dept. of Biochemistry

2013-06-15

Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes mellitus (T2DM) characterized by frequent microalbuminuria, elevated arterial blood pressure, persistent decline in glomerular filtration rate and high risk of morbidity and mortality. It encompasses long-term duration of diabetes, which has an effect on the minute blood vessels of kidney. The biochemical parameters play a key role in the prediction of nephropathy in T2DM patients. Therefore, the present study was conducted to investigate the role of biochemical markers in the prediction of DN in T2DM patients. The aim of this study was addressed in case-control setting, 230 T2DM, 200 DN patients and 110 non diabetic healthy individuals were included in order to assess the biochemical parameters and risk of DN. Patients were recruited according to WHO's criteria from various hospitals of Karachi, Pakistan. After getting informed consent from patients and control subjects, clinical data was recorded. Five hundred and forty (n=540) samples were studied for their serum blood glucose, blood pressure, glycosylated hemoglobin (HbAlc), serum creatinine, serum urea, lipid profile and urinary albumin levels. The analysis showed that incidence and the progression of the DN increased with hyperglycemia, longer duration of diabetes, dyslipidemia, elevated level of serum urea, creatinine and urinary albumin levels in patients with T2DM. Therefore, these biochemical predictors can anticipate the occurrence of nephropathy in later stages of diabetes. (author)

Thermal Injury in Human Subjects Due to 94-GHz Radio Frequency Radiation Exposures

Science.gov (United States)

2016-02-24

1161902612 Digitally signed by JOHNSON.LELAND.R.1161902612 DN: c=US, o=U.S. Government, ou=DoD, ou= PKI , ou=USAF, cn=JOHNSON.LELAND.R.1161902612 Date...2016.03.07 15:07:11 -06󈧄’ POLHAMUS.GARR ETT.D.1175839484 Digitally signed by POLHAMUS.GARRETT.D.1175839484 DN: c=US, o=U.S. Government, ou=DoD, ou= PKI

Adhoc Wireless Network Control: Energy Efficiency and Hidden Terminal Considerations

Science.gov (United States)

2009-12-01

Pnl (t) +Bn(t), Emax ) , (57) Ynl(t+ 1) = [Ynl(t)−Rnl,in(t)] + + γnl(t), (58) Dn(t+ 1) = [Dn(t...1− δ)Bn(t)] + + ∑ l∈On Pnl (t), (59) subject to constraints Rnl,in(t) ≤ Vnl(t) +Anl(t) ∀n, l, t, P (t) ∈ PS(t), ∑ l∈On Pnl (t) ≤ min ( En(t), P̂ ) ∀n...γnl(t)] ∣ ∣ ∣ ∣ ∣ ∣ X(t)   − 2E   ∑ n,l [Unl(t)µnl (S(t),P (t))−Dn(t) Pnl (t)] ∣ ∣ ∣ ∣ ∣ ∣ X(t)  − 2E   ∑ n,l [ηYnl(t)−

Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients

DEFF Research Database (Denmark)

Fagerudd, J A; Tarnow, L; Jacobsen, P

1998-01-01

Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension among parents of 73 IDDM patients with diabetic nephropathy (DN......+; persistent albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without diabetic nephropathy (DN-; urinary albumin excretion hypertension, defined as antihypertensive therapy or a 24-h ambulatory blood pressure (SpaceLabs 90207) > or = 135/85 mm...... for hypertension than were patients with DN+ and without parental treatment for hypertension (100 vs. 61%; P = 0.034; difference 39% [21-57%]). In conclusion, familial predisposition to essential hypertension increases the risk of diabetic nephropathy and may also contribute to the development of systemic...

Behaviour of enzymatic activities and root elongation in Argiudoll soils from the Argentine Humid Pampa treated with biosolids Comportamiento de actividades enzimáticas y elongación de raíces en suelos Argiudoles de la Pampa Húmeda, Argentina, tratados con biosólidos

Directory of Open Access Journals (Sweden)

E.B.R. Perotti

2008-06-01

Full Text Available The incorporation of biosolids to soil is a strategy aiming at the re-location of these materials in the environment with a useful end: soil fertilization. In this work, the response of two Argiudoll soils (one with more than 100 years of agriculture and the other, a virgin one to biosolid incorporation was studied under laboratory conditions. To measure this response, soil enzymatic biodescriptors, such as dehydrogenase and urease activities, and tests related to plant physiology (the root elongation test were employed. The addition of the biosolid to both soils had a stimulating effect though different on each soil according to the added dose. Adjustment of the regression line for dehydrogenase activity with root elongation was positive and statistically significant (pLa incorporación de biosólidos al suelo es una estrategia que tiene como objetivo la reubicación de estos materiales en el ambiente con un fin útil, como es la fertilización del suelo. En este trabajo se estudió, en condiciones controladas de laboratorio, la respuesta de dos suelos Argiudoles (uno con más de 100 años de agricultura y otro virgen frente a la perturbación físico-química y biótica que genera la incorporación de un biosólido. Para medir esta respuesta se emplearon dos biodescriptores edáficos (las actividades deshidrogenasa y ureasa y un tercero referido a la fisiología vegetal, la prueba de elongación de raíces. La incorporación del biosólido en ambos suelos, en general no deprimió el funcionamiento de las actividades enzimáticas estudiadas; contrariamente, según la dosis aportada tuvo un efecto estimulante, aunque diferente, entre ambos suelos. El ajuste de la recta de regresión de la actividad deshidrogenasa con la elongación de las plántulas fue positivo y altamente significativo, lo que indica la complementaridad de ambos descriptores. Los resultados obtenidos sugieren que los biodescriptores empleados resultaron aptos para estudiar el

Calculation of Beta Decay Half-Lives and Delayed Neutron Branching Ratio of Fission Fragments with Skyrme-QRPA

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Minato Futoshi

2016-01-01

Full Text Available Nuclear β-decay and delayed neutron (DN emission is important for the r-process nucleosynthesis after the freeze-out, and stable and safe operation of nuclear reactors. Even though radioactive beam facilities have enabled us to measure β-decay and branching ratio of neutron-rich nuclei apart from the stability line in the nuclear chart, there are still a lot of nuclei which one cannot investigate experimentally. In particular, information on DN is rather scarce than that of T1/2. To predict T1/2 and the branching ratios of DN for next JENDL decay data, we have developed a method which comprises the quasiparticle-random-phase-approximation (QRPA and the Hauser-Feshbach statistical model (HFSM. In this work, we calculate fission fragments with T1/2 ≤ 50 sec. We obtain the rms deviation from experimental half-life of 3:71. Although the result is still worse than GT2 which has been adopted in JENDL decay data, DN spectra are newly calculated. We also discuss further subjects to be done in future for improving the present approach and making next generation of JENDL decay data.

Early environmental therapy rescues brain development in a mouse model of Down syndrome.

Science.gov (United States)

Begenisic, Tatjana; Sansevero, Gabriele; Baroncelli, Laura; Cioni, Giovanni; Sale, Alessandro

2015-10-01

Down syndrome (DS), the most common genetic disorder associated with intellectual disabilities, is an untreatable condition characterized by a number of developmental defects and permanent deficits in the adulthood. Ts65Dn mice, the major animal model for DS, display severe cognitive and synaptic plasticity defects closely resembling the human phenotype. Here, we employed a multidisciplinary approach to investigate, for the first time in developing Ts65Dn mice, the effects elicited by early environmental enrichment (EE) on brain maturation and function. We report that exposure to EE resulted in a robust increase in maternal care levels displayed by Ts65Dn mothers and led to a normalization of declarative memory abilities and hippocampal plasticity in trisomic offspring. The positive effects of EE on Ts65Dn phenotype were not limited to the cognitive domain, but also included a rescue of visual system maturation. The beneficial EE effects were accompanied by increased BDNF and correction of over-expression of the GABA vesicular transporter vGAT. These findings highlight the beneficial impact of early environmental stimuli and their potential for application in the treatment of major functional deficits in children with DS. Copyright © 2015 Elsevier Inc. All rights reserved.

Bootstrap equations for N=4 SYM with defects

Energy Technology Data Exchange (ETDEWEB)

Liendo, Pedro [IMIP, Humboldt-Universität zu Berlin, IRIS Adlershof,Zum Großen Windkanal 6, 12489 Berlin (Germany); Meneghelli, Carlo [Simons Center for Geometry and Physics, Stony Brook University,Stony Brook, NY 11794-3636 (United States)

2017-01-27

This paper focuses on the analysis of 4dN=4 superconformal theories in the presence of a defect from the point of view of the conformal bootstrap. We will concentrate first on the case of codimension one, where the defect is a boundary that preserves half of the supersymmetry. After studying the constraints imposed by supersymmetry, we will obtain the Ward identities associated to two-point functions of (1/2)-BPS operators and write their solution as a superconformal block expansion. Due to a surprising connection between spacetime and R-symmetry conformal blocks, our results not only apply to 4dN=4 superconformal theories with a boundary, but also to three more systems that have the same symmetry algebra: 4dN=4 superconformal theories with a line defect, 3dN=4 superconformal theories with no defect, and OSP(4{sup ∗}|4) superconformal quantum mechanics. The superconformal algebra implies that all these systems possess a closed subsector of operators in which the bootstrap equations become polynomial constraints on the CFT data. We derive these truncated equations and initiate the study of their solutions.

Surface modification of magnesium aluminum hydroxide nanoparticles with poly(methyl methacrylate) via one-pot in situ polymerization

Energy Technology Data Exchange (ETDEWEB)

Guo Xiaojun, E-mail: guoxj6906@163.com [College of Chemistry and Chemical Engineering, Northwest Normal University, 967 Anning East Road, Lanzhou 730070 (China); Zhao Leihua; Zhang Li; Li Jing [College of Chemistry and Chemical Engineering, Northwest Normal University, 967 Anning East Road, Lanzhou 730070 (China)

2012-01-15

Hydrophobic magnesium aluminum hydroxide composite particles (PMMA-MAH) were obtained by means of grafting poly(methyl methacrylate) (PMMA) onto the surface of magnesium aluminum hydroxide(MAH) nanoparticles after a novel type of phosphate coupling agent (DN-27) modification. The introduction of functional double bonds was firstly conducted on the surface of nanoparticles by DN-27 modification, followed by one-pot in situ polymerization on the particles surface using methyl methacrylate (MMA) as monomer, azoisobutyronitrile (AIBN) as initiator and sodium dodecyl sulfate (SDS) as stabilizer to graft PMMA on the surface of DN-27-modified MAH particles. The obtained composite particles were characterized by field-emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray powder diffraction (XRD). The results show that the organic macromolecule PMMA could be successfully grafted on the surface of DN-27-modified MAH nanoparticles and the thermal stability of the PMMA-MAH composite particles had been improved. Compared with unmodified blank MAH sample, the product obtained with this method possesses better hydrophobic properties such as a higher water contact angle of 108 Degree-Sign and a well dispersion.

Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles.

Science.gov (United States)

Bruno, P; Calastretti, A; Priulla, M; Asnaghi, L; Scarlatti, F; Nicolin, A; Canti, G

2007-10-01

Akt activation assists tumor cell survival and promotes resistance to chemotherapy. Here we show that constitutively active Akt (CA-Akt) cells are highly sensitized to cell death induced by nutrient and growth factor deprivation, whereas dominant-negative Akt (DN-Akt) cells have a high rate of survival. The content of autophagosomes in starved CA-Akt cells was high, while DN-Akt cells expressed autophagic vacuoles constitutively, independently of nutrition conditions. Thus Akt down-regulation and downstream events can induce autophagosomes which were not directly determinants of cell death. Biochemical analysis in Akt-mutated cells show that (i) Akt and mTOR proteins were degraded more rapidly than the housekeeping proteins, (ii) mTOR phosphorylation at position Thr(2446) was relatively high in DN-Akt and low in CA-Akt cells, induced by starvation in mock cells only, which suggests reduced autoregulation of these pathways in Akt-mutated cells, (iii) both protein synthesis and protein degradation were significantly higher in starved CA-Akt cells than in starved DN-Akt cells or mock cells. In conclusion, constitutively active Akt, unable to control synthesis and wasting of proteins, accelerates the death of starved cells.

Effect of variation in equilibrium shape on ELMing H-mode performance in DIII-D diverted plasmas

International Nuclear Information System (INIS)

Fenstermacher, M.E.; Osborne, T.H.; Petrie, T.W.

2001-01-01

The changes in the performance of the core, pedestal, scrape-off-layer (SOL), and divertor plasmas as a result of changes in triangularity, δ, up/down magnetic balance, and secondary divertor volume were examined in shape variation experiments using ELMing H mode plasmas on DIII-D. In moderate density, unpumped plasmas, high δ∼0.7 increased the energy in the H mode pedestal and the global energy confinement of the core, primarily due to an increase in the margin by which the edge pressure gradient exceeded the value which would have been expected had it been limited by infinite-n ideal ballooning modes. In addition, a nearly balanced double-null (DN) shape was effective for sharing the peak heat flux in the divertor in these attached plasmas. For detached plasmas good heat flux sharing was obtained for a substantial range of unbalanced DN shapes. Finally, the presence of a second X-point in unbalanced DN shapes did not degrade the plasma performance if it was sufficiently far inside the vacuum vessel. These results indicate that a high δ unbalanced DN shape has some advantages over a single null shape for future high power tokamak operation. (author)

Cerebellar involvement in metabolic disorders: a pattern-recognition approach

International Nuclear Information System (INIS)

Steinlin, M.; Boltshauser, E.; Blaser, S.

1998-01-01

Inborn errors of metabolism can affect the cerebellum during development, maturation and later during life. We have established criteria for pattern recognition of cerebellar abnormalities in metabolic disorders. The abnormalities can be divided into four major groups: cerebellar hypoplasia (CH), hyperplasia, cerebellar atrophy (CA), cerebellar white matter abnormalities (WMA) or swelling, and involvement of the dentate nuclei (DN) or cerebellar cortex. CH can be an isolated typical finding, as in adenylsuccinase deficiency, but is also occasionally seen in many other disorders. Differentiation from CH and CA is often difficult, as in carbohydrate deficient glycoprotein syndrome or 2-l-hydroxyglutaric acidaemia. In cases of atrophy the relationship of cerebellar to cerebral atrophy is important. WMA may be diffuse or patchy, frequently predominantly around the DN. Severe swelling of white matter is present during metabolic crisis in maple syrup urine disease. The DN can be affected by metabolite deposition, necrosis, calcification or demyelination. Involvement of cerebellar cortex is seen in infantile neuroaxonal dystrophy. Changes in DN and cerebellar cortex are rather typical and therefore most helpful; additional features should be sought as they are useful in narrowing down the differential diagnosis. (orig.)

Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

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Xia Zou

2015-01-01

Full Text Available Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN. Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF- β and α-smooth muscle action (SMA. Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05. Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

Bootstrap equations for N=4 SYM with defects

International Nuclear Information System (INIS)

Liendo, Pedro; Meneghelli, Carlo

2017-01-01

This paper focuses on the analysis of 4dN=4 superconformal theories in the presence of a defect from the point of view of the conformal bootstrap. We will concentrate first on the case of codimension one, where the defect is a boundary that preserves half of the supersymmetry. After studying the constraints imposed by supersymmetry, we will obtain the Ward identities associated to two-point functions of (1/2)-BPS operators and write their solution as a superconformal block expansion. Due to a surprising connection between spacetime and R-symmetry conformal blocks, our results not only apply to 4dN=4 superconformal theories with a boundary, but also to three more systems that have the same symmetry algebra: 4dN=4 superconformal theories with a line defect, 3dN=4 superconformal theories with no defect, and OSP(4 ∗ |4) superconformal quantum mechanics. The superconformal algebra implies that all these systems possess a closed subsector of operators in which the bootstrap equations become polynomial constraints on the CFT data. We derive these truncated equations and initiate the study of their solutions.

Use of Dendrimers during the Synthesis of Pt-Ru Electrocatalysts for PEM Fuel Cells: Effects on the Physical and Electrochemical Properties

Directory of Open Access Journals (Sweden)

J. C. Calderón

2011-01-01

Full Text Available In this work, Pt-Ru catalysts were synthesized by a novel methodology which includes the use as encapsulating molecules of dendrimers of different generation: zero (DN-0, one (DN-1, two (DN-2, and three (DN-3. Synthesized catalysts were heat-treated at 350°C, and the effects of this treatment was established from the physical (X-ray dispersive energy (XDE and X-ray diffraction (XRD and electrochemical characterization (cyclic voltammetry and chronoamperometry. Results showed that the heat-treatment benefits the catalytic properties of synthesized materials in terms of CO and methanol electrochemical oxidation. The curves for CO stripping were more defined for heat-treated catalysts, and methanol oxidation current densities were higher for these materials. These changes are principally explained from the removal of organic residues remaining on the surface of the Pt-Ru nanoparticles after the synthesis procedure. After the activation of the catalysts by heating at 350°C, the real importance of the use of these encapsulating molecules and the effect of the generation of the dendrimer become visible. From these results, it can be concluded that synthesized catalysts are good catalytic anodes for direct methanol fuel cells (DMFCs.

Prevalence of diabetic nephropathy in Type 2 Diabetes Mellitus in rural communities of Guanajuato, Mexico. Effect after 6 months of Telmisartan treatment.

Science.gov (United States)

Zenteno-Castillo, Priscyla; Muñoz-López, Daniela Beatriz; Merino-Reyes, Benjamín; Vega-Sánchez, Ángel; Preciado-Puga, Monica; González-Yebra, Ana Lilia; Kornhauser, Carlos

2015-12-01

To determine the prevalence of Diabetic Nephropathy (DN) in patients with type 2 Diabetes Mellitus (T2DM) with over 5 years of evolution in rural communities of Guanajuato, Mexico, and evaluate the effects of an ARB treatment over 6 months in patients with DN. Patients of both sexes, 38-86 years, T2DM over 5 years of evolution and diagnosed with arterial hypertension (HT) after T2DM incidence. Monthly determination of microalbuminuria (MA), lipids, glucose, serum creatinine, and glycated hemoglobin (HbA1c). Estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. A dose of 80 mg of Telmisartan was administered daily over 6 months. The total adult population of two rural communities (3609 subjects) was studied, 335 subjects had T2DM, among them 80 (with a prevalence of 24%) had DN and HT. Sixty-seven patients received Telmisartan, and showed significant improvement in all parameters studied. A higher prevalence of DN than that reported in the Mexican National Health Survey (ENSANUT) was found. Further research is required in a larger population sample in order to confirm the results of Telmisartan treatment.

Dolor neuropático, clasificación y estrategias de manejo para médicos generales

Directory of Open Access Journals (Sweden)

Prof. DR. Correa-Illanes Gerardo

2014-03-01

Full Text Available El Dolor Neuropático (DN se origina como consecuencia directa de una lesión o enfermedad que afecta al sistema somatosensorial, es un problema importante de Salud Pública y una condición común, crónica, debilitante que afecta a un número signifi cativo de pacientes. La presencia del DN es sugerida por la historia clínica y el examen físico, con una localización del dolor neuroanatómicamente lógica y evidencia de daño del sistema nervioso. Los médicos de atención primaria tienen un rol crucial en realizar el diagnóstico de DN posible, evitar los retrasos en el diagnóstico y proveer una apropiada evaluación, manejo y/o oportuna derivación al especialista para mejorar los resultados, reducir los costos humanos a los pacientes, aliviando el dolor y la discapacidad subsecuente, y costos económicos a la sociedad. Debemos por lo tanto educar a los médicos generales en la detección, el diagnóstico y el manejo inicial del DN.

CD5−NK1.1+ γδ T Cells that Develop in a Bcl11b-Independent Manner Participate in Early Protection against Infection

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Shinya Hatano

2017-10-01

Full Text Available Summary: We recently found that a unique subset of innate-like γδ T cells develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b. Herein, we characterize these Bcl11b-independent γδ T cells in the periphery as CD5−NK1.1+ and Granzyme B+, and we show that they are capable of producing interferon (IFN-γ upon T cell receptor stimulation without Ca2+ influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues, such as the liver. Bcl11b-independent CD5−NK1.1+ γδ T cells appeared and contributed to early protection before Bcl11b-dependent CD5+NK1.1− γδ T cells following Listeria monocytogenes infection, resembling their sequential appearance during development in the thymus. : Bcl11b is essential for transition from the DN2a to the DN2b stage in the thymus. Hatano et al. find that CD5−NK1.1+ γδ T cells develop from the DN2a stage in a Bcl11b-independent manner and participate in host defense at an early stage after bacterial infection in periphery. Keywords: innate immunity, γδ T cell, Bcl11b, DN2a, IFN-γ, Granzyme, IL-17A, host defense, bacteria, Listeria monocytogenes

GRA/RIAM model development at Darlington Nuclear

International Nuclear Information System (INIS)

Plourde, J.; Parmar, R.

2006-01-01

In 2004, the Darlington Nuclear (DN) Plant of Ontario Power Generation (OPG) undertook a project, in partnership with Nuclear Safety Solutions (NSS) Limited, to develop Risk-Informed Asset Management (RIAM) and Generation Risk Assessment (GRA) models. The models are intended to optimize plant decision-making. The objective of this paper is to present the scope of the project, the methodology employed, the results and the potential applications. DN has recognized the strategic importance of RIAM in the plant decision-making process and has begun its implementation. The required work was split into three phases. Phase 1 involved industry benchmarking, along with collection and review of the industry literature such as EPRI publications and other relevant papers. Based on the review, a description of the requirements to produce a prototype RIAM model was developed. Phase 2 consisted of the development of prototype RIAM and GRA models. Phase 3, currently underway, consists of the work required to translate the prototype models into an operational decision-making tool. RIAM and GRA are relatively new concepts hence the related methodology and the tools are still evolving. NSS has tailored the available methodology to suit the needs of the DN plant. Draft EPRI guides on GRA/RIAM were used in developing DN specific methodology. The details are provided in the paper. At DN, RIAM is expected to support business decisions by facilitating the assessment of risks associated with projects, programs and business case alternatives. These applications are further discussed in the paper. (author)

Relationship between serum bilirubin concentrations and diabetic nephropathy in Shanghai Han's patients with type 1 diabetes mellitus.

Science.gov (United States)

Li, Xu; Zhang, Lei; Chen, Haibing; Guo, Kaifeng; Yu, Haoyong; Zhou, Jian; Li, Ming; Li, Qing; Li, Lianxi; Yin, Jun; Liu, Fang; Bao, Yuqian; Han, Junfeng; Jia, Weiping

2017-03-31

Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20-0.60; Q2, 0.60-0.80; Q3, 0.80-1.00; Q4, 1.00-1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. The median bilirubin level was 0.56 (interquartile: 0.43-0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58-0.89 mg/dL], P 1). Spearman's correlational analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P 1.90% to 2.00%. High bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.

Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa.

Science.gov (United States)

Borruel, Natalia; Casellas, Francesc; Antolín, María; Llopis, Marta; Carol, Monica; Espíin, Eloy; Naval, Javier; Guarner, Francisco; Malagelada, Juan R

2003-04-01

The human intestine harbors a complex microbial ecosystem, and the mucosa is the interface between the immune system and the luminal environment. The aim of this study was to elucidate whether host-bacteria interactions influence mucosal cytokine production. Macroscopically normal colonic specimens were obtained at surgery from eight patients with neoplasm, and inflamed ileal specimens were obtained from two patients with Crohn's disease. Mucosal explants were cultured for 24 h with either nonpathogenic Escherichia coli ECOR-26, Lactobacillus casei DN-114 001, L. casei DN-114 056, L. casei ATCC-334, or Lactobacillus bulgaricus LB-10. Each study included blank wells with no bacteria. Tissue and bacteria viability were confirmed by LDH release and culture. Concentration of tumor necrosis factor (TNF)alpha, transforming growth factor beta1, interleukin (IL)-8, and IL-10 was measured in supernatants. In parallel experiments, neutralizing anti-TNFalpha antibody was added to the culture. Co-culture of mucosa with bacteria did not modify LDH release. Co-culture with L. casei strains significantly reduced TNFalpha release, whereas E. coli increased it. These effects were observed both in normal and inflamed mucosa. In combination studies, L. casei DN-114 001 prevented TNFalpha stimulation by E. coli. L. casei DN-114 001 also reduced IL-8 release via a TNFalpha-independent pathway. L. casei DN-114 056 or E. coli increased IL-10 release in the presence of neutralizing anti-TNFalpha. Nonpathogenic bacteria interact with human intestinal mucosa and can induce changes in cytokine production that are strain specific.

Two-Dimensional Lead Halide Perovskites Templated by a Conjugated Asymmetric Diammonium.

Science.gov (United States)

Hautzinger, Matthew P; Dai, Jun; Ji, Yujin; Fu, Yongping; Chen, Jie; Guzei, Ilia A; Wright, John C; Li, Youyong; Jin, Song

2017-12-18

We report novel two-dimensional lead halide perovskite structures templated by a unique conjugated aromatic dication, N,N-dimethylphenylene-p-diammonium (DPDA). The asymmetrically substituted primary and tertiary ammoniums in DPDA facilitate the formation of two-dimensional network (2DN) perovskite structures incorporating a conjugated dication between the PbX 4 2- (X = Br, I) layers. These 2DN structures of (DPDA)PbI 4 and (DPDA)PbBr 4 were characterized by single-crystal X-ray diffraction, showing uniquely low distortions in the Pb-X-Pb bond angle for 2D perovskites. The Pb-I-Pb bond angle is very close to ideal (180°) for a 2DN lead iodide perovskite, which can be attributed to the ability of the rigid diammonium DPDA to insert into the PbX 6 2- octahedral pockets. Optical characterization of (DPDA)PbI 4 shows an excitonic absorption peak at 2.29 eV (541 nm), which is red-shifted in comparison to similar 2DN lead iodide structures. Temperature-dependent photoluminescence of both compounds reveals both a self-trapped exciton and free exciton emission feature. The reduced exciton absorption energy and emission properties are attributed to the dication-induced structural order of the inorganic PbX 4 2- layers. DFT calculation results suggest mixing of the conjugated organic orbital component in the valence band of these 2DN perovskites. These results demonstrate a rational new strategy to incorporate conjugated organic dications into hybrid perovskites and will spur spectroscopic investigations of these compounds as well as optoelectronic applications.

Fasudil and DETA NONOate, Loaded in a Peptide-Modified Liposomal Carrier, Slow PAH Progression upon Pulmonary Delivery.

Science.gov (United States)

Rashid, Jahidur; Nahar, Kamrun; Raut, Snehal; Keshavarz, Ali; Ahsan, Fakhrul

2018-05-07

We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long-acting nitric oxide donor, both loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC), in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified and CAR-modified liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia-induced PAH rats. We also conducted morphometric studies (degree of muscularization, arterial medial wall thickness, and collagen deposition) after treating the PAH rats with test and control formulations. When the rats were treated acutely and chronically, the reduction in mPAP was more pronounced in the liposomal formulation-treated rats than in plain drug-treated rats. CAR-modified liposomes were more selective in reducing mPAP than unmodified liposomes of the drugs. Both drugs, formulated in CAR-modified liposomes, reduced the degree of muscularization, medial arterial wall thickness, and collagen deposition more than the combination of plain drugs did. As seen with the in vivo data, CAR-modified liposomes of fasudil or DN increased the levels of the vasodilatory signaling molecule, cGMP, in the smooth muscle cells of PAH-afflicted human pulmonary arteries. Overall, fasudil and DN, formulated in liposomes, could be used as a combination therapy for a better management of PAH.

Involvement of Histone Lysine Methylation in p21 Gene Expression in Rat Kidney In Vivo and Rat Mesangial Cells In Vitro under Diabetic Conditions

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Xiangjun Li

2016-01-01

Full Text Available Diabetic nephropathy (DN, a common complication associated with type 1 and type 2 diabetes mellitus (DM, characterized by glomerular mesangial expansion, inflammation, accumulation of extracellular matrix (ECM protein, and hypertrophy, is the major cause of end-stage renal disease (ESRD. Increasing evidence suggested that p21-dependent glomerular and mesangial cell (MC hypertrophy play key roles in the pathogenesis of DN. Recently, posttranscriptional modifications (PTMs have uncovered novel molecular mechanisms involved in DN. However, precise regulatory mechanism of histone lysine methylation (HKme mediating p21 related hypertrophy associated with DN is not clear. We evaluated the roles of HKme and histone methyltransferase (HMT SET7/9 in p21 gene expression in glomeruli of diabetic rats and in high glucose- (HG- treated rat mesangial cells (RMCs. p21 gene expression was upregulated in diabetic rats glomeruli; chromatin immunoprecipitation (ChIP assays showed decreased histone H3-lysine9-dimethylation (H3K9me2 accompanied with enhanced histone H3-lysine4-methylation (H3K4me1/3 and SET7/9 occupancies at the p21 promoter. HG-treated RMCs exhibited increased p21 mRNA, H3K4me level, SET7/9 recruitment, and inverse H3K9me, which were reversed by TGF-β1 antibody. These data uncovered key roles of H3Kme and SET7/9 responsible for p21 gene expression in vivo and in vitro under diabetic conditions and confirmed preventive effect of TGF-β1 antibody on DN.

Increased adipogenesis in cultured embryonic chondrocytes and in adult bone marrow of dominant negative Erg transgenic mice.

