Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster.

PubMed

Tognon, Emiliana; Kobia, Francis; Busi, Ilaria; Fumagalli, Arianna; De Masi, Federico; Vaccari, Thomas

2016-01-01

In vertebrates, TFEB (transcription factor EB) and MITF (microphthalmia-associated transcription factor) family of basic Helix-Loop-Helix (bHLH) transcription factors regulates both lysosomal function and organ development. However, it is not clear whether these 2 processes are interconnected. Here, we show that Mitf, the single TFEB and MITF ortholog in Drosophila, controls expression of vacuolar-type H(+)-ATPase pump (V-ATPase) subunits. Remarkably, we also find that expression of Vha16-1 and Vha13, encoding 2 key components of V-ATPase, is patterned in the wing imaginal disc. In particular, Vha16-1 expression follows differentiation of proneural regions of the disc. These regions, which will form sensory organs in the adult, appear to possess a distinctive endolysosomal compartment and Notch (N) localization. Modulation of Mitf activity in the disc in vivo alters endolysosomal function and disrupts proneural patterning. Similar to our findings in Drosophila, in human breast epithelial cells we observe that impairment of the Vha16-1 human ortholog ATP6V0C changes the size and function of the endolysosomal compartment and that depletion of TFEB reduces ligand-independent N signaling activity. Our data suggest that lysosomal-associated functions regulated by the TFEB-V-ATPase axis might play a conserved role in shaping cell fate.

Activation of Peroxisome Proliferator-activated Receptor α Induces Lysosomal Biogenesis in Brain Cells

PubMed Central

Ghosh, Arunava; Jana, Malabendu; Modi, Khushbu; Gonzalez, Frank J.; Sims, Katherine B.; Berry-Kravis, Elizabeth; Pahan, Kalipada

2015-01-01

Lysosomes are ubiquitous membrane-enclosed organelles filled with an acidic interior and are central to the autophagic, endocytic, or phagocytic pathway. In contrast to its classical function as the waste management machinery, lysosomes are now considered to be an integral part of various cellular signaling processes. The diverse functionality of this single organelle requires a very complex and coordinated regulation of its activity with transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, at its core. However, mechanisms by which TFEB is regulated are poorly understood. This study demonstrates that gemfibrozil, an agonist of peroxisome proliferator-activated receptor (PPAR) α, alone and in conjunction with all-trans-retinoic acid is capable of enhancing TFEB in brain cells. We also observed that PPARα, but not PPARβ and PPARγ, is involved in gemfibrozil-mediated up-regulation of TFEB. Reporter assay and chromatin immunoprecipitation studies confirmed the recruitment of retinoid X receptor α, PPARα, and PGC1α on the PPAR-binding site on the Tfeb promoter as well. Subsequently, the drug-mediated induction of TFEB caused an increase in lysosomal protein and the lysosomal abundance in cell. Collectively, this study reinforces the link between lysosomal biogenesis and lipid metabolism with TFEB at the crossroads. Furthermore, gemfibrozil may be of therapeutic value in the treatment of lysosomal storage disorders in which autophagy-lysosome pathway plays an important role. PMID:25750174

Advanced glycation end-products suppress autophagic flux in podocytes by activating mammalian target of rapamycin and inhibiting nuclear translocation of transcription factor EB.

PubMed

Zhao, Xingchen; Chen, Yuanhan; Tan, Xiaofan; Zhang, Li; Zhang, Hong; Li, Zhilian; Liu, Shuangxin; Li, Ruizhao; Lin, Ting; Liao, Ruyi; Zhang, Qianmei; Dong, Wei; Shi, Wei; Liang, Xinling

2018-06-01

Insufficient autophagy in podocytes is related to podocyte injury in diabetic nephropathy (DN). Advanced glycation end-products (AGEs) are major factors of podocyte injury in DN. However, the role and mechanism of AGEs in autophagic dysfunction remain unknown. We investigated autophagic flux in AGE-stimulated cultured podocytes using multiple assays: western blotting, reverse transcription-quantitative PCR, immunofluorescence staining, and electron microscopy. We also utilized chloroquine and a fluorescent probe to monitor the formation and turnover of autophagosomes. Mice of the db/db strain were used to model diabetes mellitus (DM) with high levels of AGEs. To mimic DM with normal levels of AGEs as a control, we treated db/db mice with pyridoxamine to block AGE formation. AGEs impaired autophagic flux in the cultured podocytes. Compared with db/db mice with normal AGEs but high glucose levels, db/db mice with high AGEs and high glucose levels exhibited lower autophagic activity. Aberrant autophagic flux was related to hyperactive mammalian target of rapamycin (mTOR), a major suppressor of autophagy. Pharmacologic inhibition of mTOR activity restored impaired autophagy. AGEs inhibited the nuclear translocation and activity of the pro-autophagic transcription factor EB (TFEB) and thus suppressed transcription of its several autophagic target genes. Conversely, TFEB overexpression prevented AGE-induced autophagy insufficiency. Attenuating mTOR activity recovered TFEB nuclear translocation under AGE stimulation. Co-immunoprecipitation assays further demonstrated the interaction between mTOR and TFEB in AGE-stimulated podocytes and in glomeruli from db/db mice. In conclusion, AGEs play a crucial part in suppressing podocyte autophagy under DM conditions. AGEs inhibited the formation and turnover of autophagosomes in podocytes by activating mTOR and inhibiting the nuclear translocation of TFEB. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin

PubMed Central

Moruno Manchon, Jose Felix; Uzor, Ndidi-Ese; Kesler, Shelli R.; Wefel, Jeffrey S.; Townley, Debra M.; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S.; Sood, Anil K.; Tsvetkov, Andrey S.

2016-01-01

Doxorubicin, a commonly used chemotherapy agent, induces severe cardio- and neurotoxicity. Molecular mechanisms of cardiotoxicity have been extensively studied, but mechanisms by which doxorubicin exhibits its neurotoxic properties remain unclear. Here, we show that doxorubicin impairs neuronal autophagy, leading to the accumulation of an autophagy substrate p62. Neurons treated with doxorubicin contained autophagosomes, damaged mitochondria, and lipid droplets. The brains from mice treated with pegylated liposomal doxorubicin exhibited autophagosomes, often with mitochondria, lipofuscin, and lipid droplets. Interestingly, lysosomes were less acidic in doxorubicin-treated neurons. Overexpression of the transcription factor EB (TFEB), which controls the autophagy-lysosome axis, increased survival of doxorubicin-treated neurons. 2-Hydroxypropyl-β-cyclodextrin (HPβCD), an activator of TFEB, also promoted neuronal survival, decreased the levels of p62, and lowered the pH in lysosomes. Taken together, substantial changes induced by doxorubicin contribute to neurotoxicity, cognitive disturbances in cancer patients and survivors, and accelerated brain aging. The TFEB pathway might be a new approach for mitigating damage of neuronal autophagy caused by doxorubicin. PMID:27992857

TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin.

PubMed

Moruno-Manchon, Jose Felix; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

2016-12-16

Doxorubicin, a commonly used chemotherapy agent, induces severe cardio- and neurotoxicity. Molecular mechanisms of cardiotoxicity have been extensively studied, but mechanisms by which doxorubicin exhibits its neurotoxic properties remain unclear. Here, we show that doxorubicin impairs neuronal autophagy, leading to the accumulation of an autophagy substrate p62. Neurons treated with doxorubicin contained autophagosomes, damaged mitochondria, and lipid droplets. The brains from mice treated with pegylated liposomal doxorubicin exhibited autophagosomes, often with mitochondria, lipofuscin, and lipid droplets. Interestingly, lysosomes were less acidic in doxorubicin-treated neurons. Overexpression of the transcription factor EB (TFEB), which controls the autophagy-lysosome axis, increased survival of doxorubicin-treated neurons. 2-Hydroxypropyl-β-cyclodextrin (HPβCD), an activator of TFEB, also promoted neuronal survival, decreased the levels of p62, and lowered the pH in lysosomes. Taken together, substantial changes induced by doxorubicin contribute to neurotoxicity, cognitive disturbances in cancer patients and survivors, and accelerated brain aging. The TFEB pathway might be a new approach for mitigating damage of neuronal autophagy caused by doxorubicin.

Lysosomal Adaptation: How the Lysosome Responds to External Cues

PubMed Central

Settembre, Carmine; Ballabio, Andrea

2014-01-01

Recent evidence indicates that the importance of the lysosome in cell metabolism and organism physiology goes far beyond the simple disposal of cellular garbage. This dynamic organelle is situated at the crossroad of the most important cellular pathways and is involved in sensing, signaling, and transcriptional mechanisms that respond to environmental cues, such as nutrients. Two main mediators of these lysosomal adaptation mechanisms are the mTORC1 kinase complex and the transcription factor EB (TFEB). These two factors are linked in a lysosome-to-nucleus signaling pathway that provides the lysosome with the ability to adapt to extracellular cues and control its own biogenesis. Modulation of lysosomal function by acting on TFEB has a profound impact on cellular clearance and energy metabolism and is a promising therapeutic target for a large variety of disease conditions. PMID:24799353

Mitochondrial Quality Control via the PGC1α-TFEB Signaling Pathway Is Compromised by Parkin Q311X Mutation But Independently Restored by Rapamycin.

PubMed

Siddiqui, Almas; Bhaumik, Dipa; Chinta, Shankar J; Rane, Anand; Rajagopalan, Subramanian; Lieu, Christopher A; Lithgow, Gordon J; Andersen, Julie K

2015-09-16

Following its activation by PINK1, parkin is recruited to depolarized mitochondria where it ubiquitinates outer mitochondrial membrane proteins, initiating lysosomal-mediated degradation of these organelles. Mutations in the gene encoding parkin, PARK2, result in both familial and sporadic forms of Parkinson's disease (PD) in conjunction with reductions in removal of damaged mitochondria. In contrast to what has been reported for other PARK2 mutations, expression of the Q311X mutation in vivo in mice appears to involve a downstream step in the autophagic pathway at the level of lysosomal function. This coincides with increased PARIS expression and reduced expression of a reciprocal signaling pathway involving the master mitochondrial regulator peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) and the lysosomal regulator transcription factor EB (TFEB). Treatment with rapamycin was found to independently restore PGC1α-TFEB signaling in a manner not requiring parkin activity and to abrogate impairment of mitochondrial quality control and neurodegenerative features associated with this in vivo model. Losses in PGC1α-TFEB signaling in cultured rat DAergic cells expressing the Q311X mutation associated with reduced mitochondrial function and cell viability were found to be PARIS-dependent and to be independently restored by rapamycin in a manner requiring TFEB. Studies in human iPSC-derived neurons demonstrate that TFEB induction can restore mitochondrial function and cell viability in a mitochondrially compromised human cell model. Based on these data, we propose that the parkin Q311X mutation impacts on mitochondrial quality control via PARIS-mediated regulation of PGC1α-TFEB signaling and that this can be independently restored via upregulation of TFEB function. Mutations in PARK2 are generally associated with loss in ability to interact with PINK1, impacting on autophagic initiation. Our data suggest that, in the case of at least one parkin mutation, Q311X, detrimental effects are due to inhibition at the level of downstream lysosomal function. Mechanistically, this involves elevations in PARIS protein levels and subsequent effects on PGC1α-TFEB signaling that normally regulates mitochondrial quality control. Treatment with rapamycin independently restores PGC1α-TFEB signaling in a manner not requiring parkin activity and abrogates subsequent mitochondrial impairment and neuronal cell loss. Taken in total, our data suggest that the parkin Q311X mutation impacts on mitochondrial quality control via PARIS-mediated regulation of PGC1α-TFEB signaling and that this can be independently restored via rapamycin. Copyright © 2015 the authors 0270-6474/15/3512833-12$15.00/0.

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

PubMed

Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

2015-01-01

Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury.

GDC-0941 enhances the lysosomal compartment via TFEB and primes glioblastoma cells to lysosomal membrane permeabilization and cell death.

PubMed

Enzenmüller, Stefanie; Gonzalez, Patrick; Karpel-Massler, Georg; Debatin, Klaus-Michael; Fulda, Simone

2013-02-01

Since phosphatidylinositol-3-kinase (PI3K) inhibitors are primarily cytostatic against glioblastoma, we searched for new drug combinations. Here, we discover that the PI3K inhibitor GDC-0941 acts in concert with the natural compound B10, a glycosylated derivative of betulinic acid, to induce cell death in glioblastoma cells. Importantly, parallel experiments in primary glioblastoma cultures similarly show that GDC-0941 and B10 cooperate to trigger cell death, underscoring the clinical relevance of this finding. Molecular studies revealed that treatment with GDC-0941 stimulates the expression and nuclear translocation of Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, the lysosomal membrane marker LAMP-1 and the mature form of cathepsin B. Also, GDC-0941 triggers a time-dependent increase of the lysosomal compartment in a TFEB-dependent manner, since knockdown of TFEB significantly reduces this GDC-0941-stimulated lysosomal enhancement. Importantly, GDC-0941 cooperates with B10 to trigger lysosomal membrane permeabilization, leading to increased activation of Bax, loss of mitochondrial membrane potential (MMP), caspase-3 activation and cell death. Addition of the cathepsin B inhibitor CA-074me reduces Bax activation, loss of MMP, caspase-3 activation and cell death upon treatment with GDC-0941/B10. By comparison, knockdown of caspase-3 or the broad-range caspase inhibitor zVAD.fmk inhibits GDC-0941/B10-induced DNA fragmentation, but does not prevent cell death, thus pointing to both caspase-dependent and -independent pathways. By identifying the combination of GDC-0941 and B10 as a new, potent strategy to trigger cell death in glioblastoma cells, our findings have important implications for the development of novel treatment approaches for glioblastoma. Copyright © 2012. Published by Elsevier Ireland Ltd.

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

PubMed Central

Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

2015-01-01

Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

Oxidative Stress by Monoamine Oxidase-A Impairs Transcription Factor EB Activation and Autophagosome Clearance, Leading to Cardiomyocyte Necrosis and Heart Failure.

PubMed

Santin, Yohan; Sicard, Pierre; Vigneron, François; Guilbeau-Frugier, Céline; Dutaur, Marianne; Lairez, Olivier; Couderc, Bettina; Manni, Diego; Korolchuk, Viktor I; Lezoualc'h, Frank; Parini, Angelo; Mialet-Perez, Jeanne

2016-07-01

In heart failure (HF), mitochondrial quality control and autophagy are progressively impaired, but the role of oxidative stress in this process and its underlying mechanism remain to be defined. By degrading norepinephrine and serotonin, the mitochondrial enzyme, monoamine oxidase-A (MAO-A), is a potent source of reactive oxygen species (ROS) in the heart and its activation leads to the persistence of mitochondrial damage. In this study, we analyzed the consequences of ROS generation by MAO-A on the autophagy-lysosome pathway in the heart. Cardiomyocyte-driven expression of MAO-A in mice led to mitochondrial fission and translocation of Drp1 and Parkin in the mitochondrial compartment. Ventricles from MAO-A transgenic mice displayed accumulation of LC3-positive autophagosomes, together with p62 and ubiquitylated proteins, indicating impairment of autophagy. In vitro adenoviral delivery of MAO-A in cardiomyocytes and the consequent generation of ROS blocked autophagic flux with accumulation of LC3II, p62, and ubiquitylated proteins, leading to mitochondrial fission and cell necrosis. In addition, MAO-A activation induced accumulation of lysosomal proteins, cathepsin D and Lamp1, reduced lysosomal acidification, and blocked the nuclear translocation of transcription factor-EB (TFEB), a master regulator of autophagy and lysosome biogenesis. Most interestingly, overexpression of TFEB attenuated autophagosome buildup, mitochondrial fission, cardiomyocyte death, and HF associated with MAO-A activation. This study unravels a new link between MAO-dependent H2O2 production and lysosomal dysfunction. Altogether, our findings demonstrate that the MAO-A/H2O2 axis has a negative impact on the elimination and recycling of mitochondria through the autophagy-lysosome pathway, which participates in cardiomyocyte death and HF. Antioxid. Redox Signal. 25, 10-27.

Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

PubMed

Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

2016-01-28

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Inhibition of acid sphingomyelinase disrupts LYNUS signaling and triggers autophagy.

PubMed

Justice, Matthew J; Bronova, Irina; Schweitzer, Kelly S; Poirier, Christophe; Blum, Janice S; Berdyshev, Evgeny V; Petrache, Irina

2018-04-01

Activation of the lysosomal ceramide-producing enzyme, acid sphingomyelinase (ASM), by various stresses is centrally involved in cell death and has been implicated in autophagy. We set out to investigate the role of the baseline ASM activity in maintaining physiological functions of lysosomes, focusing on the lysosomal nutrient-sensing complex (LYNUS), a lysosomal membrane-anchored multiprotein complex that includes mammalian target of rapamycin (mTOR) and transcription factor EB (TFEB). ASM inhibition with imipramine or sphingomyelin phosphodiesterase 1 ( SMPD1 ) siRNA in human lung cells, or by transgenic Smpd1 +/- haploinsufficiency of mouse lungs, markedly reduced mTOR- and P70-S6 kinase (Thr 389)-phosphorylation and modified TFEB in a pattern consistent with its activation. Inhibition of baseline ASM activity significantly increased autophagy with preserved degradative potential. Pulse labeling of sphingolipid metabolites revealed that ASM inhibition markedly decreased sphingosine (Sph) and Sph-1-phosphate (S1P) levels at the level of ceramide hydrolysis. These findings suggest that ASM functions to maintain physiological mTOR signaling and inhibit autophagy and implicate Sph and/or S1P in the control of lysosomal function. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion

PubMed Central

Zhou, Jing; Tan, Shi-Hao; Nicolas, Valérie; Bauvy, Chantal; Yang, Nai-Di; Zhang, Jianbin; Xue, Yuan; Codogno, Patrice; Shen, Han-Ming

2013-01-01

Lysosome is a key subcellular organelle in the execution of the autophagic process and at present little is known whether lysosomal function is controlled in the process of autophagy. In this study, we first found that suppression of mammalian target of rapamycin (mTOR) activity by starvation or two mTOR catalytic inhibitors (PP242 and Torin1), but not by an allosteric inhibitor (rapamycin), leads to activation of lysosomal function. Second, we provided evidence that activation of lysosomal function is associated with the suppression of mTOR complex 1 (mTORC1), but not mTORC2, and the mTORC1 localization to lysosomes is not directly correlated to its regulatory role in lysosomal function. Third, we examined the involvement of transcription factor EB (TFEB) and demonstrated that TFEB activation following mTORC1 suppression is necessary but not sufficient for lysosomal activation. Finally, Atg5 or Atg7 deletion or blockage of the autophagosome-lysosome fusion process effectively diminished lysosomal activation, suggesting that lysosomal activation occurring in the course of autophagy is dependent on autophagosome-lysosome fusion. Taken together, this study demonstrates that in the course of autophagy, lysosomal function is upregulated via a dual mechanism involving mTORC1 suppression and autophagosome-lysosome fusion. PMID:23337583

Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion.

PubMed

Zhou, Jing; Tan, Shi-Hao; Nicolas, Valérie; Bauvy, Chantal; Yang, Nai-Di; Zhang, Jianbin; Xue, Yuan; Codogno, Patrice; Shen, Han-Ming

2013-04-01

Lysosome is a key subcellular organelle in the execution of the autophagic process and at present little is known whether lysosomal function is controlled in the process of autophagy. In this study, we first found that suppression of mammalian target of rapamycin (mTOR) activity by starvation or two mTOR catalytic inhibitors (PP242 and Torin1), but not by an allosteric inhibitor (rapamycin), leads to activation of lysosomal function. Second, we provided evidence that activation of lysosomal function is associated with the suppression of mTOR complex 1 (mTORC1), but not mTORC2, and the mTORC1 localization to lysosomes is not directly correlated to its regulatory role in lysosomal function. Third, we examined the involvement of transcription factor EB (TFEB) and demonstrated that TFEB activation following mTORC1 suppression is necessary but not sufficient for lysosomal activation. Finally, Atg5 or Atg7 deletion or blockage of the autophagosome-lysosome fusion process effectively diminished lysosomal activation, suggesting that lysosomal activation occurring in the course of autophagy is dependent on autophagosome-lysosome fusion. Taken together, this study demonstrates that in the course of autophagy, lysosomal function is upregulated via a dual mechanism involving mTORC1 suppression and autophagosome-lysosome fusion.

Signals for the lysosome: a control center for cellular clearance and energy metabolism

PubMed Central

Settembre, Carmine; Fraldi, Alessandro; Medina, Diego L.

2015-01-01

Preface For a long time lysosomes were considered merely to be cellular “incinerators” involved in the degradation and recycling of cellular waste. However, there is now compelling evidence indicating that lysosomes have a much broader function and that they are involved in fundamental processes such as secretion, plasma membrane repair, signaling and energy metabolism. Furthermore, the essential role of lysosomes in the autophagic pathway puts these organelles at the crossroads of several cellular processes, with significant implications for health and disease. The identification of a master gene, transcription factor EB (TFEB), that regulates lysosomal biogenesis and autophagy, has revealed how the lysosome adapts to environmental cues, such as starvation, and suggests novel therapeutic strategies for modulating lysosomal function in human disease. PMID:23609508

Lysosome biogenesis/scattering increases host cell susceptibility to invasion by Trypanosoma cruzi metacyclic forms and resistance to tissue culture trypomastigotes

PubMed Central

Cortez, Cristian; Real, Fernando

2015-01-01

Summary A fundamental question to be clarified concerning the host cell invasion by Trypanosoma cruzi is whether the insect‐borne and mammalian‐stage parasites use similar mechanisms for invasion. To address that question, we analysed the cell invasion capacity of metacyclic trypomastigotes (MT) and tissue culture trypomastigotes (TCT) under diverse conditions. Incubation of parasites for 1 h with HeLa cells in nutrient‐deprived medium, a condition that triggered lysosome biogenesis and scattering, increased MT invasion and reduced TCT entry into cells. Sucrose‐induced lysosome biogenesis increased HeLa cell susceptibility to MT and resistance to TCT. Treatment of cells with rapamycin, which inhibits mammalian target of rapamycin (mTOR), induced perinuclear lysosome accumulation and reduced MT invasion while augmenting TCT invasion. Metacylic trypomastigotes, but not TCT, induced mTOR dephosphorylation and the nuclear translocation of transcription factor EB (TFEB), a mTOR‐associated lysosome biogenesis regulator. Lysosome biogenesis/scattering was stimulated upon HeLa cell interaction with MT but not with TCT. Recently, internalized MT, but not TCT, were surrounded by colocalized lysosome marker LAMP2 and mTOR. The recombinant gp82 protein, the MT‐specific surface molecule that mediates invasion, induced mTOR dephosphorylation, nuclear TFEB translocation and lysosome biogenesis/scattering. Taken together, our data clearly indicate that MT invasion is mainly lysosome‐dependent, whereas TCT entry is predominantly lysosome‐independent. PMID:26572924

Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.

PubMed

Zhang, Jinzhong; Johnson, Jennifer L; He, Jing; Napolitano, Gennaro; Ramadass, Mahalakshmi; Rocca, Celine; Kiosses, William B; Bucci, Cecilia; Xin, Qisheng; Gavathiotis, Evripidis; Cuervo, Ana María; Cherqui, Stephanie; Catz, Sergio D

2017-06-23

The lysosomal storage disease cystinosis, caused by cystinosin deficiency, is characterized by cell malfunction, tissue failure, and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Here, we show CMA substrate accumulation in cystinotic kidney proximal tubule cells. We also found mislocalization of the CMA lysosomal receptor LAMP2A and impaired substrate translocation into the lysosome caused by defective CMA in cystinosis. The impaired LAMP2A trafficking and localization were rescued either by the expression of wild-type cystinosin or by the disease-associated point mutant CTNS-K280R, which has no cystine transporter activity. Defective LAMP2A trafficking in cystinosis was found to associate with decreased expression of the small GTPase Rab11 and the Rab7 effector RILP. Defective Rab11 trafficking in cystinosis was rescued by treatment with small-molecule CMA activators. RILP expression was restored by up-regulation of the transcription factor EB (TFEB), which was down-regulated in cystinosis. Although LAMP2A expression is independent of TFEB, TFEB up-regulation corrected lysosome distribution and lysosomal LAMP2A localization in Ctns -/- cells but not Rab11 defects. The up-regulation of Rab11, Rab7, or RILP, but not its truncated form RILP-C33, rescued LAMP2A-defective trafficking in cystinosis, whereas dominant-negative Rab11 or Rab7 impaired LAMP2A trafficking. Treatment of cystinotic cells with a CMA activator increased LAMP2A localization at the lysosome and increased cell survival. Altogether, we show that LAMP2A trafficking is regulated by cystinosin, Rab11, and RILP and that CMA up-regulation is a potential clinically relevant mechanism to increase cell survival in cystinosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Nuclear Export Inhibition Enhances HLH-30/TFEB Activity, Autophagy, and Lifespan.

PubMed

Silvestrini, Melissa J; Johnson, Joseph R; Kumar, Anita V; Thakurta, Tara G; Blais, Karine; Neill, Zachary A; Marion, Sarah W; St Amand, Victoria; Reenan, Robert A; Lapierre, Louis R

2018-05-15

Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi screen in C. elegans and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via xpo-1 silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models. Selective XPO1 inhibitors recapitulated the effect on autophagy and lifespan observed by silencing xpo-1 and protected ALS-afflicted flies from neurodegeneration. XPO1 inhibition in HeLa cells enhanced TFEB nuclear localization, autophagy, and lysosome biogenesis without affecting mTOR activity, revealing a conserved regulatory mechanism for HLH-30/TFEB. Altogether, our study demonstrates that altering the nuclear export of HLH-30/TFEB can regulate autophagy and establishes the rationale of targeting XPO1 to stimulate autophagy in order to prevent neurodegeneration. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Intracellular sphingosine releases calcium from lysosomes.

PubMed

Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

2015-11-27

To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia.

PubMed

Wu, Muzo; Gibbons, John G; DeLoid, Glen M; Bedugnis, Alice S; Thimmulappa, Rajesh K; Biswal, Shyam; Kobzik, Lester

2017-07-01

Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFNγ to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNγ-treated cells and improved survival in mice with postinfluenza pneumococcal pneumonia. Transcription factor analysis also indicated a role for transcription factor E-box (TFEB) in MARCO recovery. Overexpression of TFEB in THP-1 cells led to marked increases in MARCO. The ability of Akt activation to increase MARCO expression in IFNγ-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in postinfluenza bacterial pneumonia. Copyright © 2017 the American Physiological Society.