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Sébastien Flajollet

Full Text Available In monolayer culture, primary articular chondrocytes have an intrinsic tendency to lose their phenotype during expansion. The molecular events underlying this chondrocyte dedifferentiation are still largely unknown. Several transcription factors are important for chondrocyte differentiation. The Ets transcription factor family may be involved in skeletal development. One family member, the Erg gene, is mainly expressed during cartilage formation. To further investigate the potential role of Erg in the maintenance of the chondrocyte phenotype, we isolated and cultured chondrocytes from the rib cartilage of embryos of transgenic mice that express a dominant negative form of Erg (DN-Erg during cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days did not affect the early dedifferentiation usually observed in cultured chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes, suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray, validated by quantitative RT-PCR, revealed strong differential gene expression, with a decrease in chondrogenesis-related markers and an increase in adipogenesis-related gene expression in cultured DN-Erg chondrocytes. These results indicate that Erg is involved in either maintaining the chondrogenic phenotype in vitro or in cell fate orientation. Along with the in vitro studies, we compared adipocyte presence in wild-type and transgenic mice skeletons. Histological investigations revealed an increase in the number of adipocytes in the bone marrow of adult DN-Erg mice even though no adipocytes were detected in embryonic cartilage or bone. These findings suggest that the Ets transcription factor family may contribute to the homeostatic balance in skeleton cell plasticity.

Evolution of Lyα Forest in Redshift Range 0.5

Indian Academy of Sciences (India)

represents the number of Lyα absorption lines in the interval width of unit redshift (z); when z is equal to zero,. ( dn dz. ) is represented by. ( dn dz. ) 0. , and γ is the evolution index. In general, we are using maximum likelihood estimation to do a statistical research. For 1.7

The putative imprinted locus D15S9 within the common deletion region for the Prader-Willi and Angelman syndromes encodes two overlapping mRNAs transcribed from opposite strands

Energy Technology Data Exchange (ETDEWEB)

Glenn, C.C.; Driscoll, D.J. [Univ. of Florida, Gainesville, FL (United States); Saitoh, S. [Case Western Reserve Univ., Cleveland, OH (United States)] [and others

1994-09-01

Prader-Willi syndrome is typically caused by a deletion of paternal 15q11-q13, or maternal uniparental disomy (UPD) of chromosome 15, while Angelman syndrome is caused by a maternal deletion or paternal UPD of the same region. Therefore, these two clinically distinct neurobehavioral syndromes result from differential expression of imprinted genes within 15q11-q13. A 3.1 kb cDNA, DN34, from the D15S9 locus within 15q11-q13 was isolated from a human fetal brain library. We showed previously that DN34 probe detects a DNA methylation imprint and therefore may represent a candidate imprinted gene. Isolation of genomic clones and DNA sequencing demonstrated that the gene segment encoding the partial cDNA DN34 was split by a 2 kb intron, but did not encode a substantial open reading frame (ORF). Preliminary analysis of expression by RT-PCR suggests that this gene is expressed in fetal but not in tested tissue types from the adult, and thus its imprinting status has not been possible to assess at present. Surprisingly, we found an ORF on the antisense strand of the DN34 cDNA. This ORF encodes a putative polypeptide of 505 amino acid residues containing a RING C{sub 3}HC{sub 4} zinc-finger motif and other features of nuclear proteins. Subsequent characterization of this gene, ZNF127, and a mouse homolog, demonstrated expression of 3.2 kb transcript from all tested fetal and adult tissues. Transcripts initiate from within a CpG-island, shown to be differentially methylated on parental alleles in the human. Interestingly, functional imprinting of the mouse homolog was subsequently demonstrated in an F{sub 1} cross by analyzing a VNTR polymorphism in the mRNA. The ZNF127 gene is intronless, has significant overlap with the DN34 gene on the antisense strand, and a 1 kb 3{prime} end within the 2 kb DN34 intron.

Notch3 is dispensable for thymocyte β-selection and Notch1-induced T cell leukemogenesis.

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Sara Suliman

Full Text Available Notch1 (N1 signaling induced by intrathymic Delta-like (DL ligands is required for T cell lineage commitment as well as self-renewal during "β-selection" of TCRβ⁺CD4⁻CD8⁻ double negative 3 (DN3 T cell progenitors. However, over-expression of the N1 intracellular domain (ICN1 renders N1 activation ligand-independent and drives leukemic transformation during β-selection. DN3 progenitors also express Notch3 (N3 mRNA, and over-expression of ligand-independent mutant N3 (ICN3 influences β-selection and drives T cell leukemogenesis. However, the importance of ligand-activated N3 in promoting β-selection and ICN1-induced T cell leukemogenesis has not been examined. To address these questions we generated mice lacking functional N3. We confirmed that DN3 progenitors express N3 protein using a N3-specific antibody. Surprisingly however, N3-deficient DN3 thymocytes were not defective in generating DP thymocytes under steady state conditions or in more stringent competition assays. To determine if N3 co-operates with N1 to regulate β-selection, we generated N1;N3 compound mutants. However, N3 deficiency did not exacerbate the competitive defect of N1⁺/⁻ DN3 progenitors, demonstrating that N3 does not compensate for limiting N1 during T cell development. Finally, N3 deficiency did not attenuate T cell leukemogenesis induced by conditional expression of ICN1 in DN3 thymocytes. Importantly, we showed that in contrast to N1, N3 has a low binding affinity for DL4, the most abundant intrathymic DL ligand. Thus, despite the profound effects of ectopic ligand-independent N3 activation on T cell development and leukemogenesis, physiologically activated N3 is dispensable for both processes, likely because N3 interacts poorly with intrathymic DL4.

Carboxylesterase-involved metabolism of di-n-butyl phthalate in pumpkin (Cucurbita moschata) seedlings.

Science.gov (United States)

Lin, Qingqi; Chen, Siyuan; Chao, Yuanqing; Huang, Xiongfei; Wang, Shizhong; Qiu, Rongliang

2017-01-01

Uptake and accumulation by plants is a significant pathway in the migration and transformation of phthalate esters (PAEs) in the environment. However, limited information is available on the mechanisms of PAE metabolism in plants. Here, we investigated the metabolism of di-n-butyl phthalate (DnBP), one of the most frequently detected PAEs, in pumpkin (Cucurbita moschata) seedlings via a series of hydroponic experiments with an initial concentration of 10 mg L -1 . DnBP hydrolysis occurred primarily in the root, and two of its metabolites, mono-n-butyl phthalate (MnBP) and phthalic acid (PA), were detected in all plant tissues. The MnBP concentration was an order of magnitude higher than that of PA in shoots, which indicated MnBP was more readily transported to the shoot than was PA because of the former's dual hydrophilic and lipophilic characteristics. More than 80% of MnBP and PA were located in the cell water-soluble component except that 96% of MnBP was distributed into the two solid cellular fractions (i.e., cell wall and organelles) at 96 h. A 13-20% and 29-54% increase of carboxylesterase (CXE) activity shown in time-dependent and concentration-dependent experiments, respectively, indicated the involvement of CXEs in plant metabolism of DnBP. The level of CXE activity in root subcellular fractions was in the order: the cell water-soluble component (88-94%) > cell wall (3-7%) > cell organelles (3-4%), suggesting that the cell water-soluble component is the dominant locus of CXE activity and also the domain of CXE-catalyzed hydrolysis of DnBP. The addition of triphenyl phosphate, a CXE inhibitor, led to 43-56% inhibition of CXE activity and 16-25% increase of DnBP content, which demonstrated the involvement of CXEs in plant metabolism of DnBP. This study contributes to our understanding of enzymitic mechanisms of PAE transformation in plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinicopathological study of nondiabetic renal disease in type 2 diabetic patients: A single center experience from India

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Kamal V Kanodia

2017-01-01

Full Text Available Diabetic nephropathy (DN is a major complication of diabetes mellitus (DM, leading to chronic kidney disease/end-stage renal disease. Wide spectrum of nondiabetic renal diseases (NDRD is reported in type-2 diabetes (type-2 DM. We carried out this single-center study to find clinical, laboratory, and histological features of NDRD in type-2 DM patients and to assess the prevalence of NDRD in India. A single-center retrospective study which included analysis of renal biopsies from patients with type-2 DM, performed between January 2008 and September 2016. Biopsy findings were categorized into three groups, Group-I (isolated NDRD; Group-II (NDRD superimposed on underlying DN; and Group-III (isolated DN. Out of 152 diabetic patients (111 males and 41 females, 35 (23.03% patients were of Group-I (isolated NDRD, 35 (23.03% of Group-II (NDRD superimposed on underlying DN, and 82 (53.95% of Group-III (isolated DN. The mean age (in years was 55.08 ± 10.71, 55.65 ± 8.71, and 54.45 ± 9.01 respectively in Group-I, II, and III. Nephrotic syndrome (NS was the most common clinical presentation in all groups. Duration of DM was significantly shorter in Group-I than in Group-II. Diabetic retinopathy was absent in Group-I. Proteinuria was more in Group-III than Group-I. Low serum C3 and/or C4 levels was observed in five (14.29% cases of Group-I and Group-II each and two (2.43% cases of Group-III. Nearly, 70 (46.05% patients were found to have NDRD either in isolated form or as combined lesions. The most common histological types of NDRD were acute tubulointerstitial nephritis (38.57% followed by benign nephrosclerosis (15.72%, membranous nephropathy (10%, IgA nephropathy (7.14%, and membranoproliferative glomerulonephritis (7.14%. The incidence of NDRD (with/without DN in type-2 DM is very high. Shorter duration of diabetes, hematuria, absence of retinopathy, low serum complement levels, and nephrotic range proteinuria are predictors of NDRD.

Is guidewire exchange a better approach for subclavian vein re-catheterization for chronic hemodialysis patients?

Science.gov (United States)

Hou, Shaw-Min; Chou, Po-Ching; Huang, Chi-Hung; Chin, Chih-Hui; Wang, Pa-Chun; Chen, Ya-Hui

2006-01-01

The objectives of this study were to compare outcomes and survival rates of subclavian vein re-catheterization through guide wire exchange (GWE) or de novo insertion (DN). The study was conducted in a retrospective manner. Medical records of 36 patients who received percutaneous subclavian vein re-catheterization for hemodialysis in our institution during the period from April 1, 2001 to September 30, 2004 were reviewed. All patients had at least 2 catheter insertions records in our institute. Incidences of adverse events (infection, thrombosis) were compared between GWE and DN groups using x2 test. Predictors for adverse event occurrences were analyzed using logistic regression models. Cox proportional hazard model was used to investigate the predictors for adverse event-free catheter days. Kaplan-Meire survival curves were computed and compared using log rank test. Information were generated from 98 catheters (41 from DN, 57 from GWE groups). The average catheter usage was 2.8+/-0.9 devices per patient and the mean catheter-indwelling-day was 125.4+/-129.5 days in this cohort. We found GWE group had significantly lower thrombosis rate (49.1% vs. 85.4% for DN group, Prates for GWE were > or =30 days, 85.4%; > or =60 days, 75.5%; > or =90 days, 64.5%; > or =180 days, 44.3%. The actuarial survival rates for DN were > or =30 days, 70.7%; > or =60 days, 58.5%; > or =90 days, 34.2%; > or =180 days, 18.4%. GWE group catheters had significantly higher catheter survival rates (P=0.0009). Mahukar catheter (hazard ratio 0.514, P=0.03), non-shock (hazard ratio 3.358, P=0.04), and older age (hazard ratio 0.958, P=0.026) were predictors of adverse event-free remaining catheter days. We suggest that GWE might be a favorable option over DN insertion when revised subclavian vein catheterization is inevitable. GWE can be performed repeatedly without compromising catheter outcomes.

Detección neonatal en el Paraguay. Brechas para su cobertura universal

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Marta Ascurra

2015-08-01

Full Text Available La cobertura universal en los programas de detección neonatal (DN es una obligación de todos los países, de manera a ofrecer a la población los servicios de detección y tra-tamiento oportunos sin necesidad de que la misma incurra en gastos considerables ni pago directo al momento de recibir el servicio. El objetivo de este estudio fue determinar las brechas para la universalización de la cobertura de la DN en Paraguay. La unidad de análisis fue el Programa de Prevención de la Fibrosis Quística y Retardo Mental (PPFQRM. Se evaluaron los tres ejes de la cobertura universal sanitaria (CUS propues-to por la OMS: amplitud o proporción cubierta, profundidad definida por el número de patologías incluidas en la DN, nivel de protección financiera; así como las brechas para el logro de la universalización de la cobertura de la DN. La información se obtuvo del PPFQRM, Dirección General de Estadísticas Vitales y de la Dirección General de Estadísti-ca, Encuesta y Censo. Se encontró que los estudios de diagnóstico y tratamiento están garantizados por la Ley 2138/2003. La amplitud tuvo un aumento significativo de 0,8% en 1999 a 76,1% en 2.014. Existe necesidad de ampliar las patologías incluidas en la DN en el PPFQRM (hipotiroidismo congénito, fenilcetonuria y fibrosis quística. Se pudo comprobar los grandes esfuerzos e inversiones que el Paraguay está realizando para el logro de la universalización de la DN; con lo cual se contribuirá a romper el círculo de pobreza, considerando que la discapacidad genera pobreza y la pobreza discapacidad.

In situ atomic layer nitridation on the top and down regions of the amorphous and crystalline high-K gate dielectrics

Energy Technology Data Exchange (ETDEWEB)

Tsai, Meng-Chen [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Lee, Min-Hung [Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei 11677, Taiwan (China); Kuo, Chin-Lung; Lin, Hsin-Chih [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Chen, Miin-Jang, E-mail: mjchen@ntu.edu.tw [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China)

2016-11-30

Highlights: • The structural and electrical characteristics of the ZrO{sub 2} high-K dielectrics, treated with the in situ atomic layer doping of nitrogen into the top and down regions (top and down nitridation, TN and DN, respectively), were investigated. • The amorphous DN sample has a lower leakage current density (J{sub g}) than the amorphous TN sample, attributed to the formation of SiO{sub x}N{sub y} in the interfacial layer (IL). • The crystalline TN sample exhibited a lower CET and a similar J{sub g} as compared with the crystalline DN sample, which can be ascribed to the suppression of IL regrowth. • The crystalline ZrO{sub 2} with in situ atomic layer doping of nitrogen into the top region exhibited superior scaling limit, electrical characteristics, and reliability. - Abstract: Amorphous and crystalline ZrO{sub 2} gate dielectrics treated with in situ atomic layer nitridation on the top and down regions (top and down nitridation, abbreviated as TN and DN) were investigated. In a comparison between the as-deposited amorphous DN and TN samples, the DN sample has a lower leakage current density (J{sub g}) of ∼7 × 10{sup −4} A/cm{sup 2} with a similar capacitance equivalent thickness (CET) of ∼1.53 nm, attributed to the formation of SiO{sub x}N{sub y} in the interfacial layer (IL). The post-metallization annealing (PMA) leads to the transformation of ZrO{sub 2} from the amorphous to the crystalline tetragonal/cubic phase, resulting in an increment of the dielectric constant. The PMA-treated TN sample exhibits a lower CET of 1.22 nm along with a similar J{sub g} of ∼1.4 × 10{sup −5} A/cm{sup 2} as compared with the PMA-treated DN sample, which can be ascribed to the suppression of IL regrowth. The result reveals that the nitrogen engineering in the top and down regions has a significant impact on the electrical characteristics of amorphous and crystalline ZrO{sub 2} gate dielectrics, and the nitrogen incorporation at the top of crystalline

T cell receptor (TCR-transgenic CD8 lymphocytes rendered insensitive to transforming growth factor beta (TGFβ signaling mediate superior tumor regression in an animal model of adoptive cell therapy

Directory of Open Access Journals (Sweden)

Quatromoni Jon G

2012-06-01

Full Text Available Abstract Tumor antigen-reactive T cells must enter into an immunosuppressive tumor microenvironment, continue to produce cytokine and deliver apoptotic death signals to affect tumor regression. Many tumors produce transforming growth factor beta (TGFβ, which inhibits T cell activation, proliferation and cytotoxicity. In a murine model of adoptive cell therapy, we demonstrate that transgenic Pmel-1 CD8 T cells, rendered insensitive to TGFβ by transduction with a TGFβ dominant negative receptor II (DN, were more effective in mediating regression of established B16 melanoma. Smaller numbers of DN Pmel-1 T cells effectively mediated tumor regression and retained the ability to produce interferon-γ in the tumor microenvironment. These results support efforts to incorporate this DN receptor in clinical trials of adoptive cell therapy for cancer.

Case Records of the Massachusetts General Hospital. Case 36-2012. Recovery of a 16-Year-Old Girl from Trauma and Burns After a Car Accident

Science.gov (United States)

2012-11-22

immobilized with a cervical collar and a backboard and was transported by medical helicopter to this hospital. The patient had a history of hypothyroidism ...treat- ment of sleep disturbance, anxious despair, and panic with anxiolytic and antipsychotic agents. In this patient, treatment included carefully...J Med 2008;358:2447-56. 11. Nugent N, Herndon DN. Diagnosis and treatment of inhalation injury. In: Herndon DN, ed. Total burn care. 3rd ed

Centrality Dependence of the Charged-Particle Multiplicity Density at Midrapidity in Pb-Pb Collisions at sNN=5.02TeV

NARCIS (Netherlands)

Adam, J.; Adamová, D.; Aggarwal, M. M.; Aglieri Rinella, G.; Agnello, M.; Agrawal, N.; Ahammed, Z.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Alam, S. N.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Alfaro Molina, R.; Alici, A.; Alkin, A.; Almaraz, J. R. M.; Alme, J.; Alt, T.; Altinpinar, S.; Altsybeev, I.; Alves Garcia Prado, C.; Andrei, C.; Andronic, A.; Anguelov, V.; Antičić, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshäuser, H.; Arcelli, S.; Arnaldi, R.; Arnold, O. W.; Arsene, I. C.; Arslandok, M.; Audurier, B.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badalà, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Balasubramanian, S.; Baldisseri, A.; Baral, R. C.; Barbano, A. M.; Barbera, R.; Barile, F.; Barnaföldi, G. G.; Barnby, L. S.; Barret, V.; Bartalini, P.; Barth, K.; Bartke, J.; Bartsch, E.; Basile, M.; Bastid, N.; Basu, S.; Bathen, B.; Batigne, G.; Batista Camejo, A.; Batyunya, B.; Batzing, P. C.; Bearden, I. G.; Beck, H.; Bedda, C.|info:eu-repo/dai/nl/411263188; Behera, N. K.; Belikov, I.; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Belmont, R.; Belmont-moreno, E.; Belyaev, V.; Benacek, P.; Bencedi, G.; Beole, S.; Berceanu, I.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhati, A. K.; Bhattacharjee, B.; Bhom, J.; Bianchi, L.; Bianchi, N.; Bianchin, C.|info:eu-repo/dai/nl/371578248; Bielčík, J.; Bielčíková, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Bjelogrlic, S.|info:eu-repo/dai/nl/355079615; Blair, J. T.; Blau, D.; Blume, C.; Bock, F.; Bogdanov, A.; Bøggild, H.; Boldizsár, L.; Bombara, M.; Book, J.; Borel, H.; Borissov, A.; Borri, M.; Bossú, F.; Botta, E.; Bourjau, C.; Braun-munzinger, P.; Bregant, M.; Breitner, T.; Broker, T. A.; Browning, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Cai, X.; Caines, H.; Calero Diaz, L.; Caliva, A.|info:eu-repo/dai/nl/411885812; Calvo Villar, E.; Camerini, P.; Carena, F.; Carena, W.; Carnesecchi, F.; Castillo Castellanos, J.; Castro, A. J.; Casula, E. A. R.; Ceballos Sanchez, C.; Cerello, P.; Cerkala, J.; Chang, B.; Chapeland, S.; Chartier, M.; Charvet, J. L.; Chattopadhyay, S.; Chattopadhyay, S.; Chauvin, A.; Chelnokov, V.; Cherney, M.; Cheshkov, C.; Cheynis, B.; Chibante Barroso, V.; Chinellato, D. D.; Cho, S.; Chochula, P.; Choi, K.; Choudhury, S.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Conesa Balbastre, G.; Conesa Del Valle, Z.; Connors, M. E.; Contreras, J. G.; Cormier, T. M.; Corrales Morales, Y.; Cortés Maldonado, I.; Cortese, P.; Cosentino, M. R.; Costa, F.; Crochet, P.; Cruz Albino, R.; Cuautle, E.; Cunqueiro, L.; Dahms, T.; Dainese, A.; Danisch, M. C.; Danu, A.; Das, I.; Das, S.; Dash, A.; Dash, S.; De, S.; De Caro, A.; De Cataldo, G.; De Conti, C.; De Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; Deisting, A.; Deloff, A.; Dénes, E.; Deplano, C.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Di Nezza, P.; Diaz Corchero, M. A.; Dietel, T.; Dillenseger, P.; Divià, R.; Djuvsland, Ø.; Dobrin, A.|info:eu-repo/dai/nl/372618715; Domenicis Gimenez, D.; Dönigus, B.; Dordic, O.; Drozhzhova, T.; Dubey, A. K.; Dubla, A.|info:eu-repo/dai/nl/355502488; Ducroux, L.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Endress, E.; Engel, H.; Epple, E.; Erazmus, B.; Erdemir, I.; Erhardt, F.; Espagnon, B.; Estienne, M.; Esumi, S.; Eum, J.; Evans, D.; Evdokimov, S.; Eyyubova, G.; Fabbietti, L.; Fabris, D.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Ferencei, J.; Fernández Téllez, A.; Ferreiro, E. G.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Figueredo, M. A. S.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiore, E. M.; Fleck, M. G.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francescon, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Fusco Girard, M.; Gaardhøje, J. J.; Gagliardi, M.; Gago, A. M.; Gallio, M.; Gangadharan, D. R.; Ganoti, P.; Gao, C.; Garabatos, C.; Garcia-solis, E.; Gargiulo, C.; Gasik, P.; Gauger, E. F.; Germain, M.; Gheata, A.; Gheata, M.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Gladysz-dziadus, E.; Glässel, P.; Goméz Coral, D. M.; Gomez Ramirez, A.; Gonzalez, V.; González-zamora, P.; Gorbunov, S.; Görlich, L.; Gotovac, S.; Grabski, V.; Grachov, O. A.; Graczykowski, L. K.; Graham, K. L.; Grelli, A.|info:eu-repo/dai/nl/326052577; Grigoras, A.; Grigoras, C.; Grigoriev, V.; Grigoryan, A.; Grigoryan, S.; Grinyov, B.; Grion, N.; Gronefeld, J. M.; Grosse-oetringhaus, J. F.; Grossiord, J.-y.; Grosso, R.; Guber, F.; Guernane, R.; Guerzoni, B.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Haake, R.; Haaland, Ø.; Hadjidakis, C.; Haiduc, M.; Hamagaki, H.; Hamar, G.; Hamon, J. C.; Harris, J. W.; Harton, A.; Hatzifotiadou, D.; Hayashi, S.; Heckel, S. T.; Helstrup, H.; 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Loenne, P. I.; Loginov, V.; Loizides, C.; Lopez, X.; López Torres, E.; Lowe, A.; Luettig, P.; Lunardon, M.; Lutz, T. H.; Maevskaya, A.; Mager, M.; Mahajan, S.; Mahmood, S. M.; Maire, A.; Majka, R. D.; Malaev, M.; Maldonado Cervantes, I.; Malinina, L.; Mal’kevich, D.; Malzacher, P.; Mamonov, A.; Manko, V.; Manso, F.; Manzari, V.; Marchisone, M.; Mareš, J.; Margagliotti, G. V.; Margotti, A.; Margutti, J.|info:eu-repo/dai/nl/412461684; Marín, A.; Markert, C.; Marquard, M.; Martin Blanco, J.; Martinengo, P.; Martínez, M. I.; Martínez García, G.; Martinez Pedreira, M.; Mas, A.; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Mastroserio, A.; Matyja, A.; Mayer, C.; Mazer, J.; Mazzoni, M. A.; Mcdonald, D.; Meddi, F.; Melikyan, Y.; Menchaca-rocha, A.; Meninno, E.; Mercado Pérez, J.; Meres, M.; Miake, Y.; Mieskolainen, M. M.; Mikhaylov, K.; Milano, L.; Milosevic, J.; Minervini, L. M.; Mischke, A.|info:eu-repo/dai/nl/325781435; Mishra, A. N.; Miśkowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.|info:eu-repo/dai/nl/369405870; Mohanty, B.; Molnar, L.; Montaño Zetina, L.; Montes, E.; Moreira De Godoy, D. A.; Moreno, L. A. P.; Moretto, S.; Morreale, A.; Morsch, A.; Muccifora, V.; Mudnic, E.; Mühlheim, D.; Muhuri, S.; Mukherjee, M.; Mulligan, J. D.; Munhoz, M. G.; Munzer, R. H.; Murakami, H.; Murray, S.; Musa, L.; Musinsky, J.; Naik, B.; Nair, R.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; Natal Da Luz, H.; Nattrass, C.; Navarro, S. R.; Nayak, K.; Nayak, R.; Nayak, T. K.; Nazarenko, S.; Nedosekin, A.; Nellen, L.; Ng, F.; Nicassio, M.; Niculescu, M.; Niedziela, J.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V.; Noferini, F.; Nomokonov, P.; Nooren, G.|info:eu-repo/dai/nl/07051349X; Noris, J. C. C.; Norman, J.; Nyanin, A.; Nystrand, J.; Oeschler, H.; Oh, S.; Oh, S. K.; Ohlson, A.; Okatan, A.; Okubo, T.; Olah, L.; Oleniacz, J.; Oliveira Da Silva, A. C.|info:eu-repo/dai/nl/323375618; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Orava, R.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Ozdemir, M.; Pachmayer, Y.; Pagano, P.; Paić, G.; Pal, S. K.; Pan, J.; Papikyan, V.; Pappalardo, G. S.; Pareek, P.; Park, W. J.; Parmar, S.; Passfeld, A.; Paticchio, V.; Patra, R. N.; Paul, B.; Pei, H.; Peitzmann, T.|info:eu-repo/dai/nl/304833959; Pereira Da Costa, H.; Peresunko, D.; Pérez Lara, C. E.; Perez Lezama, E.; Peskov, V.; Pestov, Y.; Petráček, V.; Petrov, V.; Petrovici, M.; Petta, C.; Piano, S.; Pikna, M.; Pillot, P.; Pimentel, L. O. D. L.; Pinazza, O.; Pinsky, L.; Piyarathna, D. B.; Płoskoń, M.; Planinic, M.; Pluta, J.; Pochybova, S.; Podesta-lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poonsawat, W.; Pop, A.; Porteboeuf-houssais, S.; Porter, J.; Pospisil, J.; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I.; Puccio, M.; Puddu, G.; Pujahari, P.; Punin, V.; Putschke, J.; Qvigstad, H.; Rachevski, A.; Raha, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Rami, F.; Raniwala, R.; Raniwala, S.; Räsänen, S. S.; Rascanu, B. T.; Rathee, D.; Read, K. F.; 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Szczepankiewicz, A.; Szymanski, M.; Tabassam, U.; Takahashi, J.; Tambave, G. J.; Tanaka, N.; Tangaro, M. A.; Tarhini, M.; Tariq, M.; Tarzila, M. G.; Tauro, A.; Tejeda Muñoz, G.; Telesca, A.; Terasaki, K.; Terrevoli, C.; Teyssier, B.; Thäder, J.; Tieulent, R.; Timmins, A. R.; Toia, A.; Trogolo, S.; Trombetta, G.; Trubnikov, V.; Trzaska, W. H.; Tsuji, T.; Tumkin, A.; Turrisi, R.; Tveter, T. S.; Ullaland, K.; Uras, A.; Usai, G. L.; Utrobicic, A.; Vajzer, M.; Vala, M.; Valencia Palomo, L.; Vallero, S.; Van Der Maarel, J.|info:eu-repo/dai/nl/412860996; Van Hoorne, J. W.; Vanat, T.; Vande Vyvre, P.; Varga, D.; Vargas, A.; Vargyas, M.; Varma, R.; Vasileiou, M.; Vasiliev, A.; Vauthier, A.; Vechernin, V.; Veen, A. M.|info:eu-repo/dai/nl/413533751; Veldhoen, M.; Velure, A.; Venaruzzo, M.; Vercellin, E.; Vergara Limón, S.; Vernet, R.; Verweij, M.|info:eu-repo/dai/nl/330542133; Vickovic, L.; Viesti, G.; Viinikainen, J.; Vilakazi, Z.; Villalobos Baillie, O.; Villatoro Tello, A.; Vinogradov, A.; Vinogradov, L.; 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2016-01-01

The pseudorapidity density of charged particles, dN ch /dη , at midrapidity in Pb-Pb collisions has been measured at a center-of-mass energy per nucleon pair of s NN − − − − √ =5.02  TeV . For the 5% most central collisions, we measure a value of 1943±54 . The rise in dN ch /dη as a function of s NN

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women.

Science.gov (United States)

Aguilera-Barreiro, María de Los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo Y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35-55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women

Science.gov (United States)

Aguilera-Barreiro, María de los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

Background The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. Objective To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). Methods The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35–55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. Results After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). Conclusion The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels. PMID:23704856

Intake of dehydrated nopal (Opuntia ficus indica improves bone mineral density and calciuria in adult Mexican women

Directory of Open Access Journals (Sweden)

María de los Angeles Aguilera-Barreiro

2013-05-01

Full Text Available Background: The intake of dehydrated nopal (DN at a high stage of maturity along with high calcium content could improve bone mineral density (BMD and calciuria and thus prevent osteoporosis. Objective: To evaluate the effect of calcium intake from a vegetable source (DN on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM. Methods: The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35–55. Urinary calcium/creatinine index (CCI was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG, women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1, women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2, women with hypercalciuria, and a maximum dose of DN; and normal group (NG for reference in BMD. Results: After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1% and EG2 (pre 1.8% and post 2.5% groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal. Conclusion: The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Radiation synthesis and characterisation of the network structure of natural/synthetic double-network superabsorbent polymers

International Nuclear Information System (INIS)

Şen, Murat; Hayrabolulu, Hande

2012-01-01

In this study radiation synthesis and characterisation of the network structure of acrylic acid sodium salt/locust bean gum, (AAcNa/LBG) natural/synthetic double-network super absorbent polymers were investigated. Quartet systems composed of acrylic acid sodium salt/locust bean gum/N,N methylene bis acrylamide/water (AAcNa/LBG/MBAAm/water) were prepared at varying degree of neutralisations (DN) by controlling the DN value of AAc and irradiated with gamma rays at ambient temperature at a very low dose rate. The influences of the DN on the swelling and network properties were examined. It was observed that the DN strongly affected the gelation and super absorption properties of the gels. Molecular weight between crosslinks (M ¯ c ), effective crosslink density (ν e ) and mesh size (ξ) of SAPs were calculated from swelling and shear modules data obtained from compression and oscillatory frequency sweep tests. M ¯ c values obtained from the uniaxial deformation experiments were very close to those obtained from the oscillatory shear experiments excluding the completely neutralised gel system. It was concluded that the uniaxial compression technique could be used for the characterisation of the network structure of a hydrogel as along with the rheological analyses; however, a very precise control of the gel size was also needed. - Highlights: ► Radiation synthesis and characterisation of AAcNa/LBG super absorbent polymers described. ► Influences of the DN on the swelling and network properties were examined. ► Molecular weight between crosslinks and effective crosslink density of SAPs were calculated. ► Suitability of rheology technique for the characterisation of hydrogels were demonstrated.

Dry needling in a manual physiotherapy and therapeutic exercise protocol for patients with chronic mechanical shoulder pain of unspecific origin: a protocol for a randomized control trial.

Science.gov (United States)

Tejera-Falcón, Emma; Toledo-Martel, Nuria Del Carmen; Sosa-Medina, Francisco Manuel; Santana-González, Fátima; Quintana-de la Fe, Miriam Del Pino; Gallego-Izquierdo, Tomás; Pecos-Martín, Daniel

2017-09-18

Shoulder pain of musculoskeletal origin is the main cause of upper limb pain of non-traumatic origin. Despite being one of the most common reasons for consultation, there is no established protocol for treatment due to the complexity of its etiology. However, it has been shown that the presence of myofascial trigger points on the shoulder muscles is a common condition associated with patients suffering from shoulder pain. This protocol has been created which describes the design of a randomized controlled trial to evaluate the effectiveness of the inclusion of dry needling (DN) within a protocol of manual physiotherapy and therapeutic exercise in the treatment of chronic shoulder pain of unspecific origin. Thirty-six participants aged 18-65 years will be recruited having mechanical chronic shoulder pain on unspecific origin and meeting the inclusion criteria. These will be randomized to one of two interventions, (i) DN, manual physiotherapy and therapeutic exercise or (ii) sham DN, manual physiotherapy and therapeutic exercise. The protocol will cover 6 weeks of treatment, with a 6-month follow-up. Our main outcome measure will be the Visual Analogue Scale for pain. This is the first study to combine the use of DN, manual physiotherapy and an exercise program with a 6-month follow-up, thus becoming a new contribution to the treatment of chronic shoulder pain, while new lines of research may be established to help determine the effects of DN on chronic shoulder pain and the frequency and proper dosage. International Standard Randomized Controlled Trial Number Register: ISRCTN30604244 ( http://www.controlled-trials.com ) 29 June 2016.

Sleep deprivation does not affect neuronal susceptibility to mild traumatic brain injury in the rat

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Caron AM

2015-06-01

Full Text Available Aimee M Caron, Richard Stephenson Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada Abstract: Mild and moderate traumatic brain injuries (TBIs (and concussion occur frequently as a result of falls, automobile accidents, and sporting activities, and are a major cause of acute and chronic disability. Fatigue and excessive sleepiness are associated with increased risk of accidents, but it is unknown whether prior sleep debt also affects the pathophysiological outcome of concussive injury. Using the “dark neuron” (DN as a marker of reversible neuronal damage, we tested the hypothesis that acute (48 hours total sleep deprivation (TSD and chronic sleep restriction (CSR; 10 days, 6-hour sleep/day affect DN formation following mild TBI in the rat. TSD and CSR were administered using a walking wheel apparatus. Mild TBI was administered under anesthesia using a weight-drop impact model, and the acute neuronal response was observed without recovery. DNs were detected using standard bright-field microscopy with toluidine blue stain following appropriate tissue fixation. DN density was low under home cage and sleep deprivation control conditions (respective median DN densities, 0.14% and 0.22% of neurons, and this was unaffected by TSD alone (0.1%. Mild TBI caused significantly higher DN densities (0.76%, and this was unchanged by preexisting acute or chronic sleep debt (TSD, 0.23%; CSR, 0.7%. Thus, although sleep debt may be predicted to increase the incidence of concussive injury, the present data suggest that sleep debt does not exacerbate the resulting neuronal damage. Keywords: sleep deprivation, concussion, traumatic brain injury, dark neuron, neurodegeneration, rat cortex

On the onset of secondary flow and unsteady solutions through a loosely coiled rectangular duct for large aspect ratio

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Shaha, Poly Rani; Poddar, Nayan Kumar; Mondal, Rabindra Nath, E-mail: rnmondal71@yahoo.com [Department of Mathematics, Jagannath University, Dhaka-1100 (Bangladesh); Rudro, Sajal Kanti [Department of Mathematics, Notredame Colleage, Motijheel, Dhaka (Bangladesh)

2016-07-12

The study of flows through coiled ducts and channels has attracted considerable attention not only because of their ample applications in Chemical, Mechanical, Civil, Nuclear and Biomechanical engineering but also because of their ample applications in other areas, such as blood flow in the veins and arteries of human and other animals. In this paper, a numerical study is presented for the fully developed two-dimensional flow of viscous incompressible fluid through a loosely coiled rectangular duct of large aspect ratio. Numerical calculations are carried out by using a spectral method, and covering a wide range of the Dean number, Dn, for two types of curvatures of the duct. The main concern of the present study is to find out effects of curvature as well as formation of secondary vortices on unsteady solutions whether the unsteady flow is steady-state, periodic, multi-periodic or chaotic, if Dn is increased. Time evolution calculations as well as their phase spaces are performed with a view to study the non-linear behavior of the unsteady solutions, and it is found that the steady-state flow turns into chaotic flow through various flow instabilities, if Dn is increased no matter what the curvature is. It is found that the unsteady flow is a steady-state solution for small Dn’s and oscillates periodically or non-periodically (chaotic) between two- and twelve-vortex solutions, if Dn is increased. It is also found that the chaotic solution is weak for small Dn’s but strong as Dn becomes large. Axial flow distribution is also investigated and shown in contour plots.

Significant role of Fas ligand-binding but defective Fas receptor (CD95) in lymph node hyperplasia composed of abnormal double-negative T cells

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Matsuzawa, Akio; Shimizu, Motomu; Takeda, Yasutaka; Nagase, Hisashi; Sayama, Kazutoshi; Kimura, Mikio

2002-01-01

The functional differences between two mutations of the Fas (CD95) locus, Faslpr (lpr) and Faslprcg (lprcg), were investigated using bone marrow (BM) transplantation on the C3H mouse background. Both lpr/lpr and lprcg/lprcg BM transferred caused lymph node (LN) hyperplasia in lpr/+ and lprcg/+ recipients, although it was clearly smaller than that in lpr/lpr and lprcg/lprcg recipients of lpr/lpr and lprcg/lprcg BM. In addition, both BM induced significantly larger LN hyperplasia in lprcg/+ than lpr/+ recipients. Appearance of CD4− CD8−[double negative (DN)] T cells in the periphery is the most consistent phenotype of Fas mutations. Importantly, the proportion of DN T cells was higher in larger LN hyperplasia in the order of lpr/+, lprcg/+ and lpr/lpr or lprcg/lprcg recipients. On the other hand, both lpr/lpr and lprcg/lprcg BM transferred into wild-type (+/+) mice caused marked LN atrophy. The former, but not the latter, induced wasting syndrome. Faslg1d (gld)-homozygous lpr/lpr BM transferred into +/+ mice elicited LN hyperplasia of the same extent as that in lpr/lpr mice transferred with lpr/lpr BM, but not wasting syndrome. Taken together with the fact that DN T cells massively express Fas ligand (FasL), this study implied that FasL overexpressed on DN cells may be involved in the accumulation of DN T cells in LN, LN atrophy and wasting syndrome, and that lprcg Fas, which can bind to Fas ligand but not transduce apoptosis signal into cells, may modulate these pathological conditions by interfering with the binding of FasL to Fas. PMID:12153509

AMPK-α2 is involved in exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following high-fat diet.

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Abbott, Marcia J; Turcotte, Lorraine P

2014-10-15

AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2 activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2 dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61-64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2 signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD. Copyright © 2014 the American Physiological Society.

Phelan-McDermid syndrome data network: Integrating patient reported outcomes with clinical notes and curated genetic reports.

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Kothari, Cartik; Wack, Maxime; Hassen-Khodja, Claire; Finan, Sean; Savova, Guergana; O'Boyle, Megan; Bliss, Geraldine; Cornell, Andria; Horn, Elizabeth J; Davis, Rebecca; Jacobs, Jacquelyn; Kohane, Isaac; Avillach, Paul

2017-09-01

The heterogeneity of patient phenotype data are an impediment to the research into the origins and progression of neuropsychiatric disorders. This difficulty is compounded in the case of rare disorders such as Phelan-McDermid Syndrome (PMS) by the paucity of patient clinical data. PMS is a rare syndromic genetic cause of autism and intellectual deficiency. In this paper, we describe the Phelan-McDermid Syndrome Data Network (PMS_DN), a platform that facilitates research into phenotype-genotype correlation and progression of PMS by: a) integrating knowledge of patient phenotypes extracted from Patient Reported Outcomes (PRO) data and clinical notes-two heterogeneous, underutilized sources of knowledge about patient phenotypes-with curated genetic information from the same patient cohort and b) making this integrated knowledge, along with a suite of statistical tools, available free of charge to authorized investigators on a Web portal https://pmsdn.hms.harvard.edu. PMS_DN is a Patient Centric Outcomes Research Initiative (PCORI) where patients and their families are involved in all aspects of the management of patient data in driving research into PMS. To foster collaborative research, PMS_DN also makes patient aggregates from this knowledge available to authorized investigators using distributed research networks such as the PCORnet PopMedNet. PMS_DN is hosted on a scalable cloud based environment and complies with all patient data privacy regulations. As of October 31, 2016, PMS_DN integrates high-quality knowledge extracted from the clinical notes of 112 patients and curated genetic reports of 176 patients with preprocessed PRO data from 415 patients. © 2017 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

On the onset of secondary flow and unsteady solutions through a loosely coiled rectangular duct for large aspect ratio

International Nuclear Information System (INIS)

Shaha, Poly Rani; Poddar, Nayan Kumar; Mondal, Rabindra Nath; Rudro, Sajal Kanti

2016-01-01

The study of flows through coiled ducts and channels has attracted considerable attention not only because of their ample applications in Chemical, Mechanical, Civil, Nuclear and Biomechanical engineering but also because of their ample applications in other areas, such as blood flow in the veins and arteries of human and other animals. In this paper, a numerical study is presented for the fully developed two-dimensional flow of viscous incompressible fluid through a loosely coiled rectangular duct of large aspect ratio. Numerical calculations are carried out by using a spectral method, and covering a wide range of the Dean number, Dn, for two types of curvatures of the duct. The main concern of the present study is to find out effects of curvature as well as formation of secondary vortices on unsteady solutions whether the unsteady flow is steady-state, periodic, multi-periodic or chaotic, if Dn is increased. Time evolution calculations as well as their phase spaces are performed with a view to study the non-linear behavior of the unsteady solutions, and it is found that the steady-state flow turns into chaotic flow through various flow instabilities, if Dn is increased no matter what the curvature is. It is found that the unsteady flow is a steady-state solution for small Dn’s and oscillates periodically or non-periodically (chaotic) between two- and twelve-vortex solutions, if Dn is increased. It is also found that the chaotic solution is weak for small Dn’s but strong as Dn becomes large. Axial flow distribution is also investigated and shown in contour plots.

CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.

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Wei Hua

Full Text Available Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN, respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20 by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5 and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO, the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.

The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification.

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Chang, Wing Y; Bryce, Dawn M; D'Souza, Sudhir J A; Dagnino, Lina

2004-12-03

The epidermis is a stratified epithelium constantly replenished through the ability of keratinocytes in its basal layer to proliferate and self-renew. The epidermis arises from a single-cell layer ectoderm during embryogenesis. Large proliferative capacity is central to ectodermal cell and basal keratinocyte function. DP-1, a heterodimeric partner of E2F transcription factors, is highly expressed in the ectoderm and all epidermal layers during embryogenesis. To investigate the role of DP-1 in epidermal morphogenesis, we inhibited DP-1 activity through exogenous expression of a dominant-negative mutant (dnDP-1). Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein expression. Chromatin immunoprecipitation analysis demonstrated that the cyclin A promoter is predominantly bound in proliferating keratinocytes by complexes containing E2F-3 and E2F-4. Thus, the mechanisms of decreased expression of cyclin A in the presence of dnDP-1 seem to involve inactivation of DP-1 complexes containing E2F-3 and E2F-4. To assess the consequences on epidermal morphogenesis of inhibiting DP-1 activity, we expressed dnDP-1 in rat epithelial keratinocytes in organotypic culture and observed that DP-1 inhibition negatively affected stratification of these cells. Likewise, expression of dnDP-1 in embryonic ectoderm explants produced extensive disorganization of subsequently formed epidermal basal and suprabasal layers, interfering with normal epidermal formation. We conclude that DP-1 activity is required for normal epidermal morphogenesis and ectoderm-to-epidermis transition.

Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model

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Mazzilli, Sarah A.; Hershberger, Pamela A.; Reid, Mary E.; Bogner, Paul N.; Atwood, Kristopher; Trump, Donald L.; Johnson, Candace S.

2015-01-01

The chemopreventive actions of vitamin D were examined in the N-nitroso-tris-chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C) (80 μg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 μmol NTCU (N). After treatment with 15 μmol NTCU, the % of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient +NTCU (DN), 22.7 % (p<0.05 compared to vitamin D-sufficient +NTCU (SN)); DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared to SN mice, DN mice exhibited a 3-fold increase (p <0.005) in circulating white blood cells (WBC), a 20% (p <0.05) increase in IL-6 levels, and a 4 -fold (p <0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted. PMID:26276745

Combined Microencapsulated Islet Transplantation and Revascularization of Aortorenal Bypass in a Diabetic Nephropathy Rat Model

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Yunqiang He

2016-01-01

Full Text Available Objective. Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS in diabetic nephropathy (DN patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model. Methods. A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1 in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules. Results. The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated. Conclusions. The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.

Utilisation of Food and Woodworking Production By-products by Composting

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Uldis Viesturs

2004-10-01

Full Text Available The purpose of the study was to develop laboratory-scale technologies for composting milk/cheese whey, spent liquor, brewery yeast, fish processing by-products, etc., adding these by-products and special microorganism associations to the basic material - sawdust, bark, etc., also arranging different experimental composting sites. Two Trichoderma strains (Tr. lignorum, Tr. viride and a nitrification association for regulating the circulation of nitrogen-ammonification and nitrification processes were applied. Monitoring of the composting quality was realised by microbiological and chemical analyses, and biotests for compost quality (toxicity assessment. For purifying the polluted air from the composting facilities, the biofiltration technique was realised in a modified SSF system. Biodegradation of ammonia was investigated in a two-stage system with the inert packing material - dolomite broken bricks, and hemoautotrophic microorganisms: DN-1 (Pseudomonas sp., DN-2 (Nitrosomonas sp., DN-3 (Nitrobacter sp. and DN-13 (Sarcina sp.. For hydrogen sulphide biodegradation, Thiobacillus thioparus-3 was immobilised on glass bricks as the carrier material. Biodegradation efficiency of hydrogen sulphide was 87%. Biodegradation of ammonia in the first step in the two-stage system reached 77%, degradation of the gas remaining in the second step was 75%. Compost's quality was similar to black soil - brown-coloured, with good soil odour and without toxic compounds.

Comparison of Dry Needling versus Orthopedic Manual Therapy in Patients with Myofascial Chronic Neck Pain: A Single-Blind, Randomized Pilot Study

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Irene Campa-Moran

2015-01-01

Full Text Available Objective. The aim of this study was to compare the efficacy of three interventions for the treatment of myofascial chronic neck pain. Methods. Thirty-six patients were randomly assigned to one of three intervention groups: orthopedic manual therapy (OMT, dry needling and stretching (DN-S, and soft tissue techniques (STT. All groups received two treatment sessions with a 48 h time interval. Outcome measures included neck pain intensity measured using a visual analogue scale, cervical range of motion (ROM, pressure pain threshold for measuring mechanical hyperalgesia, and two self-reported questionnaires (neck disability index and pain catastrophizing scale. Results. The ANOVA revealed significant differences for the group × time interaction for neck disability, neck pain intensity, and pain catastrophizing. The DN-S and OMT groups reduced neck disability. Only the OMT group showed decreases in mechanical hyperalgesia and pain catastrophizing. The cervical ROM increased in OMT (i.e., flexion, side-bending, and rotation and DN-S (i.e., side-bending and rotation groups. Conclusions. The three interventions are all effective in reducing pain intensity. Reduction in mechanical hyperalgesia and pain catastrophizing was only observed in the OMT group. Cervical ROM improved in the DN-S and OMT groups and also neck disability being only clinically relevant for OMT group.

Renal Protection by Genetic Deletion of the Atypical Chemokine Receptor ACKR2 in Diabetic OVE Mice

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Shirong Zheng

2016-01-01

Full Text Available In diabetic nephropathy (DN proinflammatory chemokines and leukocyte infiltration correlate with tubulointerstitial injury and declining renal function. The atypical chemokine receptor ACKR2 is a chemokine scavenger receptor which binds and sequesters many inflammatory CC chemokines but does not transduce typical G-protein mediated signaling events. ACKR2 is known to regulate diverse inflammatory diseases but its role in DN has not been tested. In this study, we utilized ACKR2−/− mice to test whether ACKR2 elimination alters progression of diabetic kidney disease. Elimination of ACKR2 greatly reduced DN in OVE26 mice, an established DN model. Albuminuria was significantly lower at 2, 4, and 6 months of age. ACKR2 deletion did not affect diabetic blood glucose levels but significantly decreased parameters of renal inflammation including leukocyte infiltration and fibrosis. Activation of pathways that increase inflammatory gene expression was attenuated. Human biopsies stained with ACKR2 antibody revealed increased staining in diabetic kidney, especially in some tubule and interstitial cells. The results demonstrate a significant interaction between diabetes and ACKR2 protein in the kidney. Unexpectedly, ACKR2 deletion reduced renal inflammation in diabetes and the ultimate response was a high degree of protection from diabetic nephropathy.

Abatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of Diabetic Nephropathy.

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Jenny Norlin

Full Text Available Diabetic nephropathy (DN is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept, a molecule that binds and blocks B7-1 and is licensed for the treatment of rheumatoid arthritis, could ameliorate DN. This study was designed to assess whether B7-1 signalling constitutes a promising therapeutic pathway for DN. Mice injected with streptozotocin (STZ were treated with abatacept and glycemia and renal function were assessed. No differences were found in diabetes progression, albumin excretion rates or albumin/creatine ratios, while mesangial expansion was unaltered at endpoint. Except for increased renal CCL5, treatment did not affect a panel of gene expression endpoints reflecting early fibrotic changes, inflammation and kidney injury. Finally, abatacept treatment effectively reduced the accumulation of activated CD4+ T cells in the kidney, suggesting that renal T cell inflammation is not a driving factor in the pathology of the STZ model. In conjunction with the recent data discounting the expression of B7-1 on podocytes, our present data do not support a role for abatacept in DN treatment.

Proteomic profile in glomeruli of type-2 diabetic KKAy mice using 2-dimensional differential gel electrophoresis.

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Liu, Xiaodan; Yang, Gang; Fan, Qiuling; Wang, Lining

2014-12-17

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. To search for glomerular proteins associated with early-stage DN, glomeruli of spontaneous type 2 diabetic KKAy mice were analyzed by 2-dimensional differential gel electrophoresis (2D-DIGE). Glomeruli of 20-week spontaneous type 2 diabetic KKAy mice and age-matched C57BL/6 mice were isolated by kidney perfusion with magnetic beads. Proteomic profiles of glomeruli were investigated by using 2D-DIGE and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Western blot analysis was used to confirm the results of proteomics. Immunohistochemical and semi-quantitative analysis were used to confirm the differential expression of prohibitin and annexin A2 in glomeruli. We identified 19 differentially expressed proteins - 17 proteins were significantly up-regulated and 2 proteins were significantly down-regulated in glomeruli of diabetic KKAy mice. Among them, prohibitin and annexin A2 were up-regulated and Western blot analysis validated the same result in proteomics. Immunohistochemical analysis also revealed up-regulation of prohibitin and annexin A2 in glomeruli of KKAy mice. Our findings suggest that prohibitin and annexin A2 may be associated with early-stage DN. Further functional research might help to reveal the pathogenesis of DN.

Heterogeneity of breast cancer stem cells as evidenced with Notch-dependent and Notch-independent populations

International Nuclear Information System (INIS)

Wong, Nelson K Y; Fuller, Megan; Sung, Sandy; Wong, Fred; Karsan, Aly

2012-01-01

Studies have suggested the potential importance of Notch signaling to the cancer stem cell population in some tumors, but it is not known whether all cells in the cancer stem cell fraction require Notch activity. To address this issue, we blocked Notch activity in MCF-7 cells by expressing a dominant-negative MAML-GFP (dnMAML) construct, which inhibits signaling through all Notch receptors, and quantified the effect on tumor-initiating activity. Inhibition of Notch signaling reduced primary tumor sphere formation and side population. Functional quantification of tumor-initiating cell numbers in vivo showed a significant decrease, but not a complete abrogation, of these cells in dnMAML-expressing cells. Interestingly, when assessed in secondary assays in vitro or in vivo, there was no difference in tumor-initiating activity between the dnMAML-expressing cells and control cells. The fact that a subpopulation of dnMAML-expressing cells was capable of forming primary and secondary tumors indicates that there are Notch-independent tumor-initiating cells in the breast cancer cell line MCF-7. Our findings thus provide direct evidence for a heterogeneous cancer stem cell pool, which will require combination therapies against multiple oncogenic pathways to eliminate the tumor-initiating cell population

Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy

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Sonia Sifuentes-Franco

2018-01-01

Full Text Available Diabetic nephropathy (DN is the second most frequent and prevalent complication of diabetes mellitus (DM. The increase in the production of oxidative stress (OS is induced by the persistent hyperglycemic state capable of producing oxidative damage to the macromolecules (lipids, carbohydrates, proteins, and nucleic acids. OS favors the production of oxidative damage to the histones of the double-chain DNA and affects expression of the DNA repairer enzyme which leads to cell death from apoptosis. The chronic hyperglycemic state unchains an increase in advanced glycation end-products (AGE that interact through the cellular receptors to favor activation of the transcription factor NF-κB and the protein kinase C (PKC system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the extracellular matrix (ECM in DN. The reactive oxygen species (ROS play an important role in the pathogenesis of diabetic complications because the production of ROS increases during the persistent hyperglycemia. The primary source of the excessive production of ROS is the mitochondria with the capacity to exceed production of endogenous antioxidants. Due to the fact that the mechanisms involved in the development of DN have not been fully clarified, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN.

Enhancing assertiveness in district nurse specialist practice.

Science.gov (United States)

Green, Julie

2016-08-02

District nurse (DN) care delivery has undergone substantial change in recent years due to changing demographics and service delivery demands that have called for a move of care delivery from secondary to primary care. The title District Nurse is recorded with the Nursing and Midwifery Council (NMC) on completion of the Specialist Practice Qualification in District Nursing (SPQ DN), which purports to be a 'transformational' course that prepares future caseload holders to manage their team and prioritise care delivery effectively. This article explores the need for assertiveness skills in this role in response to Australian research, and outlines the pedagogic interventions implemented during the SPQ DN course to enhance this skill. Assertiveness scores were monitored for the duration of the course and demonstrated a significant increase-a topic that is now the subject of a future, funded study.

On invariant MASAs for endomorphisms of the Cuntz algebras

DEFF Research Database (Denmark)

Hong, Jeong Hee; Skalski, Adam; Szymanski, Wojciech

2010-01-01

The problem of existence of standard (i.e. product-type) invariant MASAs for endomorphisms of the Cuntz algebras O_n is studied. In particular, endomorphisms which preserve the canonical diagonal MASA D_n are investigated. Conditions on a unitary w equivalent to the fact that the corresponding...... endomorphism λ_w preserves D_n are found, and it is shown that they may be satisfied by unitaries which do not normalize D_n. Unitaries giving rise to endomorphisms which leave all standard MASAs invariant and have identical actions on them are characterized. Finally, some properties of examples of finite......-index endomorphisms of O_n given by Izumi and related to sector theory are discussed and it is shown that they lead to an endomorphism of O_2 associated to a matrix unitary which does not preserve any standard MASA....

Clinical significance of determination of changes of serum visfatin and adiponectin levels in patients with type 2 diabetic nephropathy

International Nuclear Information System (INIS)

Xu Ning

2009-01-01

Objective: To study the clinical significance of changes of serum visfatin and adiponectin levels in patients with type 2 diabetic nephropathy (DN). Methods: Serum visfatin (with ELISA) and serum adiponectin (with RIA) levels were determined in 41 cases of DM2 without nephropathy, 32 cases of DN and 35 controls. Results: Serum visfatin levels in the diabetic patients were significantly higher than those in controls (P<0.01), while the serum adiponectin levels were significantly lower than those in controls (P<0.01). Serum visfatin levels were significantly negatively correlated with those of serum adiponectin (r=-0.4108, P<0.05). The levels of serum adiponectin in patients with DN is higher than those in patients with DM2 but without nephropathy. Conclusion: The development of type 2 diabetic nephropathy might be related to the levels of visfatin and adipone. (authors)

Semiempirical Quantum-Chemical Orthogonalization-Corrected Methods: Benchmarks for Ground-State Properties.

Science.gov (United States)

Dral, Pavlo O; Wu, Xin; Spörkel, Lasse; Koslowski, Axel; Thiel, Walter

2016-03-08

The semiempirical orthogonalization-corrected OMx methods (OM1, OM2, and OM3) go beyond the standard MNDO model by including additional interactions in the electronic structure calculation. When augmented with empirical dispersion corrections, the resulting OMx-Dn approaches offer a fast and robust treatment of noncovalent interactions. Here we evaluate the performance of the OMx and OMx-Dn methods for a variety of ground-state properties using a large and diverse collection of benchmark sets from the literature, with a total of 13035 original and derived reference data. Extensive comparisons are made with the results from established semiempirical methods (MNDO, AM1, PM3, PM6, and PM7) that also use the NDDO (neglect of diatomic differential overlap) integral approximation. Statistical evaluations show that the OMx and OMx-Dn methods outperform the other methods for most of the benchmark sets.

Genetic Variation in the Matrix Metalloproteinase Genes and Diabetic Nephropathy in Type 1 Diabetes

OpenAIRE

Kure, Masahiko; Pezzolesi, Marcus G.; Poznik, G. David; Katavetin, Pisut; Skupien, Jan; Dunn, Jonathon S.; Mychaleckyj, Josyf C.; Warram, James H.; Krolewski, Andrzej S.

2011-01-01

Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type...

Delphian node metastasis in head and neck cancers--oracle or myth?

Science.gov (United States)

Iyer, N Gopalakrishna; Shaha, Ashok R; Ferlito, Alfio; Thomas Robbins, K; Medina, Jesus E; Silver, Carl E; Rinaldo, Alessandra; Takes, Robert P; Suárez, Carlos; Rodrigo, Juan P; Bradley, Patrick J; Werner, Jochen A

2010-09-15

Delphian node (DN) refers to the pre-laryngeal or pre-cricoid nodal tissue often identified during laryngeal or thyroid surgery. The original nomenclature is based on the assumption that metastasis to this node was predictive of aggressive disease and poor outcome for patients. In this article, we review the existing literature on the topic to determine the significance of DN metastasis in laryngeal, hypopharyngeal and thyroid cancers. (c) 2010 Wiley-Liss, Inc.