Aneuploidy-induced cellular stresses limit autophagic degradation

PubMed Central

Santaguida, Stefano; Vasile, Eliza; White, Eileen; Amon, Angelika

2015-01-01

An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Aneuploid cells experience a number of stresses that are caused by aneuploidy-induced proteomic changes. How the aneuploidy-associated stresses affect cells and whether cells respond to them are only beginning to be understood. Here we show that autophagosomal cargo such as protein aggregates accumulate within lysosomes in aneuploid cells. This causes a lysosomal stress response. Aneuploid cells activate the transcription factor TFEB, a master regulator of autophagic and lysosomal gene expression, thereby increasing the expression of genes needed for autophagy-mediated protein degradation. Accumulation of autophagic cargo within the lysosome and activation of TFEB-responsive genes are also observed in cells in which proteasome function is inhibited, suggesting that proteotoxic stress causes TFEB activation. Our results reveal a TFEB-mediated lysosomal stress response as a universal feature of the aneuploid state. PMID:26404941

TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress.

PubMed

Raben, Nina; Puertollano, Rosa

2016-10-06

In recent years, our vision of lysosomes has drastically changed. Formerly considered to be mere degradative compartments, they are now recognized as key players in many cellular processes. The ability of lysosomes to respond to different stimuli revealed a complex and coordinated regulation of lysosomal gene expression. This review discusses the participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysosomal pathway in cellular adaptation to a variety of stress conditions, including nutrient deprivation, mitochondrial dysfunction, protein misfolding, and pathogen infection. We also describe how cancer cells make use of TFEB and TFE3 to promote their own survival and highlight the potential of these transcription factors as therapeutic targets for the treatment of neurological and lysosomal diseases.

Intracellular sphingosine releases calcium from lysosomes

PubMed Central

Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

2015-01-01

To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC. DOI: http://dx.doi.org/10.7554/eLife.10616.001 PMID:26613410

Embryonic expression of zebrafish MiT family genes tfe3b, tfeb, and tfec.

PubMed

Lister, James A; Lane, Brandon M; Nguyen, Anhthu; Lunney, Katherine

2011-11-01

The MiT family comprises four genes in mammals: Mitf, Tfe3, Tfeb, and Tfec, which encode transcription factors of the basic-helix-loop-helix/leucine zipper class. Mitf is well-known for its essential role in the development of melanocytes, however the functions of the other members of this family, and of interactions between them, are less well understood. We have now characterized the complete set of MiT genes from zebrafish, which totals six instead of four. The zebrafish genome contain two mitf (mitfa and mitfb), two tfe3 (tfe3a and tfe3b), and single tfeb and tfec genes; this distribution is shared with other teleosts. We present here the sequence and embryonic expression patterns for the zebrafish tfe3b, tfeb, and tfec genes, and identify a new isoform of tfe3a. These findings will assist in elucidating the roles of the MiT gene family over the course of vertebrate evolution. Copyright © 2011 Wiley-Liss, Inc.

Cardiomyocyte-Restricted Low Density Lipoprotein Receptor-Related Protein 6 (LRP6) Deletion Leads to Lethal Dilated Cardiomyopathy Partly Through Drp1 Signaling

PubMed Central

Chen, Zhidan; Li, Yang; Wang, Ying; Qian, Juying; Ma, Hong; Wang, Xiang; Jiang, Guoliang; Liu, Ming; An, Yanpeng; Ma, Leilei; Kang, Le; Jia, Jianguo; Yang, Chunjie; Zhang, Guoping; Chen, Ying; Gao, Wei; Fu, Mingqiang; Huang, Zheyong; Tang, Huiru; Zhu, Yichun; Ge, Junbo; Gong, Hui; Zou, Yunzeng

2018-01-01

Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group. Tamoxifen-inducible cardiac-specific LRP6 knockout mice developed acute heart failure and mitochondrial dysfunction with reduced survival. Proteomic analysis suggests the fatty acid metabolism disorder involving peroxisome proliferator-activated receptors (PPARs) signaling in the LRP6 deficient heart. Accumulation of mitochondrial targeting to autophagosomes and lipid droplet were observed in LRP6 deletion hearts. Further analysis revealed cardiac LRP6 deletion suppressed autophagic degradation and fatty acid utilization, coinciding with activation of dynamin-related protein 1 (Drp1) and downregulation of nuclear TFEB (Transcription factor EB). Injection of Mdivi-1, a Drp1 inhibitor, not only promoted nuclear translocation of TFEB, but also partially rescued autophagic degradation, improved PPARs signaling, and attenuated cardiac dysfunction induced by cardiac specific LRP6 deletion. Conclusions: Cardiac LRP6 deficiency greatly suppressed autophagic degradation and fatty acid utilization, and subsequently leads to lethal dilated cardiomyopathy and cardiac dysfunction through activation of Drp1 signaling. It suggests that heart failure progression may be attenuated by therapeutic modulation of LRP6 expression. PMID:29344294

Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals

PubMed Central

Nakamura, Shuhei; Karalay, Özlem; Jäger, Philipp S.; Horikawa, Makoto; Klein, Corinna; Nakamura, Kayo; Latza, Christian; Templer, Sven E.; Dieterich, Christoph; Antebi, Adam

2016-01-01

Germline removal provokes longevity in several species and shifts resources towards survival and repair. Several Caenorhabditis elegans transcription factors regulate longevity arising from germline removal; yet, how they work together is unknown. Here we identify a Myc-like HLH transcription factor network comprised of Mondo/Max-like complex (MML-1/MXL-2) to be required for longevity induced by germline removal, as well as by reduced TOR, insulin/IGF signalling and mitochondrial function. Germline removal increases MML-1 nuclear accumulation and activity. Surprisingly, MML-1 regulates nuclear localization and activity of HLH-30/TFEB, a convergent regulator of autophagy, lysosome biogenesis and longevity, by downregulating TOR signalling via LARS-1/leucyl-transfer RNA synthase. HLH-30 also upregulates MML-1 upon germline removal. Mammalian MondoA/B and TFEB show similar mutual regulation. MML-1/MXL-2 and HLH-30 transcriptomes show both shared and preferential outputs including MDL-1/MAD-like HLH factor required for longevity. These studies reveal how an extensive interdependent HLH transcription factor network distributes responsibility and mutually enforces states geared towards reproduction or survival. PMID:27001890

[Renal cell carcinoma with t(6;11)(p21.2;q13)/MALAT1-TFEB fusion: a clinical and pathological analysis].

PubMed

Xia, Qiuyuan; Shi, Shanshan; Shen, Qin; Wei, Xue; Wang, Xuan; Ma, Henghui; Lu, Zhenfeng; Zhou, Xiaojun; Rao, Qiu

2015-12-01

To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion. A total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature. The age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E-cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis. TFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis.

Effects of ambroxol on the autophagy-lysosome pathway and mitochondria in primary cortical neurons.

PubMed

Magalhaes, J; Gegg, M E; Migdalska-Richards, A; Schapira, A H

2018-01-23

Glucocerebrosidase (GBA1) mutations are the major genetic risk factor for Parkinson's Disease (PD). The pathogenic mechanism is still unclear, but alterations in lysosomal-autophagy processes are implicated due to reduction of mutated glucocerebrosidase (GCase) in lysosomes. Wild-type GCase activity is also decreased in sporadic PD brains. Small molecule chaperones that increase lysosomal GCase activity have potential to be disease-modifying therapies for GBA1-associated and sporadic PD. Therefore we have used mouse cortical neurons to explore the effects of the chaperone ambroxol. This chaperone increased wild-type GCase mRNA, protein levels and activity, as well as increasing other lysosomal enzymes and LIMP2, the GCase transporter. Transcription factor EB (TFEB), the master regulator of the CLEAR pathway involved in lysosomal biogenesis was also increased upon ambroxol treatment. Moreover, we found macroautophagy flux blocked and exocytosis increased in neurons treated with ambroxol. We suggest that ambroxol is blocking autophagy and driving cargo towards the secretory pathway. Mitochondria content was also found to be increased by ambroxol via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Our data suggest that ambroxol, besides being a GCase chaperone, also acts on other pathways, such as mitochondria, lysosomal biogenesis, and the secretory pathway.

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

PubMed

Zeng, Wei; Xiao, Tao; Cai, Anlie; Cai, Weiliang; Liu, Huanhuan; Liu, Jingling; Li, Jie; Tan, Miduo; Xie, Li; Liu, Ying; Yang, Xiangcheng; Long, Yi

2017-01-01

Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

Glycogen Synthase Kinase 3 Inhibition Promotes Lysosomal Biogenesis and Autophagic Degradation of the Amyloid-β Precursor Protein

PubMed Central

Parr, Callum; Carzaniga, Raffaela; Gentleman, Steve M.; Van Leuven, Fred; Walter, Jochen

2012-01-01

Alzheimer's disease (AD) has been associated with altered activity of glycogen synthase kinase 3 (GSK3) isozymes, which are proposed to contribute to both neurofibrillary tangles and amyloid plaque formation. However, the molecular basis by which GSK3 affects the formation of Aβ remains unknown. Our aim was to identify the underlying mechanisms of GSK3-dependent effects on the processing of amyloid precursor protein (APP). For this purpose, N2a cells stably expressing APP carrying the Swedish mutation were treated with specific GSK3 inhibitors or transfected with GSK3α/β short interfering RNA. We show that inhibition of GSK3 leads to decreased expression of APP by enhancing its degradation via an increase in the number of lysosomes. This induction of the lysosomal/autophagy pathway was associated with nuclear translocation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis. Our data indicate that GSK3 inhibition reduces Aβ through an increase of the degradation of APP and its carboxy-terminal fragment (CTF) by activation of the lysosomal/autophagy pathway. These results suggest that an increased propensity toward autophagic/lysosomal alterations in AD patients could have consequences for neuronal function. PMID:22927642

Regulation of lysosomal ion homeostasis by channels and transporters.

PubMed

Xiong, Jian; Zhu, Michael X

2016-08-01

Lysosomes are the major organelles that carry out degradation functions. They integrate and digest materials compartmentalized by endocytosis, phagocytosis or autophagy. In addition to more than 60 hydrolases residing in the lysosomes, there are also ion channels and transporters that mediate the flux or transport of H(+), Ca(2+), Na(+), K(+), and Cl(-) across the lysosomal membranes. Defects in ionic exchange can lead to abnormal lysosome morphology, defective vesicle trafficking, impaired autophagy, and diseases such as neurodegeneration and lysosomal storage disorders. The latter are characterized by incomplete lysosomal digestion and accumulation of toxic materials inside enlarged intracellular vacuoles. In addition to degradation, recent studies have revealed the roles of lysosomes in metabolic pathways through kinases such as mechanistic target of rapamycin (mTOR) and transcriptional regulation through calcium signaling molecules such as transcription factor EB (TFEB) and calcineurin. Owing to the development of new approaches including genetically encoded fluorescence probes and whole endolysosomal patch clamp recording techniques, studies on lysosomal ion channels have made remarkable progress in recent years. In this review, we will focus on the current knowledge of lysosome-resident ion channels and transporters, discuss their roles in maintaining lysosomal function, and evaluate how their dysfunction can result in disease.

SNAT7 is the primary lysosomal glutamine exporter required for extracellular protein-dependent growth of cancer cells

PubMed Central

Verdon, Quentin; Boonen, Marielle; Ribes, Christopher; Jadot, Michel; Sagné, Corinne

2017-01-01

Lysosomes degrade cellular components sequestered by autophagy or extracellular material internalized by endocytosis and phagocytosis. The macromolecule building blocks released by lysosomal hydrolysis are then exported to the cytosol by lysosomal transporters, which remain undercharacterized. In this study, we designed an in situ assay of lysosomal amino acid export based on the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis that detects lysosomal storage. This assay was used to screen candidate lysosomal transporters, leading to the identification of sodium-coupled neutral amino acid transporter 7 (SNAT7), encoded by the SLC38A7 gene, as a lysosomal transporter highly selective for glutamine and asparagine. Cell fractionation confirmed the lysosomal localization of SNAT7, and flux measurements confirmed its substrate selectivity and showed a strong activation by the lysosomal pH gradient. Interestingly, gene silencing or editing experiments revealed that SNAT7 is the primary permeation pathway for glutamine across the lysosomal membrane and it is required for growth of cancer cells in a low free-glutamine environment, when macropinocytosis and lysosomal degradation of extracellular proteins are used as an alternative source of amino acids. SNAT7 may, thus, represent a novel target for glutamine-related anticancer therapies. PMID:28416685

Performance Demonstration of Mcmb-LiNiCoO2 Cells Containing Electrolytes Designed for Wide Operating Temperature Range

NASA Technical Reports Server (NTRS)

Smart, M. C.; Ratnakumar, B. V.; Whicanack, L. D.; Smith, K. A.; Santee, S.; Puglia, F. J.; Gitzendanner, R.

2009-01-01

With the intent of improving the performance of Li-ion cells over a wide operating temperature range, we have investigated the use of co-solvents to improve the properties of electrolyte formulations. In the current study, we have focused upon evaluating promising electrolytes which have been incorporated into large capacity (7 Ah) prototype Li-ion cells, fabricated by Yardney Technical Products, Inc. The electrolytes selected for performance evaluation include the use of a number of esters as co-solvents, including methyl propionate (MP), ethyl propionate (EP), ethyl butyrate (EB), propyl butyrate (PB), and 2,2,2-trifluoroethyl butyrate (TFEB). The performance of the prototype cells containing the ester-based electrolytes was compared with an extensive data base generated on cells containing previously developed all carbonate-based electrolytes. A number of performance tests were performed, including determining (i) the discharge rate capacity over a wide range of temperatures, (ii) the charge characteristics, (iii) the cycle life characteristics under various conditions, and (iv) the impedance characteristics.

Melanotic MiT family translocation neoplasms: Expanding the clinical and molecular spectrum of this unique entity of tumors.

PubMed

Saleeb, Rola M; Srigley, John R; Sweet, Joan; Doucet, Cedric; Royal, Virginie; Chen, Ying-Bei; Brimo, Fadi; Evans, Andrew

2017-11-01

MiT family translocation tumors are a group of neoplasms characterized by translocations involving MiT family transcription factors. The translocation renal cell carcinomas, TFE3 (Xp11.2) and TFEB (t6;11) are known members of this family. Melanotic Xp11 translocation renal cancer is a more recently described entity. To date only 14 cases have been described. It is characterized by a distinct set of features including a nested epithelioid morphology, melanin pigmentation, labeling for markers of melanocytic differentiation, lack of labeling for markers of renal tubular differentiation, predominance in a younger age population and association with aggressive clinical behavior. There are noted similarities between that entity and TFE3 associated PEComas. There are no cases reported of equivalent melanotic TFEB translocation renal cancer. We report 2 rare cases of melanotic translocation renal neoplasms. The first is a melanotic TFE3 translocation renal cancer with an indolent clinical course, occurring in a patient more than 3-decades older than the usual average age in which such tumors have been described. The other case is, to our knowledge, the first reported melanotic TFEB translocation cancer of the kidney. Both cases exhibit the same H&E morphology as previously reported in melanotic translocation renal cancers and label accordingly with HMB45 and Melan-A. While the TFE3 melanotic tumor lacked any evidence of renal tubular differentiation, the TFEB melanotic cancer exhibited some staining for renal tubular markers. Based on the unique features noted above, these two cases expand the clinical and molecular spectrum of the melanotic translocation renal cancers. Copyright © 2017 Elsevier GmbH. All rights reserved.

MiT family translocation renal cell carcinoma.

PubMed

Argani, Pedram

2015-03-01

The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy

PubMed Central

Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao

2017-01-01

Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF-α, IL-1β, MIP-1α, and MIP-2) along with their master regulator NFκB. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries. PMID:28828145

Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy.

PubMed

Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao; Hao, Enkui

2017-01-01

Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF- α , IL-1 β , MIP-1 α , and MIP-2) along with their master regulator NF κ B. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries.

MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.

PubMed

Magers, Martin J; Udager, Aaron M; Mehra, Rohit

2015-10-01

Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease. Thus, distinguishing t-RCC from its morphologic, immunophenotypic, and molecular mimics may have important clinical implications. The differential diagnosis for t-RCC includes a variety of common renal neoplasms, particularly those demonstrating clear cell and papillary features; in addition, because of immunophenotypic overlap and/or shared molecular abnormalities (ie, TFE3 gene rearrangement), a distinctive set of nonepithelial renal tumors may also warrant consideration. Directed ancillary testing is an essential aspect to the workup of t-RCC cases and may include a panel of immunohistochemical stains, such as PAX8, pancytokeratins, epithelial membrane antigen, carbonic anhydrase IX, HMB-45, and Melan-A. Dual-color, break-apart fluorescent in situ hybridization for TFE3 or TFEB gene rearrangement may be helpful in diagnostically challenging cases or when molecular confirmation is needed.

Novel gene fusion of PRCC-MITF defines a new member of MiT family translocation renal cell carcinoma: clinicopathological analysis and detection of the gene fusion by RNA sequencing and FISH.

PubMed

Xia, Qiu-Yuan; Wang, Xiao-Tong; Ye, Sheng-Bing; Wang, Xuan; Li, Rui; Shi, Shan-Shan; Fang, Ru; Zhang, Ru-Song; Ma, Heng-Hui; Lu, Zhen-Feng; Shen, Qin; Bao, Wei; Zhou, Xiao-Jun; Rao, Qiu

2018-04-01

MITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC-MITF gene fusion by RNA sequencing. Histological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in-situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription-polymerase chain reaction confirmed the presence of a PRCC-MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break-apart probes and PRCC-MITF fusion probes to detect the MITF gene rearrangement. This study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs. © 2017 John Wiley & Sons Ltd.

Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia.

PubMed

Holler, Christopher J; Taylor, Georgia; McEachin, Zachary T; Deng, Qiudong; Watkins, William J; Hudson, Kathryn; Easley, Charles A; Hu, William T; Hales, Chadwick M; Rossoll, Wilfried; Bassell, Gary J; Kukar, Thomas

2016-06-24

Progranulin (PGRN) is a secreted growth factor important for neuronal survival and may do so, in part, by regulating lysosome homeostasis. Mutations in the PGRN gene (GRN) are a common cause of frontotemporal lobar degeneration (FTLD) and lead to disease through PGRN haploinsufficiency. Additionally, complete loss of PGRN in humans leads to neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Importantly, Grn-/- mouse models recapitulate pathogenic lysosomal features of NCL. Further, GRN variants that decrease PGRN expression increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Together these findings demonstrate that insufficient PGRN predisposes neurons to degeneration. Therefore, compounds that increase PGRN levels are potential therapeutics for multiple neurodegenerative diseases. Here, we performed a cell-based screen of a library of known autophagy-lysosome modulators and identified multiple novel activators of a human GRN promoter reporter including several common mTOR inhibitors and an mTOR-independent activator of autophagy, trehalose. Secondary cellular screens identified trehalose, a natural disaccharide, as the most promising lead compound because it increased endogenous PGRN in all cell lines tested and has multiple reported neuroprotective properties. Trehalose dose-dependently increased GRN mRNA as well as intracellular and secreted PGRN in both mouse and human cell lines and this effect was independent of the transcription factor EB (TFEB). Moreover, trehalose rescued PGRN deficiency in human fibroblasts and neurons derived from induced pluripotent stem cells (iPSCs) generated from GRN mutation carriers. Finally, oral administration of trehalose to Grn haploinsufficient mice significantly increased PGRN expression in the brain. This work reports several novel autophagy-lysosome modulators that enhance PGRN expression and identifies trehalose as a promising therapeutic for raising PGRN levels to treat multiple neurodegenerative diseases.

Targeting Androgen Receptor by Lysosomal Degradation in Prostate Cancer

DTIC Science & Technology

2014-09-01

chloroquine for 12 h or left untreated. Lysosomes were prepared using the Lysosome Enrichment Kit for Tissue and Cultured Cells (#89839, Pierce... chloroquine for 12 h or left untreated, and the luciferase activity was determined using the same amount of protein lysate (left). The cells were treated...degradation pathway either by increasing the TFEB levels or by activating TFEB using mTORC1 kinase inhibitor, torin 1. Additionally, we determined that the

HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.

PubMed

Chen, Huan-Da; Kao, Cheng-Yuan; Liu, Bang-Yu; Huang, Shin-Whei; Kuo, Cheng-Ju; Ruan, Jhen-Wei; Lin, Yen-Hung; Huang, Cheng-Rung; Chen, Yu-Hung; Wang, Horng-Dar; Aroian, Raffi V; Chen, Chang-Shi

2017-02-01

Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.

[Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

PubMed

Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

2008-10-14

To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

Nurses' Perceptions of Implementing Fall Prevention Interventions to Mitigate Patient-Specific Fall Risk Factors.

PubMed

Wilson, Deleise S; Montie, Mary; Conlon, Paul; Reynolds, Margaret; Ripley, Robert; Titler, Marita G

2016-08-01

Evidence-based (EB) fall prevention interventions to mitigate patient-specific fall risk factors are readily available but not routinely used in practice. Few studies have examined nurses' perceptions about both the use of these EB interventions and implementation strategies designed to promote their adoption. This article reports qualitative findings of nurses' perceptions about use of EB fall prevention interventions to mitigate patient-specific fall risks, and implementation strategies to promote use of these interventions. The findings revealed five major themes: before-study fall prevention practices, use of EB fall prevention interventions tailored to patient-specific fall risk factors, beneficial implementation strategies, overall impact on approach to fall prevention, and challenges These findings are useful to guide nurses' engagement and use of EB fall prevention practices tailored to patient-specific fall risk factors. © The Author(s) 2016.

Ehrlichia Activation of Wnt-PI3K-mTOR Signaling Inhibits Autolysosome Generation and Autophagic Destruction by the Mononuclear Phagocyte

PubMed Central

Luo, Tian; Velayutham, Thangam-Sudha; Das, Seema

2017-01-01

ABSTRACT In multicellular organisms, autophagy is induced as an innate defense mechanism. Notably, the obligate intracellular bacterium Ehrlichia chaffeensis resides in early endosome-like vacuoles and circumvents lysosomal fusion through an unknown mechanism, thereby avoiding destruction in the autophagolysosome. In this report, we reveal that Wnt signaling plays a crucial role in inhibition of lysosomal fusion and autolysosomal destruction of ehrlichiae. During early infection, autophagosomes fuse with ehrlichial vacuoles to form an amphisome indicated by the presence of autophagy markers such as LC3 (microtubule-associated protein 1 light chain 3), Beclin-1, and p62. LC3 colocalized with ehrlichial morulae on days 1, 2, and 3 postinfection, and increased LC3II levels were detected during infection, reaching a maximal level on day 3. Ehrlichial vacuoles did not colocalize with the lysosomal marker LAMP2, and lysosomes were redistributed and dramatically reduced in level in the infected cells. An inhibitor specific for the Wnt receptor signaling component Dishevelled induced lysosomal fusion with ehrlichial inclusions corresponding to p62 degradation and promoted transcription factor EB (TFEB) nuclear localization. E. chaffeensis infection activated the phosphatidylinositol 3-kinase (PI3K)–Akt–mTOR (mechanistic target of rapamycin) pathway, and activation was induced by three ehrlichial tandem repeat protein (TRP) effectors, with TRP120 inducing the strongest activation. Moreover, induction of glycogen synthase kinase-3 (GSK3) performed using a Wnt inhibitor and small interfering RNA (siRNA) knockdown of critical components of PI3K-GSK3-mTOR signaling decreased ehrlichial survival. This report reveals Ehrlichia exploitation of the evolutionarily conserved Wnt pathway to inhibit autolysosome generation, thereby leading to evasion of this important innate immune defense mechanism. PMID:28993455

Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

PubMed

Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

2017-03-01

Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

RNA Sequencing Reveals the Alteration of the Expression of Novel Genes in Ethanol-Treated Embryoid Bodies.

PubMed

Mandal, Chanchal; Kim, Sun Hwa; Chai, Jin Choul; Oh, Seon Mi; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

2016-01-01

Fetal alcohol spectrum disorder is a collective term representing fetal abnormalities associated with maternal alcohol consumption. Prenatal alcohol exposure and related anomalies are well characterized, but the molecular mechanism behind this phenomenon is not well characterized. In this present study, our aim is to profile important genes that regulate cellular development during fetal development. Human embryonic carcinoma cells (NCCIT) are cultured to form embryoid bodies and then treated in the presence and absence of ethanol (50 mM). We employed RNA sequencing to profile differentially expressed genes in the ethanol-treated embryoid bodies from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH data sets. A total of 632, 205 and 517 differentially expressed genes were identified from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH, respectively. Functional annotation using bioinformatics tools reveal significant enrichment of differential cellular development and developmental disorders. Furthermore, a group of 42, 15 and 35 transcription factor-encoding genes are screened from all of the differentially expressed genes obtained from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH, respectively. We validated relative gene expression levels of several transcription factors from these lists by quantitative real-time PCR. We hope that our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of alcohol-mediated anomalies and ease further research.

Investigation of electron beam irradiation effects on anti-nutritional factors, chemical composition and digestion kinetics of whole cottonseed, soybean and canola seeds

NASA Astrophysics Data System (ADS)

Ebrahimi-Mahmoudabad, S. R.; Taghinejad-Roudbaneh, M.

2011-12-01

This study was completed to determine effects of electron beam (EB) irradiation at doses of 15, 30 and 45 kGy on anti-nutritional factors, ruminal degradation and in vitro crude protein (CP) digestibility of whole cottonseed (WCS), soybean (SB) and canola seeds (CS). EB-irradiation eliminated completely ( P<0.001) phytic acid of WCS, SB and CS at a dose of 30 kGy. EB-irradiation decreased linearly ( P<0.001) the total glucosinolate content of CS. Trypsin inhibitor activity of 15, 30 and 45 kGy EB-irradiated SB was decreased by 19, 73 and 88%, respectively. Free gossypol content of WCS was reduced linearly ( P<0.001) by irradiation. EB-irradiation increased linearly ( P<0.001) CP digestibility of feeds. In conclusion, EB-irradiation was an effective processing method for improving the nutritive value of WCS, SB and CS.

Esophageal Sensorimotor Function and Psychological Factors Each Contribute to Symptom Severity in Globus Patients.

PubMed

Rommel, Nathalie; Van Oudenhove, Lukas; Arts, Joris; Caenepeel, Philip; Tack, Jan; Pauwels, Ans

2016-10-01

Altered upper esophageal sphincter (UES) and esophageal body (EB) sensorimotor function and psychosocial factors may both be involved in symptom generation in globus, but their common impact is not yet assessed. The aim of the study is (1) to compare UES and EB sensitivity and compliance of globus patients with healthy controls (HC); (2) to study the association of globus symptom severity (GSS) with UES and EB sensitivity and compliance, UES motor function and psychosocial factors. In 58 globus patients, GSS, somatization, and anxiety disorders were determined using validated questionnaires. In 26 HC and 42/58 patients, UES and EB sensitivity and compliance were assessed twice using barostat measurements. UES function of 27 globus patients was evaluated using high-resolution manometry. Bivariate correlations and a general linear model tested the association of these factors with GSS. UES and EB compliance did not differ between globus patients and HC. Upon repeated distension, UES habituation was seen in both groups, whereas EB sensitization (23.3±1.3 vs. 19.5±1.5 mm Hg, P<0.0001) only occurred in globus patients, (P=0.038). UES compliance (ρ=0.37, P=0.04), change in EB compliance upon repeated distension (ρ=0.45, P=0.007), somatization (ρ=0.43, P=0.003), panic disorder (t=3.04, P=0.004), and post-traumatic stress severity (ρ=0.40, P=0.005) were associated with GSS. UES compliance and somatization were independently associated with GSS. A trend (P=0.061) was found for the association of GSS with change in EB compliance. UES compliance, change in EB compliance, and somatization explain 40% of the variance in GSS. This indicates that globus is a complex disorder of the brain-gut axis rather than a "psychosomatic" disorder or a peripheral esophageal disorder.