Dependecia a la nicotina en Bucaramanga, Colombia: Prevalencia y factores de riesgo. Nicotine dependecne in Bucaramanga, Colombia: Prevalence and risk factors

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Germas Eduardo Rueda-Jaimes, MD

2010-11-01

Full Text Available Antecedentes: La dependencia a la nicotina (DN es la dependencia más frecuente en la población general colombiana; sin embargo, a la fecha no se conocen los factores asociados.Objetivo: Determinar la prevalencia y los factores asociados a DN en adultos del área urbana de Bucaramanga, Colombia. Método: Se diseñó un estudio poblacional transversal para estudiar una muestra probabilística de personas entre 18 y 65 años. La DN se determinó en fumadores diarios durante el último mes con la escala de Etter para dependencia al cigarrillo (CDS, con un punto de corte de 30/60. Mediante regresión logística se ajustaron las variables asociadas.Resultados: Participaron 2.496 personas con edad promedio de 38,0 años (DE=13,5, 69,7% mujeres. Un total de 250 (10,0% personas informaron consumo diario de cigarrillo; de este grupo, 154 (61,6% presentaron DN. La prevalencia ajustada de DN en la población global fue 5,6%. La DN fue más frecuente en varones (3,0; IC95% 2,0-4,4, en personas con menor escolaridad (OR=1,1; (IC95% 1,0-1,1, en personas empleadas (OR=1,5; IC95% 1,0-2,2, en residentes en estrato bajo (OR=1,7; IC95% 1,2-2,4, en consumidores diarios de café (OR=2,8; IC95% 1,9-4,1, en presencia de consumo abusivo de alcohol (OR=4,1; IC95% 2,4-7,2 y quienes informaron trastornos mentales comunes (OR=3,5; IC95% 2,3-5,1.Conclusiones: La prevalencia de DN es alta en la población general de Bucaramanga, Colombia. Dos tercios de los fumadores diarios presentan DN. La DN se asocia a consumo diario de café, consumo abusivo de alcohol y la presencia de trastornos mentales comunes.Background: Nicotine dependence (ND is the most common substance dependence in Colombian population. However, its factors associated are unknown. Objective: To establish the prevalence and factors associated with ND among adults in Bucaramanga, Colombia. Method: A cross-sectional study was done with adults aged between 18 and 65 years. Among current cigarette smokers, the ND

Acción de la miotoxina del veneno de Bothrops brazili Hoge, 1953 (Ophidia: Viperidae

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Carmen Pantigoso

2013-06-01

Full Text Available Se ha estudiado el modo de acción de la miotoxina aislada del veneno de la serpiente Bothrops brazili. La inoculación de la miotoxina en el músculo gastrocnemius de ratones albinos produce durante la primera hora de acción la liberación de creatina kinasa y lactato deshidrogenasa, mientras que por PAGE-SDS, se revela que la incubación de la miotoxina con músculo gastrocnemius aislado, produce además la liberación de otras proteínas musculares. Asimismo, la miotoxina produce hipercontracción, lesiones delta e incrementa los niveles de calcio intramuscular, tanto in vivo como in vitro, lo cual no depende del ingreso de calcio extracelular vía receptores de dihidropiridina. Este incremento de calcio explicaría la hipercontracción observada y podría generar la activación de proteasas y lipasas endógenas dependientes de calcio, que conducirían a la necrosis muscular.

Purificación y caracterización parcial de una toxina (Hm3 del veneno de Hadruroides mauryi (Francke y Soleglad, 1980 (Scorpiones, Iuridae

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Luz Velásquez

2013-06-01

Full Text Available Se ha purificado una toxina (Hm3 del veneno del escorpión Hadruroides mauryi, por cromatografía de intercambio iónico en CM-Sephadex C-25 con buffer acetato de amonio 0,05M, pH 7. La toxina produce contracción y parálisis en la extremidad inoculada de ratones albinos y se caracteriza por ser de naturaleza básica y tener un peso molecular de 4,5 kDa. Después de 45 minutos de ser inoculada en el músculo gastrocnemius de ratones albinos, Hm3 (30,4 µg aumenta los niveles plasmáticos de creatina kinasa desde 252,6 UI/L hasta 3779,3 UI/L y de lactato deshidrogenasa, desde 142,7 UI/L hasta 248,2 UI/L; igualmente incrementa los niveles de calcio intramuscular desde 34,1 nmoles hasta 69,3 nmoles. Esta toxina carece de actividad proteolítica y fosfolipásica.

The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: a meta-analysis.

Science.gov (United States)

Wang, Bin; Chen, Shibo; Yan, Xiufeng; Li, Mingdi; Li, Daqi; Lv, Pin; Ti, Guixiang

2015-01-01

Diabetic nephropathy (DN) is the main cause of end-stage kidney disease in developed countries. Current therapy can slow the rate of progression of DN, but eventually end-stage renal failure will occur in a proportion of patients. Identification of new strategies and additional complementary and alternative therapies for treating DN are important. The research team wanted to assess the beneficial and harmful effects of using puerarin plus angiotensin converting enzyme inhibitor (ACEI) compared with using only ACEI for treatment of individuals with stage III DN. The research team performed a meta-analysis of randomized, controlled trials (RCTs) by searching the following electronic databases: (1) the Cochrane Database of Systematic Reviews, (2) the Cochrane Central Register of Controlled Trials (CENTRAL), (3) PubMed, (4) EMBASE (Elsevier), (5) the Allied and Complementary Medicine Database (AMED), (6) the Chinese Biomedicine Database (CBM), (7) the China National Knowledge Infrastructure (CNKI), and (8) the Chinese Biomedical Journals (VIP), with no language restrictions, as well as databases of clinical trials. Measured outcomes included (1) urinary protein measured as urinary albumin excretion rate (UAER) (μg/min) and 24-h urine protein (24-h UP) (mg/24 h); (2) renal function measured as blood urea nitrogen (BUN) (mmol/L) and serum creatinine (SCr) (μmol/L); (3) α1-microglobulin (α1-MG) (mg/24 h) and endothelin-1 (ET-1) (ng/24 h); (4) end points (EPs); and (5) adverse events (AEs). Ten RCTs involving 669 participants were included. All trials were conducted and published in China. Treatment of DN with puerarin plus ACEI significantly decreased the UAER-P < .0001, MD = -23.43 (95% CI, -33.95 to -12.91), and had no effect on 24-h UP-P = .09, MD = -56.76 (95% CI, -122.65 to 9.12); BUN-P = .17, MD = -0.51 (95% CI, -1.24 to 0.21); and SCr-P = .26, MD = -4.43 (95% CI, -12.05 to 3.20). One trial reported abdominal discomfort and nausea (2 cases) in the treatment

Cord blood Vα24-Vβ11 natural killer T cells display a Th2-chemokine receptor profile and cytokine responses.

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Susanne Harner

Full Text Available BACKGROUND: The fetal immune system is characterized by a Th2 bias but it is unclear how the Th2 predominance is established. Natural killer T (NKT cells are a rare subset of T cells with immune regulatory functions and are already activated in utero. To test the hypothesis that NKT cells are part of the regulatory network that sets the fetal Th2 predominance, percentages of Vα24(+Vβ11(+ NKT cells expressing Th1/Th2-related chemokine receptors (CKR were assessed in cord blood. Furthermore, IL-4 and IFN-γ secreting NKT cells were quantified within the single CKR(+ subsets. RESULTS: Cord blood NKT cells expressed the Th2-related CCR4 and CCR8 at significantly higher frequencies compared to peripheral blood NKT cells from adults, while CXCR3(+ and CCR5(+ cord blood NKT cells (Th1-related were present at lower percentages. Within CD4(negCD8(neg (DN NKT cells, the frequency of IL-4 producing NKT cells was significantly higher in cord blood, while frequencies of IFN-γ secreting DN NKT cells tended to be lower. A further subanalysis showed that the higher percentage of IL-4 secreting DN NKT cells was restricted to CCR3(+, CCR4(+, CCR5(+, CCR6(+, CCR7(+, CCR8(+ and CXCR4(+ DN subsets in cord blood. This resulted in significantly decreased IFN-γ /IL-4 ratios of CCR3(+, CCR6(+ and CCR8(+ cord blood DN NKT cells. Sequencing of VA24AJ18 T cell receptor (TCR transcripts in sorted cord blood Vα24Vβ11 cells confirmed the invariant TCR alpha-chain ruling out the possibility that these cells represent an unusual subset of conventional T cells. CONCLUSIONS: Despite the heterogeneity of cord blood NKT cells, we observed a clear Th2-bias at the phenotypic and functional level which was mainly found in the DN subset. Therefore, we speculate that NKT cells are important for the initiation and control of the fetal Th2 environment which is needed to maintain tolerance towards self-antigens as well as non-inherited maternal antigens.

Structural control on gold mineralization in the Satulinmäki and Riukka prospects, Häme Schist Belt, southern Finland

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Kerstin Saalmann

2007-01-01

Full Text Available The Satulinmäki and Riukka prospects located in the Häme Schist Belt in southern Finland are dominated by mafic and intermediate to felsic metavolcanic rocks of the Forssa Group formed in a continental arc setting. This magmatic belt formed some 1890–1880 Ma ago and has been deformed during the Svecofennian orogeny. The dominant penetrative foliation is represented by Sn+1, which is axial planar to cm- to dm-scale iscolinal Fn+1 folds and thus parallel to the layering Sn. Associated ductile shearing might reflect early thrusting. Dn+2 post-dating peak metamorphism is characterized by small-scale to regional-scale refolding of Fn+1 folds around ~SW-NE fold axes. This phase is transitional to development of SW-NE to WSW-ENE and NW-SE striking shear zones and faults formed due to dextral transpressionduring Dn+3 at retrograde conditions crossing the brittle-ductile transition. Many mineralized quartz veins have formed during this event. Later faults and quartz veins and reactivation of pre-existing structures during Dn+4 indicate rotation of the stress field to ~NESWoriented compression. A clear ~SW-NE trend of sulphide mineralization and elevated gold contents and the spatial association to Dn+3 quartz veins, shear zones and faults suggest a strong structural control, typical of orogenic gold deposits, and that mineralization took place during Dn+3. The controlling structures, (i WSW-ENE to SW-NE shear zones and faults and (ii NW-SE oriented fault, are second and third order structures to major regional-scale shear zones. The fault zones and their intersection points impart a directional permeability so that the mineralising fluids were channelled along dilatant zones. Approximately (WNW-(ESE trending faults being (reactivated as extensional faults or dilatant shear planes during Dn+3 transpression with WNW-ESE to NW-SE oriented compression direction could have acted as conduits for fluids during upward flow from deeper crustal level. Future

Benazepril affects integrin-linked kinase and smooth muscle α-actin expression in diabetic rat glomerulus and cultured mesangial cells.

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Niu, Honglin; Nie, Lei; Liu, Maodong; Chi, Yanqing; Zhang, Tao; Li, Ying

2014-08-20

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and is associated with excessive cardiovascular morbidity and mortality. The angiotensin converting enzyme inhibitor (ACEI) benazepril has been shown to slow the progression of chronic renal disease and have beneficial effects in patients with a combination of chronic renal disease and cardiovascular disease. Transforming growth factor-β(1) (TGF-β(1)) plays a central role in the pathogenesis and progression of DN. Integrin-linked kinase (ILK) can modulate TGF-β(1)-induced glomerular mesangial cell (GMC) injury, which is a prominent characteristic of renal pathology in kidney diseases. As an integrin cytoplasmic-binding protein, ILK regulates fibronectin (FN) matrix deposition and the actin cytoskeleton. Smooth muscle α-actin (α-SMA) is involved in progressive renal dysfunction in both human and experimental renal disease. To explore the mechanisms of benazepril's reno-protective effects, we examined the expression of TGF-β(1), ILK, and α-SMA in GMC exposed to high glucose (HG) and in the kidneys of streptozotocin (STZ)-induced diabetic rats using real-time quantitative RT-PCR and western blot analysis. To elucidate the mechanism(s) of the effect of benazepril on GMC cellular processes, we assessed the effect of benazepril on Angiotensin II (Ang II) signalling pathways using western blot analysis. The expression of TGF-β(1), ILK, and α-SMA increased significantly in the diabetic group compared with the control group. Benazepril treatment inhibited the expression of these genes in DN but failed to rescue the same levels in the control group. Similar results were found in GMC treated with HG or benazepril. Ang II increased ERK and Akt phosphorylation in the HG group, and benazepril could not completely block these responses, suggesting that other molecules might be involved in the progression of DN. Our findings suggest that benazepril decreases ILK and α-SMA expression, at least in

Functional inhibition of Ubiquitin conjugating Enzyme (UBE2C) reduces proliferation and sensitizes cervical and breast cancer cells to radiation, doxorubicin, tamoxifen and letrozole

International Nuclear Information System (INIS)

Bose, Mayil Vahanan; Rawat, Akhilesh; Gopisetty, Gopal; Thangarajan, Rajkumar; Ganesharaja, Selvaluxmy

2014-01-01

Cervical cancer is the second most common cancer in women, worldwide. About 80% of cervical cancer cases occur in developing countries. Breast cancer has overtaken cervical cancer in most of the urban centers in India. In recent years, interest in the role of Ubiquitin conjugating Enzyme E2C (UBE2C) in cancer has shown a dramatic increase. Several studies have reported UBE2C as a potential oncogene and therapeutic target. The objective of the study was to elucidate radiation and chemo-sensitivity in response to functional inhibition of UBE2C in cervical and breast cancer cell lines. Taqman Real time PCR was performed to measure UBE2C levels in cervical and breast cancer cell lines. A dominant negative form of UBE2C (DN-UBE2C) was used to functionally inhibit wild type UBE2C. Cell proliferation and anchorage independent growth were measured by colorimetric assay and soft agar assay respectively. Radiation and chemo response of cell lines were assessed by colorimetric assay and clonogenic assay. Difference in sensitivity to radiation was observed among the cervical cancer cell lines studied. The growth rate of SiHa and HeLa transfected with DN- UBE2C was significantly reduced compared to vector control. Further, DN-UBE2C mediated radio-sensitivity was correlated with a significant decrease in resistance to radiation by SiHa and HeLa cells after transfection when compared to control cultures. Similarly, both the growth rate and the anchorage independent growth of MCF7 and MDAMB231 cells transfected with DN-UBE2C were significantly reduced compared to cells transfected with vector alone. MCF7 and MDAMB231 cells expressing DN-UBE2C were significantly more sensitive to different doses of radiation and doxorubicin compared to controls. In addition, DN-UBE2C transfected MCF7 cells were more sensitive to inhibition by tamoxifen and letrozole compared to vector controls. These results suggest that UBE2C can be used as a potential therapeutic target for cervical and breast

Hemoglobin A1c, Diabetes Mellitus, Diabetic Nephropathy and Chronic Kidney Disease

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Alicia G. Cercado

2017-12-01

To prevent, diagnose and treat DM, DN and CKD, it is essential to have state-of-theart tools available to all people. In our region, access to trials, equipment and laboratories within HbA1c standardization programs, internationally accepted, is a pending task. Millions of individuals from the present and future generations of South America will suffer from DM, DN and CKD, so we need to take the voice of science to these people through the daily "doing".

Emotional and cognitive stimuli differentially engage the default network during inductive reasoning

OpenAIRE

Eldaief, Mark C.; Deckersbach, Thilo; Carlson, Lindsay E.; Beucke, Jan C.; Dougherty, Darin D.

2011-01-01

The brain’s default network (DN) is comprised of several cortical regions demonstrating robust intrinsic connectivity at rest. The authors sought to examine the differential effects of emotional reasoning and reasoning under certainty upon the DN through the employment of an event-related fMRI design in healthy participants. Participants were presented with syllogistic arguments which were organized into a 2 × 2 factorial design in which the first factor was emotional salience and the second ...

On Dirichlet-to-Neumann Maps and Some Applications to Modified Fredholm Determinants

OpenAIRE

Gesztesy, Fritz; Mitrea, Marius; Zinchenko, Maxim

2010-01-01

We consider Dirichlet-to-Neumann maps associated with (not necessarily self-adjoint) Schrodinger operators in $L^2(\\Omega; d^n x)$, $n=2,3$, where $\\Omega$ is an open set with a compact, nonempty boundary satisfying certain regularity conditions. As an application we describe a reduction of a certain ratio of modified Fredholm perturbation determinants associated with operators in $L^2(\\Omega; d^n x)$ to modified Fredholm perturbation determinants associated with operators in $L^2(\\partial\\Om...

Effect of the administration of a fermented milk containing Lactobacillus casei DN-114001 on intestinal microbiota and gut associated immune cells of nursing mice and after weaning until immune maturity

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Carmuega Esteban

2008-06-01

Full Text Available Abstract Background Microbial colonization of the intestine after birth is an important step for the development of the gut immune system. The acquisition of passive immunity through breast-feeding may influence the pattern of bacterial colonization in the newborn. The aim of this work was to evaluate the effect of the administration of a probiotic fermented milk (PFM containing yogurt starter cultures and the probiotic bacteria strain Lactobacillus casei DN-114001 to mothers during nursing or their offspring, on the intestinal bacterial population and on parameters of the gut immune system. Results Fifteen mice of each group were sacrificed at ages 12, 21, 28 and 45 days. Large intestines were taken for determination of intestinal microbiota, and small intestines for the study of secretory-IgA (S-IgA in fluid and the study of IgA+ cells, macrophages, dendritic cells and goblet cells on tissue samples. The consumption of the PFM either by the mother during nursing or by the offspring after weaning modified the development of bifidobacteria population in the large intestine of the mice. These modifications were accompanied with a decrease of enterobacteria population. The administration of this PFM to the mothers improved their own immune system and this also affected their offspring. Offspring from mice that received PFM increased S-IgA in intestinal fluids, which mainly originated from their mother's immune system. A decrease in the number of macrophages, dendritic cells and IgA+ cells during the suckling period in offspring fed with PFM was observed; this could be related with the improvement of the immunity of the mothers, which passively protect their babies. At day 45, the mice reach maturity of their own immune system and the effects of the PFM was the stimulation of their mucosal immunity. Conclusion The present work shows the beneficial effect of the administration of a PFM not only to the mothers during the suckling period but also to

Design development of bellows for the DNB beam source

International Nuclear Information System (INIS)

Singh, Dhananjay Kumar; Venkata Nagaraju, M.; Joshi, Jaydeep; Patel, Hitesh; Yadav, Ashish; Pillai, Suraj; Singh, Mahendrajit; Bandyopadhyay, Mainak; Chakraborty, A.K.; Sharma, Dheeraj

2017-01-01

Establishing a procedure and mechanism for alignment of Ion beams in Neutral Beam (NB) sources for ITER like systems are complex due to large traversal distances (∼21 m) and restricted use of flexible elements into the system. For the beam source of DNB, movement requirements for beam alignment are the combination of tilting (±9mrad), rotation (±9mrad) and translation (±25mm). The present work describes the design development of a system composed of three single ply ‘Gimbal’ type bellow system, placed in series, in L-shaped hydraulic lines (size DN50, DN20 and DN15). The paper shall detail out the generation of initial requirements, transformation of movements at bellow locations, selection of bellows/combination of bellows, minimizing the induced movements by optimization of bellows location, estimation of movements through CEASAR II and the design compliance with respect to EJMA code

A Framework for Similarity Search with Space-Time Tradeoffs using Locality Sensitive Filtering

DEFF Research Database (Denmark)

Christiani, Tobias Lybecker

2017-01-01

that satisfies certain locality-sensitivity properties, we can construct a dynamic data structure that solves the approximate near neighbor problem in $d$-dimensional space with query time $dn^{\\rho_q + o(1)}$, update time $dn^{\\rho_u + o(1)}$, and space usage $dn + n^{1 + \\rho_u + o(1)}$ where $n$ denotes......We present a framework for similarity search based on Locality-Sensitive Filtering~(LSF),generalizing the Indyk-Motwani (STOC 1998) Locality-Sensitive Hashing~(LSH) framework to support space-time tradeoffs. Given a family of filters, defined as a distribution over pairs of subsets of space...... the number of points in the data structure.The space-time tradeoff is tied to the tradeoff between query time and update time (insertions/deletions), controlled by the exponents $\\rho_q, \\rho_u$ that are determined by the filter family. \\\\ Locality-sensitive filtering was introduced by Becker et al. (SODA...

Development of BATAN’s texture diffractometer (current status)

Energy Technology Data Exchange (ETDEWEB)

Priyanto, T. H., E-mail: thardi@batan.go.id; Bharoto,; Mugirahardjo, H.; Muslih, R.; Ramadhani, A.; Sairun [Center for Nuclear Industrial Material Technology (PTBIN) National Nuclear Energy Agency (BATAN) Kawasan Puspiptek Serpong, Tangerang Selatan (Indonesia)

2015-04-16

Texture Diffractometer, called DN2, is one of neutron diffractometers in BATAN which is dedicated for texture measurement using neutron diffraction method. To obtain better performance of the DN2, a flight tube goniometer have been installed between the monochromator and sample position. By adjusting the flight tube goniometer, defocusing effect at direct beam and background effect could be reduced significantly. Some experiments have been carried out to characterize DN2 performance. The flight tube goniometer alignment and neutron wavelength calibration were characterized using silicon standard sample Si640d. Data refinement of diffraction pattern was analyzed using MAUD software and it is obtained reliability factor with background, R{sub wpb}, reduced significantly, from 42.53 % to 19.36 % after setting of flight tube goniometer. Reliability factor without background (R{sub wp}) was reduced from 27.41% to 21.36%. Calibrated of neutron wavelengh, λ = 1,2799 Angstrom is obtained.

Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory.

Science.gov (United States)

Ballinger, Michael D; Saito, Atsushi; Abazyan, Bagrat; Taniguchi, Yu; Huang, Ching-Hsun; Ito, Koki; Zhu, Xiaolei; Segal, Hadar; Jaaro-Peled, Hanna; Sawa, Akira; Mackie, Ken; Pletnikov, Mikhail V; Kamiya, Atsushi

2015-10-01

Cannabis is an increasingly popular and controversial drug used worldwide. Cannabis use often begins during adolescence, a highly susceptible period for environmental stimuli to alter functional and structural organization of the developing brain. Given that adolescence is a critical time for the emergence of mental illnesses before full-onset in early adulthood, it is particularly important to investigate how genetic insults and adolescent cannabis exposure interact to affect brain development and function. Here we show for the first time that a perturbation in disrupted in schizophrenia 1 (DISC1) exacerbates the response to adolescent exposure to delta-9-tetrahydrocannabinol (Δ(9)-THC), a major psychoactive ingredient of cannabis, consistent with the concept that gene-environment interaction may contribute to the pathophysiology of psychiatric conditions. We found that chronic adolescent treatment with Δ(9)-THC exacerbates deficits in fear-associated memory in adult mice that express a putative dominant-negative mutant of DISC1 (DN-DISC1). Synaptic expression of cannabinoid receptor 1 (CB1R) is down-regulated in the prefrontal cortex, hippocampus, and amygdala, critical brain regions for fear-associated memory, by either expression of DN-DISC1 or adolescent Δ(9)-THC treatment. Notably, elevation of c-Fos expression evoked by context-dependent fear memory retrieval is impaired in these brain regions in DN-DISC1 mice. We also found a synergistic reduction of c-Fos expression induced by cue-dependent fear memory retrieval in DN-DISC1 with adolescent Δ(9)-THC exposure. These results suggest that alteration of CB1R-mediated signaling in DN-DISC1 mice may underlie susceptibility to detrimental effects of adolescent cannabis exposure on adult behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Time Demand and Radiation Dose in 3D-Fluoroscopy-based Navigation-assisted 3D-Fluoroscopy-controlled Pedicle Screw Instrumentations.

Science.gov (United States)

Balling, Horst

2018-05-01

Prospective single-center cohort study to record additional time requirements and radiation dose in navigation-assisted O-arm-controlled pedicle screw (PS) instrumentations. The aim of this study was to evaluate amount of extra-time and radiation dose for navigation-assisted PS instrumentations of the thoracolumbosacral spine using O-arm 3D-real-time-navigation (O3DN) compared to non-navigated spinal procedures (NNSPs) with a single C-arm and postoperative computed tomography (CT) scan for controlling PS positions. 3D-navigation is reported to enhance PS insertion accuracy. But time-consuming navigational steps and considerable additional radiation doses seem to limit this modern technique's attraction. A detailed analysis of additional time demand and extra-radiation dose in 3D-navigated spine surgery is not provided in literature, yet. From February 2011 through July 2015, 306 consecutive posterior instrumentations were performed in vertebral levels T10-S1 using O3DN for PS insertion. The duration of procedure-specific navigational steps of the overall collective (I) and the last cohort of 50 consecutive O3DN-surgeries (II) was compared to the average duration of analogous surgical steps in 100 consecutive NNSP using a single C-arm. 3D-radiation dose (dose-length-product, DLP) of navigational and postinstrumentation O-arm scans in group I and II was compared to the average DLP of 100 diagnostic lumbar CT scans. The average presurgical time from patient positioning on the operating table to skin incision was 46.2 ± 10.1 minutes (O3DN, I) and 40.6 ± 9.8 minutes (O3DN, II) versus 30.6 ± 8.3 minutes (NNSP) (P demand of 13.0 minutes compared to NNSP, and with a total DLP below that of a diagnostic lumbar CT scan (P ≈ 0.81). 4.

'Huang Qi Elixir' for proteinuria in patients with diabetic nephropathy: a study protocol for a randomized controlled pilot trial.

Science.gov (United States)

Tu, Xiang; Liu, Fang; Jordan, James B; Ye, Xue Feng; Fu, Ping; Wang, Fei; Zhong, Sen

2013-07-18

Diabetic nephropathy (DN) is the major complication of diabetes; proteinuria is the hall mark of DN. Currently, the treatment for proteinuria is mainly limited to angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). According to Traditional Chinese Medicine (TCM) theory, Chinese medicinals 'securing essence and tonifying the kidney' may be appropriate for proteinuria. The most promising Chinese medicinals and formulae are introduced in the present study to form a potent formula for DN proteinuria. To make oral administration convenient, the formula will be processed in the form of granules. A randomized, multi-center pilot trial will be conducted. Forty eight participants with DN will be randomly assigned to one of four treatment groups: 1. A granule group, at 10 grams, three times daily (G10 group, n = 12); 2. A granule group, at 20 grams, three times daily (G20 group, n = 12); 3. A decoction group (D group, n = 12); and 4. An irbesartan group (Aprovel group, n = 12).The following outcome measures will be used: the percentage change of the albumin-to-creatinine ratio; and the changes in serum creatinine, glomerular filtration rate, fasting plasma glucose and hemoglobulin from baseline to the end of the trial. It is notable that most published clinical trials which assessed the efficacy of TCM on DN were of poor methodology and, therefore, their results have been invalidated. It is necessary to carry out well-designed clinical trials to provide sound evidence. The present trial is a study with potentially great value, for it will provide the parameters for future randomized, placebo-controlled, clinical trials with large sample sizes. The trial is registered on the Chinese Clinical Trial Registry: ChiCTR-TRC-12002718 (http://www.chictr.org/cn/proj/show.aspx?proj=3820).

糖尿病视网膜病变与糖尿病肾病的相关性及危险因素分析%CORRELATION BETWEEN DIABETIC RETINOPATHY AND DIABETIC NEPHROPATHY AND RISK FACTORS ANALYSIS

Institute of Scientific and Technical Information of China (English)

赵大伟; 谢秀娟; 李宪华; 马兴祥

2017-01-01

目的：：分析糖尿病视网膜病变( DR)与糖尿病肾病( DN)的相关性及危险因素。方法：选取我院眼科及内分泌科2013-06~2015-05住院或门诊就诊的2型糖尿病病人351例,回顾性分析其临床资料及实验室检查,根据眼底照相及眼底荧光血管造影检查结果将其分成NDR组(无视网膜病变)、NPDR组(非增殖性视网膜病变)、PDR组(增殖性视网膜病变)；根据肾脏损害程度,参考尿微量蛋白( ALB)的排泄水平,分成NAU组(无蛋白尿,ALB300mg/24h)。检测各组临床与生化指标,分析糖尿病视网膜病变(DR)与糖尿病肾病(DN)的相关性。结果：DR中各组之间DN的发病率比较差异有统计学意义(P 300 mg/24 h ) . Clinical and biochemical parameters were detected to analyze the relationship between diabetic retinopathy( DR) and diabetic ne-phropathy ( DN ) . Results:The difference of the incidence of DN among the groups in DR was statistically significant(P<0. 05). With the aggravation of DR damage,DN also gradually increased,DR and. Conclusion:Diabetic retinopathy and diabetic nephropathy have a positive correlation with the extent of the lesion,and the appearance of diabetic retinopathy can predict the extent of renal damage.

Cardiac Effects of Attenuating Gsα - Dependent Signaling.

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Marcus R Streit

Full Text Available Inhibition of β-adrenergic signalling plays a key role in treatment of heart failure. Gsα is essential for β-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing β-adrenergic signalling in the heart at the level of Gsα is a promising option.We analyzed the influence of Gsα on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice overexpressing a dominant negative Gsα-mutant under control of the α-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic β-adrenergic stimulation. At rest, Gsα-DN-mice showed bradycardia (602 ± 13 vs. 660 ± 17 bpm, p<0.05 and decreased dp/dtmax (5037 ± 546- vs. 6835 ± 505 mmHg/s, p = 0.02. No significant differences were found regarding ejection fraction, heart weight and cardiomyocyte size. β-blockade by propranolol revealed no baseline differences of hemodynamic parameters between wildtype and Gsα-DN-mice. Acute adrenergic stimulation resulted in decreased β-adrenergic responsiveness in Gsα-DN-mice. Under chronic adrenergic stimulation, wildtype mice developed myocardial hypertrophy associated with increase of LV/BW-ratio by 23% (4.4 ± 0.2 vs. 3.5 ± 0.1 mg/g, p<0.01 and cardiac myocyte size by 24% (14927 ± 442 px vs. 12013 ± 583 px, p<0.001. In contrast, both parameters were unchanged in Gsα-DN-mice after chronic isoproterenol stimulation.Overexpression of a dominant negative mutant of Gsα leads to decreased β-adrenergic responsiveness and is protective against isoproterenol-induced hypertrophy. Thus, Gsα-DN-mice provide novel insights into β-adrenergic signal transduction and its modulation in myocardial overload and failure.

Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years.

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Pam Factor-Litvak

Full Text Available Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP, butylbenzyl phthalate (BBzP, di-isobutyl phthalate (DiBP, di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ.Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = -2.69 (95% confidence interval [CI] = -4.33, -1.05 and b = -2.69 (95% CI = -4.22, -1.16 per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4 and 7.6 (95% CI = 3.2, 12.1 points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning.Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children's intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.

Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

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Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

2014-10-01

Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: Short-term results

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Matsuda Hidetoshi

2013-01-01

Full Text Available Abstract Background A double-network (DN gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid and poly(N,N’-dimethyl acrylamide, can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Methods Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control. Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface in the defect. The regenerated tissues were evaluated with the Wayne’s gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. Results According to the total Wayne’s score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p  Conclusions The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction.

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Patel, Samir J; Suki, Wadi N; Loucks-DeVos, Jennifer; Graviss, Edward A; Nguyen, Duc T; Knight, Richard J; Kuten, Samantha A; Moore, Linda W; Teeter, Larry D; Gaber, Lillian W; Gaber, A Osama

2016-08-01

Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. © 2016 Steunstichting ESOT.

Comprehensive approach to diabetic nephropathy

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Bancha Satirapoj

2014-09-01

Full Text Available Diabetic nephropathy (DN is a leading cause of mortality and morbidity in patients with diabetes. This complication reflects a complex pathophysiology, whereby various genetic and environmental factors determine susceptibility and progression to end-stage renal disease. DN should be considered in patients with type 1 diabetes for at least 10 years who have microalbuminuria and diabetic retinopathy, as well as in patients with type 1 or type 2 diabetes with macroalbuminuria in whom other causes for proteinuria are absent. DN may also present as a falling estimated glomerular filtration rate with albuminuria as a minor presenting feature, especially in patients taking renin–angiotensin–aldosterone system inhibitors (RAASi. The pathological characteristic features of disease are three major lesions: diffuse mesangial expansion, diffuse thickened glomerular basement membrane, and hyalinosis of arterioles. Functionally, however, the pathophysiology is reflected in dysfunction of the mesangium, the glomerular capillary wall, the tubulointerstitium, and the vasculature. For all diabetic patients, a comprehensive approach to management including glycemic and hypertensive control with RAASi combined with lipid control, dietary salt restriction, lowering of protein intake, increased physical activity, weight reduction, and smoking cessation can reduce the rate of progression of nephropathy and minimize the risk for cardiovascular events. This review focuses on the latest published data dealing with the mechanisms, diagnosis, and current treatment of DN.

Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.

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Cignetto, Simona; Modica, Chiara; Chiriaco, Cristina; Fontani, Lara; Milla, Paola; Michieli, Paolo; Comoglio, Paolo M; Vigna, Elisa

2016-06-01

The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

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Jianzhong Chen

2017-01-01

Full Text Available Objective. We aimed to explore whether squamous cell carcinoma antigen (SCC, cytokeratin 19 fragment (Cyfra21-1, neuron-specific enolase (NSE, and carcinoembryonic antigen (CEA are elevated in diabetic nephropathy (DN and the association between urinary albumin-to-creatinine ratio (UACR and tumor markers in diabetic patients. Methods. Nondialysis patients with diabetes (n=261 and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results. Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001. In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05. Conclusions. Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies.

A systematic review and meta-analysis of genetic association studies for the role of inflammation and the immune system in diabetic nephropathy

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Tziastoudi, Maria; Hadjigeorgiou, Georgios M.; Stravodimos, Konstantinos; Zintzaras, Elias

2017-01-01

Abstract Background: Despite the certain contribution of metabolic and haemodynamic factors in diabetic nephropathy (DN), many lines of evidence highlight the role of immunologic and inflammatory mechanisms. To elucidate the contribution of the immune system in the development of DN, we explored the contribution of gene variants (polymorphisms) in relevant pathophysiologic pathways. Methods: We selected six major pathways related to immune response from the Kyoto Encyclopaedia of Genes and Genomes database and thereafter we traced all available genetic association studies (GASs) involving gene variants in these pathways from PubMed and HuGE Navigator. Finally, we used meta-analytic methods for synthesizing the results of the GASs. Results: One hundred three GASs were retrieved that included 443 variants from 75 genes. Of those variants, 138 were meta-analysed and 61 produced significant results; seven variants were investigated in single GASs and showed significant association. Variants in CCL2, CCR5, IL6, IL8, EPO, IL1A, IL1B, IL100, IL1RN, GHRL, MMP9, TGFB1, VEGFA, MMP3, MMP12, IL12RB1, PRKCE, TNF and TNFRSF19 genes were associated with an increased risk of DN. Conclusions: There is evidence that variants related with immunologic response affect the course of DN. However, the present results should be interpreted with caution since the current number of available GASs is limited. PMID:28616206

Ultrasound-Guided Miniscalpel-Needle Release versus Dry Needling for Chronic Neck Pain: A Randomized Controlled Trial

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Yongjun Zheng

2014-01-01

Full Text Available Objective. To compare ultrasound-guided miniscalpel-needle (UG-MSN release versus ultrasound-guided dry needling (UG-DN for chronic neck pain. Methods. A total of 169 patients with chronic neck pain were randomized to receive either UG-MSN release or UG-DN. Before treatment and at 3 and 6 months posttreatment, pain was measured using a 10-point visual analogue scale (VAS. Neck function was examined using the neck disability index. Health-related quality of life was examined using the physical component score (PCS and mental component score (MCS of the SF-36 health status scale. Results. Patients in the UG-MSN release had greater improvement on the VAS (by 2 points at 3 months and 0.9 points at 6 months versus in the UG-DN arm; (both P<0.0001. Patients receiving UG-MSN release also showed significantly lower scores on the adjusted neck disability index, as well as significantly lower PCS. No severe complications were observed. Conclusion. UG-MSN release was superior to UG-DN in reducing pain intensity and neck disability in patients with chronic neck pain and was not associated with severe complications. The procedural aspects in the two arms were identical; however, we did not verify the blinding success. As such, the results need to be interpreted with caution.

Effects of Long-Term Treatment with Ranirestat, a Potent Aldose Reductase Inhibitor, on Diabetic Cataract and Neuropathy in Spontaneously Diabetic Torii Rats

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Ayumi Ota

2013-01-01

Full Text Available We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN in spontaneously diabetic Torii (SDT rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg or epalrestat (100 mg/kg for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal to 3 (mature cataract. The combined scores (0–6 from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P<0.01. Ranirestat significantly (P<0.01 inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s in SDT rats dose-dependently (P<0.01. Epalrestat also reversed the prevented MNCV decrease (P<0.05. Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g, which ranirestat significantly suppressed dose-dependently, (P<0.05, <0.01, and <0.01; epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only.

[Effect of treatment in 39 patients with diabetic nephropathy by safflor yellow and benazepril in combination].

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Guo, Deng-Zhou; Wang, Yue-Hua; Chen, Zhi-Qiang

2008-04-01

To observe the clinical effect of combined treatment with safflor yellow powder injection and benazepril in treating patients with diabetic nephropathy (DN). Seventy-six patients with DN were randomly assigned to the treatment group (39 cases) and the control group (37 cases). Conventional treatment for lowering blood glucose was given to both groups, but to the control group 10 mg benazepril was given orally once a day additionally, while to those in the treatment group the same dosage of benazepril po. and 150 mg/d of safflor yellow powder injection by adding in 250 mL 0.9% normal saline for intravenous dripping. The therapeutic course for them all was 15 days, and all patients received two courses with an interval of 5 days. Changes of clinical symptoms, urinary albumin excretion rate (UAER), blood and urinary levels of beta2 -microglobulin (beta2 -MG), urinary level of alpha1-microglobulin (alpha1 -MG), D-dimer (D-D) and plasma fibrinogen (FIB) were observed. The total effective rate in the treatment group was higher than that in the control group (84.62% vs 59.45 %, P benazepril is superior to benazepril alone in reducing urinary albumin, improving renal function and blood hyperviscosity manner for patients with DN, suggesting the combination of the two could play their respective superiorities and act in cooperation for retarding the progression of DN.

Heterogeneity within the frontoparietal control network and its relationship to the default and dorsal attention networks.

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Dixon, Matthew L; De La Vega, Alejandro; Mills, Caitlin; Andrews-Hanna, Jessica; Spreng, R Nathan; Cole, Michael W; Christoff, Kalina

2018-02-13

The frontoparietal control network (FPCN) plays a central role in executive control. It has been predominantly viewed as a unitary domain general system. Here, we examined patterns of FPCN functional connectivity (FC) across multiple conditions of varying cognitive demands, to test for FPCN heterogeneity. We identified two distinct subsystems within the FPCN based on hierarchical clustering and machine learning classification analyses of within-FPCN FC patterns. These two FPCN subsystems exhibited distinct patterns of FC with the default network (DN) and the dorsal attention network (DAN). FPCN A exhibited stronger connectivity with the DN than the DAN, whereas FPCN B exhibited the opposite pattern. This twofold FPCN differentiation was observed across four independent datasets, across nine different conditions (rest and eight tasks), at the level of individual-participant data, as well as in meta-analytic coactivation patterns. Notably, the extent of FPCN differentiation varied across conditions, suggesting flexible adaptation to task demands. Finally, we used meta-analytic tools to identify several functional domains associated with the DN and DAN that differentially predict activation in the FPCN subsystems. These findings reveal a flexible and heterogeneous FPCN organization that may in part emerge from separable DN and DAN processing streams. We propose that FPCN A may be preferentially involved in the regulation of introspective processes, whereas FPCN B may be preferentially involved in the regulation of visuospatial perceptual attention.

Left Ventricular Structure during Antihypertensive Treatment in Patients with Chronic Kidney Disease

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Batir T. Daminov

2016-03-01

Full Text Available The aim of our study was to investigate the left ventricular (LV echocardiographic parameters and estimate the antiremodeling efficacy of eprosartan and lercanidipine in patients with CKD, depending on the presence or absence of diabetic nephropathy (DN. Materials and Methods: The study included 121 patients (mean age 52.4±5.7 years with CKD stage 3 (KDOQI, 2002. Patients were distributed in two groups according to the etiology of CKD. Group 1 consisted of 67 patients with non-diabetic CKD. Group 2 consisted of 54 CKD patients with DN. All patients had arterial hypertension grade 1 or 2 (ESH/ESC, 2013. All patients underwent clinical examination, echocardiography; GFR was estimated by the Cockcroft-Gault formula. Stages of chronic kidney disease (CKD were determined according to the KDOQI 2002 classification. Eprosartan and lercanidipine were prescribed to patients after one week of lavage from previous antihypertensive therapy. This 6-month follow-up study compared the effectiveness of two courses of treatment. Results: LVH was observed in all CKD patients regardless of the presence or absence of DN. Eprosartan and lercanidipine showed the high antihypertensive efficacy expressing a reliable decrease in absolute values of SBP and DBP. In CKD patients with DN, on the background of a comparable antihypertensive effect, eprosartan, in comparison with lercanidipine, showed a more pronounced effect on the LV echocardiographic parameters associated with LVH regression.

Gadolinium deposition in the brain: association with various GBCAs using a generalized additive model

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Bae, Sohi; Lee, Ho-Joon; Han, Kyunghwa; Park, Yae-Won; Choi, Yoon Seong; Ahn, Sung Soo; Kim, Jinna; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of)

2017-08-15

To determine the relationship between the number of administrations of various gadolinium-based contrast agents (GBCAs) and increased T1 signal intensity in the globus pallidus (GP) and dentate nucleus (DN). This retrospective study included 122 patients who underwent double-dose GBCA-enhanced magnetic resonance imaging. Two radiologists calculated GP-to-thalamus (TH) signal intensity ratio, DN-to-pons signal intensity ratio and relative change (R{sub change}) between the baseline and final examinations. Interobserver agreement was evaluated. The relationships between R{sub change} and several factors, including number of each GBCA administrations, were analysed using a generalized additive model. Six patients (4.9%) received linear GBCAs (mean 20.8 number of administration; range 15-30), 44 patients (36.1%) received macrocyclic GBCAs (mean 26.1; range 14-51) and 72 patients (59.0%) received both types of GBCAs (mean 31.5; range 12-65). Interobserver agreement was almost perfect (0.99; 95% CI: 0.99-0.99). R{sub change} (DN:pons) was associated with gadodiamide (p = 0.006) and gadopentetate dimeglumine (p < 0.001), but not with other GBCAs. R{sub change} (GP:TH) was not associated with GBCA administration. Previous administration of linear agents gadoiamide and gadopentetate dimeglumine is associated with increased T1 signal intensity in the DN, whereas macrocyclic GBCAs do not show an association. (orig.)

A study of the impact of disease burden in quality of life of people with pre-End-Stage and End-Stage Renal Disease

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Helen Georgiadou

2017-10-01

Full Text Available Introduction: Diabetes Mellitus (DM is a common chronic disease accompanied by severe complications. It is the leading cause of End-Stage Renal Disease (ESRD requiring management either by haemodialysis (HD or peritoneal dialysis (PD. The chronicity of the disease, and its complications, affects the psychological, family and social life of the patients and their Quality of Life (QoL. Aim: of the present study was to estimate the disease burden of patients with diabetic nephropathy (DN during pre-ESRD and during End-Stage Renal Disease. Methods: A sample of 103 patients with DN treated at the General Hospital of Veria were studied during May and June 2016. The study was conducted using the Dialysis Symptoms Index (DSI for the assessment of Chronic Kidney Disease (CKD symptom load and the European Quality of Life (EuroQol questionnaire for assessing the QoL of patients in the Renal Outpatient Clinic, Haemodialysis and Peritoneal Dialysis Unit. Results: It was found that the Renal Replacement Method (HD or PD, the presence of DM and CKD’s stage affect significantly the patients’ self-assessment regarding painful symptoms of DN. Furthermore, the above factors have major impact on some aspects of patients’ QoL, such as mobility and self-care. Conclusions: Pre-End Stage patients experience more severe painful symptoms of DN compared to patients on Renal Replacement Therapies.

Relationship of stature to gamma and neutron exposure among atomic bomb survivors aged less than 10 at the time of the bomb, Hiroshima and Nagasaki

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Ishimaru, Toranosuke; Amano, Takako; Kawamoto, Sadahisa.

1982-10-01

A reanalysis has been undertaken of the relationship of attained adult height of Hiroshima and Nagasaki atomic bomb survivors aged less than 10 at the time of the bomb (ATB) to radiation dose based upon new dosimetry data. The present analysis aims to examine the relationship of stature to radiation dose in terms of gamma rays and neutrons, separately. The 628 individuals were selected from Hiroshima and Nagasaki survivors, aged less than 10 ATB, whose doses were available, and whose statures were recorded at the Adult Health Study (AHS) biennial health examination during 1970-72. To ascertain the relationship of attained adult stature to gamma and neutron doses three doseresponse models were applied to the data. The analysis revealed that the attained height is a separate function of exposure to gamma rays and neutrons. The model assuming a squared term dependence on gamma rays and a linear dependence on neutrons provides a better explanation of the data. The regression coefficient associated with the squared gamma dose is -0.00000927 and the coefficient associated with neutron dose is -0.0172. The relative biological effectiveness of neutrons in relation to gamma radiation with respect to the effect for diminished development of stature is estimated as 43.1 / √Dn in kerma (Dn=neutron dose). The 95% confidence limits are 19.3 / √Dn--96.5 / √Dn. (author)

Luminescence of a new class of UV-blue-emitting phosphors MSi2O2-deltaN2+2/3delta:Ce3+ (M = Ca, Sr, Ba)

NARCIS (Netherlands)

Li, Y.Q.; With, de G.; Hintzen, H.T.J.M.

2005-01-01

The luminescence properties of Ce3+,Na+-codoped MSi2O22dN2+2/3d (M 5 Ca, Sr, Ba) are reported. The undoped and Ce3+,Na+-codoped MSi2O22dN2+2/3d powders were prepared by a solid-state reaction at temperatures between 1300–1400 uC under N2–H2 (10%) atmosphere in the system MO–SiO2–Si3N4 (M 5 Ca, Sr,

Combination of evidence in recommendation systems characterized by distance functions

Energy Technology Data Exchange (ETDEWEB)

Rocha, L. M. (Luis Mateus)

2002-01-01

Recommendation systems for different Document Networks (DN) such as the World Wide Web (WWW), Digitnl Libarries, or Scientific Databases, often make use of distance functions extracted from relationships among documents and between documents and semantic tags. For instance, documents In the WWW are related via a hyperlink network, while documents in bibliographic databases are related by citation and collaboration networks.Furthermore, documents can be related to semantic tags such as keywords used to describe their content, The distance functions computed from these relations establish associative networks among items of the DN, and allow recommendation systems to identify relevant associations for iudividoal users. The process of recommendation can be improved by integrating associative data from different sources. Thus we are presented with a problem of combining evidence (about assochaons between items) from different sonrces characterized by distance functions. In this paper we summarize our work on (1) inferring associations from semi-metric distance functions and (2) combining evidence from different (distance) associative DN.

Validation of the design of small diameter pulsed columns for the process line DRA. Tests reliability compared with the industrial scale

International Nuclear Information System (INIS)

Leybros, J.

2000-01-01

As part of the Spin program related to the management of nuclear wastes, studies have been undertaken to develop partitioning processes like Diamex process. The process line CCBP/DRA in Atalante facility forms one of the main equipment devoted to these studies. On this line industrial apparatus are used but some like pulsed columns need to be adapted because of the specificity of the installation: limiting amount of nuclear matter, gaseous waste minimization, safety, limiting amounts of new extractants,... This article presents the comparison of 2 air pulsed columns, one with a standard diameter of 25 (DN25), the other with a reduced diameter of 15 (DN15). This comparison is based on 3 main criteria: pulsation capability, superficial throughput and mass transfer efficiency. The overall comparison shows that a DN15 pulsed column can be considered as a representative tool of research and development. Particularly, the study demonstrates the possibility of scaling up the results

Low-Dimensional-Networked Metal Halide Perovskites: The Next Big Thing

KAUST Repository

Saidaminov, Makhsud I.

2017-03-03

Low-dimensional-networked (low-DN) perovskite derivatives are bulk quantum materials in which charge carriers are localized within ordered metal halide sheets, rods, or clusters that are separated by cationic lattices. After two decades of hibernation, this class of semiconductors reemerged in the past two years, largely catalyzed by the interest in alternative, more stable absorbers to CH3NH3PbI3-type perovskites in photovoltaics. Whether low-DN perovskites will surpass other photovoltaic technologies remains to be seen, but their impressively high photo- and electroluminescence yields have already set new benchmarks in light emission applications. Here we offer our perspective on the most exciting advances in materials design of low-DN perovskites for energy- and optoelectronic-related applications. The next few years will usher in an explosive growth in this tribe of quantum materials, as only a few members have been synthesized, while the potential library of compositions and structures is believed to be much larger and is yet to be discovered.

SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Daiji Kawanami

2017-05-01

Full Text Available Diabetic nephropathy (DN is a major cause of end-stage renal disease (ESRD worldwide. Glycemic and blood pressure (BP control are important but not sufficient to attenuate the incidence and progression of DN. Sodium–glucose cotransporter (SGLT 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D and type 2 diabetes (T2D, indicating a potential renoprotective effect beyond glucose reduction. Renoprotection by SGLT2 inhibitors has been demonstrated in T2D patients with a high cardiovascular risk in randomized controlled trials (RCTs. These favorable effects of SGLT2 inhibitors are explained by several potential mechanisms, including the attenuation of glomerular hyperfiltration, inflammation and oxidative stress. In this review article, we discuss the renoprotective effects of SGLT2 inhibitors by integrating experimental findings with the available clinical data.

SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy.

Science.gov (United States)

Kawanami, Daiji; Matoba, Keiichiro; Takeda, Yusuke; Nagai, Yosuke; Akamine, Tomoyo; Yokota, Tamotsu; Sango, Kazunori; Utsunomiya, Kazunori

2017-05-18

Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium-glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction. Renoprotection by SGLT2 inhibitors has been demonstrated in T2D patients with a high cardiovascular risk in randomized controlled trials (RCTs). These favorable effects of SGLT2 inhibitors are explained by several potential mechanisms, including the attenuation of glomerular hyperfiltration, inflammation and oxidative stress. In this review article, we discuss the renoprotective effects of SGLT2 inhibitors by integrating experimental findings with the available clinical data.

Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage.

Science.gov (United States)

Dashtsoodol, Nyambayar; Shigeura, Tomokuni; Aihara, Minako; Ozawa, Ritsuko; Kojo, Satoshi; Harada, Michishige; Endo, Takaho A; Watanabe, Takashi; Ohara, Osamu; Taniguchi, Masaru

2017-03-01

Although invariant V α 14 + natural killer T cells (NKT cells) are thought to be generated from CD4 + CD8 + double-positive (DP) thymocytes, the developmental origin of CD4 - CD8 - double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (T H 1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage. These findings provide new insight into understanding of the development of NKT cells and propose a role for timing of expression of the invariant T cell antigen receptor in determining the functional properties of NKT cells.

The Emerging Roles of Microparticles in Diabetic Nephropathy.

Science.gov (United States)

Lu, Chen Chen; Ma, Kun Ling; Ruan, Xiong Zhong; Liu, Bi Cheng

2017-01-01

Microparticles (MPs) are a type of extracellular vesicles (EVs) shed from the outward budding of plasma membranes during cell apoptosis and/or activation. These microsized particles then release specific contents (e.g., lipids, proteins, microRNAs) which are active participants in a wide range of both physiological and pathological processes at the molecular level, e.g., coagulation and angiogenesis, inflammation, immune responses. Research limitations, such as confusing nomenclature and overlapping classification, have impeded our comprehension of these tiny molecules. Diabetic nephropathy (DN) is currently the greatest contributor to end-stage renal diseases (ESRD) worldwide, and its public health impact will continue to grow due to the persistent increase in the prevalence of diabetes mellitus (DM). MPs have recently been considered as potentially involved in DN onset and progression, and this review juxtaposes some of the research updates about the possible mechanisms from several relevant aspects and insights into the therapeutic perspectives of MPs in clinical management and pharmacological treatment of DN patients.

A Glimpse of the Pathogenetic Mechanisms of Wnt/β-Catenin Signaling in Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Li Xiao

2013-01-01

Full Text Available The Wnt family of proteins belongs to a group of secreted lipid-modified glycoproteins with highly conserved cysteine residues. Prior results indicate that Wnt/β-catenin signaling plays a prominent role in cell differentiation, adhesion, survival, and apoptosis and is involved in organ development, tumorigenesis, and tissue fibrosis, among other functions. Accumulating evidence has suggested that Wnt/β-catenin exhibits a pivotal function in the progression of diabetic nephropathy (DN. In this review, we focused on discussing the dual role of Wnt/β-catenin in apoptosis and epithelial mesenchymal transition (EMT formation of mesangial cells. Moreover, we also elucidated the effect of Wnt/β-catenin in podocyte dysfunction, tubular EMT formation, and renal fibrosis under DN conditions. In addition, the molecular mechanisms involved in this process are introduced. This information provides a novel molecular target of Wnt/β-catenin for the protection of kidney damage and in delay of the progression of DN.

Studies of high-δ (baffled) and low-δ (open) pumped divertor operation on DIII-D

International Nuclear Information System (INIS)

Allen, S.L.; Fenstermacher, M.E.; Greenfield, C.M.

1998-08-01

The authors report new experimental results with the RDP-OB (Radiative Divertor Project-outer baffle) and cryopump in both upper single-null (USN) and double-null (DN) ELMing H-mode discharges. The baffled divertor reduced the core ionization (∼2--2.5x), in reasonable agreement with predictions from UEDGE/DEGAS modeling (∼3.75x). The upper cryopump achieved density control of n e /n gw ∼ 0.22 (line density/Greenwald density) with Z eff ∼ 2 in high-δ plasmas. The measured exhaust is comparable to the lower pump, except at lower core electron densities (n e 19 m -3 ). Efficient impurity exhaust was obtained with deuterium SOL flow. Preliminary experiments with DN operation has shown that the particle exhaust to the upper pump depends on the up/down magnetic balance. Preliminary experiments indicate that the DN exhaust is roughly 40--50% of the USN exhaust at n e ∼ 4 x 10 19 m -3

Surveying the quantum group symmetries of integrable open spin chains

Science.gov (United States)

Nepomechie, Rafael I.; Retore, Ana L.

2018-05-01

Using anisotropic R-matrices associated with affine Lie algebras g ˆ (specifically, A2n(2), A2n-1 (2) , Bn(1), Cn(1), Dn(1)) and suitable corresponding K-matrices, we construct families of integrable open quantum spin chains of finite length, whose transfer matrices are invariant under the quantum group corresponding to removing one node from the Dynkin diagram of g ˆ . We show that these transfer matrices also have a duality symmetry (for the cases Cn(1) and Dn(1)) and additional Z2 symmetries that map complex representations to their conjugates (for the cases A2n-1 (2) , Bn(1) and Dn(1)). A key simplification is achieved by working in a certain "unitary" gauge, in which only the unbroken symmetry generators appear. The proofs of these symmetries rely on some new properties of the R-matrices. We use these symmetries to explain the degeneracies of the transfer matrices.

Runoff load estimation of particulate and dissolved nitrogen in Lake Inba watershed using continuous monitoring data on turbidity and electric conductivity.

Science.gov (United States)

Kim, J; Nagano, Y; Furumai, H

2012-01-01

Easy-to-measure surrogate parameters for water quality indicators are needed for real time monitoring as well as for generating data for model calibration and validation. In this study, a novel linear regression model for estimating total nitrogen (TN) based on two surrogate parameters is proposed based on evaluation of pollutant loads flowing into a eutrophic lake. Based on their runoff characteristics during wet weather, electric conductivity (EC) and turbidity were selected as surrogates for particulate nitrogen (PN) and dissolved nitrogen (DN), respectively. Strong linear relationships were established between PN and turbidity and DN and EC, and both models subsequently combined for estimation of TN. This model was evaluated by comparison of estimated and observed TN runoff loads during rainfall events. This analysis showed that turbidity and EC are viable surrogates for PN and DN, respectively, and that the linear regression model for TN concentration was successful in estimating TN runoff loads during rainfall events and also under dry weather conditions.

A closer look at the relationship between the default network, mind wandering, negative mood, and depression.

Science.gov (United States)

Konjedi, Shaghayegh; Maleeh, Reza

2017-08-01

By a systematic analysis of the current literature on the neural correlates of mind wandering, that is, the default network (DN), and by shedding light on some determinative factors and conditions which affect the relationship between mind wandering and negative mood, we show that (1) mind wandering per se does not necessarily have a positive correlation with negative mood and, on the higher levels, depression. We propose that negative mood as a consequence of mind wandering generally depends on two determinative conditions, that is, whether mind wandering is with or without meta-awareness and whether mind wandering occurs during high or low vigilance states; (2) increased activity of the DN is not necessarily followed by an increase in unhappiness and depression. We argue that while in some kinds of meditation practices we witness an increase in the structure and in the activity of the DN, no increase in unhappiness and depression is observed.

Improvement in clinical outcomes after dry needling in a patient with occipital neuralgia

Science.gov (United States)

Bond, Bryan M.; Kinslow, Christopher

2015-01-01

The primary purpose of this case report is to outline the diagnosis, intervention and clinical outcome of a patient presenting with occipital neuralgia. Upon initial presentation, the patient described a four-year history of stabbing neck pain and headaches. After providing informed consent, the patient underwent a total of four dry needling (DN) sessions over a two-week duration. During each of the treatment sessions, needles were inserted into the trapezii and suboccipital muscles. Post-intervention, the patient reported a 32-point change in her neck disability index score along with a 28-point change in her headache disability index score. Thus, it appears that subsequent four sessions of DN over two weeks, our patient experienced meaningful improvement in her neck pain and headaches. To the best of our knowledge, this is the first case report describing DN to successfully improve clinical outcomes in a patient diagnosed with occipital neuralgia. PMID:26136602

Some quantum Lie algebras of type Dn positive

International Nuclear Information System (INIS)

Bautista, Cesar; Juarez-Ramirez, Maria Araceli

2003-01-01

A quantum Lie algebra is constructed within the positive part of the Drinfeld-Jimbo quantum group of type D n . Our quantum Lie algebra structure includes a generalized antisymmetry property and a generalized Jacobi identity closely related to the braid equation. A generalized universal enveloping algebra of our quantum Lie algebra of type D n positive is proved to be the Drinfeld-Jimbo quantum group of the same type. The existence of such a generalized Lie algebra is reduced to an integer programming problem. Moreover, when the integer programming problem is feasible we show, by means of the generalized Jacobi identity, that the Poincare-Birkhoff-Witt theorem (basis) is still true

Linking a dermal permeation and an inhalation model to a simple pharmacokinetic model to study airborne exposure to di(n-butyl) phthalate

OpenAIRE

Lorber, M.; Weschler, C.J.; Morrison, G.; Bekö, G.; Gong, M.; Koch, H.M.; Salthammer, T.; Schripp, T.; Toftum, J.; Clausen, G.