Enrichment of cardiac differentiation of mouse embryonic stem cells by optimizing the hanging drop method.

PubMed

Chen, Ming; Lin, Yong-Qing; Xie, Shuang-Lun; Wu, Hong-Fu; Wang, Jing-Feng

2011-04-01

Hanging drop (HD) culture is used to induce differentiation of embryonic stem cells (ESCs) into other cell types including cardiomyocytes. However, the factors affecting cardiac differentiation of ESCs with this method remain incompletely understood. We have investigated the effects of the starting number of ESCs in embryoid bodies (EBs) and the time of EB adherence to gelatin-coated plates on cardiac differentiation: cardiac differentiation was increased in the EBs by a larger number of ESCs and was decreased by plating EBs at day 4 or earlier. These two factors can thus be optimized to enrich the cardiac differentiation in ESCs using the HD method.

[Prevalence of factors associated with the duration of exclusive breastfeeding during the first 6 months of life in the INMA birth cohort in Gipuzkoa].

PubMed

Oribe, Madalen; Lertxundi, Aitana; Basterrechea, Mikel; Begiristain, Haizea; Santa Marina, Loreto; Villar, María; Dorronsoro, Miren; Amiano, Pilar; Ibarluzea, Jesús

2015-01-01

To estimate the prevalence of exclusive breastfeeding (EB) during the first 6 months of life in the Gipuzkoa birth cohort, identify the reasons for abandonment of EB, and establish the associated factors. The study population consisted of 638 pregnant women from the INMA-Gipuzkoa (Infancia y Medio Ambiente, www.proyectoinma.org) birth cohort, who were followed up from the third trimester of pregnancy until the child was aged 14 months. To determine the factors related to abandonment of EB, logistic regression models were used in two different stages (4 months or early stage and 6 months or late stage). The prevalence of EB within the Gipuzkoa cohort was 84.8% after hospital discharge, 53.7% at 4 months of life and 15.4% at 6 months of life. The reasons given by the mothers for early EB cessation were: breastfeeding problems, low weight gain and hypogalactia. Other factors influencing the early phase were the intention to provide EB, parity, area of residence and social class. Abandonment in the late stage was influenced by the length of maternity leave. From a public health perspective, the results of this study could help health professionals to develop strategies to support breastfeeding mothers, taking into account the main reasons for early and late abandonment. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

47 CFR 27.1214 - EBS spectrum leasing arrangements and grandfathered leases.

Code of Federal Regulations, 2010 CFR

2010-10-01

... not employ channel loading technology. (3) The licensee may shift its requisite EBS educational usage... educational use requirements in light of changes in educational needs, technology, and other relevant factors... Educational Broadband Service § 27.1214 EBS spectrum leasing arrangements and grandfathered leases. (a) A...

p62/Sequestosome-1, Autophagy-related Gene 8, and Autophagy in Drosophila Are Regulated by Nuclear Factor Erythroid 2-related Factor 2 (NRF2), Independent of Transcription Factor TFEB.

PubMed

Jain, Ashish; Rusten, Tor Erik; Katheder, Nadja; Elvenes, Julianne; Bruun, Jack-Ansgar; Sjøttem, Eva; Lamark, Trond; Johansen, Terje

2015-06-12

The selective autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in oxidative stress signaling in two ways in mammals. First, p62 is transcriptionally induced upon oxidative stress by the NF-E2-related factor 2 (NRF2) by direct binding to an antioxidant response element in the p62 promoter. Second, p62 accumulation, occurring when autophagy is impaired, leads to increased p62 binding to the NRF2 inhibitor KEAP1, resulting in reduced proteasomal turnover of NRF2. This gives chronic oxidative stress signaling through a feed forward loop. Here, we show that the Drosophila p62/SQSTM1 orthologue, Ref(2)P, interacts directly with DmAtg8a via an LC3-interacting region motif, supporting a role for Ref(2)P in selective autophagy. The ref(2)P promoter also contains a functional antioxidant response element that is directly bound by the NRF2 orthologue, CncC, which can induce ref(2)P expression along with the oxidative stress-associated gene gstD1. However, distinct from the situation in mammals, Ref(2)P does not interact directly with DmKeap1 via a KEAP1-interacting region motif; nor does ectopically expressed Ref(2)P or autophagy deficiency activate the oxidative stress response. Instead, DmAtg8a interacts directly with DmKeap1, and DmKeap1 is removed upon programmed autophagy in Drosophila gut cells. Strikingly, CncC induced increased Atg8a levels and autophagy independent of TFEB/MitF in fat body and larval gut tissues. Thus, these results extend the intimate relationship between oxidative stress-sensing NRF2/CncC transcription factors and autophagy and suggest that NRF2/CncC may regulate autophagic activity in other organisms too. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis.

PubMed

Batalla, A; Vicente, A; Bartrons, J; Prada, F; Fortuny, C; González-Enseñat, M A

In recent decades, an association has been reported between epidermolysis bullosa (EB) and dilated cardiomyopathy (DC). DC is typically in an advanced phase when detected, leading to a poorer prognosis. Our objective was to determine the prevalence of DC in patients with EB seen in Hospital San Joan de Déu in Barcelona, Spain, between May 1986 and April 2015. This was a descriptive, cross-sectional chart-review study in which we recorded the type and main subtypes of EB and the presence or absence of DC. Fifty-seven patients with EB were found, 19 with EB simplex, 10 with junctional EB, 27 with dystrophic EB (14 dominant dystrophic and 13 recessive dystrophic), and just 1 with Kindler syndrome. DC was detected in only 2 patients with recessive dystrophic EB. Twenty-three patients had presented factors that could have had a causal relationship with the potential onset of DC. DC is a possible complication of EB, particularly in recessive dystrophic EB. Periodic follow-up should be performed to make an early diagnosis and start treatment. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Fgf3 and Fgf10a work in concert to promote maturation of the epibranchial placodes in zebrafish.

PubMed

McCarroll, Matthew N; Nechiporuk, Alex V

2013-01-01

Essential cellular components of the paired sensory organs of the vertebrate head are derived from transient thickenings of embryonic ectoderm known as cranial placodes. The epibranchial (EB) placodes give rise to sensory neurons of the EB ganglia that are responsible for relaying visceral sensations form the periphery to the central nervous system. Development of EB placodes and subsequent formation of EB ganglia is a multistep process regulated by various extrinsic factors, including fibroblast growth factors (Fgfs). We discovered that two Fgf ligands, Fgf3 and Fgf10a, cooperate to promote EB placode development. Whereas EB placodes are induced in the absence of Fgf3 and Fgf10a, they fail to express placode specific markers Pax2a and Sox3. Expression analysis and mosaic rescue experiments demonstrate that Fgf3 signal is derived from the endoderm, whereas Fgf10a is emitted from the lateral line system and the otic placode. Further analyses revealed that Fgf3 and Fgf10a activities are not required for cell proliferation or survival, but are required for placodal cells to undergo neurogenesis. Based on these data, we conclude that a combined loss of these Fgf factors results in a failure of the EB placode precursors to initiate a transcriptional program needed for maturation and subsequent neurogenesis. These findings highlight the importance and complexity of reiterated Fgf signaling during cranial placode formation and subsequent sensory organ development.

Fgf3 and Fgf10a Work in Concert to Promote Maturation of the Epibranchial Placodes in Zebrafish

PubMed Central

McCarroll, Matthew N.; Nechiporuk, Alex V.

2013-01-01

Essential cellular components of the paired sensory organs of the vertebrate head are derived from transient thickenings of embryonic ectoderm known as cranial placodes. The epibranchial (EB) placodes give rise to sensory neurons of the EB ganglia that are responsible for relaying visceral sensations form the periphery to the central nervous system. Development of EB placodes and subsequent formation of EB ganglia is a multistep process regulated by various extrinsic factors, including fibroblast growth factors (Fgfs). We discovered that two Fgf ligands, Fgf3 and Fgf10a, cooperate to promote EB placode development. Whereas EB placodes are induced in the absence of Fgf3 and Fgf10a, they fail to express placode specific markers Pax2a and Sox3. Expression analysis and mosaic rescue experiments demonstrate that Fgf3 signal is derived from the endoderm, whereas Fgf10a is emitted from the lateral line system and the otic placode. Further analyses revealed that Fgf3 and Fgf10a activities are not required for cell proliferation or survival, but are required for placodal cells to undergo neurogenesis. Based on these data, we conclude that a combined loss of these Fgf factors results in a failure of the EB placode precursors to initiate a transcriptional program needed for maturation and subsequent neurogenesis. These findings highlight the importance and complexity of reiterated Fgf signaling during cranial placode formation and subsequent sensory organ development. PMID:24358375

Renal cell carcinoma with t(6:11) (p21;q12). A case report highlighting distinctive immunohistologic features of this rare tumor.

PubMed

Arneja, Sarabjeet Kaur; Gujar, Neeraj

2015-01-01

Renal cell carcinoma (RCC) with t(6:11) (p21;q12) are extremely rare, fewer than 30 cases have been reported in literature. These tumors are characterized by specific chromosomal translocation involving TFEB, as against the more commonly known TFE3 (Xp11.2) translocation associated RCCs. The distinctive immnohistologic features are helpful in enabling a diagnosis of this rare tumor, otherwise diagnosed by fluorescence in situ hybridization assay, specific for detecting TFEB gene rearrangement. Herein, we report a case of this rare tumor in a 11 years old boy, with the objective of highlighting distinctive light microscopic and immuno-phenotypic features of this rare sub-type of translocation associated renal cell carcinoma, otherwise diagnosed by fluorescence in situ hybridization technique. Morphologically tumor showed distinctive biphasic population of cells, large epitheloid cells with voluminous eosinophillic cytoplasm and smaller cells with much lesser amount of cytoplasm and small rounded nuclei. The smaller cells at places clustered around hyaline pink material forming "pseudorosettes". population. Immunohistochemically both types of tumor cells showed negativity for pan CK (cytokeratin), EMA (epitheleal membrane antigen) and TFE3 (transcription factor E3). HMB 45 (human melanoma black 45) and Melan- A /MART 1 (melanoma antigen recognized by T cells) were moderate to strongly expressed. On review of literature, most RCCs with t(6;11) translocation have been reported to be negative for pan cytokeratins and EMA. Published literature also shows that the most distinctive immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for TFEB protein. Immunostains for TFE3 have always been negative in the reported cases. It is noteworthy that immunoreactivity for melanocytic markers HMB45 and Melan A and immunonegativity for epithelial markers pan CK and EMA may lead to misdiagnosis of angiomyolipoma to the unwary. Knowledge of distinctive morphological and immuno-histochemical features of this tumor can help in establishing a diagnosis of this rare subset of translocation associated RCC on routine hematoxylin and eosin (H and E) staining and immunophenotyping. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Searching for Components of Conceptual Ecology That Mediate Development of Epistemological Beliefs in Science

NASA Astrophysics Data System (ADS)

Deniz, Hasan

2011-12-01

This paper articulates the importance of epistemological beliefs (EBs) and draws a parallel between EBs literature in educational psychology and nature of science (NOS) literature in science education. The paper stresses that EBs in science and NOS ideas have common ground and they can be best improved through explicit-reflective instruction informed by conceptual change theory. The paper concludes that future studies should explore the factors that mediate the development of EBs in science and NOS ideas rather than documenting the changes in students' and teachers' EBs in science and NOS ideas after explicit-reflective instruction through pre- and post assessments.

Liquid marble as microbioreactor for bioengineering applications

NASA Astrophysics Data System (ADS)

Sarvi, Fatemeh; Jain, Kanika; Alhasan, Layla; Arbatan, Tina; Shen, Wei; Chan, Peggy P. Y.

2015-12-01

This paper reports the use of liquid marbles (LMs) as miniature bioreactors to produce three-dimensional (3D) spheroids including tumor-like spheriods from cancer cells and embryoid bodies (EBs) from stem cells. A liquid marble microbioreactor is prepared by placing a drop of cell suspension onto a polytetrafluoroethylene (PTFE) particle bed. Without the addition of growth factors, suspended EBs from liquid marbles exhibit spontaneous contraction. These results indicate that the liquid marble provides a suitable microenvironment to induce EB formation and spontaneous cardiac differentiation. The EBs were further plated onto gelatin-coated tissue culture dishes. Plated EBs express mature cardiomyocyte marker cardiac troponinT (cTnT), indicating that these EBs have differentiated into functional cardiomyocytes. The cardiomyocytes generated using this liquid marble approach could be useful for transplantation.

The amino acid transporter SLC36A4 regulates the amino acid pool in retinal pigmented epithelial cells and mediates the mechanistic target of rapamycin, complex 1 signaling.

PubMed

Shang, Peng; Valapala, Mallika; Grebe, Rhonda; Hose, Stacey; Ghosh, Sayan; Bhutto, Imran A; Handa, James T; Lutty, Gerard A; Lu, Lixia; Wan, Jun; Qian, Jiang; Sergeev, Yuri; Puertollano, Rosa; Zigler, J Samuel; Xu, Guo-Tong; Sinha, Debasish

2017-04-01

The dry (nonneovascular) form of age-related macular degeneration (AMD), a leading cause of blindness in the elderly, has few, if any, treatment options at present. It is characterized by early accumulation of cellular waste products in the retinal pigmented epithelium (RPE); rejuvenating impaired lysosome function in RPE is a well-justified target for treatment. It is now clear that amino acids and vacuolar-type H + -ATPase (V-ATPase) regulate the mechanistic target of rapamycin, complex 1 (mTORC1) signaling in lysosomes. Here, we provide evidence for the first time that the amino acid transporter SLC36A4/proton-dependent amino acid transporter (PAT4) regulates the amino acid pool in the lysosomes of RPE. In Cryba1 (gene encoding βA3/A1-crystallin) KO (knockout) mice, where PAT4 and amino acid levels are increased in the RPE, the transcription factors EB (TFEB) and E3 (TFE3) are retained in the cytoplasm, even after 24 h of fasting. Consequently, genes in the coordinated lysosomal expression and regulation (CLEAR) network are not activated, and lysosomal function remains low. As these mice age, expression of RPE65 and lecithin retinol acyltransferase (LRAT), two vital visual cycle proteins, decreases in the RPE. A defective visual cycle would possibly slow down the regeneration of new photoreceptor outer segments (POS). Further, photoreceptor degeneration also becomes obvious during aging, reminiscent of human dry AMD disease. Electron microscopy shows basal laminar deposits in Bruch's membrane, a hallmark of development of AMD. For dry AMD patients, targeting PAT4/V-ATPase in the lysosomes of RPE cells may be an effective means of preventing or delaying disease progression. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

National Institutes of Health Toolbox Emotion Battery for English- and Spanish-speaking adults: normative data and factor-based summary scores.

PubMed

Babakhanyan, Ida; McKenna, Benjamin S; Casaletto, Kaitlin B; Nowinski, Cindy J; Heaton, Robert K

2018-01-01

The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) is a "common currency", computerized assessment developed to measure the full spectrum of emotional health. Though comprehensive, the NIHTB-EB's 17 scales may be unwieldy for users aiming to capture more global indices of emotional functioning. NIHTB-EB was administered to 1,036 English-speaking and 408 Spanish-speaking adults as a part of the NIH Toolbox norming project. We examined the factor structure of the NIHTB-EB in English- and Spanish-speaking adults and developed factor analysis-based summary scores. Census-weighted norms were presented for English speakers, and sample-weighted norms were presented for Spanish speakers. Exploratory factor analysis for both English- and Spanish-speaking cohorts resulted in the same 3-factor solution: 1) negative affect, 2) social satisfaction, and 3) psychological well-being. Confirmatory factor analysis supported similar factor structures for English- and Spanish-speaking cohorts. Model fit indices fell within the acceptable/good range, and our final solution was optimal compared to other solutions. Summary scores based upon the normative samples appear to be psychometrically supported and should be applied to clinical samples to further validate the factor structures and investigate rates of problematic emotions in medical and psychiatric populations.

A High Proliferation Rate is Critical for Reproducible and Standardized Embryoid Body Formation from Laminin-521-Based Human Pluripotent Stem Cell Cultures.

PubMed

Dziedzicka, Dominika; Markouli, Christina; Barbé, Lise; Spits, Claudia; Sermon, Karen; Geens, Mieke

2016-12-01

When aiming for homogenous embryoid body (EB) differentiation, the use of equal-sized EBs is required to avoid a size-induced differentiation bias. In this study we developed an efficient and standardized EB formation protocol for human pluripotent stem cells (hPSC) cultured in a laminin-521-based xeno-free system. As the cell proliferation rate of the cells growing on laminin-521 strongly affected the efficiency of aggregate formation, we found that recently passaged cells, as well as the addition of ROCK inhibitor, were essential for reproducible EB formation from hPSC single-cell suspensions. EBs could be obtained in a variety of differentiation media, in 96-well round-bottom plates and in hanging drops. Gene expression studies on differentially sized EBs from three individual human embryonic stem cell lines demonstrated that the medium used for differentiation influenced the differentiation outcome to a much greater extent than the number of cells used for the initial EB formation. Our findings give a new insight into factors that influence the EB formation and differentiation process. This optimized method allows us to easily manipulate EB formation and provide an excellent starting point for downstream EB-based differentiation protocols.

VEGF and IHH rescue definitive hematopoiesis in Gata-4 and Gata-6-deficient murine embryoid bodies.

PubMed

Pierre, Monique; Yoshimoto, Momoko; Huang, Lan; Richardson, Matthew; Yoder, Mervin C

2009-09-01

Murine embryonic stem cells can be differentiated into embryoid bodies (EBs), which serve as an in vitro model recapitulating many aspects of embryonic yolk sac hematopoiesis. Differentiation of embryonic stem cells deficient in either Gata-4 or Gata-6 results in EBs with disrupted visceral endoderm (VE). While lack of VE has detrimental effects on hematopoiesis in vivo, it is unclear whether lack of VE affects hematopoiesis in EBs. Therefore, we compared Gata-4 null (G4N) and Gata-6 null (G6N) EBs with wild-type EBs to assess their ability to commit to hematopoietic cells. EB VE formation was examined using cell-sorting techniques and analysis visceral endoderm gene expression. Hematopoietic progenitor potential of EBs cultured under various conditions was assessed using colony-forming assays. Definitive erythroid, granulocyte-macrophage, and mixed colonies were significantly reduced in G4N and G6N EBs compared to wild-type EBs. Vascular endothelial growth factor (VEGF) expression and secretion were also reduced in both G4N and G6N EBs, consistent with VE serving as a site of VEGF production. Addition of exogenous VEGF(165), to EB cultures completely rescued definitive colony-forming cells in G4N and G6N EBs. This rescue response could be blocked by addition of soluble Flk-1 Fc to EB cultures. Similarly, addition of exogenous Indian hedgehog to EB cultures also recovers the diminishment in definitive hematopoiesis in a reversible manner. These results suggest that the absence of VE in G4N and G6N EBs does not prevent emergence of definitive progenitors from EBs. However, the decreased level of VEGF and Indian hedgehog production in VE devoid G4N and G6N EBs attenuates definitive hematopoietic progenitor cell expansion.

The interaction between temperament and the family environment in adolescent substance use and externalizing behaviors: Support for diathesis–stress or differential susceptibility?

PubMed Central

Rioux, Charlie; Castellanos-Ryan, Natalie; Parent, Sophie; Séguin, Jean R.

2016-01-01

Both individual and environmental factors predict externalizing behaviors and substance use (EB-SU); however, different patterns of interaction among these factors may have different implications. This review first examines how temperament and the family environment interact in the prediction of adolescent EB-SU. Second, studies are reviewed according to two theoretical models: (1) diathesis–stress, i.e., certain individual characteristics are linked to vulnerability and later problems in adverse environments; (2) differential susceptibility, i.e., these characteristics are linked to susceptibility, predicting problems in adverse environments, but also better than average outcomes in good environments. Fourteen studies focusing on the prediction of EB-SU at ages 12–18 were selected through a literature search. Results showed that certain temperament traits (high levels of impulsivity and disinhibition; low levels of effortful control, negative affect, fearfulness and shyness), hereby designated as “adventurous” disposition, were associated with higher levels of EB-SU in adverse family environments. Some studies also showed that children with “adventurous” temperament traits in positive environments had the lowest levels of EB-SU. This suggests that prevention of EB-SU might target family factors such as parenting and focus on children with “adventurous” temperament traits. Further, studies that supported the differential susceptibility model were those assessing temperament and the family environment in childhood and studies that supported the diathesis–stress model assessed these variables in adolescence. It is thus possible that some of these “adventurous” temperament traits, with regard to EB-SU, would be indicators of susceptibility to both enriched and adverse environments in childhood but no longer in adolescence, when they would only be indicators of vulnerability to adverse environments. PMID:27413247

Eckols reduce dental pulp inflammation through the ERK1/2 pathway independent of COX-2 inhibition.

PubMed

Paudel, U; Lee, Y H; Kwon, T H; Park, N H; Yun, B S; Hwang, P H; Yi, H K

2014-11-01

The aim of this study was to elucidate the role of 6-6 bieckol (EB1) and pholorofucofuroeckol-A (EB5) from brown seaweed marine algae (Eisenia bicyclis) on lipopolysaccharide (LPS)-induced inflammation in human dental pulp cells (HDPCs). The cytotoxicity of EB1 and EB5 was examined by MTT assay on LPS-induced human dental pulp cells. Their role on expression of inflammatory, odontogenic, and osteogenic molecules was determined by Western blot analysis. The dentin mineralization was checked by alkaline phosphatase activity. The five compounds from E. bicyclis have different structure with non-cytotoxic in HDPCs. EB1 and EB5 showed anti-inflammatory properties and inhibited phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) and phosphorylated-c-jun N-terminal kinases (p-JNK) without any cytotoxicity. In particular, EB1 inhibited cyclooxygenase-2 (COX-2) and p-ERK1/2 signaling, and EB5 inhibited only p-ERK1/2 signaling but not COX-2. Both compounds inhibited nuclear factor kappa-B (NF-κB) translocation. Furthermore, EB1 and EB5 increased dentinogenic and osteogenic molecules, and dentin mineralized via alkaline phosphatase activity (ALP) in LPS-induced HDPCs. This study elucidates that EB1 and EB5 have different types of anti-inflammatory property and help in dentin formation. Therefore, these compounds derived from marine algae of E. bicyclis may be used as selective therapeutic strategies for pulpitis and oral diseases. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The PHD-containing protein EARLY BOLTING IN SHORT DAYS regulates seed dormancy in Arabidopsis.

PubMed

Narro-Diego, Laura; López-González, Leticia; Jarillo, Jose A; Piñeiro, Manuel

2017-10-01

The Arabidopsis protein EARLY BOLTING IN SHORT DAYS (EBS), a plant-specific transcriptional regulator, is involved in the control of flowering time by repressing the floral integrator FT. The EBS protein binds the H3K4me3 histone mark and interacts with histone deacetylases to modulate gene expression. Here, we show that EBS also participates in the regulation of seed dormancy. ebs mutations cause a reduction in seed dormancy, and the concurrent loss of function of the EBS homologue SHORT LIFE (SHL) enhances this dormancy alteration. Transcriptomic analyses in ebs mutant seeds uncovered the misregulation of several regulators of seed dormancy including the MADS box gene AGAMOUS-LIKE67 (AGL67). AGL67 interacts genetically with EBS in seed dormancy regulation, indicating that both loci act in the same pathway. Interestingly, EBS functions independently of the master regulator gene of dormancy DELAY OF GERMINATION 1 (DOG1) and other genes encoding chromatin remodelling factors involved in the control of seed dormancy. Altogether, these data show that EBS is a central repressor of germination during seed dormancy and that SHL acts redundantly with EBS in the control of this developmental process. Our observations suggest that a tightly regulated crosstalk among histone modifications is necessary for a proper control of seed dormancy. © 2017 John Wiley & Sons Ltd.

A protocol describing the use of a recombinant protein-based, animal product-free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies.

PubMed

Ng, Elizabeth S; Davis, Richard; Stanley, Edouard G; Elefanty, Andrew G

2008-01-01

In order to promote the uniform and reproducible differentiation of human embryonic stem cells (HESCs) in response to exogenously added growth factors, we have developed a method (spin embryoid bodies (EBs)) that uses a recombinant protein-based, animal product-free medium in which HESCs are aggregated by centrifugation to form EBs. In this protocol we describe the formulation of this medium, denoted APEL (Albumin Polyvinylalcohol Essential Lipids), and its use in spin EB differentiation of HESCs. We also describe a more economical variant, BPEL (Bovine Serum Albumin (BSA) Polyvinylalchohol Essential Lipids), in which BSA replaces the recombinant human albumin. The integration of a medium that includes only defined and recombinant components with a defined number of cells to initiate EB formation results in a generally applicable, robust platform for growth factor-directed HESC differentiation.

ROCK inhibitor is not required for embryoid body formation from singularized human embryonic stem cells.

PubMed

Pettinato, Giuseppe; Vanden Berg-Foels, Wendy S; Zhang, Ning; Wen, Xuejun

2014-01-01

We report a technology to form human embryoid bodies (hEBs) from singularized human embryonic stem cells (hESCs) without the use of the p160 rho-associated coiled-coil kinase inhibitor (ROCKi) or centrifugation (spin). hEB formation was tested under four conditions: +ROCKi/+spin, +ROCKi/-spin, -ROCKi/+spin, and -ROCKi/-spin. Cell suspensions of BG01V/hOG and H9 hESC lines were pipetted into non-adherent hydrogel substrates containing defined microwell arrays. hEBs of consistent size and spherical geometry can be formed in each of the four conditions, including the -ROCKi/-spin condition. The hEBs formed under the -ROCKi/-spin condition differentiated to develop the three embryonic germ layers and tissues derived from each of the germ layers. This simplified hEB production technique offers homogeneity in hEB size and shape to support synchronous differentiation, elimination of the ROCKi xeno-factor and rate-limiting centrifugation treatment, and low-cost scalability, which will directly support automated, large-scale production of hEBs and hESC-derived cells needed for clinical, research, or therapeutic applications.

High Frequency of Programmed Death-ligand 1 Expression in Emphysematous Bullae-associated Lung Adenocarcinomas.