2017-01-01

Six males clad only in shorts were exposed to high levels of airborne di(n-butyl) phthalate (DnBP) and diethyl phthalate (DEP) in chamber experiments conducted in 2014. In two 6 h sessions, the subjects were exposed only dermally while breathing clean air from a hood, and both dermally and via inhalation when exposed without a hood. Full urine samples were taken before, during, and for 48 h after leaving the chamber and measured for key DnBP and DEP metabolites. The data clearly demonstrated ...

Materials and methods appendix for valuation of ecosystem services of green infrastructure in Oslo

OpenAIRE

Barton, David Nicholas; Vågnes Traaholt, Nora; Blumentrath, Stefan

2015-01-01

The material in this report constitutes a Methods and Materials appendix for two reports dis-seminating the results to a wider audience in English and Norwegian. We recommend that readers start with one of the cited reports below, using the appendix as a companion report to look up specifics: Barton, D.N. , N. Vågnes Traaholt, S. Blumentrath (2015) Naturen i Oslo verdt milliarder. Verd-setting av urbane økosystem-tjenester fra grønn infrastruktur. NINA Report 1113. Barton, D.N., E. Stan...

New space--time model for hadron--nucleus collisions at high energies

International Nuclear Information System (INIS)

Bialkowski, G.; Chiu, C.B.; Tow, D.M.

1976-12-01

A new space-time model for hadron-nucleus collisions is proposed, where particles at the instant of creation are immature and their maturity rate is enhanced in the presence of other hadronic matter, as in a nucleus. With only one free parameter, the model can explain dn/sub A//sup p//d eta, dn/sub A//sup pi//d eta, R/sub A//sup p/(E/sub L/), and the A-dependences of sigma/sub in/sup pA/ and sigma/sub in/sup pi A/

Live births profile, Maranguape – CE from 2000 to 2003

OpenAIRE

Nancy Costa de Oliveira; Escolástica Rejane Ferreira Moura; Cristiana Ferreira da Silva

2012-01-01

It was objectified to analyze the profile of the live births in Maranguape-CE registered in the Live Births Information System (SINASC) between January, 2000 and December, 2003.5.032 declarations of live births (DN) of resident mother were analyzed. The DN was included in the SINASC Software of the Health Ministry and the data were presented in tabular format. The maternal age between 21 and 30 was predominant, education between4 and 11 years of study, the increase in the percentage of single...

Optimization of combined delayed neutron and differential die-away prompt neutron signal detection for characterization of spent nuclear fuel assemblies

International Nuclear Information System (INIS)

Blanc, Pauline; Tobin, Stephen J.; Croft, Stephen; Menlove, Howard O.; Swinhoe, M.; Lee, T.

2010-01-01

The Next Generation Safeguards Initiative (NGSI) of the U.S. Department of Energy (DOE) has funded multiple laboratories and universities to develop a means to accurately quantify the Plutonium (Pu) mass in spent nuclear fuel assemblies and ways to also detect potential diversion of fuel pins. Delayed Neutron (DN) counting provides a signature somewhat more sensitive to 235 U than Pu while Differential Die-Away (DDA) is complementary in that it has greater sensitivity to Pu. The two methods can, with care, be combined into a single instrument which also provides passive neutron information. Individually the techniques cannot robustly quantify the Pu content but coupled together the information content in the signatures enables Pu quantification separate to the total fissile content. The challenge of merging DN and DDA, prompt neutron (PN) signal, capabilities in the same design is the focus of this paper. Other possibilities also suggest themselves, such as a direct measurement of the reactivity (multiplication) by either the boost in signal obtained during the active interrogation itself or by the extension of the die-away profile. In an early study, conceptual designs have been modeled using a neutron detector comprising fission chambers or 3He proportional counters and a ∼14 MeV neutron Deuterium-Tritium (DT) generator as the interrogation source. Modeling was performed using the radiation transport code Monte Carlo N-Particles eXtended (MCNPX). Building on this foundation, the present paper quantifies the capability of a new design using an array of 3 He detectors together with fission chambers to optimize both DN and PN detections and active characterization, respectively. This new design was created in order to minimize fission in 238 U (a nuisance DN emitter), to use a realistic neutron generator, to reduce the cost and to achieve near spatial interrogation and detection of the DN and PN, important for detection of diversion, all within the constraints of

Deletion of the N-terminus of IKKγ induces apoptosis in keratinocytes and impairs the AKT/PTEN signaling pathway

International Nuclear Information System (INIS)

Leis, Hugo; Sanchis, Ana; Perez, Paloma

2007-01-01

The regulatory subunit IKKγ/NEMO is crucial for skin development and function and although devoid of kinase activity, loss of IKKγ function completely abolishes the activation of NF-κB by all pro-inflammatory cytokines. To inhibit the IκB kinase (IKK) complex in keratinocytes, we have used a dominant negative approach by generating stable transfectants of an N-terminal deletion of IKKγ (IKKγ-DN97) that uncouples formation of the IKK complex. Expression of this mutant in PB keratinocytes (PB-IKKγ-DN97) delayed growth kinetics, caused morphological changes and dramatically augmented apoptosis even in the absence of pro-apoptotic stimuli, as determined by cell morphology, TUNEL and caspase-3 cleavage. Moreover, in PB-IKKγ-DN97 cells, TNF-α and IL-1 treatment failed to induce degradation of IκBα, phosphorylation of p65 on Ser 536 and nuclear translocation which, consequently, reduced κB-binding activity. In PB-IKKγ-DN97 cells, accumulation of IκBα correlated with a downregulation of AKT activity and an increase of PTEN protein levels whereas pro-apoptotic p53 target genes Bax and Puma were upregulated. These effects were most likely mediated through IKK since coexpression of the wild-type form of IKKγ in keratinocytes partially reversed apoptosis and reduced PTEN expression. Thus, our data suggest a negative cross-talk mechanism involving PTEN and NF-κB, critical for the anti-apoptotic role of NF-κB in keratinocytes

Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity.

Science.gov (United States)

Zhang, Jin; Ruhlman, Tracey A; Sabir, Jamal S M; Blazier, John Chris; Weng, Mao-Lun; Park, Seongjun; Jansen, Robert K

2016-02-17

Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear-plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Non-diabetic renal disease in patients with type 2 diabetes: a single centre study.

Science.gov (United States)

Fan, Jian-Zhen; Wang, Rong

2018-04-01

Non-diabetic renal disease (NDRD) has been widely known in diabetic patients. The clinical differentiation between diabetic nephropathy (DN) and NDRD is still not so clear and effective. To analyse the pathological characteristics and distribution of renal injury in selected type 2 diabetic patients. Comparison between DN and NDRD in clinical characteristics, to find important predictors for NDRD. To conduct retrospective analysis of clinical, laboratory and pathohistological data of type 2 diabetic patients in whom renal biopsies were performed from March 2010 to September 2014 in Shandong Provincial Hospital affiliated to Shandong University (n = 88). According to the findings of renal biopsy, the incidences of DN, NDRD and DN complicated with NDRD were 20.46, 72.73 and 6.82% respectively. The most common NDRD found were: membranous nephropathy, followed by IgA nephropathy and focal segmental glomerulosclerosis. In multivariate logistic-analysis, fasting blood glucose (odds ratio (OR) 0.714; 95% confidence interval (CI) = 0.543-0.939; P = 0.016) and absence of diabetic retinopathy (OR 18.602; 95% CI = 2.176-159.018; P = 0.003) were independent predictors of NDRD. This study confirmed a considerably high prevalence of NDRD in type 2 diabetic patients with renal injury. As some cases of NDRD are readily treatable or remittable, we should consider renal biopsy in selected diabetic patients with renal involvement, especially in those with effective blood glucose control and the absence of diabetic retinopathy. © 2017 Royal Australasian College of Physicians.

Dry Needling Related Short-Term Vasodilation in Chronic Sciatica under Infrared Thermovision

Directory of Open Access Journals (Sweden)

Elżbieta Skorupska

2015-01-01

Full Text Available Vasomotor responses to dry needling (DN of trigger points (TrPs under infrared thermovision (IRT camera control and TrPs coexistence in chronic sciatica patients have never been studied. Materials and Methods. Fifty consecutive chronic sciatica patients were enrolled in the study. DN under IRT control was performed for all patients regardless of gluteus minimus (GM active TrPs examination. Then, the vasomotor response and its agreement with TrPs examination were evaluated. Results. The prevalence of GM active TrPs was 32%. DN provokes intensive vasodilatation for TrPs-positive patients only, with the localization dependent on referred pain during the procedure (r=0.896;  P=0.000 not the daily complaint. The increase of vasodilatation was, for example, for thigh, TrPs-positive +30.29% (P<0.05 versus TrPs-negative +4.08%. Additionally, a significant skin temperature increase was observed for TrPs-positive only, for example, thigh +1.5 ± 1.3°C (maximum and +1.2 ± 1.0°C (average (both P<0.05. Conclusion. GM active TrPs prevalence among chronic sciatica patients was around one in three. Every TrPs-positive subject presented with vasodilatation under IRT in the area of DN related referred pain. Although TrPs involvement in chronic sciatica patients is possible, further studies on a bigger group of patients are still required.

LRP5 Signaling in Osteosarcomagenesis: a Cautionary Tale of Translation from Cell Lines to Tumors

Directory of Open Access Journals (Sweden)

Logan Horne

2016-10-01

Full Text Available Previous reports document expression of low-density lipoprotein receptor-related protein 5 (LRP5 in osteosarcoma (OS tissue. Expression of this Wnt receptor correlated with metastatic disease and poor disease-free survival. Forced expression of dominant-negative LRP5 (dnLRP5, which lacks the membrane binding domain of the native protein and therefore functions as a soluble receptor-sponge for Wnt ligands, reduced in vitro cellular invasion and in vivo xenograft tumor growth for osteosarcoma cell lines. Here, we use a genetically engineered mouse model of osteosarcomagenesis with and without expression of dnLRP5 to assess to what degree tumorigenesis is affected and whether Wnt/β-catenin signaling is circumvented or maintained. Each cohort of mice developed osteosarcoma at a similar ultimate prevalence, but after a slightly increased latency in those also expressing dnLRP5. On histology, there was no difference between groups, despite previous reports that the dnLRP5 osteosarcoma cells specifically undergo a mesenchymal-to-epithelial transition in vitro. Finally, immunohistochemistry showed the presence of cytosolic and nuclear β-catenin and nuclear Cyclin D1, markers consistent with preserved Wnt/β-catenin signaling despite constitutive blockade of the cell surface receipt of Wnt signaling ligand. These data suggest that canonical Wnt signaling plays a role in OS progression and that while blockade of singular nodes in signaling pathways can have dramatic effects on individual cell lines, real tumors readily evade such focused attacks.

Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy.

Science.gov (United States)

Kanda, Tomonori; Fukusato, Toshio; Matsuda, Megumi; Toyoda, Keiko; Oba, Hiroshi; Kotoku, Jun'ichi; Haruyama, Takahiro; Kitajima, Kazuhiro; Furui, Shigeru

2015-07-01

To use inductively coupled plasma mass spectroscopy (ICP-MS) to evaluate gadolinium accumulation in brain tissues, including the dentate nucleus (DN) and globus pallidus (GP), in subjects who received a gadolinium-based contrast agent (GBCA). Institutional review board approval was obtained for this study. Written informed consent for postmortem investigation was obtained either from the subject prior to his or her death or afterward from the subject's relatives. Brain tissues obtained at autopsy in five subjects who received a linear GBCA (GBCA group) and five subjects with no history of GBCA administration (non-GBCA group) were examined with ICP-MS. Formalin-fixed DN tissue, the inner segment of the GP, cerebellar white matter, the frontal lobe cortex, and frontal lobe white matter were obtained, and their gadolinium concentrations were measured. None of the subjects had received a diagnosis of severely compromised renal function (estimated glomerular filtration rate brain regions. Gadolinium was detected in all specimens in the GBCA agent group (mean, 0.25 µg per gram of brain tissue ± 0.44 [standard deviation]), with significantly higher concentrations in each region (P = .004 vs the non-GBCA group for all regions). In the GBCA group, the DN and GP showed significantly higher gadolinium concentrations (mean, 0.44 µg/g ± 0.63) than other regions (0.12 µg/g ± 0.16) (P = .029). Even in subjects without severe renal dysfunction, GBCA administration causes gadolinium accumulation in the brain, especially in the DN and GP.

The concentrations of phthalates in settled dust in Bulgarian homes in relation to building characteristic and cleaning habits in the family

DEFF Research Database (Denmark)

Kolarik, Barbara; Bornehag, Carl-Gustaf; Naydenov, Kiril Georgiev

2008-01-01

. Dust samples from the child's bedroom were collected in 177 homes and analysed for the content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di-n-octyl phthalate (DnOP) and DEHP. Information on building characteristics and family...... spectra, and wood flooring. However, in a sub-group of homes with no use of polish, the concentration of DEHP was higher in homes with inspector-observed balatum compared with wood flooring but the difference was not significant may be due to a too small sample size....

Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

DEFF Research Database (Denmark)

Winkelmann, Juliane; Lin, Ling; Schormair, Barbara

2012-01-01

to HDAC2. It is also highly expressed in immune cells and required for the differentiation of CD4+ into T regulatory cells. Mutations in exon 20 of this gene were recently reported to cause hereditary sensory neuropathy with dementia and hearing loss (HSAN1). Our mutations are all located in exon 21......Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT...

Some sufficient conditions for Hamiltonian property in terms of ...

Indian Academy of Sciences (India)

[1, D], or Wf (G) ≥ f (1). 2 n2 + [f(2) − 3. 2 f(1)]n − 2[f(2) − f(1)] for a monotonically decreasing function f(x) on x ∈ [1, D], then G is Hamiltonian, unless G ∼= K∗ n or K2∨3K1. Proof. Assume that G is not a Hamiltonian graph with degree sequence (d1,d2,...,dn), where d1 ≤ d2 ≤ ··· ≤ dn and n ≥ 3. By Lemma 1, there is a ...

The association between phthalates in dust and allergic diseases among Bulgarian children

DEFF Research Database (Denmark)

Kolarik, Barbara; Naydenov, Kiril Georgiev; Larsson, Martin

2008-01-01

BACKGROUND: Recent studies have identified associations between the concentration of phthalates in indoor dust and allergic symptoms in the airways, nose, and skin. OBJECTIVES: Our goal was to investigate the associations between allergic symptoms in children and the concentration of phthalate...... (controls). The dust samples were analyzed for their content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP). RESULTS: A higher concentration of DEHP was found in homes...

Content-Aware Adaptive Compression of Satellite Imagery Using Artificial Vision

Science.gov (United States)

2013-09-01

pixel samples. The S vector, once calculated, will be passed onto the SVM. Note: The LL sub-band is not part of the S vector. aVn =< LH1,LH2...LHm >,aHn...HL1,HL2...HLm >,aDn =< HH1,HH2...HHm > (3.7) S =< aV0,aH0,aD0,aV1,aH1,aD1... aVn ,aHn,aDn > (3.8) 3.3.2 Training OASIC uses a single 512× 512 pixel

Mass identified particle yields in antiproton-proton collisions at √s = 1.8 TeV

International Nuclear Information System (INIS)

Alexopoulos, T.; Erwin, A.; Findeisen, C.; Nelson, K.; Thompson, M.; Banerjee, S.; Beery, P.D.; Biswas, N.N.; Kenney, V.P.; LoSecco, J.M.; McManus, A.P.; Piekarz, J.; Stampke, S.R.; Carter, T.; Goshaw, A.T.; Oh, S.H.; Walker, W.D.; Wesson, D.K.

1989-01-01

In anti p-p collisions at √s = 1.8 TeV, the yields and the transverse momentum distributions of π ± , K ± , p ± in the central region have been measured up to a charged particle pseudo rapidity density of (dn c /dη) ≅ 16. The dependence of the average transverse momentum on the charged particle rapidity density of the Centrally Produced Matter is presented. We observe that the increase of t > with increasing dn/dη is more significant for heavier particles than that for lighter particles. (orig.)

Heritability of the severity of diabetic retinopathy: the FIND-Eye study.

Science.gov (United States)

Arar, Nedal H; Freedman, Barry I; Adler, Sharon G; Iyengar, Sudha K; Chew, Emily Y; Davis, Mathew D; Satko, Scott G; Bowden, Donald W; Duggirala, Ravi; Elston, Robert C; Guo, Xiuxing; Hanson, Robert L; Igo, Robert P; Ipp, Eli; Kimmel, Paul L; Knowler, William C; Molineros, Julio; Nelson, Robert G; Pahl, Madeleine V; Quade, Shannon R E; Rasooly, Rebekah S; Rotter, Jerome I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Zager, Philip G; Abboud, Hanna E

2008-09-01

Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib-sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (chi(2) = 658.14, df = 20; P FIND-Eye sample. These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy.

Science.gov (United States)

Oses, Carolina; Olivares, Belén; Ezquer, Marcelo; Acosta, Cristian; Bosch, Paul; Donoso, Macarena; Léniz, Patricio; Ezquer, Fernando

2017-01-01

Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when

Optimization of the diabetic nephropathy treatment with attention to the special features of cellular inflammation mechanisms

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Тетяна Дмитрівна Щербань

2016-02-01

Full Text Available Aim. Optimization of the diabetic nephropathy (DN treatment in association with hypertonic disease (HD based on the study of neutrophil chain of pathogenic cellular mechanisms of these diseases development and the special features of its clinical course.Materials and methods. There were complexly examined 86 patients with HD associated with DN and 30 patients with isolated HD. The control group was formed by 30 practically healthy persons. The activity of NO-synthases in neutrophils was detected by Green colorimetric methods using Griess reagent. The expression of ІСАМ-1 (CD54, CD11b-integrin and inducible NO-synthase on neutrophils was detected by the indirect immunocytochemical method. Oxygen-depending activity of neutrophils was assessed in NBT-test.Results. Expression of adhesive molecules of CD54and CD11b-integrin on neutrophils of peripheral blood essentially increases (р <0,001 in patients with DN in association with HD comparing with isolated HD and the control group.At associated pathology on the background of high oxygen-depending activity of neutrophils its functional reserve decreases that results in intensification of inflammatory processes in kidneys (р<0,001.In comorbid patients chronization of pathological process results in imbalance of NO-synthases system in neutrophils: on the background of decrease of activity of constituent NO-synthases the expression and activity of inducible NO-synthase increase (р<0,001 .The use of L-arginine hydrochloride in the complex therapy of patients with DN associated with HD intensifies organoprotective effect of basal therapy, results in facilitation of the clinical course, decreases albuminuria, corrects the functional indices of neutrophils and diminishes imbalance in NO-synthases system.Conclusions. In patients with DN in association with HD the neutrophil chain of cellular inflammation mechanisms are activated: expression of adhesive molecules grows, oxygen-depending metabolism is

DNA methyltransferase 1 mutations and mitochondrial pathology: is mtDNA methylated?

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Alessandra eMaresca

2015-03-01

Full Text Available Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN and Hereditary sensory neuropathy with dementia and hearing loss (HSN1E are two rare, overlapping neurodegenerative syndromes that have been recently linked to allelic dominant pathogenic mutations in the DNMT1 gene, coding for DNA (cytosine-5-methyltransferase 1. DNMT1 is the enzyme responsible for maintaining the nuclear genome methylation patterns during the DNA replication and repair, thus regulating gene expression. The mutations responsible for ADCA-DN and HSN1E affect the replication foci targeting sequence domain, which regulates DNMT1 binding to chromatin. DNMT1 dysfunction is anticipated to lead to a global alteration of the DNA methylation pattern with predictable downstream consequences on gene expression. Interestingly, ADCA-DN and HSN1E phenotypes share some clinical features typical of mitochondrial diseases, such as optic atrophy, peripheral neuropathy and deafness, and some biochemical evidence of mitochondrial dysfunction. The recent discovery of a mitochondrial isoform of DNMT1 and its proposed role in methylating mitochondrial DNA (mtDNA suggests that DNMT1 mutations may directly affect mtDNA and mitochondrial physiology. On the basis of this latter finding the link between DNMT1 abnormal activity and mitochondrial dysfunction in ADCA-DN and HSN1E appears intuitive, however mtDNA methylation remains highly debated. In the last years several groups demonstrated the presence of 5-methylcytosine in mtDNA by different approaches, but, on the other end, the opposite evidence that mtDNA is not methylated has also been published. Since over 1500 mitochondrial proteins are encoded by the nuclear genome, the altered methylation of these genes may well have a critical role in leading to the mitochondrial impairment observed in ADCA-DN and HSN1E. Thus, many open questions still remain unanswered, such as why mtDNA should be methylated, and how this process is

C26 cancer-induced muscle wasting is IKKβ-dependent and NF-kappaB-independent.

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Evangeline W Cornwell

Full Text Available Existing data suggest that NF-kappaB signaling is a key regulator of cancer-induced skeletal muscle wasting. However, identification of the components of this signaling pathway and of the NF-κB transcription factors that regulate wasting is far from complete. In muscles of C26 tumor bearing mice, overexpression of dominant negative (d.n. IKKβ blocked muscle wasting by 69% and the IκBα-super repressor blocked wasting by 41%. In contrast, overexpression of d.n. IKKα or d.n. NIK did not block C26-induced wasting. Surprisingly, overexpression of d.n. p65 or d.n. c-Rel did not significantly affect muscle wasting. Genome-wide mRNA expression arrays showed upregulation of many genes previously implicated in muscle atrophy. To test if these upregulated genes were direct targets of NF-κB transcription factors, we compared genome-wide p65 binding to DNA in control and cachectic muscle using ChIP-sequencing. Bioinformatic analysis of ChIP-sequencing data from control and C26 muscles showed very little p65 binding to genes in cachexia and little to suggest that upregulated p65 binding influences the gene expression associated with muscle based cachexia. The p65 ChIP-seq data are consistent with our finding of no significant change in protein binding to an NF-κB oligonucleotide in a gel shift assay, no activation of a NF-κB-dependent reporter, and no effect of d.n.p65 overexpression in muscles of tumor bearing mice. Taken together, these data support the idea that although inhibition of IκBα, and particularly IKKβ, blocks cancer-induced wasting, the alternative NF-κB signaling pathway is not required. In addition, the downstream NF-κB transcription factors, p65 and c-Rel do not appear to regulate the transcriptional changes induced by the C26 tumor. These data are consistent with the growing body of literature showing that there are NF-κB-independent substrates of IKKβ and IκBα that regulate physiological processes.

EARTH, MOON, SUN, AND CV ACCRETION DISKS

International Nuclear Information System (INIS)

Montgomery, M. M.

2009-01-01

Net tidal torque by the secondary on a misaligned accretion disk, like the net tidal torque by the Moon and the Sun on the equatorial bulge of the spinning and tilted Earth, is suggested by others to be a source to retrograde precession in non-magnetic, accreting cataclysmic variable (CV) dwarf novae (DN) systems that show negative superhumps in their light curves. We investigate this idea in this work. We generate a generic theoretical expression for retrograde precession in spinning disks that are misaligned with the orbital plane. Our generic theoretical expression matches that which describes the retrograde precession of Earths' equinoxes. By making appropriate assumptions, we reduce our generic theoretical expression to those generated by others, or to those used by others, to describe retrograde precession in protostellar, protoplanetary, X-ray binary, non-magnetic CV DN, quasar, and black hole systems. We find that spinning, tilted CV DN systems cannot be described by a precessing ring or by a precessing rigid disk. We find that differential rotation and effects on the disk by the accretion stream must be addressed. Our analysis indicates that the best description of a retrogradely precessing spinning, tilted, CV DN accretion disk is a differentially rotating, tilted disk with an attached rotating, tilted ring located near the innermost disk annuli. In agreement with the observations and numerical simulations by others, we find that our numerically simulated CV DN accretion disks retrogradely precess as a unit. Our final, reduced expression for retrograde precession agrees well with our numerical simulation results and with selective observational systems that seem to have main-sequence secondaries. Our results suggest that a major source to retrograde precession is tidal torques like that by the Moon and the Sun on the Earth. In addition, these tidal torques should be common to a variety of systems where one member is spinning and tilted, regardless if

Effects of osteochondral defect size on cartilage regeneration using a double-network hydrogel.

Science.gov (United States)

Higa, Kotaro; Kitamura, Nobuto; Goto, Keiko; Kurokawa, Takayuki; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

2017-05-22

There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal osteochondral defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of osteochondral defects. A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter osteochondral defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm osteochondral defect in Group II, and a 5.8-mm osteochondral defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. The present study demonstrated that all sizes of the DN gel implanted defects as well as the 2.5mm untreated defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O'Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted defects than the untreated defects at 4 and 12 weeks (p regeneration in defects between 2.5 and 5.8 mm, offering a promising device to establish a cell-free cartilage regeneration therapy and applicable to various sizes of osteochondral defects.

Diabetic Nephropathy Determinant Factor in Diabetes Mellitus at RSUD Dr. M. Soewandhie Surabaya

Directory of Open Access Journals (Sweden)

Rahmadany Isya Putri

2015-01-01

Full Text Available Non communicable diseases are an important health problem related with the shift in the pattern of death cause, which is from infectious diseases to non-infectious diseases. Diabetes mellitus (DM ranked 5 of the top 10 causes of non-infectious diseases in hospitals in Indonesia. If not properly controlled, DM can lead to chronic complications such as Diabetic Nephropathy (DN. This study, conducted at Internal Medicine Clinic, Outpatient Care, Dr. M. Soewandhie Hospital Surabaya, in June-July 2014, aimed to analyze correlation between non-clinical factors according to the concept of Hendrik L. Blum, such as compliance to treatment, education level, income, and social support for the incidence of DN in DM patients. This study was an observational analytic study with case-control design. Case samples in this study were DM patients who experienced DN complications and undergoing treatment at Internal Medicine Clinic, Outpatient Care, Dr. M. Soewandhie Hospital Surabaya, by 36 respondents. Control samples in this study were diabetic patients who did not experience complications DN undergoing treatment at Internal Medicine Clinic, Outpatient Care, Dr. M. Soewandhie Hospital Surabaya, by 36 respondents. Samples were taken by using a convenience sampling method. Relation streght analysis between dependent and independent variables used Contingency Coefficient by Chi Square test with 95% Confidence Interval (α=0.05. To determine the amount of risk between dependent and independent variables, we used OR (odds ratio calculation. The results showed that non-compliance to treatment (OR=2.8 with contigency coefficient 0.243, low education (OR=1.5 with contigency coefficient 0.091, income < District Minimum Wage (OR=1.21 with contigency coefficient 0.036, and not receiving social support (OR=1.65 with contigency coefficient 0.117. In conclusion, compliance to treatment, education level, income, and social support affect the incidence of DN in DM patients

Characterization of Delayed-Particle Emission Signatures for Pyroprocessing. Part 1: ABTR Fuel Assembly.