PubMed

Toyokawa, Gouji; Takada, Kazuki; Okamoto, Tatsuro; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Takamori, Shinkichi; Akamine, Takaki; Katsura, Masakazu; Shoji, Fumihiro; Oda, Yoshinao; Maehara, Yoshihiko

2017-09-01

Emphysematous bullae (EB) are known to be associated with a high incidence of lung cancer; however, the reason for this has yet to be elucidated. The objective of the present study was to clarify the prevalence of programmed death-ligand-1 (PD-L1) expression in EB-associated lung adenocarcinomas. A total of 369 patients with resected lung adenocarcinoma whose preoperative computed tomography findings were available for the examination of EB were analyzed for PD-L1 expression by immunohistochemistry and evaluated to determine the association between PD-L1 expression and EB-related adenocarcinomas. Among 369 patients, EB and cancer adjoining EB (Ca-ADJ) were identified in 81 (22.0%) and 50 (13.6%) patients, respectively. EB and Ca-ADJ were significantly associated with male gender, a smoking habit, a decreased forced expiratory volume in 1 second, a relatively higher tumor grade, advanced T status and stage, the presence of pleural and vessel invasion, invasive pathologic subtypes, and wild-type epidermal growth factor receptor. Seventy patients (19.0%) were positive for PD-L1 expression, whereas the remaining 299 patients (81.0%) were negative. Thirty-six (44.4%) and 29 (58.0%) of 81 and 50 patients with EB and Ca-ADJ, respectively, were positive for PD-L1 expression, which was shown to be significant by the Fisher exact test (P < .001 and P < .001, respectively). Among the 81 lung adenocarcinomas with EB, Ca-ADJ was significantly associated with PD-L1 expression (P = .021). In a multivariate analysis, the presence of Ca-ADJ was found to be an independent predictor of PD-L1 expression. EB-associated lung adenocarcinomas express PD-L1 protein more frequently than those without EB. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of electron beam irradiation on chemical composition, antinutritional factors, ruminal degradation and in vitro protein digestibility of canola meal

NASA Astrophysics Data System (ADS)

Taghinejad-Roudbaneh, M.; Ebrahimi, S. R.; Azizi, S.; Shawrang, P.

2010-12-01

The aim of the present study was to determine the impact of electron beam (EB) irradiation at doses of 15, 30 and 45 kGy on the nutritional value of canola meal. The phytic acid and total glucosinolate content of EB-irradiated canola meal decreased as irradiation doses increased ( P<0.01). From in situ results, irradiation of canola meal at doses of 45 kGy decreased ( P<0.05) the effective degradibility of crude protein (CP) by 14%, compared with an untreated sample. In vitro CP digestibility of EB-irradiated canola meal at doses of 15 and 30 kGy was improved ( P<0.05). Electrophoresis results showed that napin and cruciferin sub-units of 30 and 45 kGy EB-irradiated canola meal were more resistant to degradation, compared with an untreated sample. Electron beam irradiation was effective in protecting CP from ruminal degradation and reducing antinutritional factors of irradiated canola meal.

Evidence-Based Programs for Older Adults: A Disconnect Between U.S. National Strategy and Local Senior Center Implementation.

PubMed

Bobitt, Julie; Schwingel, Andiara

2017-01-01

While U.S. national policies have been developed to support evidence-based (EB) lifestyle programs for older adults, there has been limited research to determine the extent to which these programs actually reach local communities. This study sought to identify factors that impact the implementation of EB physical activity, nutrition, and chronic disease management programs at regional (Area Agencies on Aging [AAAs]) and community levels (senior Centers [SCs]). Interviews were conducted with directors of four AAAs and 12 SCs to understand their perspectives on EB program implementation. Narratives revealed differences between AAAs and SCs regarding knowledge about EB programs and reasons to promote and adopt these programs. The only agreement occurred when discussing concerns about funding and program inflexibility. Substantial gaps exist between how EB lifestyle programs are promoted and implemented at the regional and community levels.

Thermal barrier coating life prediction model development, phase 2

NASA Technical Reports Server (NTRS)

Meier, Susan Manning; Sheffler, Keith D.; Nissley, David M.

1991-01-01

The objective of this program was to generate a life prediction model for electron-beam-physical vapor deposited (EB-PVD) zirconia thermal barrier coating (TBC) on gas turbine engine components. Specific activities involved in development of the EB-PVD life prediction model included measurement of EB-PVD ceramic physical and mechanical properties and adherence strength, measurement of the thermally grown oxide (TGO) growth kinetics, generation of quantitative cyclic thermal spallation life data, and development of a spallation life prediction model. Life data useful for model development was obtained by exposing instrumented, EB-PVD ceramic coated cylindrical specimens in a jet fueled burner rig. Monotonic compression and tensile mechanical tests and physical property tests were conducted to obtain the EB-PVD ceramic behavior required for burner rig specimen analysis. As part of that effort, a nonlinear constitutive model was developed for the EB-PVD ceramic. Spallation failure of the EB-PVD TBC system consistently occurred at the TGO-metal interface. Calculated out-of-plane stresses were a small fraction of that required to statically fail the TGO. Thus, EB-PVD spallation was attributed to the interfacial cracking caused by in-plane TGO strains. Since TGO mechanical properties were not measured in this program, calculation of the burner rig specimen TGO in-plane strains was performed by using alumina properties. A life model based on maximum in-plane TGO tensile mechanical strain and TGO thickness correlated the burner rig specimen EB-PVD ceramic spallation lives within a factor of about plus or minus 2X.

Impact of inherited epidermolysis bullosa on parental interpersonal relationships, marital status and family size.

PubMed

Fine, J-D; Johnson, L B; Weiner, M; Suchindran, C

2005-05-01

The presence in a family of a child or children with epidermolysis bullosa (EB) may have profound psychological implications for other family members. To assess the impact of the presence of EB in one or more children on the personal relationships between their parents. Standardized questionnaires were used. In general, the presence of a child severely affected with EB had profound effects on many aspects of marriage. This included a lack of interest in participating in activities as couples [junctional EB (JEB), 45%; recessive dystrophic EB (RDEB), 25%], a lack of energy to invest in such pursuits (JEB, 82%; RDEB, 50%), limitations in opportunities for sharing nonintimate physical activities (reported by most parents having children with some type of generalized EB), and negatively altered parental sex life (JEB, 55%; RDEB, 39%). This is consistent with the fact that 10%, 64%, 25% and 36% of parents of an affected child with EB simplex (EBS), JEB, dominant dystrophic EB (DDEB) and RDEB, respectively, characterized their relationships as couples as revolving almost exclusively around the day-to-day care of their affected children. The severity of disease in an affected child clearly influenced parental decisions about having more children: 24% and 64% of parents of children with JEB and RDEB, respectively, chose not to have additional children, compared with 26% and 54% of parents with children having EBS or DDEB. This choice was most often pursued via tubal ligation; less often, alternative means of surgical sterilization were chosen. Divorce was common among parents of children with EB (range: 17% in EBS to 31% in JEB) and, with the exception of parents of children with EBS, was usually directly attributed by one or both parents to the profound impact that this disease had exerted on their marriage. Physicians caring for children with EB need to give more consideration to the many psychological factors that may contribute to their patients' well being. They may need to assist these children's parents in seeking support and counselling to prevent destruction of the family unit.

Cells differentiated from mouse embryonic stem cells via embryoid bodies express renal marker molecules.

PubMed

Kramer, Jan; Steinhoff, Jürgen; Klinger, Matthias; Fricke, Lutz; Rohwedel, Jürgen

2006-03-01

Differentiation of mouse embryonic stem (ES) cells via embryoid bodies (EB) is established as a suitable model to study cellular processes of development in vitro. ES cells are known to be pluripotent because of their capability to differentiate into cell types of all three germ layers including germ cells. Here, we show that ES cells differentiate into renal cell types in vitro. We found that genes were expressed during EB cultivation, which have been previously described to be involved in renal development. Marker molecules characteristic for terminally differentiated renal cell types were found to be expressed predominantly during late stages of EB cultivation, while marker molecules involved in the initiation of nephrogenesis were already expressed during early steps of EB development. On the cellular level--using immunostaining--we detected cells expressing podocin, nephrin and wt-1, characteristic for differentiated podocytes and other cells, which expressed Tamm-Horsfall protein, a marker for distal tubule epithelial cells of kidney tissue. Furthermore, the proximal tubule marker molecules renal-specific oxido reductase, kidney androgen-related protein and 25-hydroxyvitamin D3alpha-hydroxylase were found to be expressed in EBs. In particular, we could demonstrate that cells expressing podocyte marker molecules assemble to distinct ring-like structures within the EBs. Because the differentiation efficiency into these cell types is still relatively low, application of fibroblast growth factor (FGF)-2 in combination with leukaemia inhibitory factor was tested for induction, but did not enhance ES cell-derived renal differentiation in vitro.

Development and Validation of the Self-Acceptance Scale for Persons with Early Blindness: The SAS-EB

PubMed Central

Morgado, Fabiane Frota da Rocha; Campana, Angela Nogueira Neves Betanho; Tavares, Maria da Consolação Gomes Cunha Fernandes

2014-01-01

Investigations of self-acceptance are critical to understanding the development and maintenance of psychological health. However, valid and reliable instruments for measuring self-acceptance in persons with early blindness have yet to be developed. The current research describes three studies designed to develop and validate the Self-acceptance Scale for Persons with Early Blindness (SAS-EB). In Study 1, we developed the initial item pool. Thirty-three items were generated, based on data from specialized literature and from 2 focus groups. Items were organized in a three-factor structure, theoretically predicted for SAS-EB - (1) body acceptance, (2) self-protection from social stigmas, and (3) feeling and believing in one's capacities. In Study 2, information obtained from a panel of 9 experts and 22 persons with early blindness representing the target population was used to refine the initial item pool, generating a new pool of 27 items. In Study 3, 318 persons with early blindness (141 women and 177 men), between 18 and 60 years of age (M = 37.74 years, SD = 12.37) answered the new pool of 27 items. After the elimination of 9 items using confirmatory factor analysis, we confirmed the theoretical three-factor structure of the SAS-EB. Study 3 also provided support for the scale's internal consistency and construct validity. Finally, the psychometric properties of the SAS-EB, its utility, and its limitations are discussed along with considerations for future research. PMID:25268633

EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration.

PubMed

Xiang, Jinyi; Bandura, Jennifer; Zhang, Peng; Jin, Yinhua; Reuter, Hanna; Edgar, Bruce A

2017-05-09

Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors. Mature ECs lack EGF receptors and are refractory to growth signalling. Genetic tests indicated that stress-dependent EGFR/MAPK promotes gut regeneration via a novel mechanism that operates independently of Insulin/Pi3K/TOR signalling, which is nevertheless required in nonstressed conditions. The E2f1 transcription factor is required for and sufficient to drive EC endoreplication, and Ras/Raf signalling upregulates E2f1 levels posttranscriptionally. We illustrate how distinct signalling mechanisms direct stress-dependent versus homeostatic regeneration, and highlight the importance of postmitotic cell growth in gut epithelial repair.

EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration

PubMed Central

Xiang, Jinyi; Bandura, Jennifer; Zhang, Peng; Jin, Yinhua; Reuter, Hanna; Edgar, Bruce A.

2017-01-01

Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors. Mature ECs lack EGF receptors and are refractory to growth signalling. Genetic tests indicated that stress-dependent EGFR/MAPK promotes gut regeneration via a novel mechanism that operates independently of Insulin/Pi3K/TOR signalling, which is nevertheless required in nonstressed conditions. The E2f1 transcription factor is required for and sufficient to drive EC endoreplication, and Ras/Raf signalling upregulates E2f1 levels posttranscriptionally. We illustrate how distinct signalling mechanisms direct stress-dependent versus homeostatic regeneration, and highlight the importance of postmitotic cell growth in gut epithelial repair. PMID:28485389

TGF-β1 induces the formation of vascular-like structures in embryoid bodies derived from human embryonic stem cells.

PubMed

Wang, Yan; Qian, DE-Jian; Zhong, Wen-Yu; Lu, Jun-Hong; Guo, Xiang-Kai; Cao, Yi-Lin; Liu, Ju

2014-07-01

Human embryonic stem cells (ESCs) can differentiate into endothelial cells in response to stimuli from extracellular cytokines. Transforming growth factor (TGF)-β1 signaling is involved in stem cell renewal and vascular development. Previously, human ESCs were isolated from inner cell mass and a stable ESC line was developed. In the present study, the effects of extracellular TGF-β1 were investigated on human ESC-derived embryoid bodies (EB) in suspension. The structures of the EBs were analyzed with light and electron microscopy, while the cellular composition of the EBs was examined via the expression levels of specific markers. Vascular-like tubular structures and cardiomyocyte-like beating cells were observed in the EBs at day 3 and 8, respectively. The frequencies of vascular-like structures and beating cells in the TGF-β1 treated group were significantly higher compared with the control group (84.31 vs. 12.77%; P<0.001; 37.25 vs. 8.51%; P<0.001, respectively). Electron microscopy revealed the presence of lumens and gap junctions in the sections of the tubular structures. Semiquantitative polymerase chain reaction revealed elevated expression levels of CD31 and fetal liver kinase-1 in EBs cultured with TGF-β1. In addition, extensive staining of von Willebrand factor was observed in the vascular-like structures of TGF-β1-treated EBs. Therefore, the results of the present study may aid the understanding of the underlying mechanisms of human ESC differentiation and improve the methods of propagating specific cell types for the clinical therapy of cardiovascular diseases.

The role of exclusive breastfeeding and sugar-sweetened beverage consumption on preschool children's weight gain.

PubMed

Silveira, J A C; Colugnati, F A B; Poblacion, A P; Taddei, J A A C

2015-04-01

Sugar-sweetened beverages (SSBs) and breastfeeding practices have been recognized as important factors linked to children's weight status. However, no other studies have simultaneously investigated the role of each factor on children's conditional weight gain (CWG). To evaluate the role of exclusive breastfeeding (EB) and the SSBs consumption on CWG from birth to the survey date among Brazilian preschool children (24-59 months old). A nationally represented cross-sectional survey with complex probability sampling (n = 2421) was conducted. The outcome variable - CWG - represents how much an individual has deviated from its expected weight gain, given his or her prior weight. The multivariate linear regression to analyse the effects of EB and the consumption of SSBs on CWG were adjusted for economic status and maternal variables. There was a significantly protective effect of EB duration during the first year of life on CWG from birth to the survey date (-0.02 [-0.03; 0.00 95% confidence interval]); however, the SSBs intake promoted an effect on the weight gain that was 2.5-fold higher (0.05 [0.02; 0.08 95% confidence interval]) than the EB. As hypothesized, the exposure variables acted in opposite directions, but the harmful effect of SSBs intake had greater magnitude than the beneficial effect of EB on children's CWG. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.

Epistemological beliefs and therapeutic health concepts of physiotherapy students and professionals.

PubMed

Bientzle, Martina; Cress, Ulrike; Kimmerle, Joachim

2014-10-01

Health knowledge develops fast and includes a lot of ambiguous or tentative information. In their daily routine, both health care students and professionals continuously have to make judgments about the viability of health knowledge. People's epistemological beliefs (EBs) and their therapeutic health concepts are factors that influence how they deal with health knowledge. However, very little is known about the occurrence of these factors at different stages of people's career. The present study examines the EBs and therapeutic health concepts of physiotherapy students in their vocational training and the EBs and therapeutic health concepts of professionals. In a cross-sectional study physiotherapy students and professional physiotherapists filled in a questionnaire that measured their personal EBs about physiotherapy and medicine, as well as their biomedical and biopsychosocial therapeutic health concepts. We compared the participants' EBs regarding both knowledge domains, and their therapeutic health concepts using paired samples t-tests. We also examined the differences between first-year students, advanced students, and professionals regarding their EBs and their therapeutic health concepts using ANOVAs. Eighty-three students and 84 professionals participated in this study, 114/167 (68%) participants were female. EBs as well as therapeutic health concepts differed depending upon the participants' training status. Professionals had more sophisticated EBs than students regarding both knowledge in physiotherapy (F(2, 164) = 6.74, P = 0.002, η(2)(p) = 0.08) and knowledge in medicine (F(2, 164) = 5.93, P = 0.003, η(2)(p) = 0.07). In addition, high values in a biopsychosocial therapeutic health concept already occurred in an early phase of training (F(2, 164) = 5.39, P = 0.005, η(2)(p) = 0.06), whereas increased values in a biomedical concept did not occur until people's professional life (F(2, 164) = 10.99, P < 0.001, η(2)(p) = 0.12). The specificities of personal EBs and therapeutic health concepts in different stages of health care training have so far been insufficiently considered in medical education research. The current study has aimed to shed light on the occurrence of these concepts in students as compared to professionals. We point out implications of our findings for educational practice and make suggestions for future research.

A Multidimensional Screening Tool for Preschoolers with Externalizing Behavior: Factor Structure and Factorial Invariance

ERIC Educational Resources Information Center

Vancraeyveldt, Caroline; Verschueren, Karine; Wouters, Sofie; Van Craeyevelt, Sanne; Colpin, Hilde

2014-01-01

Externalizing behavior (EB) in preschool has been found to predict maladjustment later in life. Therefore, it is important to identify children most at risk for continuing EB beyond preschool. To date, a number of questionnaires are available for teachers to assist in identifying those children. A frequently overlooked aspect in this screening…

Evaluation of fatigue crack behavior in electron beam irradiated polyethylene pipes

NASA Astrophysics Data System (ADS)

Pokharel, Pashupati; Jian, Wei; Choi, Sunwoong

2016-09-01

A cracked round bar (CRB) fatigue test was employed to determine the slow crack growth (SCG) behavior of samples from high density polyethylene (HDPE) pipes using PE4710 resin. The structure property relationships of fatigue failure of polyethylene CRB specimens which have undergone various degree of electron beam (EB) irradiation were investigated by observing fatigue failure strength and the corresponding fracture surface morphology. Tensile test of these HDPE specimens showed improvements in modulus and yield strength while the failure strain decreased with increasing EB irradiation. The CRB fatigue test of HDPE pipe showed remarkable effect of EB irradiation on number of cycles to failure. The slopes of the stress-cycles to failure curve were similar for 0-100 kGy; however, significantly higher slope was observed for 500 kGy EB irradiated pipe. Also, the cycle to fatigue failure was seen to decrease as with EB irradiation in the high stress range, ∆σ=(16 MPa to 10.8 MPa); however, 500 kGy EB irradiated samples showed longer cycles to failure than the un-irradiated specimens at the stress range below 9.9 MPa and the corresponding initial stress intensity factor (∆KI,0)=0.712 MPa m1/2. The fracture surface morphology indicated that the cross-linked network in 500 kGy EB irradiated PE pipe can endure low dynamic load more effectively than the parent pipe.

Three-dimensional bioprinting of embryonic stem cells directs highly uniform embryoid body formation.

PubMed

Ouyang, Liliang; Yao, Rui; Mao, Shuangshuang; Chen, Xi; Na, Jie; Sun, Wei

2015-11-04

With the ability to manipulate cells temporarily and spatially into three-dimensional (3D) tissue-like construct, 3D bioprinting technology was used in many studies to facilitate the recreation of complex cell niche and/or to better understand the regulation of stem cell proliferation and differentiation by cellular microenvironment factors. Embryonic stem cells (ESCs) have the capacity to differentiate into any specialized cell type of the animal body, generally via the formation of embryoid body (EB), which mimics the early stages of embryogenesis. In this study, extrusion-based 3D bioprinting technology was utilized for biofabricating ESCs into 3D cell-laden construct. The influence of 3D printing parameters on ESC viability, proliferation, maintenance of pluripotency and the rule of EB formation was systematically studied in this work. Results demonstrated that ESCs were successfully printed with hydrogel into 3D macroporous construct. Upon process optimization, about 90% ESCs remained alive after the process of bioprinting and cell-laden construct formation. ESCs continued proliferating into spheroid EBs in the hydrogel construct, while retaining the protein expression and gene expression of pluripotent markers, like octamer binding transcription factor 4, stage specific embryonic antigen 1 and Nanog. In this novel technology, EBs were formed through cell proliferation instead of aggregation, and the quantity of EBs was tuned by the initial cell density in the 3D bioprinting process. This study introduces the 3D bioprinting of ESCs into a 3D cell-laden hydrogel construct for the first time and showed the production of uniform, pluripotent, high-throughput and size-controllable EBs, which indicated strong potential in ESC large scale expansion, stem cell regulation and fabrication of tissue-like structure and drug screening studies.

Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk

PubMed Central

Zeng, Chenjie; Matsuda, Koichi; Jia, Wei-Hua; Chang, Jiang; Kweon, Sun-Seog; Xiang, Yong-Bing; Shin, Aesun; Jee, Sun Ha; Kim, Dong-Hyun; Zhang, Ben; Cai, Qiuyin; Guo, Xingyi; Long, Jirong; Wang, Nan; Courtney, Regina; Pan, Zhi-Zhong; Wu, Chen; Takahashi, Atsushi; Shin, Min-Ho; Matsuo, Keitaro; Matsuda, Fumihiko; Gao, Yu-Tang; Oh, Jae Hwan; Kim, Soriul; Jung, Keum Ji; Ahn, Yoon-Ok; Ren, Zefang; Li, Hong-Lan; Wu, Jie; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Li, Bingshan; Ji, Bu-Tian; Brenner, Hermann; Schoen, Robert E.; Küry, Sébastien; Gruber, Stephen B.; Schumacher, Fredrick R.; Stenzel, Stephanie L.; Casey, Graham; Hopper, John L.; Jenkins, Mark A.; Kim, Hyeong-Rok; Jeong, Jin-Young; Park, Ji Won; Tajima, Kazuo; Cho, Sang-Hee; Kubo, Michiaki; Shu, Xiao-Ou; Lin, Dongxin; Zeng, Yi-Xin; Zheng, Wei

2016-01-01

Background & Aims Known Genetic factors explain only a small fraction of genetic variation in colorectal cancer (CRC). We conducted a genome-wide association study (GWAS) to identify risk loci for CRC. Methods This discovery stage included 8027 cases and 22577 controls of East-Asian ancestry. Promising variants were evaluated in studies including as many as 11044 cases and 12047 controls. Tumor-adjacent normal tissues from 188 patients were analyzed to evaluate correlations of risk variants with expression levels of nearby genes. Potential functionality of risk variants were evaluated using public genomic and epigenomic databases. Results We identified 4 loci associated with CRC risk; P values for the most significant variant in each locus ranged from 3.92×10−8 to 1.24×10−12: 6p21.1 (rs4711689), 8q23.3 (rs2450115, rs6469656), 10q24.3 (rs4919687), and 12p13.3 (rs11064437). We also identified 2 risk variants at loci previously associated with CRC: 10q25.2 (rs10506868) and 20q13.3 (rs6061231). These risk variants, conferring an approximate 10%–18% increase in risk per allele, are located either inside or near protein-coding genes that include TFEB (lysosome biogenesis and autophagy), EIF3H (initiation of translation), CYP17A1 (steroidogenesis), SPSB2 (proteasome degradation), and RPS21 (ribosome biogenesis). Gene expression analyses showed a significant association (P <.05) for rs4711689 with TFEB, rs6469656 with EIF3H, rs11064437 with SPSB2, and rs6061231 with RPS21. Conclusions We identified susceptibility loci and genes associated with CRC risk, linking CRC predisposition to steroid hormone, protein synthesis and degradation, and autophagy pathways and providing added insight into the mechanism of CRC pathogenesis. PMID:26965516

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

PubMed

Nakai, Yousuke; Yamamoto, Ryuichi; Matsuyama, Masato; Sakai, Yuji; Takayama, Yukiko; Ushio, Jun; Ito, Yukiko; Kitamura, Katsuya; Ryozawa, Shomei; Imamura, Tsunao; Tsuchida, Kouhei; Hayama, Jo; Itoi, Takao; Kawaguchi, Yoshiaki; Yoshida, Yu; Sugimori, Kazuya; Shimura, Kenji; Mizuide, Masafumi; Iwai, Tomohisa; Nishikawa, Ko; Yagioka, Hiroshi; Nagahama, Masatsugu; Toda, Nobuo; Saito, Tomotaka; Yasuda, Ichiro; Hirano, Kenji; Togawa, Osamu; Nakamura, Kenji; Maetani, Iruru; Sasahira, Naoki; Isayama, Hiroyuki

2018-05-01

Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence.

PubMed

Choy, Christopher H; Saffi, Golam; Gray, Matthew A; Wallace, Callen; Dayam, Roya M; Ou, Zhen-Yi A; Lenk, Guy; Puertollano, Rosa; Watkins, Simon C; Botelho, Roberto J

2018-05-21

Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects, including embryonic lethality, neurodegeneration and overt inflammation. The reasons for such drastic lysosome enlargement remain unclear. Here, we examined whether biosynthesis and/or fusion-fission dynamics contribute to swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF, enhancing lysosome gene expression. However, this did not augment lysosomal protein levels during acute PIKfyve inhibition, and deletion of TFEB and/or related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition led to fewer but enlarged lysosomes, suggesting that an imbalance favouring lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells. © 2018. Published by The Company of Biologists Ltd.

Formation of gut-like structures in vitro from mouse embryonic stem cells.

PubMed

Torihashi, Shigeko

2006-01-01

Embryonic stem (ES) cells have the potential to differentiate into all cell types originating from the three germ layers; however, there are still few reports about the formation of functional organs from embryonic stem cells. Recently, we reported that by hanging drops of mouse ES cells, embryoid bodies (EBs) formed gut-like structures in vitro composed of three layers corresponding to the epithelium, lamina propria, and musculature. The morphological features and the process of formation are similar to gut and its organogenesis in vivo. Thus, this is a good model for development of the gut and a useful tool for analysis of the factors required for gut organogenesis. The protocol basically involves a method of hanging drops to make EBs, which are then plated on coated dishes for outgrowth. EBs develop to form gut-like structures when induced to spontaneously enter a program of differentiation in vitro without addition of any extrinsic factors.

The influence of double-credit evidence-based continuing medical education on presenters and learners.

PubMed

Lawrence, Steven L; Morzinski, Jeffrey A; Radjenovich, Mary Ellen

2008-07-01

Medical specialties are adopting methods to improve continuing medical education (CME). A "double credit" option, sponsored by the American Academy of Family Physicians, is now available for presentations submitted and approved as evidence based (EB). To compare usual and double-credit CME presentations to determine differences in preparation resources and time, and to compare conference attendees' satisfaction. Those not submitting double-credit applications were asked about perceived barriers. Three pretested, written surveys were administered at a 2.5 day CME conference held annually in Southeastern Wisconsin. Subjects were 38 presenters and 172 attendees, mostly primary care physicians. Twelve presentations were approved for double-credit; these presenters used a greater percentage of on-line EB resources to prepare their talks (64% versus 23%), and preparation required an additional 4.75 hours on average. Over 90% of attendees perceived greater conference quality due to the EB emphasis. Top barriers to double-credit EB applications were time limits and perceptions that topics were inappropriate. Double-credit presenters use a greater percentage of EB resources, while their counterparts used more professional experience to prepare CME presentations. Attendees reported improved quality and value with increased EB CME. Time is a perceived and real factor in preparing double-credit applications.

CMB EB and TB cross-spectrum estimation via pseudospectrum techniques

NASA Astrophysics Data System (ADS)

Grain, J.; Tristram, M.; Stompor, R.