Energy Technology Data Exchange (ETDEWEB)

Durkee, Jr., Joe W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-06-19

A three-part study is conducted using the MCNP6 Monte Carlo radiation-transport code to calculate delayed-neutron (DN) and delayed-gamma (DG) emission signatures for nondestructive assay (NDA) metal-fuel pyroprocessing. In Part 1, MCNP6 is used to produce irradiation-induced used nuclear fuel (UNF) isotopic inventories for an Argonne National Laboratory (ANL) Advanced Burner Test Reactor (ABTR) preconceptual design fuel assembly (FA) model. The initial fuel inventory consists of uranium mixed with light-water-reactor transuranic (TRU) waste and 10 wt% zirconium (U-LWR-SFTRU-10%Zr). To facilitate understanding, parametric evaluation is done using models for 3% and 5% initial ²³⁵U a% enrichments, burnups of 5, 10, 15, 20, 30, …, 120 GWd/MTIHM, and 3-, 5-, 10-, 20-, and 30- year cooling times. Detailed delayed-particle radioisotope source terms for the irradiate FA are created using BAMF-DRT and SOURCES3A. Using simulation tallies, DG activity ratios (DGARs) are developed for ¹³⁴Cs/¹³⁷Cs ¹³⁴Cs/¹⁵⁴Eu, and ¹⁵⁴Eu/¹³⁷Cs markers as a function of (1) burnup and (2) actinide mass, including elemental uranium, neptunium, plutonium, americium, and curium. Spectral-integrated DN emission is also tallied. The study reveals a rich assortment of DGAR behavior as a function of DGAR type, enrichment, burnup, and cooling time. Similarly, DN emission plots show variation as a function of burnup and of actinide mass. Sensitivity of DGAR and DN signatures to initial ²³⁵U enrichment, burnup, and cooling time is evident. Comparisons of the ABTR radiation signatures and radiation signatures previously reported for a generic Westinghouse oxide-fuel assembly indicate that there are pronounced differences in the ABTR and Westinghouse oxide-fuel DN and DG signatures. These differences are largely attributable to the initial TRU inventory in the ABTR fuel. The actinide and nonactinide inventories for the

The Main Shear Zone in Sør Rondane: A key feature for reconstructing the geodynamic evolution of East Antarctica

Science.gov (United States)

Ruppel, Antonia; Läufer, Andreas; Lisker, Frank; Jacobs, Joachim; Elburg, Marlina; Damaske, Detlef; Lucka, Nicole

2013-04-01

Structural investigations were carried out along the Main Shear Zone (MSZ) of western Sør Rondane (22°-25°E, 71.5°-72.5°S) to gain new information about the position of the East-/West-Gondwana suture and the ancient plate tectonic configuration during Gondwana amalgamation. The WSW-ENE striking MSZ divides south-western Sør Rondane in a northern amphibolite-facies terrane and a southern tonalite-trondhjemite-granodiorite (TTG) terrane. The structure can be traced over a distance of ca. 100 km and reaches several hundred meters in width. It is characterized by a right-lateral sense of movement and marked by a transpressional and also transtensional regime. Ductilely deformed granitoids (ca. 560 Ma: SHRIMP U-Pb of zircon) and ductile - brittle structures, which evolved in a transitional ductile to brittle regime in an undeformed syenite (ca. 499-459 Ma, Ar-Ar mica), provide a late Proterozoic/ early Paleozoic time limit for the activity of the shear zone (Shiraishi et al., 2008; Shiraishi et al., 1997). Documentation of ductile and brittle deformation allows reconstructing up to eight deformation stages. Cross-cutting relationships of structural features mapped in the field complemented by published kinematic data reveal the following relative age succession: [i] Dn+1 - formation of the main foliation during peak metamorphism, [ii] Dn+2 - isoclinal, intrafolial folding of the main foliation, mostly foliation-parallel mylonitic shear zones (1-2 meter thick), [iii] Dn+3 - formation of tight to closed folds, [iv] Dn+4 - formation of relatively upright, large-scale open folds, [v] Dn+5 - granitoid intrusion (e.g. Vengen granite), [vi] Dn+6 - dextral shearing between amphibolite and TTG terranes, formation of the MSZ, [vii] Dn+7 - intrusion of late- to post-tectonic granitoids, first stage of brittle deformation (late shearing along MSZ), intrusion of post-kinematic mafic dykes, [viii] Dn+8 - second stage of brittle deformation including formation of conjugate fault

Is subdiaphragmatic aortic cross-clamping a suitable model for spinal cord ischemia/reperfusion injury study in rats? O pinçamento sub-diagragmático da aorta é um modelo adequado para o estudo da lesão medular de isquemia/reperfusão em ratos?

Directory of Open Access Journals (Sweden)

Sonia Elizabeth Lopez Carrillo

2006-08-01

sanguíneas de piruvato, lactato, glicose e as concentrações medulares de trifosfato de adenosina (ATP foram determinadas por ensaios enzimáticos. RESULTADOS: As concentrações de piruvato e glicose (sangue e tecido e de lactato e ATP (medula não foram diferentes,comparando G-1 versus G-2. A lactacemia elevou-se significantemente no G-2, comparado ao G-1, durante a reperfusão (T-10. CONCLUSÃO: O modelo experimental de pinçamento subdiafragmático da aorta não é adequado para o estudo da lesão de isquemia/reperfusão na medula de ratos, uma vez que não proporciona alterações nas concentrações in vivo de metabólitos teciduais, por exemplo de lactato ou ATP, compatíveis com aquelas encontradas em tecidos sujeitos à isquemia/reperfusão.

Evaluation of Populus and Salix continuously irrigated with landfill leachate II. soils and early tree development.

Science.gov (United States)

Zalesny, Ronald S; Bauer, Edmund O

2007-01-01

Soil contaminant levels and early tree growth data are helpful for assessing phytoremediation systems. Populus (DN17, DN182, DN34, NM2, and NM6) and Salix (94003, 94012, S287, S566, and SX61) genotypes were irrigated with landfill leachate or municipal water and tested for differences in (1) element concentrations (P, K, Ca, Mg, S, Zn, B, Mn, Fe, Cu, Al, and Na) of a topsoil layer and a layer of sand in tanks with a cover crop of trees or no trees and (2) height, diameter, volume, and dry mass of leaves, stems, and roots. Trees were irrigated with leachate or water during the final 12 wk of the 18-wk study. Differences in most soil element concentrations were negligible (P > 0.05) for irrigation treatments and cover main effects. Phosphorous, K, Mg, S, Zn, Mn, Fe, and Al concentrations were greater in topsoil than sand (P = 0.0011 for Mg; P tree yield. From a practical standpoint, these results may be used as a baseline for the development of future remediation systems.

The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus.

Science.gov (United States)

Bernin, Hannah; Fehling, Helena; Marggraff, Claudia; Tannich, Egbert; Lotter, Hannelore

2016-08-01

Sex-related variations in natural killer T (NKT) cells may influence immunoregulation and outcome of infectious and autoimmune diseases. We analyzed sex-specific differences in peripheral blood NKTs and peripheral blood mononuclear cells (PBMCs) from men and women and determined the frequencies of NKT cells and their subpopulations [CD4(+); CD8(+); double negative (DN)] and the levels of cytokine production following stimulation with the NKT cell ligands α-Galactosylceramide (αGalCer) and Entamoeba histolytica lipopeptidephosphoglycan (Lotter et al. in PLoS Pathog 5(5):e1000434, 2009). Total and DN NKT cells were more abundant in women than in men. In women, αGalCer induced higher production of intracellular IFNγ, IL-4, IL-17 and TNF by CD4(+) and DN(+)NKT cells. Both ligands induced expression of multiple cytokines in PBMCs and influenced the ratio of NKT cell subpopulations during long-term culture. Although the sex-specific differences in frequencies of NKT cells and their subpopulations were marginal, the significant sex-specific differences in cytokine production might influence disease outcomes.

Energy dependence of relative abundances and periods of separate groups of delayed neutrons at neutron induced fission of 239Pu in a range of neutrons energies 0.37 - 5 MeV

International Nuclear Information System (INIS)

Roschenko, V.A.; Piksaikin, V.M.; Kazakov, L.E.; Isaev, S.G.; Korolev, G.G.; Tarasko, M.Z.; Tertychnyi, R.G.

2001-01-01

The fundamental role of delayed neutrons in behavior, control and safety of reactors is well known today. Delayed neutron data are of great interest not only for reactor physics but also for nuclear fission physics and astrophysics. The purpose of the present work was the measurement of energy dependence of delayed neutrons (DN) group parameters at fission of nuclei 239 Pu in a range of energies of primary neutrons from 0.37 up to 5 MeV. The measurements were executed on installation designed on the basis of the electrostatic accelerator of KG - 2.5 SSC RF IPPE. The data are obtained in 6-group representation. It is shown, that there is a significant energy dependence of DN group parameters in a range of primary neutrons energies from thermal meanings up to 5 MeV, which is expressed in reduction of the average half-life of nuclei of the DN precursors on 10 %. The data, received in the present work, can be used at creation of a set of group constants for reactors with an intermediate spectrum of neutrons. (authors)

Day/night whole sky imagers for 24-h cloud and sky assessment: history and overview.

Science.gov (United States)

Shields, Janet E; Karr, Monette E; Johnson, Richard W; Burden, Art R

2013-03-10

A family of fully automated digital whole sky imagers (WSIs) has been developed at the Marine Physical Laboratory over many years, for a variety of research and military applications. The most advanced of these, the day/night whole sky imagers (D/N WSIs), acquire digital imagery of the full sky down to the horizon under all conditions from full sunlight to starlight. Cloud algorithms process the imagery to automatically detect the locations of cloud for both day and night. The instruments can provide absolute radiance distribution over the full radiance range from starlight through daylight. The WSIs were fielded in 1984, followed by the D/N WSIs in 1992. These many years of experience and development have resulted in very capable instruments and algorithms that remain unique. This article discusses the history of the development of the D/N WSIs, system design, algorithms, and data products. The paper cites many reports with more detailed technical documentation. Further details of calibration, day and night algorithms, and cloud free line-of-sight results will be discussed in future articles.

The regulation effect of STAT 5 signaling pathway on the cell cycle progression of irradiated KG-1 cells

International Nuclear Information System (INIS)

Guo Dehuang; Dong Bo; Luo Qingliang; Wen Gengyun; Mao Bingzhi

2000-01-01

The author investigated the role of the JAK/STAT signaling pathway regulating cell cycle progression in the irradiated KG-1 cells. By permanent transfecting the cells with DN-STAT 5 cDNA to block the JAK/STAT signaling pathway and then transient transfecting with cyclin D 1 or cyclin B 1 cDNA, the effects of cyclin D 1 protein and cyclin B 1 protein on the cell cycle progression were examined. Results showed that after irradiation with 8Gy 60 Co rays, the irradiated KG-1 cells transfected with only DN-STAT 5 cDNA can not recover form the G 1 arrest, even though GM-CSF was added. Meanwhile, the cells transfected with both the DN-STAT 5 cDNA and cyclin D 1 cDNA or cyclin B 1 cDNA can recover from the G 1 arrest or the G 2 arrest to a great extent. Thus, it was proved indirectly that the JAK/STAT signaling pathway activated by GM-CSF regulated the cell cycle progression through cyclin D 1 and cyclin B 1 protein

Effects of Minocycline on Urine Albumin, Interleukin-6, and Osteoprotegerin in Patients with Diabetic Nephropathy: A Randomized Controlled Pilot Trial

Science.gov (United States)

Wang, Ying; Tong, Lili; Pak, Youngju; Andalibi, Ali; LaPage, Janine A.; Adler, Sharon G.

2016-01-01

Background We tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi) in diabetic nephropathy (DN) and measured urinary biomarkers to evaluate minocycline’s biological effects. Methods Design: Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance > 30 mL/min; proteinuria ≥ 1.0 g/day; Age ≥30 years; BP minocycline patients (6 month P:Cr ÷ Baseline P:Cr, 0.85 vs. 0.92) was not significant (p = 0.27). Creatinine clearance did not differ in the 2 groups. Urine IL-6:Cr (p = 0.03) and osteoprotegerin/Cr (p = 0.046) decrements were significant. Minocycline modified the relationship between urine IL-6 and proteinuria, suggesting a protective biological effect. Conclusions Although the decline in U P:Cr in minocycline patients was not statistically significant, the significant differences in urine IL-6 and osteoprotegerin suggest that minocycline may confer cytoprotection in patients with DN, providing a rationale for further study. Trial Registration Clinicaltrials.gov NCT01779089 PMID:27019421

ΔN-TRPV1: A Molecular Co-detector of Body Temperature and Osmotic Stress

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Cristian Zaelzer

2015-10-01

Full Text Available Thirst and antidiuretic hormone secretion occur during hyperthermia or hypertonicity to preserve body hydration. These vital responses are triggered when hypothalamic osmoregulatory neurons become depolarized by ion channels encoded by an unknown product of the transient receptor potential vanilloid-1 gene (Trpv1. Here, we show that rodent osmoregulatory neurons express a transcript of Trpv1 that mediates the selective translation of a TRPV1 variant that lacks a significant portion of the channel’s amino terminus (ΔN-TRPV1. The mRNA transcript encoding this variant (Trpv1dn is widely expressed in the brains of osmoregulating vertebrates, including the human hypothalamus. Transfection of Trpv1dn into heterologous cells induced the expression of ion channels that could be activated by either hypertonicity or by heating in the physiological range. Moreover, expression of Trpv1dn rescued the osmosensory and thermosensory responses of single hypothalamic neurons obtained from Trpv1 knockout mice. ΔN-TRPV1 is therefore a co-detector of core body temperature and fluid tonicity.

Man/machine interface algorithm for advanced delayed-neutron signal characterization system

International Nuclear Information System (INIS)

Gross, K.C.

1985-01-01

The present failed-element rupture detector (FERD) at Experimental Breeder Reactor II (EBR-II) consists of a single bank of delayed-neutron (DN) detectors at a fixed transit time from the core. Plans are currently under way to upgrade the FERD in 1986 and provide advanced DN signal characterization capability that is embodied in an equivalent-recoil-area (ERA) meter. The new configuration will make available to the operator a wealth of quantitative diagnostic information related to the condition and dynamic evolution of a fuel breach. The diagnostic parameters will include a continuous reading of the ERA value for the breach; the transit time, T/sub tr/, for DN emitters traveling from the core to the FERD; and the isotopic holdup time, T/sub h/, for the source. To enhance the processing, interpretation, and display of these parameters to the reactor operator, a man/machine interface (MMI) algorithm has been developed to run in the background on EBR-II's data acquisition system (DAS). The purpose of this paper is to describe the features and implementation of this newly developed MMI algorithm

Historic Archaeology of the Johnson (41DN248) and Jones (41DN250) Farmsteads in the Ray Roberts Lake Area: 1850-1950

Science.gov (United States)

1996-08-15

9 settlement, little bluestem was the dominant grass ( McCormick et al. 1975:4). According to Hill (1887:293), the increased fertility of the soils in...recovered from Block I during mitigation. Other identified bottles in Block 1 included snuff (n=12 sherds), condiment (n=8), brandy/bitters (n=9), case...bottle sherds were 13 medicinal/extract, 1 lightning iall fruit jar, 1 liquor/beverage, 9 fruit jar inset caps, 8 fruit jars, and 1 food/ condiment jar

GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy.

Science.gov (United States)

Li, Mengjie; Wang, Xufang; Aa, Jiye; Qin, Weisong; Zha, Weibin; Ge, Yongchun; Liu, Linsheng; Zheng, Tian; Cao, Bei; Shi, Jian; Zhao, Chunyan; Wang, Xinwen; Yu, Xiaoyi; Wang, Guangji; Liu, Zhihong

2013-06-01

Early diagnosis of diabetic nephropathy (DN) is difficult although it is of crucial importance to prevent its development. To probe potential markers and the underlying mechanism of DN, an animal model of DN, the db/db mice, was used and serum and urine metabolites were profiled using gas chromatography/time-of-flight mass spectrometry. Metabolic patterns were evaluated based on serum and urine data. Principal component analysis of the data revealed an obvious metabonomic difference between db/db mice and controls, and db/db mice showed distinctly different metabolic patterns during the progression from diabetes to early, medium, and later DN. The identified metabolites discriminating between db/db mice and controls suggested that db/db mice have perturbations in the tricarboxylic acid cycle (TCA, citrate, malate, succinate, and aconitate), lipid metabolism, glycolysis, and amino acid turnover. The db/db mice were characterized by acidic urine, high TCA intermediates in serum at week 6 and a sharp decline thereafter, and gradual elevation of free fatty acids in the serum. The sharp drop of serum TCA intermediates from week 6 to 8 indicated the downregulated glycolysis and insulin resistance. However, urinary TCA intermediates did not decrease in parallel with those in the serum from week 6 to 10, and an increased portion of TCA intermediates in the serum was excreted into the urine at 8, 10, and 12 wk than at 6 wk, indicating kidney dysfunction occurred. The relative abundances of TCA intermediates in urine relative to those in serum were suggested as an index of renal damage.

Evaluation on changes of early renal function in patients with diabetic nephropathy with contrast-enhanced ultrasound and its clinical significance

International Nuclear Information System (INIS)

Guo Xinmin; Jin Hong; Pan Liwen; Chen Hui; Liu Wei; Quan Xianyue

2013-01-01

Objective: To quantitatively assess the parameter alteration of renal blood flow in patients with diabetic nephropathy (DN) with the contrast-enhanced ultrasound (CEUS), and to evaluate value of the technique in diagnosis of early renal function changes of DN patients. Methods: 40 diabetic patients were equally divided into two group according to Mogensen's staging criteria: normal albuminuria group (group Ⅰ) and early DN group (group Ⅱ); and 15 cases of healthy volunteers were used as control group (N group) (n=15). All subjects were performed renal CEUS perfusion imaging, and QontraXt image analysis software was applied to select the region of interest (ROI) in the renal cortex. Then the time intensity curve (TIC) and kidney blood perfusion parameters were collected. Results: The renal blood perfusion was clearly shown in real time CEUS; compared with N group, the time to peak (TTP), regional blood volume (RBV), and mean transit time (MTT) of the patients in group Ⅰ were increased, there were significant differences (P<0.05); but there were no significant differences of derived peak intensity (DPI) and regional blood flow (RBF) between two groups (P>0.05). Compared with group Ⅰ and N group, the RBV, TTP and MTT of the patients were increased, the DPI and RBF were reduced in group Ⅱ, there were significant differences (P<0.05). Conclusion: The CEUS technical analysis can be used in evaluating renal abnormality of the DN patients in early period by showing the changes of renal perfusion parameters. (authors)

The effects of intradermal botulinum toxin type a injections on pain symptoms of patients with diabetic neuropathy

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Majid Ghasemi

2014-01-01

Full Text Available Background: Considering the dramatic increasing rate of diabetes and consequently its related complications, most importantly diabetic peripheral neuropathy (DPN, challenges regarding proper treatment of DPN and its effect on the quality-of-life and care of diabetic patients, the aim of this current study is to evaluate the effect of intradermal botulinum toxin type A (BTX-A injections on pain symptoms of patients with diabetic neuropathic pain. Materials and Methods: In this randomized double-blind placebo-controlled clinical trial study, diabetic patients aged <70 years with neuropathic pain in both feet were enrolled. Diabetic neuropathy (DN in selected patients was diagnosed using DN4 questionnaire and nerve conduction velocity examinations. They randomized in two intervention (BTX-A injection/100 unit, N = 20 and placebo groups (normal saline injection, N = 20. The outcome of injection on diabetic neuropathic pain was assessed using neuropathy pain scale (NPS and visual analog scale (VAS score and compared in two studied groups. Results: There was no significant difference in DN4, NPS and VAS scales of studied population after intervention in the placebo group. Intradermal injection of BTX-A reduced NPS scores for all items except cold sensation (P = 0.05. It reduced DN4 scores for electric shocks, burning, pins and needles and brushing (P < 0.05. According to VAS scale 30% and 0% of patients in intervention and placebo groups have no pain after intervention (P = 0.01. Conclusion: Intradermal injection of BTX-A is a well-tolerated agent that has a significant effect on DPN pain.

Epigenetic modifications and diabetic nephropathy

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Marpadga A. Reddy

2012-09-01

Full Text Available Diabetic nephropathy (DN is a major complication associated with both type 1 and type 2 diabetes, and a leading cause of end-stage renal disease. Conventional therapeutic strategies are not fully efficacious in the treatment of DN, suggesting an incomplete understanding of the gene regulation mechanisms involved in its pathogenesis. Furthermore, evidence from clinical trials has demonstrated a “metabolic memory” of prior exposure to hyperglycemia that continues to persist despite subsequent glycemic control. This remains a major challenge in the treatment of DN and other vascular complications. Epigenetic mechanisms such as DNA methylation, nucleosomal histone modifications, and noncoding RNAs control gene expression through regulation of chromatin structure and function and post-transcriptional mechanisms without altering the underlying DNA sequence. Emerging evidence indicates that multiple factors involved in the etiology of diabetes can alter epigenetic mechanisms and regulate the susceptibility to diabetes complications. Recent studies have demonstrated the involvement of histone lysine methylation in the regulation of key fibrotic and inflammatory genes related to diabetes complications including DN. Interestingly, histone lysine methylation persisted in vascular cells even after withdrawal from the diabetic milieu, demonstrating a potential role of epigenetic modifications in metabolic memory. Rapid advances in high-throughput technologies in the fields of genomics and epigenomics can lead to the identification of genome-wide alterations in key epigenetic modifications in vascular and renal cells in diabetes. Altogether, these findings can lead to the identification of potential predictive biomarkers and development of novel epigenetic therapies for diabetes and its associated complications.

Age differences in default and reward networks during processing of personally relevant information.

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Grady, Cheryl L; Grigg, Omer; Ng, Charisa

2012-06-01

We recently found activity in default mode and reward-related regions during self-relevant tasks in young adults. Here we examine the effect of aging on engagement of the default network (DN) and reward network (RN) during these tasks. Previous studies have shown reduced engagement of the DN and reward areas in older adults, but the influence of age on these circuits during self-relevant tasks has not been examined. The tasks involved judging personality traits about one's self or a well known other person. There were no age differences in reaction time on the tasks but older adults had more positive Self and Other judgments, whereas younger adults had more negative judgments. Both groups had increased DN and RN activity during the self-relevant tasks, relative to non-self tasks, but this increase was reduced in older compared to young adults. Functional connectivity of both networks during the tasks was weaker in the older relative to younger adults. Intrinsic functional connectivity, measured at rest, also was weaker in the older adults in the DN, but not in the RN. These results suggest that, in younger adults, the processing of personally relevant information involves robust activation of and functional connectivity within these two networks, in line with current models that emphasize strong links between the self and reward. The finding that older adults had more positive judgments, but weaker engagement and less consistent functional connectivity in these networks, suggests potential brain mechanisms for the "positivity bias" with aging. Copyright © 2012 Elsevier Ltd. All rights reserved.

Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.

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Herbach, Nadja; Schairer, Irene; Blutke, Andreas; Kautz, Sabine; Siebert, Angela; Göke, Burkhard; Wolf, Eckhard; Wanke, Ruediger

2009-04-01

Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.

Reconstruction of radical prostatectomy-induced urethral damage using skeletal muscle-derived multipotent stem cells.

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Hoshi, Akio; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Akatsuka, Akira; Usui, Yukio; Terachi, Toshiro

2008-06-15

Postoperative damage of the urethral rhabdosphincter (URS) and neurovascular bundle (NVB) is a major operative complication of radical prostatectomy. It is generally recognized to be caused by unavoidable surgical damage to the muscle-nerve-blood vessel units around the urethra. We attempted to treat this damage using skeletal muscle-derived stem cells, which are able to reconstitute muscle-nerve-blood vessel units. Cells were enzymatically extracted and sorted by flow cytometry as CD34/45 (Sk-34) and CD34/45 (Sk-DN) cells from green fluorescent protein transgenic mice and rats. URS-NVB damage was induced by manually removing one-third of the total URS and unilateral invasion of NVB in wild-type Sprague-Dawley and node rats. Freshly isolated Sk-34, Sk-34+Sk-DN cells, and cultured Sk-DN cells were directly transplanted into the damaged portion. At 4 and 12 weeks after transplantation, urethral pressure profile by electrical stimulation through the sacral surface (L6-S1) was evaluated as functional recovery. The recovery ratio in the control and transplanted groups was 37.6% and 72.9%, at 4 weeks, and 41.6% and 78.4% at 12 weeks, respectively (Pcells differentiated into numerous skeletal muscle fibers having neuromuscular junctions (innervation) and nerve bundle-related Schwann cells and perineurium, and blood vessel-related endothelial cells and pericyte around the urethra. Thus, we conclude that transplantation of skeletal muscle-derived multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of postoperative damage of URS and NVB after radical prostatectomy.

Improved photochemotherapy of malignant cells with daunomycin and the KTP laser.

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Paiva, M B; Saxton, R E; Graeber, I P; Jongewaard, N; Eshraghi, A A; Suh, M J; Paek, W H; Castro, D J

1998-01-01

Laser photochemotherapy of malignancies may become an effective palliative treatment for advanced had and neck cancer using light-sensitive, chemotherapeutic drugs activated in tumors via interstitial laser fiberoptics. Previously, it was reported that cultured human P3 squamous cells incubated 2 hours with daunomycin (Dn) exhibited tenfold enhanced cytotoxicity after exposure to argon laser light at 514 nm. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and daunomycin topoisomerase inhibition. In the current study phototoxicity of Dn-sensitized human cancer cells was tested using broad-spectrum white light compared to monochromatic green-wavelength light. Drug uptake and laser energy levels were optimized for maximum synergy. To test light-enhanced chemotherapy in vitro, the kinetics of cell uptake and toxicity of daunomycin was measured at 1, 2, and 5 microg/ml in three human tumor cell lines: P3 squamous-cell carcinoma, M26 melanoma, and TE671 fibrosarcoma. After 2 hr Dn uptake, all cell lines were tested for phototherapy response by exposure to 300- to 900-nm visible light from a xenon lamp or monochromatic 532-nm green light from a KTP laser. When the KTP laser output was varied from 0 to 120 Joules in Dn-sensitized tumor cells, a linear phototherapy response was seen with energy as low as 12 J inducing drug phototoxicity. These results provide evidence that daunomycin cytotoxicity is enhanced when exposed to 532-nm laser illumination in the three tumor types tested and confirm that the response is related to both energy level and drug dose.

NiO nanoparticles supported on graphene 3D network current collector for high-performance electrochemical energy storage

International Nuclear Information System (INIS)

Wang, Mingjun; Song, Xuefen; Dai, Shuge; Xu, Weina; Yang, Qi; Liu, Jianlin; Hu, Chenguo; Wei, Dapeng

2016-01-01

Owing to the faradaic oxidation and reduction reactions mainly taking place on surface, enlarging the specific surface of redox materials is one of the most effective ways to achieve excellent electrochemical performance. Here we report a binder-free three dimensional (3D) architecture electrode consisting of a graphene 3D network (G3DN) structure growing on flexible carbon paper (CP) by chemical vapor deposition and NiO nanoparticles growing on the G3DN by in-situ thermal decomposition for high rate battery and high-performance electrochemical capacitors. Such a nanostructure provides a large specific surface and fast electronic transmission channels. The unique structure design for this electrode enables outstanding performance, showing high specific capacity of 89.1 mAh cm −2 (119.2 mAh/g) at current density of 0.5 mA cm −2 (0.67 A/g) with the NiO loading of 0.7471 mg cm −2 . Meanwhile the electrode displays excellent rate capability and cycling stability, which keeps 85.48% of initial capacity after 3000 deep-discharge cycles. Furthermore, a solid-state symmetric electrochemical capacitor based on two NiO/G3DN/CP electrodes with an area of 4 cm 2 each is fabricated, and two pieces of them in series can light up 100 green LEDs for 2 min. The architecture of G3DN loaded with NiO might be generally applied to different kinds of nanomaterials for high-rate energy storage to improve their overall electrochemical performance.

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model.

Science.gov (United States)

Shao, Minglong; Yu, Lechu; Zhang, Fangfang; Lu, Xuemian; Li, Xiaokun; Cheng, Peng; Lin, Xiufei; He, Luqing; Jin, Shunzi; Tan, Yi; Yang, Hong; Zhang, Chi; Cai, Lu

2015-07-01

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways. Copyright © 2015 the American Physiological Society.

Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.

Science.gov (United States)

Carranza, Katherine; Veron, Dolores; Cercado, Alicia; Bautista, Noemi; Pozo, Wilson; Tufro, Alda; Veron, Delma

2015-01-01

The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives. Copyright © 2015. Published by Elsevier España, S.L.U.

Variabilidad genética en Lutzomyia ( verrucarum evansi (Núñez-Tovar, 1924, vector de Leishmaniosis visceral americana

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Charles Porter

2001-04-01

Full Text Available

Lutzomyia evansi (Núñez-Tovar, 1924, Lutzomyia longipalpis
(Lutz y Neiva, 1912 y Lutzomyia cruzi (Mangabeira, 1938, son los
vectores de Leishmania infantum Nicolle, 1908, en el neotrópico. Lu. evansi ha sido incriminada como vector en zonas rurales de la Costa Caribe Colombiana, y algunas zonas de Venezuela y Nicaragua. A pesar de que esta especie reviste gran importancia en Salud Pública, no existen a la fecha estudios sobre su variabilidad genética, desconociéndose si existe o no flujo genético entre las poblaciones rurales y urbanas, endémicas y no endémicas de leishmaniosis visceral (LV. Con base en los genes mitocondriales Citocromo b, RNA de transferencia para Serina, subunidades uno y cuatro de la NADH deshidrogenasa, se estudió la variabilidad genética entre las distintas poblaciones de Lu. evansi en la Costa Caribe, incluyendo la población
geográficamente aislada de Isla Fuerte, y una población de Venezuela.

Systematic of delayed neutron parameters

International Nuclear Information System (INIS)

Isaev, S.G.; Piksaikin, V.M.

2000-01-01

The experimental studies of the energy dependence of the delayed neutron (DN) parameters for various fission systems has shown that the behaviour of a some combination of delayed neutron parameters has a similar features. On the basis of this findings the systematics of delayed neutron experimental data for thorium, uranium, plutonium and americium isotopes have been investigated with the purpose to find a correlation of DN parameters with characteristics of fissioning system as well as a correlation between the delayed neutron parameters themselves. It was presented the preliminary results which were obtained during study the physics interpretation of the results [ru

Acoustic control of sodium leakage in valve gates of NPP

International Nuclear Information System (INIS)

Trykov, E.L.; Kovtun, S.N.; Anan'ev, A.A.; Yugov, S.I.