2012-10-01

We discuss methods for estimating EB and TB spectra of the cosmic microwave background anisotropy maps covering limited sky area. Such odd-parity correlations are expected to vanish whenever parity is not broken. As this is indeed the case in the standard cosmologies, any evidence to the contrary would have a profound impact on our theories of the early Universe. Such correlations could also become a sensitive diagnostic of some particularly insidious instrumental systematics. In this work we introduce three different unbiased estimators based on the so-called standard and pure pseudo-spectrum techniques and later assess their performance by means of extensive Monte Carlo simulations performed for different experimental configurations. We find that a hybrid approach combining a pure estimate of B-mode multipoles with a standard one for E-mode (or T) multipoles, leads to the smallest error bars for both EB (or TB respectively) spectra as well as for the three other polarization-related angular power spectra (i.e., EE, BB, and TE). However, if both E and B multipoles are estimated using the pure technique, the loss of precision for the EB spectrum is not larger than ˜30%. Moreover, for the experimental configurations considered here, the statistical uncertainties-due to sampling variance and instrumental noise-of the pseudo-spectrum estimates is at most a factor ˜1.4 for TT, EE, and TE spectra and a factor ˜2 for BB, TB, and EB spectra, higher than the most optimistic Fisher estimate of the variance.

Synergistic effect of Ebselen and gamma radiation on breast cancer cells.

PubMed

Thabet, Noura M; Moustafa, Enas M

2017-08-01

To explore the synergistic effect of a seleno-organic compound Ebselen (Ebs) and/or γ-radiation to exert antitumor effects on human breast cancer (MCF-7) cell line in vitro. Ebs cytotoxicity at various concentrations (10, 25, 50 and 75 μg), cell proliferation and clonogenic assay of Ebs and/or γ-radiation (at 1, 3 and 6 Gy), expression of p-IκBα and NF-κB, inflammatory cytokines levels (TNF-α, IL-2, INF-γ, IL-10 and TGF-β), apoptotic factors (Caspase-3, Granzyme-B and TRAIL) and angiogenic factor (VEGF) were investigated. The results showed that the effective dosage of this combination was observed at 25 μg/ml of Ebs with γ-radiation at 6 Gy. Data displayed a significant reduction in NF-κB mRNA along with an elevation in granzyme-B mRNA and TRAIL mRNA expression. Furthermore, protein expression of caspase-3 was elevated, whereas p-IκBα and p-NF-κB(p65) protein expression was reduced significantly. Also, a significant decline in TNF-α, IL-2, INF-γ, TGF-β with a significant increase in IL-10 levels were revealed. Meanwhile, a significant decrease in VEGF level and proliferation capacity were observed. We conclude that a combination of Ebs with radiotherapy has a major antitumor efficiency in inducing apoptosis and inhibiting cancer cell progression, due to the synergistic effect in regulating gene and protein expression, and in a modulating response of pro-and anti-inflammatory cytokines.

Generating size-controlled embryoid bodies using laser direct-write.

PubMed

Dias, A D; Unser, A M; Xie, Y; Chrisey, D B; Corr, D T

2014-06-01

Embryonic stem cells (ESCs) have the potential to self-renew and differentiate into any specialized cell type. One common method to differentiate ESCs in vitro is through embryoid bodies (EBs), three-dimensional cellular aggregates that spontaneously self-assemble and generally express markers for the three germ layers, endoderm, ectoderm, and mesoderm. It has been previously shown that both EB size and 2D colony size each influence differentiation. We hypothesized that we could control the size of the EB formed by mouse ESCs (mESCs) by using a cell printing method, laser direct-write (LDW), to control both the size of the initial printed colony and the local cell density in printed colonies. After printing mESCs at various printed colony sizes and printing densities, two-way ANOVAs indicated that the EB diameter was influenced by printing density after three days (p = 0.0002), while there was no effect of the printed colony diameter on the EB diameter at the same timepoint (p = 0.74). There was no significant interaction between these two factors. Tukey's honestly significant difference test showed that high-density colonies formed significantly larger EBs, suggesting that printed mESCs quickly aggregate with nearby cells. Thus, EBs can be engineered to a desired size by controlling printing density, which will influence the design of future differentiation studies. Herein, we highlight the capacity of LDW to control the local cell density and colony size independently, at prescribed spatial locations, potentially leading to better stem cell maintenance and directed differentiation.

Colonization with extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species in long-term care facility residents.

PubMed

Lautenbach, Ebbing; Han, Jennifer; Santana, Evelyn; Tolomeo, Pam; Bilker, Warren B; Maslow, Joel

2012-03-01

We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EB) in the long-term care facility (LTCF) setting. Colonization prevalence differed significantly across the 3 LTCFs evaluated in the study, with recent use of levofloxacin and fecal incontinence demonstrating borderline significant associations with ESBL-EB colonization.

Colonization with Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella Species in Long-Term Care Facility Residents

PubMed Central

Lautenbach, Ebbing; Han, Jennifer; Santana, Evelyn; Tolomeo, Pam; Bilker, Warren B.; Maslow, Joel

2012-01-01

We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EB) in the long-term care facility (LTCF) setting. Colonization prevalence differed significantly across the 3 LTCFs evaluated in the study, with recent use of levofloxacin and fecal incontinence demonstrating borderline significant associations with ESBL-EB colonization. PMID:22314070

Emotional burnout, perceived sources of job stress, professional fulfillment, and engagement among medical residents in Malaysia.

PubMed

Al-Dubai, Sami Abdo Radman; Ganasegeran, Kurubaran; Perianayagam, Wilson; Rampal, Krishna Gopal

2013-01-01

This study was the first to explore factors associated with emotional burnout (EB) among medical residents in Malaysia. A cross-sectional study was conducted in a universal sample of 205 medical residents in a Malaysian general hospital. The self-administered questionnaire used consisted of questions on sociodemographics and work characteristics, sources of job stress, professional fulfillment, engagement, and EB. EB was measured using the emotional exhaustion subscale, the Maslach Burnout Inventory (MBI). Mean (±SD) age of the respondents was 26.5 (±1.6). The most common source of job stress was "fear of making mistakes." Most of the participants were dissatisfied with the increase of residentship period from one year to two years. A high level of EB was reported by 36.6% of the respondents. In multivariate analysis, the most important correlates of EB were sources of job stress, professional fulfillment, and engagement. A high prevalence of EB was found among medical residents. Sociodemographic characteristics, performance pressure, and satisfaction with policies were significantly associated with EB. Although this study was limited by its cross-sectional design, its findings posit a sufficient foundation to relevant authorities to construct, amend, and amalgamate existing and future policies. Nothing will sustain you more potently than the power to recognize in your humdrum routine, as perhaps it may be thought, the true poetry of life-the poetry of the common place, of the common man, of the plain, toil-worn woman, with their loves and their joys, their sorrows and their grief.SirWilliam Osler, Aphorisms from the Student Life (Aequanimitas, 1952).

[Methane fluxes of Cyperus malaccensis tidal wetland in Minjiang River estuary].

PubMed

Zeng, Cong-Sheng; Wang, Wei-Qi; Zhang, Lin-Hai; Lin, Lu-Ying; Ai, Jin-Quan; Zhang, Wen-Long

2010-02-01

By using enclosed static chamber-gas chromatograph techniques, this paper measured the methane fluxes of Cyperus malaccensis tidal wetland in Minjiang River estuary. The diurnal variation of the methane fluxes in summer and winter were in the range of 1.29-2.93 mg x m(-2) x h(-1) and 0.06-0.22 mg x m(-2) x h(-1), respectively. The methane fluxes before flooding, in the process of flooding and ebbing, and after ebbing were 0.11-1.52 mg x m(-2) x h(-1), 0.10-1.05 mg x m(-2) x h(-1), and 0.05-1.70 mg x m(-2) x h(-1), and the monthly averaged fluxes were 0.73, 0.47, and 0.72 mg x m(-2) x h(-1), respectively. The methane fluxes peaked in September and reached the lowest in March, and were significantly lower in the process of flooding and ebbing than before flooding and after ebbing (P < 0.05). The seasonal variation of the methane fluxes was in the order of summer > autumn > spring > winter. Tide was the key factor affecting the diurnal variation of the methane fluxes, while plant growth stage and temperature were the key factors determining the monthly or seasonal variation of the methane fluxes.

Review of renal carcinoma with t(6;11)(p21;q12) with focus on clinical and pathobiological aspects.

PubMed

Kuroda, Naoto; Tanaka, Azusa; Sasaki, Naomi; Ishihara, Akira; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Inoue, Keiji; Petersson, Fredrik; Martignoni, Guido; Michal, Michal; Hes, Ondrej

2013-06-01

Recently, a new category of MiTF/TFE family translocation carcinomas of the kidney has been proposed. This category includes Xp11.2 renal cell carcinoma (RCC) and the t(6;11) RCC. These tumors share clinical, morphological, immunohistochemical and molecular genetic features. In this article, we review t(6;11) RCC. This tumor predominantly affects children and young adults. Macroscopically, the tumor generally forms a well circumscribed mass. Satellite nodules may be observed. Histologically, the tumor comprises large cells and small cells surrounded by basement membrane material. Immunohistochemically, tumor cells show nuclear immunolabeling for TFEB and usually express Cathepsin-K in the cytoplasm. Karyotyping detects the rearrangement between chromosome 6p21 and chromosome 11q12. Alpha-TFEB fusion can be detected by reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Most cases affecting children and young adults seem to be indolent, but some adult cases have presented with metastasis or caused death. As previously reported cases remain limited to date, further examination in a large scale study will be needed in order to elucidate clinical behavior and molecular characteristics.

Emotional Burnout, Perceived Sources of Job Stress, Professional Fulfillment, and Engagement among Medical Residents in Malaysia

PubMed Central

Al-Dubai, Sami Abdo Radman; Perianayagam, Wilson; Rampal, Krishna Gopal

2013-01-01

This study was the first to explore factors associated with emotional burnout (EB) among medical residents in Malaysia. A cross-sectional study was conducted in a universal sample of 205 medical residents in a Malaysian general hospital. The self-administered questionnaire used consisted of questions on sociodemographics and work characteristics, sources of job stress, professional fulfillment, engagement, and EB. EB was measured using the emotional exhaustion subscale, the Maslach Burnout Inventory (MBI). Mean (±SD) age of the respondents was 26.5 (±1.6). The most common source of job stress was “fear of making mistakes.” Most of the participants were dissatisfied with the increase of residentship period from one year to two years. A high level of EB was reported by 36.6% of the respondents. In multivariate analysis, the most important correlates of EB were sources of job stress, professional fulfillment, and engagement. A high prevalence of EB was found among medical residents. Sociodemographic characteristics, performance pressure, and satisfaction with policies were significantly associated with EB. Although this study was limited by its cross-sectional design, its findings posit a sufficient foundation to relevant authorities to construct, amend, and amalgamate existing and future policies. Nothing will sustain you more potently than the power to recognize in your humdrum routine, as perhaps it may be thought, the true poetry of life—the poetry of the common place, of the common man, of the plain, toil-worn woman, with their loves and their joys, their sorrows and their grief. SirWilliam Osler, Aphorisms from the Student Life (Aequanimitas, 1952) PMID:24367238

Distinct associations between energy balance and the sleep characteristics slow wave sleep and rapid eye movement sleep.

PubMed

Rutters, F; Gonnissen, H K; Hursel, R; Lemmens, S G; Martens, E A; Westerterp-Plantenga, M S

2012-10-01

Epidemiologically, an inverse relationship between body mass index (BMI) and sleep duration is observed. Intra-individual variance in the amount of slow wave sleep (SWS) or rapid eye movement (REM) sleep has been related to variance of metabolic and endocrine parameters, which are risk factors for the disturbance of energy balance (EB). To investigate inter-individual relationships between EB (EB= energy intake-energy expenditure∣, MJ/24 h), SWS or REM sleep, and relevant parameters in normal-weight men during two 48 h stays in the controlled environment of a respiration chamber. A total of 16 men (age 23±3.7 years, BMI 23.9±1.9 kg m(-2)) stayed in the respiration chamber twice for 48 h to assure EB. Electroencephalography was used to monitor sleep (2330-0730 hrs). Hunger and fullness were scored by visual analog scales; mood was determined by State Trait Anxiety Index-state and food reward by liking and wanting. Baseline blood and salivary samples were collected before breakfast. Subjects were fed in EB, except for the last dinner, when energy intake was ad libitum. The subjects slept on average 441.8±49 min per night, and showed high within-subject reliability for the amount of SWS and REM sleep. Linear regression analyses showed that EB was inversely related to the amount of SWS (r=-0.43, P<0.03), and positively related to the amount of REM sleep (r=0.40, P<0.05). Relevant parameters such as hunger, reward, stress and orexigenic hormone concentrations were related to overeating, as well as to the amount of SWS and REM sleep, however, after inclusion of these parameters in a multiple regression, the amount of SWS and REM sleep did not add to the explained variance of EB, which suggests that due to their individual associations, these EB parameters are mediator variables. A positive EB due to overeating, was explained by a smaller amount of SWS and higher amount of REM sleep, mediated by hunger, fullness, State Trait Anxiety Index-state scores, glucose/insulin ratio, and ghrelin and cortisol concentrations.

The application of exhaled breath analysis in racing Thoroughbreds and the influence of high intensity exercise and ambient temperature on the concentration of carbon monoxide and pH in exhaled breath.

PubMed

Cathcart, Michael P; Love, Sandy; Sutton, David G M; Reardon, Richard J M; Hughes, Kristopher J

2013-08-01

Analyses of exhaled breath (EB) and exhaled breath condensate (EBC) are non-invasive modalities for assessing the lower airways but these methods have not been applied to Thoroughbred racehorses in training. The aims of this study were to determine whether EB and EBC could be obtained from Thoroughbred racehorses in the field and to investigate the effects of exercise per se and during different ambient temperatures and humidity on exhaled concentrations of nitric oxide (eNO), carbon monoxide (eCO) and EBC pH. EB and EBC samples were obtained from 28 Thoroughbred racehorses pre- and post-exercise during warm (n=23) and/or cold (n=19) ambient temperatures. eNO was detected in 19/84 EB samples. eCO was measured in 39/42 EB samples pre-exercise (median 1.3 ppm) and concentrations decreased significantly post-exercise (median 0.8 ppm, P<0.005) and were associated with ambient temperature. EBC pH was 4.51 ± 0.23 pre-exercise and increased significantly post-exercise (4.79 ± 0.59, P=0.003). The study documented the collection of EB and EBC from Thoroughbred racehorses in a field setting. Alterations in concentrations of volatile gases and EBC pH occurred in response to exercise, and were likely to have been influenced by environmental factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Testicular cell conditioned medium supports differentiation of embryonic stem cells into ovarian structures containing oocytes.

PubMed

Lacham-Kaplan, Orly; Chy, Hun; Trounson, Alan

2006-02-01

Previous reports and the current study have found that germ cell precursor cells appear in embryoid bodies (EBs) formed from mouse embryonic stem cells as identified by positive expression of specific germ cell markers such as Oct-3/4, Mvh, c-kit, Stella, and DAZL. We hypothesized that if exposed to appropriate growth factors, the germ cell precursor cells within the EBs would differentiate into gametes. The source for growth factors used in the present study is conditioned medium collected from testicular cell cultures prepared from the testes of newborn males. Testes at this stage of development contain most growth factors required for the transformation of germ stem cells into differentiated gametes. When EBs were cultured in the conditioned medium, they developed into ovarian structures, which contained putative oocytes. The oocytes were surrounded by one to two layers of flattened cells and did not have a visible zona pellucida. However, oocyte-specific markers such as Fig-alpha and ZP3 were found expressed by the ovarian structures. The production of oocytes using this method is repeatable and reliable and may be applicable to other mammalian species, including the human.

The evaluation of family impact of recessive dystrophic epidermolysis bullosa using the Italian version of the Family Dermatology Life Quality Index.

PubMed

Sampogna, F; Tabolli, S; Di Pietro, C; Castiglia, D; Zambruno, G; Abeni, D

2013-09-01

Severe skin diseases, such as epidermolysis bullosa (EB), may have a strong impact not only on patients but also on caregivers. A specific questionnaire evaluating the family impact of dermatological conditions has been created, the Family Dermatology Life Quality Index (FDLQI), but it has not yet been translated in Italian and validated. To evaluate the burden of recessive dystrophic EB on family caregivers, using for the first time the Italian version of the FDLQI, and to validate the instrument. Patients with recessive dystrophic EB participated in a postal survey enquiring about the burden of EB on family caregivers. They completed the Family Strain Questionnaire and the FDLQI and they marked on a silhouette of the human body the skin lesion distribution. Data on 62 family caregivers were collected. The overall mean FDLQI score was 9.8. The most frequently reported problems were the time spent on looking after the patient, emotional distress, physical well-being, and increased household expenditure. FDLQI scores were higher in family caregivers of patients between 10 and 20 years. The Italian FDLQI showed high internal consistency, construct and convergent validity. Factor analysis revealed the presence of one factor structure underlying the items of the FDLQI, which explained 51.5% of the total variance, very similar to the original questionnaire (55.8%). The Italian version of the FDLQI seems to be a useful tool to evaluate the impact of EB on family caregivers. Further studies are necessary to test this instrument in other dermatological conditions. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Co-liquefaction with acetone and GC analysis of volatile compounds in exhaled breath as lung cancer biomarkers

PubMed Central

Jouyban, Abolghasem; Djozan, Djavanshir; Mohammadandashti, Parastou; Alizadeh-Nabil, Aliakbar; Ghorbanpour, Hooshangh; Khoubnasabjafari, Maryam; Mohammadzadeh, Mohammad

2017-01-01

Introduction: A simple, rapid and low cost method for enrichment of volatile organic compounds (VOCs) from exhaled breath (EB) is presented. Methods: A 1000 mL home-made extraction device was filled with EB. The VOCs were extracted and condensed in 0.5 mL acetone. Recognition of volatiles in the real studied EB samples was performed by a GC-MS. Results: The method displays an extraction efficiency of >86% with the enrichment factor of 1929 for octanal. Limits of detection and quantification, and linear dynamic range were 0.008, 0.026 and 0.026-400 ng/mL respectively. Analysis of real samples showed the existence of more than 100 compounds in EB of healthy volunteers and patients with lung cancer before and after treatment. Exhaled octanal concentration was significantly higher in lung cancer patient than in healthy volunteers and lung cancer patient after treatment. Conclusion: Having used the proposed approach, high extraction recovery (up to 86%) was attained for the lung cancer marker, octanal, as an important biomarker. Our findings on smaples of EB of healthy controls and patients with lung cancer before and after treatment provide complelling evidence upon the effectiveness of the developed method. PMID:28752074

Measurement of heterophil antibody and antibodies to EB viral capsid antigen IgG and IgM in suspected cases of infectious mononucleosis.

PubMed

Blake, J M; Edwards, J M; Fletcher, W; McSwiggan, D A; Pereira, M S

1976-09-01

The EBV IgG titres in acute and convalescent specimens from 97 cases of infectious mononucleosis were compared with titres from acute and convalescent sera from 96 students with illnesses resembling infectious mononucleosis but without heterophil antibody, EB IgM or EB IgG seroconversion; and also with titres from 91 healthy students known to have had EB IgG antibody for at least six months. These titres were related to the titre of the Research Standard A.66/235 for infectious mononucleosis serum prepared by the National Institute for Biological Standards and Control. Serial sera were tested for heterophil antibody and EBVCA specific IgG and IgM from 61 university students with infectious mononucleosis. The period of persistence of heterophil antibody and EBV IgM after illness was outlined from the results of the tests. Single sera from 406 patients in hospital or general practice sent to the diagnostic laboratory for heterophil antibody tests were also tested for EBV antibodies without prior knowledge of the heterophil antibody result. The close agreement between heterophil antibody and EBV IgM results is shown. False positive EB IgM results were correlated with the presence of rheumatoid factor.

Optimized Li-Ion Electrolytes Containing Fluorinated Ester Co-Solvents

NASA Technical Reports Server (NTRS)

Prakash, G. K. Surya; Smart, Marshall; Smith, Kiah; Bugga, Ratnakumar

2010-01-01

A number of experimental lithium-ion cells, consisting of MCMB (meso-carbon microbeads) carbon anodes and LiNi(0.8)Co(0.2)O2 cathodes, have been fabricated with increased safety and expanded capability. These cells serve to verify and demonstrate the reversibility, low-temperature performance, and electrochemical aspects of each electrode as determined from a number of electrochemical characterization techniques. A number of Li-ion electrolytes possessing fluorinated ester co-solvents, namely trifluoroethyl butyrate (TFEB) and trifluoroethyl propionate (TFEP), were demonstrated to deliver good performance over a wide temperature range in experimental lithium-ion cells. The general approach taken in the development of these electrolyte formulations is to optimize the type and composition of the co-solvents in ternary and quaternary solutions, focusing upon adequate stability [i.e., EC (ethylene carbonate) content needed for anode passivation, and EMC (ethyl methyl carbonate) content needed for lowering the viscosity and widening the temperature range, while still providing good stability], enhancing the inherent safety characteristics (incorporation of fluorinated esters), and widening the temperature range of operation (the use of both fluorinated and non-fluorinated esters). Further - more, the use of electrolyte additives, such as VC (vinylene carbonate) [solid electrolyte interface (SEI) promoter] and DMAc (thermal stabilizing additive), provide enhanced high-temperature life characteristics. Multi-component electrolyte formulations enhance performance over a temperature range of -60 to +60 C. With the need for more safety with the use of these batteries, flammability was a consideration. One of the solvents investigated, TFEB, had the best performance with improved low-temperature capability and high-temperature resilience. This work optimized the use of TFEB as a co-solvent by developing the multi-component electrolytes, which also contain non-halogenated esters, film forming additives, thermal stabilizing additives, and flame retardant additives. Further optimization of these electrolyte formulations is anticipated to yield improved performance. It is also anticipated that much improved performance will be demonstrated once these electrolyte solutions are incorporated into hermetically sealed, large capacity prototype cells, especially if effort is devoted to ensure that all electrolyte components are highly pure.

47 CFR 27.5 - Frequencies.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-2560 MHz EBS Channel C2: 2560-2566 MHz EBS Channel D2: 2566-2572 MHz EBS Channel C3: 2572-2578 MHz EBS... MHz EBS Channel D1: 2551.5-2557 MHz EBS Channel D2: 2557-2562.5 MHz EBS Channel D3: 2562.5-2568 MHz...

Investigating the effects of the fixed and varying dispersion parameters of Poisson-gamma models on empirical Bayes estimates.

PubMed

Lord, Dominique; Park, Peter Young-Jin

2008-07-01

Traditionally, transportation safety analysts have used the empirical Bayes (EB) method to improve the estimate of the long-term mean of individual sites; to correct for the regression-to-the-mean (RTM) bias in before-after studies; and to identify hotspots or high risk locations. The EB method combines two different sources of information: (1) the expected number of crashes estimated via crash prediction models, and (2) the observed number of crashes at individual sites. Crash prediction models have traditionally been estimated using a negative binomial (NB) (or Poisson-gamma) modeling framework due to the over-dispersion commonly found in crash data. A weight factor is used to assign the relative influence of each source of information on the EB estimate. This factor is estimated using the mean and variance functions of the NB model. With recent trends that illustrated the dispersion parameter to be dependent upon the covariates of NB models, especially for traffic flow-only models, as well as varying as a function of different time-periods, there is a need to determine how these models may affect EB estimates. The objectives of this study are to examine how commonly used functional forms as well as fixed and time-varying dispersion parameters affect the EB estimates. To accomplish the study objectives, several traffic flow-only crash prediction models were estimated using a sample of rural three-legged intersections located in California. Two types of aggregated and time-specific models were produced: (1) the traditional NB model with a fixed dispersion parameter and (2) the generalized NB model (GNB) with a time-varying dispersion parameter, which is also dependent upon the covariates of the model. Several statistical methods were used to compare the fitting performance of the various functional forms. The results of the study show that the selection of the functional form of NB models has an important effect on EB estimates both in terms of estimated values, weight factors, and dispersion parameters. Time-specific models with a varying dispersion parameter provide better statistical performance in terms of goodness-of-fit (GOF) than aggregated multi-year models. Furthermore, the identification of hazardous sites, using the EB method, can be significantly affected when a GNB model with a time-varying dispersion parameter is used. Thus, erroneously selecting a functional form may lead to select the wrong sites for treatment. The study concludes that transportation safety analysts should not automatically use an existing functional form for modeling motor vehicle crashes without conducting rigorous analyses to estimate the most appropriate functional form linking crashes with traffic flow.

In vitro differentiation of mouse embryonic stem (mES) cells using the hanging drop method.

PubMed

Wang, Xiang; Yang, Phillip

2008-07-23

Stem cells have the remarkable potential to develop into many different cell types. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, This promising of science is leading scientists to investigate the possibility of cell-based therapies to treat disease. When culture in suspension without antidifferentiation factors, embryonic stem cells spontaneously differentiate and form three-dimensional multicellular aggregates. These cell aggregates are called embryoid bodies(EB). Hanging drop culture is a widely used EB formation induction method. The rounded bottom of hanging drop allows the aggregation of ES cells which can provide mES cells a good environment for forming EBs. The number of ES cells aggregatied in a hanging drop can be controlled by varying the number of cells in the initial cell suspension to be hung as a drop from the lid of Petri dish. Using this method we can reproducibly form homogeneous EBs from a predetermined number of ES cells.

Rethinking chemisorption: New insights into the factors controlling the binding energy

NASA Astrophysics Data System (ADS)

Alcantara Ortigoza, Marisol; Stolbov, Sergey

2015-03-01

Chemisorption of atomic and molecular species on a substrate induces electronic charge redistribution upon which substrate nuclei respond by adjusting their positions. This lattice distortion has been linked to the binding energy EB of the adsorbed species and attached to the so-called surface relaxation energy, Erx. We have found, however, that for transition metals the energy associated with the mere charge redistribution Eelec is much larger than Erx and thus both contributions must be considered [1]. In this work, we quantify the electronic and structural perturbation energy EP brought by various adsorbates on surfaces to understand anomalous adsorbate binding energies, i.e., those in which EP strongly influences the magnitude of EB. For example, for O adsorption on Au(111), while Erx is only 0.25 eV, the overall perturbation energy EP affecting EB(O) is ~ 1 eV [1]. This indicates that EP cannot be ignored but also that local bonds may not be as weak as portrayed by EB, even though EB is significantly reduced. We expose cases in which EP is really dominated by the lattice distortion energy, as well as a rationale for its trends as a function of the substrate and adsorbate. We discuss the implications of the fact that EB is not always predominately controlled by the bond-strength on heterogeneous catalysis, as well as the applications of the same fact. M. Alcántara Ortigoza and S. Stolbov; ``The Perturbation Energy: The missing key to understand gold `nobleness.' '' Submitted in October 2014 This work was supported the NSF under Grant CBET-1249134.

Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

PubMed Central

Hernández, Damián; Millard, Rodney; Sivakumaran, Priyadharshini; Wong, Raymond C. B.; Crombie, Duncan E.; Hewitt, Alex W.; Liang, Helena; Hung, Sandy S. C.; Pébay, Alice; Shepherd, Robert K.; Dusting, Gregory J.; Lim, Shiang Y.

2016-01-01

Background. Human induced pluripotent stem cells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin)-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used. PMID:26788064

Directional control of WAVE2 membrane targeting by EB1 and phosphatidylinositol 3,4,5-triphosphate.

PubMed

Takahashi, Kazuhide; Tanaka, Tacu; Suzuki, Katsuo

2010-03-01

Membrane targeting of WAVE2 along microtubules is mediated by a motor protein kinesin and requires Pak1, a downstream effector of Rac1. However, the mechanism by which WAVE2 targeting to the leading edge is directionally controlled remains largely unknown. Here we demonstrate that EB1, a microtubule plus-end-binding protein, constitutively associates with stathmin, a microtubule-destabilizing protein, in human breast cancer cells. Stimulation of the cells with insulin-like growth factor I (IGF-I) induced Pak1-dependent binding of the EB1-stathmin complex to microtubules that bear WAVE2 and colocalization of the complex with WAVE2 at the leading edge. Depletion of EB1 by small interfering RNA (siRNA) abrogated the IGF-I-induced WAVE2 targeting and stathmin binding to microtubules. On the other hand, chemotaxis chamber assays indicated that the IGF-I receptor (IGF-IR) was locally activated in the region facing toward IGF-I. In addition, IGF-I caused phosphatidylinositol 3-kinase (PI 3-kinase)-dependent production of phosphatidylinositol 3,4,5-triphosphate (PIP3) near activated IGF-IR and WAVE2 colocalization with it. Collectively, WAVE2-membrane targeting is directionally controlled by binding of the EB1-stathmin complex to WAVE2-bearing microtubules and by the interaction between WAVE2 and PIP3 produced near IGF-IR that is locally activated by IGF-I.

[DEONTOLOGICAL QUESTIONS IN PROPHYLACTIC OF ENDOSCOPIC COMPLICATIONS: THE SIGNIFICANCE OF RATIONAL AND PSYCHOLOGICAL FACTORS (analytical overview)].

PubMed

Vernik, N V; Ivantsova, M A; Yashin, D I

2015-01-01

To evaluate the ways of reduction complications during endoscopic procedures based on principals of professional ethics and improving the quality of working area. Data of fundamental literature, evidence based medicine, science publications and internet portals. Deontology is the fundamental principle of medical practice and one of the main factors of professional effectiveness. Complications in endoscopy are often the investigations of deviation from the deontological principals. The whole number of psychological factors influences on professional activity of endoscopists, where the emotional "burn-out" syndrome (EBS) occupies one of the main places. Prophylactic and timely relief of EBS serves improvement of the practical work quality. Creation of favorable working area is the strategically important task in prophylactics of endoscopy complications. The questions of practical realization of deontological principles in endoscopy are the subject of further discussion.

The microtubule end-binding protein EB2 is a central regulator of microtubule reorganisation in apico-basal epithelial differentiation.

PubMed

Goldspink, Deborah A; Gadsby, Jonathan R; Bellett, Gemma; Keynton, Jennifer; Tyrrell, Benjamin J; Lund, Elizabeth K; Powell, Penny P; Thomas, Paul; Mogensen, Mette M

2013-09-01

Microtubule end-binding (EB) proteins influence microtubule dynamic instability, a process that is essential for microtubule reorganisation during apico-basal epithelial differentiation. Here, we establish for the first time that expression of EB2, but not that of EB1, is crucial for initial microtubule reorganisation during apico-basal epithelial differentiation, and that EB2 downregulation promotes bundle formation. EB2 siRNA knockdown during early stages of apico-basal differentiation prevented microtubule reorganisation, whereas its downregulation at later stages promoted microtubule stability and bundle formation. Interestingly, although EB1 is not essential for microtubule reorganisation, its knockdown prevented apico-basal bundle formation and epithelial elongation. siRNA depletion of EB2 in undifferentiated epithelial cells induced the formation of straight, less dynamic microtubules with EB1 and ACF7 lattice association and co-alignment with actin filaments, a phenotype that could be rescued by inhibition with formin. Importantly, in situ inner ear and intestinal crypt epithelial tissue revealed direct correlations between a low level of EB2 expression and the presence of apico-basal microtubule bundles, which were absent where EB2 was elevated. EB2 is evidently important for initial microtubule reorganisation during epithelial polarisation, whereas its downregulation facilitates EB1 and ACF7 microtubule lattice association, microtubule-actin filament co-alignment and bundle formation. The spatiotemporal expression of EB2 thus dramatically influences microtubule organisation, EB1 and ACF7 deployment and epithelial differentiation.

Dexamethasone facilitates erythropoiesis in murine embryonic stem cells differentiating into hematopoietic cells in vitro

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

Srivastava, Anand S.; Kaushal, Sharmeela; Mishra, Rangnath

2006-07-28

Differentiating embryonic stem (ES) cells are increasingly emerging as an important source of hematopoietic progenitors with a potential to be useful for both basic and clinical research applications. It has been suggested that dexamethasone facilitates differentiation of ES cells towards erythrocytes but the mechanism responsible for sequential expression of genes regulating this process are not well-understood. Therefore, we in vitro induced differentiation of murine ES cells towards erythropoiesis and studied the sequential expression of a set of genes during the process. We hypothesized that dexamethasone-activates its cognate nuclear receptors inducing up-regulation of erythropoietic genes such as GATA-1, Flk-1, Epo-R, andmore » direct ES cells towards erythropoietic differentiation. ES cells were cultured in primary hematopoietic differentiation media containing methyl-cellulose, IMDM, IL-3, IL-6, and SCF to promote embryoid body (EB) formation. Total RNA of day 3, 5, and 9-old EBs was isolated for gene expression studies using RT-PCR. Cells from day 9 EBs were subjected to secondary differentiation using three different cytokines and growth factors combinations: (1) SCF, EPO, dexamethasone, and IGF; (2) SCF, IL-3, IL-6, and TPO; and (3) SCF IL-3, IL-6, TPO, and EPO. Total RNA from day 12 of secondary differentiated ES cells was isolated to study the gene expression pattern during this process. Our results demonstrate an up-regulation of GATA-1, Flk-1, HoxB-4, Epo-R, and globin genes ({alpha}-globin, {beta}H-1 globin, {beta}-major globin, {epsilon} -globin, and {zeta}-globin) in the 9-day-old EBs, whereas, RNA from 5-day-old EBs showed expression of HoxB-4, {epsilon}-globin, {gamma}-globin, {beta}H1-globin, and Flk-1. Three-day-old EBs showed only HoxB-4 and Flk-1 gene expression and lacked expression of all globin genes. These findings indicate that erythropoiesis-specific genes are activated later in the course of differentiation. Gene expression studies on the ES cells of secondary EB origin cultured in media containing dexamethasone showed a down-regulation of GATA-3 and an up-regulation of GATA-1, Flk-1, and Epo-R in comparison to the two other cytokines and growth factor combinations containing media. The secondary differentiation also showed an enhanced production of erythrocytic precursors in dexamethasone containing media in comparison to that in the control media. Our results indicate that dexamethasone can prove to be an effective agent which can be employed to enhance differentiation towards erythrocytic progenitors from ES cells.« less

CLASPs are required for proper microtubule localization of End-binding proteins

PubMed Central

Grimaldi, Ashley D.; Maki, Takahisa; Fitton, Benjamin P.; Roth, Daniel; Yampolsky, Dmitry; Davidson, Michael W.; Svitkina, Tatyana; Straube, Anne; Hayashi, Ikuko; Kaverina, Irina

2014-01-01

Summary Microtubule (MT) plus-end tracking proteins (+TIPs) preferentially localize to MT plus-ends. End-binding proteins (EBs) are master regulators of the +TIP complex; however, it is unknown whether EBs are regulated by other +TIPs. Here, we show that Cytoplasmic linker associated proteins (CLASPs) modulate EB localization at MTs. In CLASP-depleted cells, EBs localized along the MT lattice in addition to plus-ends. The MT-binding region of CLASP was sufficient for restoring normal EB localization, while neither EB-CLASP interactions nor EB tail-binding proteins are involved. In vitro assays revealed that CLASP directly functions to remove EB from MTs. Importantly, this effect occurs specifically during MT polymerization, but not at pre-formed MTs. Increased GTP-tubulin content within MTs in CLASP-depleted cells suggests that CLASPs facilitate GTP-hydrolysis to reduce EB lattice binding. Together, these findings suggest that CLASPs influence the MT lattice itself to regulate EB and determine exclusive plus-end localization of EBs in cells. PMID:25117684

PTEN induces apoptosis and cavitation via HIF-2-dependent Bnip3 upregulation during epithelial lumen formation.

PubMed

Qi, Y; Liu, J; Saadat, S; Tian, X; Han, Y; Fong, G-H; Pandolfi, P P; Lee, L Y; Li, S

2015-05-01

The tumor suppressor phosphatase and tensin homolog (PTEN) dephosphorylates PIP3 and antagonizes the prosurvival PI3K-Akt pathway. Targeted deletion of PTEN in mice led to early embryonic lethality. To elucidate its role in embryonic epithelial morphogenesis and the underlying mechanisms, we used embryonic stem cell-derived embryoid body (EB), an epithelial cyst structurally similar to the periimplantation embryo. PTEN is upregulated during EB morphogenesis in parallel with apoptosis of core cells, which mediates EB cavitation. Genetic ablation of PTEN causes Akt overactivation, apoptosis resistance and cavitation blockade. However, rescue experiments using mutant PTEN and pharmacological inhibition of Akt suggest that the phosphatase activity of PTEN and Akt are not involved in apoptosis-mediated cavitation. Instead, hypoxia-induced upregulation of Bnip3, a proapoptotic BH3-only protein, mediates PTEN-dependent apoptosis and cavitation. PTEN inactivation inhibits hypoxia- and reactive oxygen species-induced Bnip3 elevation. Overexpression of Bnip3 in PTEN-null EBs rescues apoptosis of the core cells. Mechanistically, suppression of Bnip3 following PTEN loss is likely due to reduction of hypoxia-inducible factor-2α (HIF-2α) because forced expression of an oxygen-stable HIF-2α mutant rescues Bnip3 expression and apoptosis. Lastly, we show that HIF-2α is upregulated by PTEN at both transcriptional and posttranscriptional levels. Ablation of prolyl hydroxylase domain-containing protein 2 (PHD2) in normal EBs or inhibition of PHD activities in PTEN-null EBs stabilizes HIF-2α and induces Bnip3 and caspase-3 activation. Altogether, these results suggest that PTEN is required for apoptosis-mediated cavitation during epithelial morphogenesis by regulating the expression of HIF-2α and Bnip3.

Derivation and characterization of gut-like structures from embryonic stem cells.

PubMed

Yamada, Takatsugu; Nakajima, Yoshiyuki

2006-01-01

Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages of all three embryonic germ layers in vitro. The hanging drop culture of ES cell suspension in the absence of leukemia inhibitory factor induces aggregation and differentiation of the cells into simple or cystic embryoid bodies (EBs). After 6 d of hanging drop culture, the resulting EBs are plated onto plastic dishes for the outgrowth culture. At d 21 after outgrowth culture, cell populations of EBs can give rise to three-dimensional gut-like structures that exhibit spontaneous contraction and highly coordinated peristalsis. The gut-like structures have large lumens surrounded by three layers: epithelium, lamina propria, and muscularis. Ganglia are scattered along the periphery, and interstitial cells of Cajal are distributed among the smooth muscle cells. The fundamental process of formation of the in vitro organized gut-like structures is similar to embryonic gastrointestinal development in vivo. The EBs at the 6-d egg-cylinder stage may have the potential to regulate developmental programs associated with cell lineage commitment and provide an appropriate microenvironment to differentiate ES cells into enteric derivatives of all three embryonic germ layers and reproduce the gut organization process in vitro.

Enhanced thermoelectric properties of phase-separating bismuth selenium telluride thin films via a two-step method

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

Takashiri, Masayuki, E-mail: takashiri@tokai-u.jp; Kurita, Kensuke; Hagino, Harutoshi

2015-08-14

A two-step method that combines homogeneous electron beam (EB) irradiation and thermal annealing has been developed to enhance the thermoelectric properties of nanocrystalline bismuth selenium telluride thin films. The thin films, prepared using a flash evaporation method, were treated with EB irradiation in a N{sub 2} atmosphere at room temperature and an acceleration voltage of 0.17 MeV. Thermal annealing was performed under Ar/H{sub 2} (5%) at 300 °C for 60 min. X-ray diffraction was used to determine that compositional phase separation between bismuth telluride and bismuth selenium telluride developed in the thin films exposed to higher EB doses and thermal annealing. We proposemore » that the phase separation was induced by fluctuations in the distribution of selenium atoms after EB irradiation, followed by the migration of selenium atoms to more stable sites during thermal annealing. As a result, thin film crystallinity improved and mobility was significantly enhanced. This indicates that the phase separation resulting from the two-step method enhanced, rather than disturbed, the electron transport. Both the electrical conductivity and the Seebeck coefficient were improved following the two-step method. Consequently, the power factor of thin films that underwent the two-step method was enhanced to 20 times (from 0.96 to 21.0 μW/(cm K{sup 2}) that of the thin films treated with EB irradiation alone.« less

Phosphoproteomic analysis of the Chlamydia caviae elementary body and reticulate body forms.

PubMed

Fisher, Derek J; Adams, Nancy E; Maurelli, Anthony T

2015-08-01

Chlamydia are Gram-negative, obligate intracellular bacteria responsible for significant diseases in humans and economically important domestic animals. These pathogens undergo a unique biphasic developmental cycle transitioning between the environmentally stable elementary body (EB) and the replicative intracellular reticulate body (RB), a conversion that appears to require extensive regulation of protein synthesis and function. However, Chlamydia possess a limited number of canonical mechanisms of transcriptional regulation. Ser/Thr/Tyr phosphorylation of proteins in bacteria has been increasingly recognized as an important mechanism of post-translational control of protein function. We utilized 2D gel electrophoresis coupled with phosphoprotein staining and MALDI-TOF/TOF analysis to map the phosphoproteome of the EB and RB forms of Chlamydia caviae. Forty-two non-redundant phosphorylated proteins were identified (some proteins were present in multiple locations within the gels). Thirty-four phosphorylated proteins were identified in EBs, including proteins found in central metabolism and protein synthesis, Chlamydia-specific hypothetical proteins and virulence-related proteins. Eleven phosphorylated proteins were identified in RBs, mostly involved in protein synthesis and folding and a single virulence-related protein. Only three phosphoproteins were found in both EB and RB phosphoproteomes. Collectively, 41 of 42 C. caviae phosphoproteins were present across Chlamydia species, consistent with the existence of a conserved chlamydial phosphoproteome. The abundance of stage-specific phosphoproteins suggests that protein phosphorylation may play a role in regulating the function of developmental-stage-specific proteins and/or may function in concert with other factors in directing EB-RB transitions.

On the structure and dynamics of Ellerman bombs. Detailed study of three events and modelling of Hα

NASA Astrophysics Data System (ADS)

Bello González, N.; Danilovic, S.; Kneer, F.

2013-09-01

Aims: We study the structure and dynamics of three Ellerman bombs (EBs) observed in an evolving active region. Methods: The active region NOAA 11271 was observed with the Vacuum Tower Telescope at Observatorio del Teide/Tenerife on August 18, 2011. We used the two-dimensional Triple Etalon SOlar Spectrometer (TESOS) to obtain time sequences of the active region and of EBs in Hα at a cadence of 15 s. Simultaneously, we obtained full Stokes profiles with the Tenerife Infrared Polarimeter (TIP II) in the two magnetically sensitive Fe i infrared lines (IR) at 1.56 μ, scanning spatial sections of the area with cadences of 28-46 s. The Hα data were reconstructed with speckle methods to study the evolution of the atmospheric stratification. Two methods were used to extract magnetic field information from the IR Stokes profiles: 1) fitting of the (Q,U,V) profiles by Gaussians; and 2) applying the Milne-Eddington approximation, assuming two separate magnetic structures in the resolution element and fitting by trial and error some profiles from the EB areas. Data from SDO-HMI and -AIA were also used. We performed two-dimensional (2D) non-LTE radiative transfer calculations of Hα in parameterised models of EBs. Results: The three EBs studied in detail occurred in a complex active region near sunspots. They were very bright with a factor of 1.5-2.8 brighter than the nearby area. They lived for 1/2 h and longer. They were related to broadband faculae, but the latter were not the brightest features in the field of view. The EBs occurred in magnetic field configurations with opposite polarity close together. One EB was located at the outskirts of a penumbra of a complex sunspot and showed repeated "flaring" in SDO-AIA data. Another was close to a strong field patch and moved into this during the end of its lifetime. The third EB showed clear changes of field structure during the time it was observed. We obtained from the 2D modelling that heating and increase in Hα opacity are likely to occur at heights of 300-800 km. Line shifts and asymmetries can well be reproduced by velocities at these heights and also at much larger heights. Conclusions: The three EBs occurred at sites with magnetic fields of opposite polarity, which were likely the cause of the Hα brightening upon reconnection.

TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion.

PubMed

Xia, Qin; Wang, Hongfeng; Hao, Zongbing; Fu, Cheng; Hu, Qingsong; Gao, Feng; Ren, Haigang; Chen, Dong; Han, Junhai; Ying, Zheng; Wang, Guanghui

2016-01-18

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by selective loss of motor neurons in brain and spinal cord. TAR DNA-binding protein 43 (TDP-43) was identified as a major component of disease pathogenesis in ALS, frontotemporal lobar degeneration (FTLD), and other neurodegenerative disease. Despite the fact that TDP-43 is a multi-functional protein involved in RNA processing and a large number of TDP-43 RNA targets have been discovered, the initial toxic effect and the pathogenic mechanism underlying TDP-43-linked neurodegeneration remain elusive. In this study, we found that loss of TDP-43 strongly induced a nuclear translocation of TFEB, the master regulator of lysosomal biogenesis and autophagy, through targeting the mTORC1 key component raptor. This regulation in turn enhanced global gene expressions in the autophagy-lysosome pathway (ALP) and increased autophagosomal and lysosomal biogenesis. However, loss of TDP-43 also impaired the fusion of autophagosomes with lysosomes through dynactin 1 downregulation, leading to accumulation of immature autophagic vesicles and overwhelmed ALP function. Importantly, inhibition of mTORC1 signaling by rapamycin treatment aggravated the neurodegenerative phenotype in a TDP-43-depleted Drosophila model, whereas activation of mTORC1 signaling by PA treatment ameliorated the neurodegenerative phenotype. Taken together, our data indicate that impaired mTORC1 signaling and influenced ALP may contribute to TDP-43-mediated neurodegeneration. © 2015 The Authors.

Significance of two distinct types of tryptophan synthase beta chain in Bacteria, Archaea and higher plants.

PubMed

Xie, Gary; Forst, Christian; Bonner, Carol; Jensen, Roy A

2002-01-01

Tryptophan synthase consists of two subunits, alpha and beta. Two distinct subgroups of beta chain exist. The major group (TrpEb_1) includes the well-studied beta chain of Salmonella typhimurium. The minor group of beta chain (TrpEb_2) is most frequently found in the Archaea. Most of the amino-acid residues important for catalysis are highly conserved between both TrpE subfamilies. Conserved amino-acid residues of TrpEb_1 that make allosteric contact with the TrpEa subunit (the alpha chain) are absent in TrpEb_2. Representatives of Archaea, Bacteria and higher plants all exist that possess both TrpEb_1 and TrpEb_2. In those prokaryotes where two trpEb genes coexist, one is usually trpEb_1 and is adjacent to trpEa, whereas the second is trpEb_2 and is usually unlinked with other tryptophan-pathway genes. TrpEb_1 is nearly always partnered with TrpEa in the tryptophan synthase reaction. However, by default at least six lineages of the Archaea are likely to use TrpEb_2 as the functional beta chain, as TrpEb_1 is absent. The six lineages show a distinctive divergence within the overall TrpEa phylogenetic tree, consistent with the lack of selection for amino-acid residues in TrpEa that are otherwise conserved for interfacing with TrpEb_1. We suggest that the standalone function of TrpEb_2 might be to catalyze the serine deaminase reaction, an established catalytic capability of tryptophan synthase beta chains. A coincident finding of interest is that the Archaea seem to use the citramalate pathway, rather than threonine deaminase (IlvA), to initiate the pathway of isoleucine biosynthesis.

Evaluation of the Health Protection Event-Based Surveillance for the London 2012 Olympic and Paralympic Games.

PubMed

Severi, E; Kitching, A; Crook, P

2014-06-19

The Health Protection Agency (HPA) (currently Public Health England) implemented the Health Protection Event-Based Surveillance (EBS) to provide additional national epidemic intelligence for the 2012 London Olympic and Paralympic Games (the Games). We describe EBS and evaluate the system attributes. EBS aimed at identifying, assessing and reporting to the HPA Olympic Coordination Centre (OCC) possible national infectious disease threats that may significantly impact the Games. EBS reported events in England from 2 July to 12 September 2012. EBS sourced events from reports from local health protection units and from screening an electronic application 'HPZone Dashboard' (DB). During this period, 147 new events were reported to EBS, mostly food-borne and vaccine-preventable diseases: 79 from regional units, 144 from DB (76 from both). EBS reported 61 events to the OCC: 21 of these were reported onwards. EBS sensitivity was 95.2%; positive predictive value was 32.8%; reports were timely (median one day; 10th percentile: 0 days - same day; 90th percentile: 3.6 days); completeness was 99.7%; stability was 100%; EBS simplicity was assessed as good; the daily time per regional or national unit dedicated to EBS was approximately 4 hours (weekdays) and 3 hours (weekends). OCC directors judged EBS as efficient, fast and responsive. EBS provided reliable, reassuring, timely, simple and stable national epidemic intelligence for the Games.

Effects of hanging drop culture conditions on embryoid body formation and neuronal cell differentiation using mouse embryonic stem cells: optimization of culture conditions for the formation of well-controlled embryoid bodies.

PubMed

Ohnuki, Yoshitsugu; Kurosawa, Hiroshi

2013-05-01

Hanging drop (HD) cultures were carried out with a drop volume of either 20 or 30 μl. An incubation period of 3 days was determined to be appropriate for the formation of well-controlled embryoid bodies (EBs), and the initial cell number was identified as the most critical factor in the growth and neuronal cell differentiation of EBs. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Estrogen alters gonadal soma-derived factor (Gsdf)/Foxl2 expression levels in the testes associated with testis-ova differentiation in adult medaka, Oryzias latipes.

PubMed

Kobayashi, Tohru; Chiba, Ayaka; Sato, Tadashi; Myosho, Taijun; Yamamoto, Jun; Okamura, Tetsuro; Onishi, Yuta; Sakaizumi, Mitsuru; Hamaguchi, Satoshi; Iguchi, Taisen; Horie, Yoshifumi

2017-10-01

Testis-ova differentiation in sexually mature male medaka (Oryzias latipes) is easily induced by estrogenic chemicals, indicating that spermatogonia persist in sexual bipotentiality, even in mature testes in medaka. By contrast, the effects of estrogen on testicular somatic cells associated with testis-ova differentiation in medaka remain unclear. In this study, we focused on the dynamics of sex-related genes (Gsdf, Dmrt1, and Foxl2) expressed in Sertoli cells in the mature testes of adult medaka during estrogen-induced testis-ova differentiation. When mature male medaka were exposed to estradiol benzoate (EB; 800ng/L), testis-ova first appeared after EB treatment for 14days (observed as the first oocytes of the leptotene-zygotene stage). However, the testis remained structurally unchanged, even after EB treatment for 28days. Although Foxl2 is a female-specific sex gene, EB treatment for 7days induced Foxl2/FOXL2 expression in all Sertoli cell-enclosed spermatogonia before testis-ova first appeared; however, Foxl2 was not detected in somatic cells in control testes. Conversely, Sertoli-cell-specific Gsdf mRNA expression levels significantly decreased after EB treatment for 14days, and no changes were observed in DMRT1 localization following EB treatment, whereas Dmrt1 mRNA levels increased significantly. Furthermore, after EB exposure, FOXl2 and DMRT1 were co-localized in Sertoli cells during testis-ova differentiation, although FOXL2 localization was undetectable in Sertoli-cell-enclosed apoptotic testis-ova, whereas DMRT1 remained localized in Sertoli cells. These results indicated for the first time that based on the expression of female-specific sex genes, feminization of Sertoli cells precedes testis-ova differentiation induced by estrogen in mature testes in medaka; however, complete feminization of Sertoli cells was not induced in this study. Additionally, it is suggested strongly that Foxl2 and Gsdf expression constitute potential molecular markers for evaluating the effects of estrogenic chemicals on testicular somatic cells associated with estrogen-induced testis-ova differentiation in mature male medaka. Copyright © 2017 Elsevier B.V. All rights reserved.

Implementing school nursing strategies to reduce LGBTQ adolescent suicide: a randomized cluster trial study protocol.

PubMed

Willging, Cathleen E; Green, Amy E; Ramos, Mary M

2016-10-22

Reducing youth suicide in the United States (U.S.) is a national public health priority, and lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) youth are at elevated risk. The Centers for Disease Control and Prevention (CDC) endorses six evidence-based (EB) strategies that center on meeting the needs of LGBTQ youth in schools; however, fewer than 6 % of U.S. schools implement all of them. The proposed intervention model, "RLAS" (Implementing School Nursing Strategies to Reduce LGBTQ Adolescent Suicide), builds on the Exploration, Preparation, Implementation, and Sustainment (EPIS) conceptual framework and the Dynamic Adaptation Process (DAP) to implement EB strategies in U.S. high schools. The DAP accounts for the multilevel context of school settings and uses Implementation Resource Teams (IRTs) to facilitate appropriate expertise, advise on acceptable adaptations, and provide data feedback to make schools implementation ready and prepared to sustain changes. Mixed methods will be used to examine individual, school, and community factors influencing both implementation process and youth outcomes. A cluster randomized controlled trial will assess whether LGBTQ students and their peers in RLAS intervention schools (n = 20) report reductions in suicidality, depression, substance use, bullying, and truancy related to safety concerns compared to those in usual care schools (n = 20). Implementation progress and fidelity for each EB strategy in RLAS intervention schools will be examined using a modified version of the Stages of Implementation Completion checklist. During the implementation and sustainment phases, annual focus groups will be conducted with the 20 IRTs to document their experiences identifying and advancing adaptation supports to facilitate use of EB strategies and their perceptions of the DAP. The DAP represents a data-informed, collaborative, multiple stakeholder approach to progress from exploration to sustainment and obtain fidelity during the implementation of EB strategies in school settings. This study is designed to address the real-world implications of enabling the use of EB strategies by school nurses with the goal of decreasing suicide and youth risk behaviors among LGBTQ youth. Through its participatory processes to refine and sustain EB strategies in high schools, the RLAS represents a novel contribution to implementation science. ClinicalTrials.gov, NCT02875535.