2014-01-01

Short description of sodium bench and acoustic investigation results on leakage monitoring of valves DN10 and DN40 are given. It is shown that acoustic method can be used successfully to control the leakages of sodium valves. Leakages on both type of valves increase the acoustic signal dispersion by 2-3 orders. For each type of valve acoustic system of leakage determination allows to conduct the preliminary graduation of signal dispersion on the sodium discharge rate. It make possible not only to record the leakage presence but also to determine the sodium discharge rate through the valve during the leakage [ru

Prevalence data of Rickettsia slovaca and other SFG Rickettsiae species in Dermacentor marginatus in the southeastern Iberian peninsula.

Science.gov (United States)

Márquez, F J; Rojas, A; Ibarra, V; Cantero, A; Rojas, J; Oteo, J A; Muniain, M A

2006-10-01

In southern Spain, Dermacentor marginatus ticks can be infected with several genospecies of spotted fever Group (SFG) Rickettsia. We developed a nested polymerase chain reaction assay by using a species-specific probe targeting the ompA gene to detect and differentiate between the two groups of rickettsiae previously described in D. marginatus. SFG rickettsia has been detected in 85.15% of ticks studied (26.7% of positives have been to R. slovaca, the causative agent of TIBOLA-DEBONEL, and 73.3% to SFG rickettsia closely related to strains RpA4-JL-02-DnS14-DnS28).

Long-term prevention of diabetic nephropathy: an audit

DEFF Research Database (Denmark)

Schjoedt, K.J.; Hansen, H.P.; Tarnow, L.

2008-01-01

AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin......-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN. METHODS: All patients with type 1 diabetes and persistent microalbuminuria (30-300 mg/24 h) were identified (n=227...

Modelagem para o dimensionamento de um sistema de microirrigação utilizando microtubos ramificados Modeling for the design of a micro-irrigation system using branched microtubes

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Dinara G Alves

2012-02-01

Full Text Available Este trabalho foi realizado com o objetivo de se modelar e avaliar o comportamento hidráulico de microtubos ramificados, com base na relação entre vazão e comprimento dos microtubos para uma pressão de entrada, operando sob regime laminar. Dois modelos matemáticos foram estudados, em que um considerou a perda localizada de carga no dimensionamento dos microtubos ramificados e o outro a desconsiderou. O experimento para validação dos modelos foi conduzido no Laboratrio de Hidráulica da Escola Superior de Agricultura "Luiz de Queiroz" (ESALQ-USP, Piracicaba, SP, medindo-se a vazão dos emissores para as pressões de 14,7; 18,6; 39,2 e 58,9 kPa. A configuração do sistema de irrigação consistiu de uma linha lateral com diâmetro nominal (DN de 10,0 mm, na qual foram inseridos microtubos conectores com DN de 0,8 mm conectados a um segmento de tubo de derivação e acoplados seis microtubos emissores com DN de 0,7 mm. Verificou-se que, dentre os modelos matemáticos, aquele que considerou a perda localizada de carga apresentou maior exatidão pois teve elevado, um bom índice de Willmott e baixo erro quadrático médio.This study was carried out with the aim to develop a mathematical model and to evaluate the hydraulic behavior of branched microtubes, based on the relationship between discharge and microtube length for a specific inlet pressure, operating under laminar flow conditions. Two mathematical models were studied in which one considered the local head losses in irrigation system design and the another did not consider. The experiment for model validation was carried out at the Laboratory of Hydraulics, School of Agriculture "Luiz de Queiroz" (ESALQ/USP, Piracicaba-SP, where emitter discharges was verified under the pressures of 14.7; 18.6; 39.2 and 58.9 kPa. The irrigation system configuration consisted of a lateral line with nominal diameter (DN of 10.0 mm, in which are inserted microtube connectors with 0.8 mm DN. These

ELECTROPHYSIOLOGICAL EVALUATION OF THE TRANSITORY DYSFUNCTION OF THE NERVUS TRIGEMINUS AND THE NERVUS FACIALIS IN THE PATIENTS SUFFERING FROM THE DIABETES NEUROPATHY BY EXAMINING THE BLINK REFLEX

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Milica Lazovic

2000-11-01

Full Text Available In 90 patients with clinically mild diabetes neuropathy (DN with no clinic signs of any affection of the nervus trigeminus (NTR and of the nervus facialis (NF including 50 with the insulin-independent diabetes (IND and 40 with the insulin-dependent diabetes (IZD of average age between 44,23+12,56 years of average diabetes duration of 9,42±7,85 years, the latencies (in ms Rl, R2 and R2' of the blink reflex response (BR after the nervus supraorbital is electric stimulation are determined. Besides, in the given patients the values (in m/s of the motor (MBP and of the sensitive transmission rate (SBP of the impulse along the nervus peroneus (NP and the nervus tibialis (NT are also determined. The control group consisted of 50 healthy persons of respective age.On the same day when the electrophysiological examination was done, the following biochemic parameters were determined in the patients' serum, namely, the glycemia profile with calculation of the glycemia average value (MBG as well as the values of the glycolized chemoglobine (HgAl, of the basal insulin level and of sodium (Na and potassium (K. After that, the correlation between the given electrophysiological and the biochemic parameters was examined as well as that between the given parameters and the age of the examined and the diabetes duration.A statistically significant correlation (p(,(5 between the values of the other examined parameters registered.The obtained results show that hyperglycemia causes the emergence of the transitory dysfunction of the NTR and/or the NF in the patients with the IND and the clinically mild DN. The dysfunction of the NTR and/or the NF is approximately symmetrically present on the left and the right side in the patients with the IND and the clinically mild DN while in the persons with the IZD and the clinically mild DN there is asymmetry of the functional disturbance in the system of the NT-NF complex which is probably related to different effects of the

Nuevos mecanismos involucrados en la patogénesis de adenomas hipofisarios New mechanisms involved in the pathogenesis of pituitary adenomas

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D. Giacomini

2003-04-01

Full Text Available Analizamos molecularmente tumores formados por clones estables de la línea lactosomatotrofa GH3 Smad-4 (transductor de señales de la proteína morfogénica de hueso-4, BMP-4 dominante negativo (Smad-4dn que bloquea el transductor Smad que desarrollan tumores de menor tamaño que los controles en ratones nude, pero que presentaron un crecimiento tardío. Encontramos que en éstos la expresión/control de Smad-4dn se perdió y que sobreexpresan c-Myc. Concordantemente, BMP-4 se sobreexpresa y estimula la expresión de c-Myc en prolactinomas humanos pero no en otros adenomas o en hipófisis normales. Además en células GH3, ICI 182,780 (bloqueante de estrógenos inhibe la estimulación de c-Myc por BMP-4 y el cotratamiento BMP-4/estrógenos posee un efecto aditivo sobre la proliferación celular. Al bloquear BMP-4 con ICI y estrógenos (E2 con Smad-4dn se bloquea significativamente cada efecto estimulatorio sobre la proliferación. A su vez Smad-4 interacciona físicamente con los dos subtipos de receptores de estrógenos, ERa/ERb. Demostramos por primera vez el rol de BMP-4 en la tumorigénesis de prolactinomas, involucrando un crosstalk funcional BMP-4/estrógenos.We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In adittion ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17b-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17b-estradiol with

The association of yogurt starters with Lactobacillus casei DN 114.001 in fermented milk alters the composition and metabolism of intestinal microflora in germ-free rats and in human flora-associated rats.

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Djouzi, Z; Andrieux, C; Degivry, M C; Bouley, C; Szylit, O

1997-11-01

The aim of this study was to compare the effects of milk and of various fermented milks on the composition and metabolic activities of the intestinal microflora. Groups of eight rats were fed for 6 wk a diet containing 30% nonfermented milk (M), yogurt (Y), milk fermented with Lactobacillus casei (LcFM) or milk fermented with the association of L. casei DN 114.001 and yogurt starters (LcYFM). In the first study, the survival of the lactic acid bacteria from the fermented milks was assessed by bacterial enumeration in feces of germ-free rats (GF rats) fed milk or fermented milks. The metabolic activities of the lactic acid bacteria were studied in these rats by the measurement of glycolytic activities and products of bacterial fermentation, i.e., acetate and lactate (isoforms L and D). In a second study, the effects of fermented milks on the composition and metabolism [gas, glycolytic activities, short-chain fatty acids (SCFA), alcohol and ammonia] of human flora were studied using human flora-associated rats (HF rats). In GF rats, the survival of L. casei in the feces did not differ between those fed the LcFM and LcYFM diets. L. bulgaricus was detected in the feces of the rats fed Y, whereas Streptoccus thermophilus was found in the feces of the LcYFM group. In HF rats, fecal concentration of Bifidobacteria was greater in the LcFM group than in the others. beta-Glucuronidase (EC 3.2.1.31) activity was lower in rats fed LcFM and Y than in those fed M and LcYFM, whereas beta-galactosidase (3.2.1.23), alpha-glucosidase (EC 3.2.1 20) and beta-glucosidase (EC 3.2.1.21) activities were higher in the LcYFM group compared with the others. Methane excretion was higher in rats fed Y than in other groups. Cecal SCFA concentrations did not differ in LcFM, Y and M groups, but total SCFA, acetate, propionate and butyrate were significantly greater in the LcYFM group. These results suggest that milk fermented with the combination of L. casei and yogurt starters leads to specific

Relevance of NET first wall concept for DEMO DN

International Nuclear Information System (INIS)

Kiltie, J.S.

1987-01-01

Design studies for the Next European Torus (NET) have produced a design concept for the first wall. This concept features poloidal water cooling, double contained in a welded steel structure which is protected by radiatively cooled tiles. In this appendix the relevance of this concept to a DEMO is examined with particular emphasis given to the ability of the cooling tube arrangement to remove the heat. A suggested modification to the arrangement of coolant tubes is suggested so that the design can operate at the higher loadings of a DEMO. (author)

One year monitoring of fire-induced effects on dissolved organic matter and nutrient dynamics under different land-use

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Potthast, Karin; Meyer, Stefanie; Crecelius, Anna; Schubert, Ulrich; Michalzik, Beate

2016-04-01

It is supposed that the changing climate will promote extreme weather events that in turn will increase drought periods and the abundance of fire events in temperate climate regions such as Central Europe. The impact of fires on the nutrient budgets of ecosystems is highly diverse and seems to depend on the ecosystem type. For example, little is known about fire effects on water-bound organic matter (OM) and nutrient fluxes in temperate managed forest ecosystems. Fires can strongly alter the distribution (forest floor vs. mineral soil), binding forms (organic vs. inorganic) and availability (solubility by water) of OM and associated nutrients. To elucidate the effects and seasonality of low intensity fires on the mobilization of dissolved organic carbon and nutrients, an experimental ground fire was conducted in November 2014 in the Hainich region, Central Germany. In addition, differences in response patterns between two land-use types (pasture and beech forest) were investigated. Lysimeters (n=5 controls/ 5 fire-manipulated) with topsoil monoliths (0-4 cm), rainfall/throughfall samplers, littertraps as well as temperature and moisture sensors were installed on three sites of each land-use type. During the one year of monitoring (Sep14-Dec15) soil solution, rainfall, and throughfall samples were taken biweekly and analyzed for pH, dissolved and particulate organic carbon (DOC, POC) and nitrogen (DN, PN) as well as for nutrients (e.g. K, Ca, Mg, P, S). Compared to the control sites, the ground fire immediately induced a short-run release peak of DOC in both land-use types. Within two weeks these differences were muted in the post-fire period. The effect of fire was land-use specific with annual DOC fluxes of 82 and 45 kg/(ha*a) for forest and pasture sites, respectively. In contrast, nitrogen fluxes responded differently to the fire event. In the forest, a significant increase in DN concentrations was notable five months after the fire, at the beginning of the

Genetic variations in key inflammatory cytokines exacerbates the risk of diabetic nephropathy by influencing the gene expression.

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Hameed, Iqra; Masoodi, Shariq R; Malik, Perveez A; Mir, Shahnaz A; Ghazanfar, Khalid; Ganai, Bashir A

2018-06-30

Diabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. We screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-β) in 1326 unrelated subjects comprising of healthy controls (n = 464), type 2 diabetics with nephropathy (DN, n = 448) and type 2 diabetes without nephropathy (T2D, n = 414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). Individual SNP analysis showed highest association of IL-1β rs16944-TT genotype (OR = 3.51, 95%CI = 2.36-5.21, P = 0.001) and TNF-α rs1800629-AA genotype (OR = 2.75, 95% CI = 1.64-4.59, P = 0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (OR = 4.25, 95%CI = 3.3-14.20, P = 0.0016) and GACGACCTT (OR = 21.3, 95%CI = 15.1-28.33, P = 0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-fold = 4.43 ± 1.11) in DN. TNF-α, IL-6 and IL-1β transcript levels were significantly modulated by promoter region SNPs. The present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1β gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects. Copyright �

Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions

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DiGiovanni John

2006-04-01

Full Text Available Abstract Background Squamous cell carcinoma (SCC of the skin is the most aggressive form of non-melanoma skin cancer (NMSC, and is the single most commonly diagnosed cancer in the U.S., with over one million new cases reported each year. Recent studies have revealed an oncogenic role of activated signal transducer and activator of transcription 3 (Stat3 in many human tumors, especially in those of epithelial origin, including skin SCC. Stat3 is a mediator of numerous growth factor and cytokine signaling pathways, all of which activate it through phosphorylation of tyrosine 705. Results To further address the role of Stat3 in skin SCC tumorigenesis, we have analyzed a panel of human skin-derived cell lines ranging from normal human epidermal keratinocytes (NHEK, to non-tumorigenic transformed skin cells (HaCaT, to highly tumorigenic cells (SRB1-m7 and SRB12-p9 and observed a positive correlation between Stat3 phosphorylation and SCC malignancy. We next determined the role of Stat3 activity in cell proliferation and viability under serum-free culture conditions. This was accomplished by suppressing Stat3 activity in the SRB12-p9 cells through stable expression of a dominant negative acting form of Stat3β, which contains a tyrosine 705 to phenylalanine mutation (S3DN. The S3DN cells behaved similar to parental SRB12-p9 cells when cultured in optimal growth conditions, in the presence of 10% fetal calf serum. However, unlike the SRB12-p9 cells, S3DN cells underwent apoptotic cell death when cultured in serum-free medium (SFM. This was evidenced by multiple criteria, including accumulation of sub-G1 particles, induced PARP cleavage, and acquisition of the characteristic morphological changes associated with apoptosis. Conclusion This study provides direct evidence for a role for Stat3 in maintaining cell survival in the conditions of exogenous growth factor deprivation produced by culture in SFM. We also propose that delivery of the S3DN gene or

Quantification of Quercetin Obtained from Allium cepa Lam. Leaves and its Effects on Streptozotocin-induced Diabetic Neuropathy.

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Dureshahwar, Khan; Mubashir, Mohammed; Une, Hemant Devidas

2017-01-01

Antioxidant potential has protective effects in diabetic neuropathy (DN); hence, the present study was designed with an objective to quantify quercetin from shade-dried leaves of Allium cepa Lam. and to study its effects on streptozotocin (STZ)-induced chronic DN. The shade-dried leaves of A. cepa Lam. were extracted with methanol and then fractionated using ethyl acetate (ACEA). The quantification of quercetin in ACEA was evaluated by high-performance thin layer chromatography (HPTLC). The STZ (40 mg/kg) was administered to Sprague-Dawley rats (180-250 g) maintained at normal housing conditions. The STZ was administered once a day for 3 consecutive days. The elevation in blood glucose was monitored for 3 weeks periodically using flavin adenine dinucleotide-glucose dehydrogenase method by Contour TS glucometer. Rats showing blood glucose above 250 mg/dl were selected for the study. Animals were divided into eight groups. ACEA (25, 50, and 100 mg/kg), quercetin (40 mg/kg), metformin (120 mg/kg), and gabapentin (100 mg/kg) were given orally once a day for 2 weeks. The blood glucose level was again measured at the end of treatment to assess DN. Thermal hyperalgesia, cold allodynia, motor incoordination, and neurotoxicity were studied initially and at the end of 2-week treatment. Biochemical parameters were also evaluated after 2-week drug treatment. The quercetin present in ACEA was 4.82% by HPTLC. All the ACEA treatment reduces blood glucose level at the end of the 2-week study and shows a significant neuroprotective effect in STZ-induced DN in the above experimental models. The quercetin present in ACEA proved protective effect in STZ-induced DN. High-performance thin layer chromatography reveals the presence of 4.82% quercetin in Allium cepa ethyl acetate. (ACEA). Its investigation against various diabetic neuropathy biomarkers has proved that ACEA has significant blood glucose reducing action shown neuroprotective action in thermal hyperalgesia, motor

A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

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Deng, Dazhi; Jian, Chongdong; Lei, Ling; Zhou, Yijing; McSweeney, Colleen; Dong, Fengping; Shen, Yilun; Zou, Donghua; Wang, Yonggang; Wu, Yuan; Zhang, Limin; Mao, Yingwei

2017-10-17

Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 ( DISC1 ), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation. Interestingly, prenatal interruption of mouse Disc1 function in NPCs leads to abnormal depression-like deficit in adult mice. Here we took a novel unbiased metabonomics approach to identify brain-specific metabolites that are significantly changed in DN-DISC1 mice. Surprisingly, the inhibitory neurotransmitter, GABA, is augmented. Consistently, parvalbumin (PV) interneurons are increased in the cingulate cortex, retrosplenial granular cortex, and motor cortex. Interestingly, somatostatin (SST) positive and neuropeptide Y (NPY) interneurons are decreased in some brain regions, suggesting that DN-DISC1 expression affects the localization of interneuron subtypes. To further explore the cellular mechanisms that cause this change, DN-DISC1 suppresses proliferation and promotes the cell cycle exit of progenitors in the medial ganglionic eminence (MGE), whereas it stimulates ectopic proliferation of neighboring cells through cell non-autonomous effect. Mechanistically, it modulates GSK3 activity and interrupts Dlx2 activity in the Wnt activation. In sum, our results provide evidence that specific genetic insults on NSCs at a short period of time could lead to prolonged changes of brain metabolism and development, eventually behavioral defects.

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

Energy Technology Data Exchange (ETDEWEB)

Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

2014-08-15

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

Alpha particle diagnostics using impurity pellet injection (invited)

International Nuclear Information System (INIS)

Fisher, R.K.; McChesney, J.M.; Howald, A.W.; Parks, P.B.; Snipes, J.A.; Terry, J.L.; Marmar, E.S.; Zweben, S.J.; Medley, S.S.

1992-01-01

We have proposed using impurity pellet injection to measure the energy distribution of the fast confined alpha particles in a reacting plasma [R. K. Fisher et al., Fusion Technol. 13, 536 (1988)]. The ablation cloud surrounding the injected pellet is thick enough that an equilibrium fraction F ∞ 0 (E) of the incident alphas should be neutralized as they pass through the cloud. By observing neutrals created in the large spatial region of the cloud which is expected to be dominated by the heliumlike ionization state, e.g., Li + ions, we can determine the incident alpha distribution dn He 2+ /dE from the measured energy distribution of neutral helium atoms dn He 0 /dE using dn He 0 /dE = dn He 2+ /dE·F ∞ 0 (E,Li + ). Initial experiments were performed on the Texas Experimental Tokamak (TEXT) in which we compared pellet penetration with our impurity pellet ablation model [P. B. Parks et al., Nucl. Fusion 28, 477 (1988)], and measured the spatial distribution of various ionization states in carbon pellet clouds [R. K. Fisher et al., Rev. Sci. Instrum. 61, 3196 (1990)]. Experiments have recently begun on the Tokamak Fusion Test Reactor (TFTR) with the goal of measuring the alpha particle energy distribution during D--T operation in 1993--94. A series of preliminary experiments are planned to test the diagnostic concept. The first experiments will observe neutrals from beam-injected deuterium ions and the high energy 3 He tail produced during ion cyclotron (ICH) minority heating on TFTR interacting with the cloud. We will also monitor by line radiation the charge state distributions in lithium, boron, and carbon clouds

[Effects of Tangshenling Mixture and benazepril on rats with diabetic nephropathy and its mechanism].

Science.gov (United States)

He, Xue-Lin; Li, Jian-Ping; Chen, Yi-Ping; Zhang, Zhi-Gang; Lin, Wei-Qin; Chen, Jiang-Hua

2006-01-01

To investigate the effects of Tangshenling Mixture (TSLM) and benazepril on rats with diabetic nephropathy (DN) and its mechanism. Diabetic nephropathy was induced in rats by intraperitoneal injection of streptozotocin. Fifty-eight rats with DN were randomly divided into four groups: untreated group, TSLM-treated group, TSLM plus benazepril-treated group and benazepril-treated group. Another seven normal rats were included in normal control group. Then, rats in each group were accordingly given normal saline, TSLM, TSLM plus benazepril and benazepril orally for six weeks respectively. Blood and urine biochemical indexes, plasma atrial natriuretic factor (ANF), pathomorphology of renal tissue, transforming growth factor beta1 (TGF-beta1) and glucose transporter 1 (GLUT1) mRNAs in renal tissue were observed. Both TSLM and benazepril could decrease urinary albumin excretion rates, creatinine clearance and ratio of kidney weight to body weight of the rats with DN as well as reduce the pathological damages of the renal tissues. TSLM could reduce the level of plasma ANF and the expression of GLUT1 mRNA, but had no significant effect on the expression of TGF-beta1 mRNA. Benazepril could reduce the expression of TGF-beta1 mRNA, but had no significant effect on plasma ANF and the expression of GLUT1 mRNA. TSLM can reduce the pathological damages of renal tissues in rats with early-stage DN, and its mechanism may relate to decreasing the level of plasma ANF and the expression of GLUT1 mRNA which is different from that of benazepril. It seems that TSLM has synergetic effect with benazepril.

Optimasi Kualitas Akustik Room to Room Berdasarkan Nilai Transmission Loss

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Fitri Rachmawati

2013-09-01

Full Text Available Kamar tidur merupakan salah satu fasilitas utama yang disediakan pada sebuah hotel. Fasilitas ini membutuhkan kenyamanan dan ruangan yang bersifat privasi dimana privasi berkaitan dengan aspek suara yaitu bising (noise. Tingkat kebisingan pada kamar harus diatur dengan adanya insulasi suara agar tidak mengganggu kenyamanan pengunjung saat beristirahat. Nilai insulasi ini dapat digambarkan dengan transmission loss dimana nilai ini dapat diubah menjadi suatu nilai tunggal yang disebut dengan weighted sound reduction index (Rw, DnTw yang mempunyai penambahan faktor koreksi suara frekuensi rendah (C, Ctr. Pada penelitian ini dilakukan insulasi suara pada kamar tidur hotel di Bandara Juanda dengan meninjau aspek dinding partisi untuk menahan kebisingan antar ruangan kamar tidur. Hotel pada penelitian ini merupakan hotel low budget dengan kamar yang minimalis dan ditujukan untuk awak pesawat atau penumpang pesawat yang sedang transit. Walaupun minimalis, tetap diperlukan insulasi suara pada kamar yang baik sehingga dilakukan optimasi dinding partisi dengan ketentuan nilai DnTw+Ctr > 51 dB. Pengukuran pada penelitian ini dilakukan di 5 titik dengan menggunakan SLM RION dan SOLO pada saat malam hari. Berdasarkan hasil pengukuran, diketahui bahwa dinding partisi existing belum memenuhi standar dengan nilai DnTw+Ctr sebesar 35,8 dB sehingga dilakukan perancangan ulang dinding partisi. Perancangan ini menggunakan material gypsum board dan cement board dengan variasi ketebalan material serta cavity yang berbeda. Hasil perancangan yang terbaik yaitu dinding dari material cement board 12,5 mm dengan spesifikasi double panels pada masing-masing sisi dan lebar cavity 70 mm dimana menghasilkan nilai DnTw+Ctr sebesar 52,9 dB. Dengan hasil tersebut, maka dinding partisi sudah memenuhi standar dan mempunyai kualitas insulasi suara yang baik.

Dysfunction of the RAR/RXR signaling pathway in the forebrain impairs hippocampal memory and synaptic plasticity

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Nomoto Masanori

2012-02-01

Full Text Available Abstract Background Retinoid signaling pathways mediated by retinoic acid receptor (RAR/retinoid × receptor (RXR-mediated transcription play critical roles in hippocampal synaptic plasticity. Furthermore, recent studies have shown that treatment with retinoic acid alleviates age-related deficits in hippocampal long-term potentiation (LTP and memory performance and, furthermore, memory deficits in a transgenic mouse model of Alzheimer's disease. However, the roles of the RAR/RXR signaling pathway in learning and memory at the behavioral level have still not been well characterized in the adult brain. We here show essential roles for RAR/RXR in hippocampus-dependent learning and memory. In the current study, we generated transgenic mice in which the expression of dominant-negative RAR (dnRAR could be induced in the mature brain using a tetracycline-dependent transcription factor and examined the effects of RAR/RXR loss. Results The expression of dnRAR in the forebrain down-regulated the expression of RARβ, a target gene of RAR/RXR, indicating that dnRAR mice exhibit dysfunction of the RAR/RXR signaling pathway. Similar with previous findings, dnRAR mice displayed impaired LTP and AMPA-mediated synaptic transmission in the hippocampus. More importantly, these mutant mice displayed impaired hippocampus-dependent social recognition and spatial memory. However, these deficits of LTP and memory performance were rescued by stronger conditioning stimulation and spaced training, respectively. Finally, we found that pharmacological blockade of RARα in the hippocampus impairs social recognition memory. Conclusions From these observations, we concluded that the RAR/RXR signaling pathway greatly contributes to learning and memory, and LTP in the hippocampus in the adult brain.

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

International Nuclear Information System (INIS)

Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

2014-01-01

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway

Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

Science.gov (United States)

Jheng, Huei-Fen; Tsai, Pei-Jane; Chuang, Yi-Lun; Shen, Yi-Ting; Tai, Ting-An; Chen, Wen-Chung; Chou, Chuan-Kai; Ho, Li-Chun; Tang, Ming-Jer; Lai, Kuei-Tai A.; Sung, Junne-Ming; Tsai, Yau-Sheng

2015-01-01

ABSTRACT Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN. PMID:26398934

Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: short-term results.

Science.gov (United States)

Matsuda, Hidetoshi; Kitamura, Nobuto; Kurokawa, Takayuki; Arakaki, Kazunobu; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

2013-01-31

A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne's gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. According to the total Wayne's score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (phyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

Polysomnographic and neurometabolic features may mark preclinical autosomal dominant cerebellar ataxia, deafness, and narcolepsy due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1.

Science.gov (United States)

Moghadam, Keivan Kaveh; Pizza, Fabio; Tonon, Caterina; Lodi, Raffaele; Carelli, Valerio; Poli, Francesca; Franceschini, Christian; Barboni, Piero; Seri, Marco; Ferrari, Simona; La Morgia, Chiara; Testa, Claudia; Cornelio, Ferdinando; Liguori, Rocco; Winkelmann, Juliane; Lin, Ling; Mignot, Emmanuel; Plazzi, Giuseppe

2014-05-01

We aimed to report the clinical picture of two asymptomatic daughters of a patient with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1. Clinical assessment based on history, neurologic examination, sleep recordings, neurophysiologic neuroimaging, and genetic tests was performed. History and neurologic examination in both subjects were unremarkable. Genetic analysis disclosed in both the paternally-inherited heterozygous point mutation in the DNMT1 gene. Sleep recordings found sleep-onset rapid eye movement periods (SOREMPs) and proton magnetic resonance spectroscopy (MRS) revealed increased cerebellar myoinositol (mI) in both subjects. Auditory and ophthalmologic investigations as well as structural brain magnetic resonance imaging (MRI) scans revealed no abnormalities. The two asymptomatic carriers of the heterozygous DNMT1 mutation for ADCA-DN, a late-onset neurodegenerative disease, presented with SOREMPs associated with an increase of mI in the brain, a marker of glial cell activity and density characteristic of early stages of neurodegenerative diseases. Therefore, SOREMPs may precede the clinical picture of ADCA-DN as an early polysomnographic marker of central nervous system involvement detected by MRS. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurobiological foundations of multisensory processing integration in people with autism spectrum disorders: The role of the medial prefrontal cortex

Directory of Open Access Journals (Sweden)

Sonia eMartínez-Sanchis

2014-12-01

Full Text Available This review aims to relate the sensory processing problems in people with Autism spectrum disorders (ASD, especially Multisensory interaction (MSI, to the role of the medial prefrontal cortex (mPFC by exploring neuroanatomical findings; brain connectivity and Default Network (DN; global or locally directed attention; and temporal multisensory binding. The mPFC is part of the brain’s DN, which is deactivated when attention is focused on a particular task and activated on rest when spontaneous cognition emerges. In those with ASD, it is hypoactive and the higher the social impairment the greater the atypical activity. With an immature DN, cross-modal integration is impaired, resulting in a collection of disconnected fragments instead of a coherent global perception. The deficit in MSI may lie in the temporal synchronization of neural networks. The time interval in which the stimulation of one sensory channel could influence another would be higher, preventing integration in the typical shorter time range. Thus, the underconnectivity between distant brain areas would be involved in top-down information processes (relying on global integration of data from different sources and would enhance low level perception processes such as over focused attention to sensory details.