The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells.

PubMed

Mohr, Jeffrey C; Zhang, Jianhua; Azarin, Samira M; Soerens, Andrew G; de Pablo, Juan J; Thomson, James A; Lyons, Gary E; Palecek, Sean P; Kamp, Timothy J

2010-03-01

The differentiation of human embryonic stem cells (hESCs) into cardiomyocytes (CMs) using embryoid bodies (EBs) is relatively inefficient and highly variable. Formation of EBs using standard enzymatic disaggregation techniques results in a wide range of sizes and geometries of EBs. Use of a 3-D cuboidal microwell system to culture hESCs in colonies of defined dimensions, 100-500 microm in lateral dimensions and 120 microm in depth, enabled formation of more uniform-sized EBs. The 300 microm microwells produced highest percentage of contracting EBs, but flow cytometry for myosin light chain 2A (MLC2a) expressing cells revealed a similar percentage (approximately 3%) of cardiomyocytes formed in EBs from 100 microm to 300 microm microwells. These data, and immunolabeling with anti-MF20 and MLC2a, suggest that the smaller EBs are less likely to form contracting EBs, but those contracting EBs are relatively enriched in cardiomyocytes compared to larger EB sizes where CMs make up a proportionately smaller fraction of the total cells. We conclude that microwell-engineered EB size regulates cardiogenesis and can be used for more efficient and reproducible formation of hESC-CMs needed for research and therapeutic applications. (c) 2009 Elsevier Ltd. All rights reserved.

Graphene induces spontaneous cardiac differentiation in embryoid bodies

NASA Astrophysics Data System (ADS)

Ahadian, Samad; Zhou, Yuanshu; Yamada, Shukuyo; Estili, Mehdi; Liang, Xiaobin; Nakajima, Ken; Shiku, Hitoshi; Matsue, Tomokazu

2016-03-01

Graphene was embedded into the structure of mouse embryoid bodies (EBs) using the hanging drop technique. The inclusion of 0.2 mg per mL graphene in the EBs did not affect the viability of the stem cells. However, the graphene decreased the stem cell proliferation, probably by accelerating cell differentiation. The graphene also enhanced the mechanical properties and electrical conductivity of the EBs. Interestingly, the cardiac differentiation of the EB-graphene was significantly greater than that of the EBs at day 5 of culture, as confirmed by high-throughput gene analysis. Electrical stimulation (voltage, 4 V; frequency, 1 Hz; and duration, 10 ms for 2 continuous days) further enhanced the cardiac differentiation of the EBs, as demonstrated by analyses of the cardiac protein and gene expression and the beating activity of the EBs. Taken together, the results demonstrated that graphene played a major role in directing the cardiac differentiation of EBs, which has potential cell therapy and tissue regeneration applications.Graphene was embedded into the structure of mouse embryoid bodies (EBs) using the hanging drop technique. The inclusion of 0.2 mg per mL graphene in the EBs did not affect the viability of the stem cells. However, the graphene decreased the stem cell proliferation, probably by accelerating cell differentiation. The graphene also enhanced the mechanical properties and electrical conductivity of the EBs. Interestingly, the cardiac differentiation of the EB-graphene was significantly greater than that of the EBs at day 5 of culture, as confirmed by high-throughput gene analysis. Electrical stimulation (voltage, 4 V; frequency, 1 Hz; and duration, 10 ms for 2 continuous days) further enhanced the cardiac differentiation of the EBs, as demonstrated by analyses of the cardiac protein and gene expression and the beating activity of the EBs. Taken together, the results demonstrated that graphene played a major role in directing the cardiac differentiation of EBs, which has potential cell therapy and tissue regeneration applications. Electronic supplementary information (ESI) available: Fig. S1-S3, Tables S1-S4, and Movies S1-S4. See DOI: 10.1039/c5nr07059g

TIP maker and TIP marker; EB1 as a master controller of microtubule plus ends.

PubMed

Vaughan, Kevin T

2005-10-24

The EB1 protein is a member of the exciting and enigmatic family of microtubule (MT) tip-tracking proteins. EB1 acts as an exquisite marker of dynamic MT plus ends in some cases, whereas in others EB1 is thought to directly dictate the behavior of the plus ends. How EB1 differentiates between these two roles remains unclear; however, a growing list of interactions between EB1 and other MT binding proteins suggests there may be a single mechanism. Adding another layer of complexity to these interactions, two studies published in this issue implicate EB1 in cross-talk between mitotic MTs and between MTs and actin filaments (Goshima et al., p. 229; Wu et al., p. 201). These results raise the possibility that EB1 is a central player in MT-based transport, and that the activity of MT-binding proteins depends on their ability or inability to interact with EB1.

Comparison of the decomposition characteristics of aromatic VOCs using an electron beam hybrid system

NASA Astrophysics Data System (ADS)

Son, Youn-Suk; Kim, Ki-Joon; Kim, Ji-Yong; Kim, Jo-Chun

2010-12-01

We applied a hybrid technique to assess the decomposition characteristics of ethylbenzene and toluene that annexed the catalyst technique with existing electron beam (EB) technology. The removal efficiency of ethylbenzene in the EB-catalyst hybrid turned out to be 30% greater than that of EB-only treatment. We concluded that ethylbenzene was decomposed more easily than toluene by EB irradiation. We compared the independent effects of the EB-catalyst hybrid and catalyst-only methods, and observed that the efficiency of the EB-catalyst hybrid demonstrated approximately 6% improvement for decomposing toluene and 20% improvement for decomposing ethylbenzene. The G-values for ethylbenzene increased with initial concentration and reactor type: for example, the G-values by reactor type at 2800 ppmC were 7.5-10.9 (EB-only) and 12.9-25.7 (EB-catalyst hybrid). We also observed a significant decrease in by-products as well as in the removal efficiencies associated with the EB-catalyst hybrid technique.

Double-wavelength overlapping resonance Rayleigh scattering technique for the simultaneous quantitative analysis of three β-adrenergic blockade

NASA Astrophysics Data System (ADS)

Tan, Xuanping; Yang, Jidong; Li, Qin; Yang, Qiong; Shen, Yizhong

2016-05-01

Four simple and accurate spectrophotometric methods were proposed for the simultaneous determination of three β-adrenergic blockade, e.g. atenolol, metoprolol and propranolol. The methods were based on the reaction of the three drugs with erythrosine B (EB) in a Britton-Robinson buffer solution at pH 4.6. EB could combine with the drugs to form three ion-association complexes, which resulted in the resonance Rayleigh scattering (RRS) intensity that is enhanced significantly with new RRS peaks that appeared at 337 nm and 370 nm, respectively. In addition, the fluorescence intensity of EB was also quenched. The enhanced scattering intensities of the two peaks and the fluorescence quenched intensity of EB were proportional to the concentrations of the drugs, respectively. What is more, the RRS intensity overlapped with the double-wavelength of 337 nm and 370 nm (so short for DW-RRS) was also proportional to the drugs concentrations. So, a new method with highly sensitive for simultaneous determination of three bisoprolol drugs was established. Finally, the optimum reaction conditions, influencing factors and spectral enhanced mechanism were investigated. The new DW-RRS method has been applied to simultaneously detect the three β-blockers in fresh serum with satisfactory results.

The Nuclear and Adherent Junction Complex Component Protein Ubinuclein Negatively Regulates the Productive Cycle of Epstein-Barr Virus in Epithelial Cells▿

PubMed Central

Gruffat, Henri; Lupo, Julien; Morand, Patrice; Boyer, Véronique; Manet, Evelyne

2011-01-01

The Epstein-Barr Virus (EBV) productive cycle is initiated by the expression of the viral trans-activator EB1 (also called Zebra, Zta, or BZLF1), which belongs to the basic leucine zipper transcription factor family. We have previously identified the cellular NACos (nuclear and adherent junction complex components) protein ubinuclein (Ubn-1) as a partner for EB1, but the function of this complex has never been studied. Here, we have evaluated the consequences of this interaction on the EBV productive cycle and find that Ubn-1 overexpression represses the EBV productive cycle whereas Ubn-1 downregulation by short hairpin RNA (shRNA) increases virus production. By a chromatin immunoprecipitation (ChIP) assay, we show that Ubn-1 blocks EB1-DNA interaction. We also show that in epithelial cells, relocalization and sequestration of Ubn-1 to the tight junctions of nondividing cells allow increased activation of the productive cycle. We propose a model in which Ubn-1 is a modulator of the EBV productive cycle: in proliferating epithelial cells, Ubn-1 is nuclear and inhibits activation of the productive cycle, whereas in differentiated cells, Ubn-1 is sequestrated to tight junctions, thereby allowing EB1 to fully function in the nucleus. PMID:21084479

An Embryonic and Induced Pluripotent Stem Cell Model for Ovarian Granulosa Cell Development and Steroidogenesis.

PubMed

Lipskind, Shane; Lindsey, Jennifer S; Gerami-Naini, Behzad; Eaton, Jennifer L; O'Connell, Daniel; Kiezun, Adam; Ho, Joshua W K; Ng, Nicholas; Parasar, Parveen; Ng, Michelle; Nickerson, Michael; Demirci, Utkan; Maas, Richard; Anchan, Raymond M

2018-05-01

Embryoid bodies (EBs) can serve as a system for evaluating pluripotency, cellular differentiation, and tissue morphogenesis. In this study, we use EBs derived from mouse embryonic stem cells (mESCs) and human amniocyte-derived induced pluripotent stem cells (hAdiPSCs) as a model for ovarian granulosa cell (GC) development and steroidogenic cell commitment. We demonstrated that spontaneously differentiated murine EBs (mEBs) and human EBs (hEBs) displayed ovarian GC markers, such as aromatase (CYP19A1), FOXL2, AMHR2, FSHR, and GJA1. Comparative microarray analysis identified both shared and unique gene expression between mEBs and the maturing mouse ovary. Gene sets related to gonadogenesis, lipid metabolism, and ovarian development were significantly overrepresented in EBs. Of the 29 genes, 15 that were differentially regulated in steroidogenic mEBs displayed temporal expression changes between embryonic, postnatal, and mature ovarian tissues by polymerase chain reaction. Importantly, both mEBs and hEBs were capable of gonadotropin-responsive estradiol (E2) synthesis in vitro (217-759 pg/mL). Live fluorescence-activated cell sorting-sorted AMHR2 + granulosa-like cells from mEBs continued to produce E2 after purification (15.3 pg/mL) and secreted significantly more E2 than AMHR2 - cells (8.6 pg/mL, P < .05). We conclude that spontaneously differentiated EBs of both mESC and hAdiPSC origin can serve as a biologically relevant model for ovarian GC differentiation and steroidogenic cell commitment. These cells should be further investigated for therapeutic uses, such as stem cell-based hormone replacement therapy and in vitro maturation of oocytes.

An examination of the structure of self-report psychopathy measures and their relations with general traits and externalizing behaviors.

PubMed

Seibert, L Alana; Miller, Joshua D; Few, Lauren R; Zeichner, Amos; Lynam, Donald R

2011-07-01

Self-report assessment of psychopathy is plagued by inconsistencies among the relations of the various psychopathy factors. We examined the factor structure of 3 prominent self-report measures of psychopathy-the Self-Report Psychopathy Scale-III (SRP-III; Williams, Paulhus, & Hare, 2007), the Levenson Self-Report Psychopathy Scale (LSRP; Levenson, Kiehl, & Fitzpatrick, 1995), and the Psychopathic Personality Inventory-R (PPI-R; Lilienfeld & Widows, 2005). A coherent 4-factor structure resulted from conducting an exploratory factor analysis (EFA) of the psychopathy subscales along with the domains from the five-factor model. Two of these factors were consistent with traditional conceptualizations of a 2-factor structure of psychopathy (i.e., Factor 1, which loaded negatively with Agreeableness; Factor 2, which loaded negatively with Conscientiousness), while 2 additional factors emerged, 1 of which emphasized low Neuroticism and 1 of which emphasized traits related to novelty/reward-seeking and dominance-related personality traits (high Extraversion). We also investigated the relations of these factors with a variety of externalizing behaviors (EB). The psychopathy scales indicative of interpersonal antagonism (i.e., Factor 1) were most consistently and strongly related to EB. Our findings are discussed in terms of the importance of a trait-based perspective in the assessment of psychopathy.

Targeting Androgen Receptor by Lysosomal Degradation in Prostate Cancer

DTIC Science & Technology

2015-11-01

transport of TFEB, Autophagy 8 (2012) 903-914. [7] J. Brugarolas, K. Lei , R.L. Hurley, B.D. Manning, J.H. Reiling, E. Hafen, L.A. Witters, L.W. Ellisen...chromatography ~ anti-FLAG immunoprecipitation B D EWS pos~t~on mass pept~ de 416-429 1449 .66 GDATVSYEDPPTAK 571-594 2289.08 GGPGGMRGGRGGLMDRGGPGGMFR...vector 1 2 3 -- FLAG-His EWS-Fii-1 4 5 6 - FLAG tubulin c RNA helicase A pos~t~on mass pept~ de 121-141 2161 .97 AENNSEVGASGYGVPGPTWDR 200-209

The Recruitment of Social Movement Leaders: Structural Factors.

ERIC Educational Resources Information Center

Himes, Joseph S.

1979-01-01

A review of pertinent literature indicates that social movements produce their leaders by transforming and transferring some followers into the roles of leadership. A case study of the recruitment of social movement leaders in Rhodesia supports this hypothesis and illustrates some of the structural factors which condition the process. (EB)

Dissecting EB1-microtubule interactions from every direction: using single-molecule visualization and static and dynamic binding measurements

NASA Astrophysics Data System (ADS)

Lopez, Benjamin

2015-03-01

EB1 is an important microtubule associating protein (MAP) that acts as a master coordinator of protein activity at the growing plus-end of the microtubule. We can recapitulate the plus-end binding behavior of EB1 along the entire length of a static microtubule using microtubules polymerized in the presence of the nonhydrolyzable GTP analogs GMPCPP and GTP γS instead of GTP. Through the use of single-molecule TIRF imaging we find that EB1 is highly dynamic (with a sub-second characteristic binding lifetime) and continuously diffusive while bound to the microtubule. We measure the diffusion coefficient, D, through linear fitting to mean-squared displacement of individually labeled proteins, and the binding lifetime, τ, by fitting a single exponential decay to the probability distribution of trajectory lifetimes. In agreement with measurements of other diffusive MAPs, we find that D increases and τ decreases with increasing ionic strength. We also find that D is sensitive to the choice of GTP analog: EB1 proteins bound to GTP γS polymerized microtubules have a D half of that found with GMPCPP polymerized microtubules. To compare these single-molecule measurements to the bulk binding behavior of EB1, we use TIRF imaging to measure the intensity of microtubules coated with EB1-GFP as a function of EB1 concentration. We find that EB1 binding is cooperative and both the quantity of EB1 bound and the dissociation constant are sensitive to GTP analog and ionic concentration. The correlation between binding affinity and D and the cooperative nature of EB1-microtubule binding leads to a decrease in D with increasing EB1 concentration. Interestingly, we also find an increase in τ at high EB1 concentrations, consistent with attractive EB1-microtubule interactions driving the cooperativity. To further understand the nature of the cooperativity we estimate the interaction energy by measuring the association and dissociation rates (kon and koff respectively) at different concentrations of EB1.

Clearance of chlamydial elementary bodies from the conjunctival sac

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

Taylor, H.R.; Velez, V.L.

1987-07-01

The rate of disappearance of inactivated Chlamydia trachomatis elementary body (EB) preparations from the conjunctival sac was studied in monkeys. Direct fluorescent antibody (DFA) cytology showed that the majority of EB had been cleared from the eye within 24 hr of the inoculation of 1 X 10(6) inactivated EB, although small numbers of EB could be detected for up to 144 hr. The rate of clearance in normal and ocular immune animals did not differ, and formalin-killed and UV-inactivated EBs disappeared at a comparable rate. These studies suggest that chlamydial EB are cleared relatively quickly from the eye and supportmore » the notion that EBs detected by DFA cytology indicate the presence of current infection.« less

Studies on the diagnostic value of an immunofluorescence test for EB virus-specific IgM.

PubMed

Edwards, J M; McSwiggan, D A

1974-08-01

A modification of the test for EB virus/IgM introduced by Schmitz and Scherer (1972) is described. It is simple and gives reproducible results.EB virus/IgM was demonstrated in all but one case of infectious mononucleosis and in students with minor illness shown to have acquired EB virus/IgG recently. Unlike the EB virus/IgG, the IgM disappears within a few months. Although the Paul-Bunnell-Davidsohn test is still the test of choice for the diagnosis of infectious mononucleosis, the EB virus/IgM test could be useful to establish a diagnosis of current or recent EB virus infection where the Paul-Bunnell-Davidsohn test was negative or equivocal.

Insights into EB1 structure and the role of its C-terminal domain for discriminating microtubule tips from the lattice

PubMed Central

Buey, Rubén M.; Mohan, Renu; Leslie, Kris; Walzthoeni, Thomas; Missimer, John H.; Menzel, Andreas; Bjelić, Saša; Bargsten, Katja; Grigoriev, Ilya; Smal, Ihor; Meijering, Erik; Aebersold, Ruedi; Akhmanova, Anna; Steinmetz, Michel O.

2011-01-01

End-binding proteins (EBs) comprise a conserved family of microtubule plus end–tracking proteins. The concerted action of calponin homology (CH), linker, and C-terminal domains of EBs is important for their autonomous microtubule tip tracking, regulation of microtubule dynamics, and recruitment of numerous partners to microtubule ends. Here we report the detailed structural and biochemical analysis of mammalian EBs. Small-angle X-ray scattering, electron microscopy, and chemical cross-linking in combination with mass spectrometry indicate that EBs are elongated molecules with two interacting CH domains, an arrangement reminiscent of that seen in other microtubule- and actin-binding proteins. Removal of the negatively charged C-terminal tail did not affect the overall conformation of EBs; however, it increased the dwell times of EBs on the microtubule lattice in microtubule tip–tracking reconstitution experiments. An even more stable association with the microtubule lattice was observed when the entire negatively charged C-terminal domain of EBs was replaced by a neutral coiled-coil motif. In contrast, the interaction of EBs with growing microtubule tips was not significantly affected by these C-terminal domain mutations. Our data indicate that long-range electrostatic repulsive interactions between the C-terminus and the microtubule lattice drive the specificity of EBs for growing microtubule ends. PMID:21737692

Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.

PubMed

El-Sheikh, El-Sayed A; Galal, Azza A A

2015-05-01

Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB. Copyright © 2015 Elsevier B.V. All rights reserved.

Anaerobic Degradation of Ethylbenzene by a New Type of Marine Sulfate-Reducing Bacterium

PubMed Central

Kniemeyer, Olaf; Fischer, Thomas; Wilkes, Heinz; Glöckner, Frank Oliver; Widdel, Friedrich

2003-01-01

Anaerobic degradation of the aromatic hydrocarbon ethylbenzene was studied with sulfate as the electron acceptor. Enrichment cultures prepared with marine sediment samples from different locations showed ethylbenzene-dependent reduction of sulfate to sulfide and always contained a characteristic cell type that formed gas vesicles towards the end of growth. A pure culture of this cell type, strain EbS7, was isolated from sediment from Guaymas Basin (Gulf of California). Complete mineralization of ethylbenzene coupled to sulfate reduction was demonstrated in growth experiments with strain EbS7. Sequence analysis of the 16S rRNA gene revealed a close relationship between strain EbS7 and the previously described marine sulfate-reducing strains NaphS2 and mXyS1 (similarity values, 97.6 and 96.2%, respectively), which grow anaerobically with naphthalene and m-xylene, respectively. However, strain EbS7 did not oxidize naphthalene, m-xylene, or toluene. Other compounds utilized by strain EbS7 were phenylacetate, 3-phenylpropionate, formate, n-hexanoate, lactate, and pyruvate. 1-Phenylethanol and acetophenone, the characteristic intermediates in anaerobic ethylbenzene degradation by denitrifying bacteria, neither served as growth substrates nor were detectable as metabolites by gas chromatography-mass spectrometry in ethylbenzene-grown cultures of strain EbS7. Rather, (1-phenylethyl)succinate and 4-phenylpentanoate were detected as specific metabolites in such cultures. Formation of these intermediates can be explained by a reaction sequence involving addition of the benzyl carbon atom of ethylbenzene to fumarate, carbon skeleton rearrangement of the succinate moiety (as a thioester), and loss of one carboxyl group. Such reactions are analogous to those suggested for anaerobic n-alkane degradation and thus differ from the initial reactions in anaerobic ethylbenzene degradation by denitrifying bacteria which employ dehydrogenations. PMID:12570993

The EB Factory: Fundamental Stellar Astrophysics with Eclipsing Binary Stars Discovered by Kepler

NASA Astrophysics Data System (ADS)

Stassun, Keivan

Eclipsing binaries (EBs) are key laboratories for determining the fundamental properties of stars. EBs are therefore foundational objects for constraining stellar evolution models, which in turn are central to determinations of stellar mass functions, of exoplanet properties, and many other areas. The primary goal of this proposal is to mine the Kepler mission light curves for: (1) EBs that include a subgiant star, from which precise ages can be derived and which can thus serve as critically needed age benchmarks; and within these, (2) long-period EBs that include low-mass M stars or brown dwarfs, which are increa-singly becoming the focus of exoplanet searches, but for which there are the fewest available fundamental mass- radius-age benchmarks. A secondary goal of this proposal is to develop an end-to-end computational pipeline -- the Kepler EB Factory -- that allows automatic processing of Kepler light curves for EBs, from period finding, to object classification, to determination of EB physical properties for the most scientifically interesting EBs, and finally to accurate modeling of these EBs for detailed tests and benchmarking of theoretical stellar evolution models. We will integrate the most successful algorithms into a single, cohesive workflow environment, and apply this 'Kepler EB Factory' to the full public Kepler dataset to find and characterize new "benchmark grade" EBs, and will disseminate both the enhanced data products from this pipeline and the pipeline itself to the broader NASA science community. The proposed work responds directly to two of the defined Research Areas of the NASA Astrophysics Data Analysis Program (ADAP), specifically Research Area #2 (Stellar Astrophysics) and Research Area #9 (Astrophysical Databases). To be clear, our primary goal is the fundamental stellar astrophysics that will be enabled by the discovery and analysis of relatively rare, benchmark-grade EBs in the Kepler dataset. At the same time, to enable this goal will require bringing a suite of extant and new custom algorithms to bear on the Kepler data, and thus our development of the Kepler EB Factory represents a value-added product that will allow the widest scientific impact of the in-formation locked within the vast reservoir of the Kepler light curves.

Worldwide U.S. Active Duty Military Deaths: Alphabetical Index by Name, (Aakhus Daniel Joseph - Zysk Carol Rose), October 1, 1979 thru September 30, 1993

DTIC Science & Technology

1994-03-01

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MAGNETIC FLUX CANCELLATION IN ELLERMAN BOMBS

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

Reid, A.; Mathioudakis, M.; Nelson, C. J.

2016-06-01

Ellerman Bombs (EBs) are often found to be co-spatial with bipolar photospheric magnetic fields. We use H α imaging spectroscopy along with Fe i 6302.5 Å spectropolarimetry from the Swedish 1 m Solar Telescope (SST), combined with data from the Solar Dynamic Observatory , to study EBs and the evolution of the local magnetic fields at EB locations. EBs are found via an EB detection and tracking algorithm. Using NICOLE inversions of the spectropolarimetric data, we find that, on average, (3.43 ± 0.49) × 10{sup 24} erg of stored magnetic energy disappears from the bipolar region during EB burning. Themore » inversions also show flux cancellation rates of 10{sup 14}–10{sup 15} Mx s{sup −1} and temperature enhancements of 200 K at the detection footpoints. We investigate the near-simultaneous flaring of EBs due to co-temporal flux emergence from a sunspot, which shows a decrease in transverse velocity when interacting with an existing, stationary area of opposite polarity magnetic flux, resulting in the formation of the EBs. We also show that these EBs can be fueled further by additional, faster moving, negative magnetic flux regions.« less

Cervical spinal demyelination with ethidium bromide impairs respiratory (phrenic) activity and forelimb motor behavior in rats

PubMed Central

Nichols, Nicole L.; Punzo, Antonio M.; Duncan, Ian D.; Mitchell, Gordon S.; Johnson, Rebecca A.

2012-01-01

Although respiratory complications are a major cause of morbidity/mortality in many neural injuries or diseases, little is known concerning mechanisms whereby deficient myelin impairs breathing, or how patients compensate for such changes. Here, we tested the hypothesis that respiratory and forelimb motor function are impaired in a rat model of focal dorsolateral spinal demyelination (ethidium bromide, EB). Ventilation, phrenic nerve activity and horizontal ladder walking were performed 7-14 days post-C2 injection of EB or vehicle (SHAM). EB caused dorsolateral demyelination at C2-C3 followed by signficant spontaneous remyelination at 14 days post-EB. Although ventilation did not differ between groups, ipsilateral integrated phrenic nerve burst amplitude was significantly reduced versus SHAM during chemoreceptor activation at 7 days post-EB but recovered by 14 days. The ratio of ipsi- to contralateral phrenic nerve amplitude correlated with cross-sectional lesion area. This ratio was significantly reduced 7 days post-EB versus SHAM during baseline conditions, and versus SHAM and 14 day groups during chemoreceptor activation. Limb function ipsilateral to EB was impaired 7 days post-EB and partially recovered by 14 days post-EB. EB provides a reversible model of focal, spinal demyelination, and may be a useful model to study mechanisms of functional impairment and recovery via motor plasticity, or the efficacy of new therapeutic interventions to reduce severity or duration of disease. PMID:23159317

Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide

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

Altmann, S.E.; Jones, J.C.; Schultz-Cherry, S.

2009-06-05

Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC{sub 50} of 15 muM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC{sub 50} > 200 muM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption wasmore » unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of beta-galactosidase expression from an early viral promoter with an EC{sub 50} of 45 muM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.« less

Enhanced accumulation and storage of mercury on subtropical evergreen forest floor: Implications on mercury budget in global forest ecosystems

NASA Astrophysics Data System (ADS)

Wang, Xun; Lin, Che-Jen; Lu, Zhiyun; Zhang, Hui; Zhang, Yiping; Feng, Xinbin

2016-08-01

Forest ecosystems play an important role in the global cycling of mercury (Hg). In this study, we characterized the Hg cycling at a remote evergreen broadleaf (EB) forest site in southwest China (Mount Ailao). The annual Hg input via litterfall is estimated to be 75.0 ± 24.2 µg m-2 yr-1 at Mount Ailao. Such a quantity is up to 1 order of magnitude greater than those observed at remote temperate/boreal (T/B) forest sites. Production of litter biomass is found to be the most influential factor causing the high Hg input to the EB forest. Given their large areal coverage, Hg deposition through litterfall in EB forests is appropriately 9 ± 5 Mg yr-1 in China and 1086 ± 775 Mg yr-1 globally. The observed wet Hg deposition at Mount Ailao is 4.9 ± 4.5 µg m-2 yr-1, falling in the lower range of those observed at 49 T/B forest sites in North America and Europe. Given the data, the Hg deposition flux through litterfall is approximately 15 times higher than the wet Hg deposition at Mount Ailao. Steady Hg accumulation in decomposing litter biomass and Hg uptake from the environment were observed during 25 months of litter decomposition. The size of the Hg pool in the organic horizon of EB forest floors is estimated to be up to 2-10 times the typical pool size in T/B forests. This study highlights the importance of EB forest ecosystems in global Hg cycling, which requires further assessment when more data become available in tropical forests.

47 CFR 27.1214 - EBS spectrum leasing arrangements and grandfathered leases.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false EBS spectrum leasing arrangements and... Educational Broadband Service § 27.1214 EBS spectrum leasing arrangements and grandfathered leases. (a) A licensee in the EBS that is solely utilizing analog transmissions may enter into a spectrum leasing...

Effects of LEO Environment on Tensile Properties of PEEK Films

NASA Astrophysics Data System (ADS)

Nakamura, Takashi; Nakamura, Hiroshi; Shimamura, Hiroyuki

2009-01-01

To clarify the effects of space environment on mechanical properties of polymer, exposure experiments were conducted utilizing the International Space Station Russian Service Module. Poly-ether-ether-ketone (PEEK) films under tensile stress were exposed to low Earth orbit (LEO) environment, and reference samples were irradiated with atomic oxygen (AO), electron beam (EB), and ultraviolet light (UV) in ground facilities. By comparing the results of flight and ground tests, the degradation behavior and the influential factors in LEO were investigated. The following results were obtained. (1) UV was found to be the harshest factor in LEO on tensile properties, since it decreased elongation to 15% of pristine sample after 46-months exposure. (2) AO in LEO eroded the specimen surface with a cone-like morphology and reduced the thickness; however, it had no significant effect on tensile properties. (3) EB irradiation in LEO had no measurable effects on the material properties.

Engagement with beauty: appreciating natural, artistic, and moral beauty.

PubMed

Diessner, Rhett; Solom, Rebecca C; Frost, Nellie K; Parsons, Lucas; Davidson, John

2008-05-01

The Engagement With Beauty Scale (EBS), designed from the aesthetics of I. Kant (1790/1987), G. W. F. Hegel (ca. 1835/1993), and T. Aquinas (ca. 1260/1947) and the psychological work of J. Haidt (J. Haidt & D. Keltner, 2004), measures engagement with natural, artistic, and moral beauty. In Studies 1 and 2, the authors describe scale construction, exploratory factor analysis, confirmatory factor analysis, internal consistency, and temporal stability. In Studies 1 and 2, the authors also establish concurrent validity with the Appreciation of Beauty and Excellence subscale of the Values in Action Inventory of Strengths (C. Peterson & M. E. P. Seligman, 2004), the Gratitude, Resentment, and Appreciation Test (P. C. Watkins, K. Woodward, T. Stone, & R. L. Kolts, 2003), and the Spiritual Transcendence Scale (R. L. Piedmont, 2004). In Study 3, the authors used the EBS Artistic Beauty subscale to differentiate students engaged in the arts from those who were not.

Exchange Bias in Layered GdBaCo2O5.5 Cobaltite

NASA Astrophysics Data System (ADS)

Solin, N. I.; Naumov, S. V.; Telegin, S. V.; Korolev, A. V.

2017-12-01

It is established that excess oxygen content δ influences the exchange bias (EB) in layered GdBa-Co2O5 + δ cobaltite. The EB effect arises in p-type (δ > 0.5) cobaltite and disappears in n-type (δ < 0.5) cobaltite. The main parameters of EB in GdBaCo2O5.52(2) polycrystals are determined, including the field and temperature dependences of EB field H EB , blocking temperature T B , exchange coupling energy J i of antiferromagnet-ferromagnet (AFM-FM) interface, and dimensions of FM clusters. The training effect inherent in systems with EB has been studied. The results are explained in terms of exchange interaction between the FM and AFM phases. It is assumed that the EB originates from the coexistence of Co3+ and Co4+ ions that leads to the formation of monodomain FM clusters in the AFM matrix of cobaltite.

[Chronic active EB virus infection and granular lymphocytes proliferative disorders in Japan].

PubMed

Ishihara, S; Hara, J; Tawa, A; Kawa, K

1996-04-01

To clarify the characteristics of chronic active EB virus infection (CAEBV) in Japan, and to investigate the relation between granular lymphocytes proliferative disorder (GLPD) and EB virus, we conducted a survey through a questionnaire conducted throughout Japan. Among 17 registered patients with CAEBV, 9 developed various types of lymphoproliferative disorders (LPDs), and 6 patients died of LPD. Among 72 cases of GLPD, 43 were CD3-positive and 27 were CD3-negative. EB viral DNA was detected in the peripheral mononuclear cells in 6 of 7 CD3-negative and 1 of 4 CD3-positive cases. These data suggest that EB virus-associated LPDs frequently derive from patients with CAEBV. However, some GLPD patients without CAEBV, especially for CD3-negative GLPD, are associated with EB virus infection. Therefore detection of EB viral DNA is very important to understand the pathogenesis of GLPD.

First report on the pharmacokinetics of tramadol and O-desmethyltramadol in exhaled breath compared to plasma and oral fluid after a single oral dose.

PubMed

Meyer, Markus R; Rosenborg, Staffan; Stenberg, Marta; Beck, Olof

2015-12-01

Exhaled breath (EB) is a promising matrix for bioanalysis of non-volatiles and has been routinely implemented for drugs of abuse analysis. Nothing is known regarding the pharmacokinetics of therapeutics and their metabolites in EB. Therefore, we used tramadol as a model drug. Twelve volunteers received a single oral dose of tramadol and repeated sampling of EB, plasma, and oral fluid (OF) was done for 48 h using a particle filter device for EB and the Quantisal-device for OF. Samples were analyzed with LC-MS/MS and the pharmacokinetic correlations between matrices were investigated. The initial tramadol half-life in EB was shorter than in plasma but it reappeared in EB after 8-24 h. The ratio of O-desmethyltramadol to tramadol was considerably lower in EB and OF compared to plasma. This pilot study compared for the first time the pharmacokinetics of a therapeutic drug and active metabolite in different biomatrices including EB and demonstrated its potential for bioanalysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Targeted Proteolysis of Plectin Isoform 1a Accounts for Hemidesmosome Dysfunction in Mice Mimicking the Dominant Skin Blistering Disease EBS-Ogna

PubMed Central

Walko, Gernot; Vukasinovic, Nevena; Gross, Karin; Fischer, Irmgard; Sibitz, Sabrina; Fuchs, Peter; Reipert, Siegfried; Jungwirth, Ute; Berger, Walter; Salzer, Ulrich; Carugo, Oliviero; Castañón, Maria J.; Wiche, Gerhard

2011-01-01

Autosomal recessive mutations in the cytolinker protein plectin account for the multisystem disorders epidermolysis bullosa simplex (EBS) associated with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and congenital myasthenia (EBS-CMS). In contrast, a dominant missense mutation leads to the disease EBS-Ogna, manifesting exclusively as skin fragility. We have exploited this trait to study the molecular basis of hemidesmosome failure in EBS-Ogna and to reveal the contribution of plectin to hemidesmosome homeostasis. We generated EBS-Ogna knock-in mice mimicking the human phenotype and show that blistering reflects insufficient protein levels of the hemidesmosome-associated plectin isoform 1a. We found that plectin 1a, in contrast to plectin 1c, the major isoform expressed in epidermal keratinocytes, is proteolytically degraded, supporting the notion that degradation of hemidesmosome-anchored plectin is spatially controlled. Using recombinant proteins, we show that the mutation renders plectin's 190-nm-long coiled-coil rod domain more vulnerable to cleavage by calpains and other proteases activated in the epidermis but not in skeletal muscle. Accordingly, treatment of cultured EBS-Ogna keratinocytes as well as of EBS-Ogna mouse skin with calpain inhibitors resulted in increased plectin 1a protein expression levels. Moreover, we report that plectin's rod domain forms dimeric structures that can further associate laterally into remarkably stable (paracrystalline) polymers. We propose focal self-association of plectin molecules as a novel mechanism contributing to hemidesmosome homeostasis and stabilization. PMID:22144912

Evidence-based safety (EBS) management: A new approach to teaching the practice of safety management (SM).

PubMed

Wang, Bing; Wu, Chao; Shi, Bo; Huang, Lang

2017-12-01

In safety management (SM), it is important to make an effective safety decision based on the reliable and sufficient safety-related information. However, many SM failures in organizations occur for a lack of the necessary safety-related information for safety decision-making. Since facts are the important basis and foundation for decision-making, more efforts to seek the best evidence relevant to a particular SM problem would lead to a more effective SM solution. Therefore, the new paradigm for decision-making named "evidence-based practice (EBP)" can hold important implications for SM, because it uses the current best evidence for effective decision-making. Based on a systematic review of existing SM approaches and an analysis of reasons why we need new SM approaches, we created a new SM approach called evidence-based safety (EBS) management by introducing evidence-based practice into SM. It was necessary to create new SM approaches. A new SM approach called EBS was put forward, and the basic questions of EBS such as its definition and core were analyzed in detail. Moreover, the determinants of EBS included manager's attitudes towards EBS; evidence-based consciousness in SM; evidence sources; technical support; EBS human resources; organizational culture; and individual attributes. EBS is a new and effective approach to teaching the practice of SM. Of course, further research on EBS should be carried out to make EBS a reality. Practical applications: Our work can provide a new and effective idea and method to teach the practice of SM. Specifically, EBS proposed in our study can help safety professionals make an effective safety decision based on a firm foundation of high-grade evidence. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

Tau regulates the localization and function of End-binding proteins 1 and 3 in developing neuronal cells.

PubMed

Sayas, Carmen Laura; Tortosa, Elena; Bollati, Flavia; Ramírez-Ríos, Sacnicte; Arnal, Isabelle; Avila, Jesús

2015-06-01

The axonal microtubule-associated protein tau is a well-known regulator of microtubule stability in neurons. However, the putative interplay between tau and End-binding proteins 1 and 3 (EB1/3), the core microtubule plus-end tracking proteins, has not been elucidated yet. Here, we show that a cross-talk between tau and EB1/3 exists in developing neuronal cells. Tau and EBs partially colocalize at extending neurites of N1E-115 neuroblastoma cells and axons of primary hippocampal neurons, as shown by confocal immunofluorescence analyses. Tau down-regulation leads to a reduction of EB1/3 comet length, as observed in shRNA-stably depleted neuroblastoma cells and TAU-/- neurons. EB1/3 localization depends on the expression levels and localization of tau protein. Over-expression of tau at high levels induces EBs relocalization to microtubule bundles at extending neurites of N1E-115 cells. In differentiating primary neurons, tau is required for the proper accumulation of EBs at stretches of microtubule bundles at the medial and distal regions of the axon. Tau interacts with EB proteins, as shown by immunoprecipitation in different non-neuronal and neuronal cells and in whole brain lysates. A tau/EB1 direct interaction was corroborated by in vitro pull-down assays. Fluorescence recovery after photobleaching assays performed in neuroblastoma cells confirmed that tau modulates EB3 cellular mobility. In summary, we provide evidence of a new function of tau as a direct regulator of EB proteins in developing neuronal cells. This cross-talk between a classical microtubule-associated protein and a core microtubule plus-end tracking protein may contribute to the fine-tuned regulation of microtubule dynamics and stability during neuronal differentiation. We describe here a novel function for tau as a direct regulator of End binding (EB) proteins in differentiating neuronal cells. EB1/3 cellular mobility and localization in extending neurites and axons is modulated by tau levels and localization. We provide new evidence of the interplay between classical microtubule-associated proteins (MAPs) and "core" microtubule plus-end tracking proteins (+TIPs) during neuronal development. © 2015 International Society for Neurochemistry.

Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis

PubMed Central

Li, Jian; Pucéat, Michel; Perez-Terzic, Carmen; Mery, Annabelle; Nakamura, Kimitoshi; Michalak, Marek; Krause, Karl-Heinz; Jaconi, Marisa E.

2002-01-01

Calreticulin (crt) is an ubiquitously expressed and multifunctional Ca2+-binding protein that regulates diverse vital cell functions, including Ca2+ storage in the ER and protein folding. Calreticulin deficiency in mice is lethal in utero due to defects in heart development and function. Herein, we used crt − / − embryonic stem (ES) cells differentiated in vitro into cardiac cells to investigate the molecular mechanisms underlying heart failure of knockout embryos. After 8 d of differentiation, beating areas were prominent in ES-derived wild-type (wt) embryoid bodies (EBs), but not in ES-derived crt − / − EBs, despite normal expression levels of cardiac transcription factors. Crt − / − EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils. Crt − / − phenotype could be recreated in wt cells by chelating extracellular or cytoplasmic Ca2+ with EGTA or BAPTA, or by inhibiting Ca2+/calmodulin-dependent kinases (CaMKs). An imposed ionomycin-triggered cystolic-free Ca2+ concentration ([Ca2+]c) elevation restored the expression, phosphorylation, and insertion of MLC2v into sarcomeric structures and in turn the myofibrillogenesis. The transcription factor myocyte enhancer factor C2 failed to accumulate into nuclei of crt − / − cardiac cells in the absence of ionomycin-triggered [Ca2+]c increase. We conclude that the absence of calreticulin interferes with myofibril formation. Most importantly, calreticulin deficiency revealed the importance of a Ca2+-dependent checkpoint critical for early events during cardiac myofibrillogenesis. PMID:12105184

Estrogen-induced transcription factor EGR1 regulates c-Kit transcription in the mouse uterus to maintain uterine receptivity for embryo implantation.

PubMed

Park, Mira; Kim, Hye-Ryun; Kim, Yeon Sun; Yang, Seung Chel; Yoon, Jung Ah; Lyu, Sang Woo; Lim, Hyunjung Jade; Hong, Seok-Ho; Song, Haengseok

2018-07-15

Early growth response 1 (Egr1) is a key transcription factor that mediates the action of estrogen (E 2 ) to establish uterine receptivity for embryo implantation. However, few direct target genes of EGR1 have been identified in the uterus. Here, we demonstrated that E 2 induced EGR1-regulated transcription of c-Kit, which plays a crucial role in cell fate decisions. Spatiotemporal expression of c-Kit followed that of EGR1 in uteri of ovariectomized mice at various time points after E 2 treatment. E 2 activated ERK1/2 and p38 to induce EGR1, which then activated c-Kit expression in the uterus. EGR1 transfection produced rapid and transient induction of c-KIT in a time- and dose-dependent manner. Furthermore, luciferase assays to measure c-Kit promoter activity confirmed that a functional EGR1 binding site(s) (EBS) was located within -1 kb of the c-Kit promoter. Site-directed mutagenesis and chromatin immunoprecipitation-PCR for three putative EBS within -1 kb demonstrated that the EBS at -818/-805 was critical for EGR1-dependent c-Kit transcription. c-Kit expression was significantly increased in the uterus on day 4 and administration of Masitinib, a c-Kit inhibitor, effectively interfered with embryo implantation. Collectively, our results showed that estrogen induces transcription factor EGR1 to regulate c-Kit transcription for uterine receptivity for embryo implantation in the mouse uterus. Copyright © 2017 Elsevier B.V. All rights reserved.

Illitization within bentonite engineered barrier system in clay repositories for nuclear waste and its effect on the swelling stress: a coupled THMC modeling study

NASA Astrophysics Data System (ADS)

Zheng, L.; Rutqvist, J.; Birkholzer, J. T.; Liu, H. H.

2014-12-01

Geological repositories for disposal of high-level nuclear waste generally rely on a multi-barrier system to isolate radioactive waste from the biosphere. An engineered barrier system (EBS), which comprises in many design concepts a bentonite backfill, is widely used. Clay formations have been considered as a host rock throughout the world. Illitization, the transformation of smectite to illite, could compromise some beneficiary features of EBS bentonite and clay host rock such as sorption and swelling capacity. It is the major determining factor to establish the maximum design temperature of the repositories because it is believed that illitization could be greatly enhanced at temperatures higher than 100 oC. However, existing experimental and modeling studies on the occurrence of illitization and related performance impacts are not conclusive, in part because the relevant couplings between the thermal, hydrological, chemical, and mechanical (THMC) processes have not been fully represented in the models. Here we present a fully coupled THMC simulation study of a generic nuclear waste repository in a clay formation with a bentonite-backfilled EBS. Two scenarios were simulated for comparison: a case in which the temperature in the bentonite near the waste canister can reach about 200 oC and a case in which the temperature in the bentonite near the waste canister peaks at about 100 oC. The model simulations demonstrate that illitization is in general more significant under higher temperature. However, the quantity of illitization is affected by many chemical factors and therefore varies a great deal. The most important chemical factors are the concentration of K in the pore water as well as the abundance and dissolution rate of K-feldspar. For the particular case and bentonite properties studied, the reduction in swelling stress as a result of chemical changes vary from 2% up to 70% depending on chemical and temperature conditions, and key mechanical parameters. The modeling work is illustrative in light of the relative importance of different processes occurring in EBS bentonite and clay host rock at higher than 100 oC conditions, and could be of greater use when site specific data are available.

Production of double repeated B subunit of Shiga toxin 2e at high levels in transgenic lettuce plants as vaccine material for porcine edema disease.

PubMed

Matsui, Takeshi; Takita, Eiji; Sato, Toshio; Aizawa, Michie; Ki, Misa; Kadoyama, Yumiko; Hirano, Kenji; Kinjo, Satoko; Asao, Hiroshi; Kawamoto, Keiko; Kariya, Haruko; Makino, Sou-Ichi; Hamabata, Takashi; Sawada, Kazutoshi; Kato, Ko

2011-08-01

Pig edema disease is a bacterial disease caused by enterohemorrhagic Escherichia coli. E. coli produces Shiga toxin 2e (Stx2e), which is composed of one A subunit (Stx2eA) and five B subunits (Stx2eB). We previously reported production of Stx2eB in lettuce plants as a potential edible vaccine (Matsui et al. in Biosci Biotechnol Biochem 73:1628-1634, 2009). However, the accumulation level was very low, and it was necessary to improve expression of Stx2eB for potential use of this plant-based vaccine. Therefore, in this study, we optimized the Stx2eB expression cassette and found that a double repeated Stx2eB (2× Stx2eB) accumulates to higher levels than a single Stx2eB in cultured tobacco cells. Furthermore, a linker peptide between the two Stx2eB moieties played an important role in maximizing the effects of the double repeat. Finally, we generated transgenic lettuce plants expressing 2× Stx2eB with a suitable linker peptide that accumulate as much as 80 mg per 100 g fresh weight, a level that will allow us to use these transgenic lettuce plants practically to generate vaccine material.

Electric bicycle-related injuries presenting to a provincial hospital in China: A retrospective study.

PubMed

Zhou, Sheng Ang; Ho, Andrew Fu Wah; Ong, Marcus Eng Hock; Liu, Nan; Pek, Pin Pin; Wang, Yi Qing; Jin, Tao; Yan, Guang Zhao; Han, Nan Nan; Li, Gang; Xu, Li Ming; Cai, Wen Wei

2017-06-01

The use of electric bicycles (EBs) in China is growing. In the present study, we aimed to characterize the pattern and outcomes of EB-related injuries presenting to a major general hospital in China.This was a retrospective review of EB-related injuries presenting to Zhejiang Provincial People's Hospital from 2008 to 2011. Cases were identified from medical records according to diagnosis codes. Data captured included demographics, injury characteristics, and outcomes.A total of 3156 cases were reviewed in the present study. There were 1460 cases of traffic accidents, of which 482 cases were EB-related (32.7%). In addition, most of EB-related cases (44.6%) belonged to the 41- to 60-year-old age group. Median injury severity score was 10. Moreover, 34.9% underwent surgery and 24.7% were admitted to intensive care unit. The median hospitalization cost was 14,269 USD. Fracture (56.5%) was the most frequently diagnosed injury type, and head was the most commonly injured body region (31.1%).EB-related injuries have become a major health concern, making up a sizeable proportion of injuries presenting to the emergency department. Therefore, it is necessary to establish injury prevention and strategies for EB road safety. Implementation of policy such as compulsory helmet use, as well as popularization of EB road safety education should be considered to improve the current situation of EB-related injuries in China.

Dipole-induced exchange bias.

PubMed

Torres, Felipe; Morales, Rafael; Schuller, Ivan K; Kiwi, Miguel

2017-11-09

The discovery of dipole-induced exchange bias (EB), switching from negative to positive sign, is reported in systems where the antiferromagnet and the ferromagnet are separated by a paramagnetic spacer (AFM-PM-FM). The magnitude and sign of the EB is determined by the cooling field strength and the PM thickness. The same cooling field yields negative EB for thin spacers, and positive EB for thicker ones. The EB decay profile as a function of the spacer thickness, and the change of sign, are attributed to long-ranged dipole coupling. Our model, which accounts quantitatively for the experimental results, ignores the short range interfacial exchange interactions of the usual EB theories. Instead, it retains solely the long range dipole field that allows for the coupling of the FM and AFM across the PM spacer. The experiments allow for novel switching capabilities of long range EB systems, while the theory allows description of the structures where the FM and AFM are not in atomic contact. The results provide a new approach to design novel interacting heterostructures.

Evans Blue Dye: A Revisit of Its Applications in Biomedicine.

PubMed

Yao, Linpeng; Xue, Xing; Yu, Peipei; Ni, Yicheng; Chen, Feng

2018-01-01

Evans blue (EB) dye has owned a long history as a biological dye and diagnostic agent since its first staining application by Herbert McLean Evans in 1914. Due to its high water solubility and slow excretion, as well as its tight binding to serum albumin, EB has been widely used in biomedicine, including its use in estimating blood volume and vascular permeability, detecting lymph nodes, and localizing the tumor lesions. Recently, a series of EB derivatives have been labeled with PET isotopes and can be used as theranostics with a broad potential due to their improved half-life in the blood and reduced release. Some of EB derivatives have even been used in translational applications in clinics. In addition, a novel necrosis-avid feature of EB has recently been reported in some preclinical animal studies. Given all these interesting and important advances in EB study, a comprehensive revisiting of EB has been made in its biomedical applications in the review.

DDA3 associates with microtubule plus ends and orchestrates microtubule dynamics and directional cell migration

PubMed Central

Zhang, Liangyu; Shao, Hengyi; Zhu, Tongge; Xia, Peng; Wang, Zhikai; Liu, Lifang; Yan, Maomao; Hill, Donald L.; Fang, Guowei; Chen, Zhengjun; Wang, Dongmei; Yao, Xuebiao

2013-01-01

Cell motility and adhesion involve orchestrated interaction of microtubules (MTs) with their plus-end tracking proteins (+TIPs). However, the mechanisms underlying regulations of MT dynamics and directional cell migration are still elusive. Here, we show that DDA3-EB1 interaction orchestrates MT plus-end dynamics and facilitates directional cell migration. Biochemical characterizations reveal that DDA3 interacts with EB1 via its SxIP motif within the C-terminal Pro/Ser-rich region. Time-lapse and total internal reflection fluorescence (TIRF) microscopic assays demonstrate that DDA3 exhibits EB1-dependent, MT plus-end loading and tracking. The EB1-based loading of DDA3 is responsible for MT plus-ends stabilization at the cell cortex, which in turn orchestrates directional cell migration. Interestingly, the DDA3-EB1 interaction is potentially regulated by EB1 acetylation, which may account for physiological regulation underlying EGF-elicited cell migration. Thus, the EB1-based function of DDA3 links MT dynamics to directional cell migration. PMID:23652583

EB1 contributes to microtubule bundling and organization, along with root growth, in Arabidopsis thaliana.

PubMed

Molines, Arthur T; Marion, Jessica; Chabout, Salem; Besse, Laetitia; Dompierre, Jim P; Mouille, Grégory; Coquelle, Frédéric M

2018-06-26

Microtubules are involved in plant development and adaptation to their environment, but the sustaining molecular mechanisms remain elusive. Microtubule-End-Binding 1 (EB1) proteins participate in directional root growth in Arabidopsis thaliana. However, a connection to the underlying microtubule array has not been established yet. We show here that EB1 proteins contribute to the organization of cortical microtubules in growing epidermal plant cells, without significant modulation of microtubule dynamics. Using super-resolution STED microscopy and an original quantification approach, we also demonstrate a significant reduction of apparent microtubule bundling in cytoplasmic-EB1-deficient plants, suggesting a function for EB1 in the interaction between adjacent microtubules. Furthermore, we observed root growth defects in EB1-deficient plants, which are not related to cell division impairment. Altogether, our results support a role for EB1 proteins in root development, in part by maintaining the organization of cortical microtubules. © 2018. Published by The Company of Biologists Ltd.

Observations and NLTE modeling of Ellerman bombs

NASA Astrophysics Data System (ADS)

Berlicki, A.; Heinzel, P.

2014-07-01

Context. Ellerman bombs (EBs) are short-lived, compact, and spatially well localized emission structures that are observed well in the wings of the hydrogen Hα line. EBs are also observed in the chromospheric CaII lines and in UV continua as bright points located within active regions. Hα line profiles of EBs show a deep absorption at the line center and enhanced emission in the line wings with maxima around ±1 Å from the line center. Similar shapes of the line profiles are observed for the CaII IR line at 8542 Å. In CaII H and K lines the emission peaks are much stronger, and EBs emission is also enhanced in the line center. Aims: It is generally accepted that EBs may be considered as compact microflares located in lower solar atmosphere that contribute to the heating of these low-lying regions, close to the temperature minimum of the atmosphere. However, it is still not clear where exactly the emission of EBs is formed in the solar atmosphere. High-resolution spectrophotometric observations of EBs were used for determining of their physical parameters and construction of semi-empirical models. Obtained models allow us to determine the position of EBs in the solar atmosphere, as well as the vertical structure of the activated EB atmosphere Methods: In our analysis we used observations of EBs obtained in the Hα and CaII H lines with the Dutch Open Telescope (DOT). These one-hour long simultaneous sequences obtained with high temporal and spatial resolution were used to determine the line emissions. To analyze them, we used NLTE numerical codes for the construction of grids of 243 semi-empirical models simulating EBs structures. In this way, the observed emission could be compared with the synthetic line spectra calculated for all such models. Results: For a specific model we found reasonable agreement between the observed and theoretical emission and thus we consider such model as a good approximation to EBs atmospheres. This model is characterized by an enhanced temperature in the lower chromosphere and can be considered as a compact structure (hot spot), which is responsible for the emission observed in the wings of chromospheric lines, in particular in the Hα and CaII H lines. Conclusions: For the first time the set of two lines Hα and CaII H was used to construct semi-empirical models of EBs. Our analysis shows that EBs can be described by a "hot spot" model, with the temperature and/or density increase through a few hundred km atmospheric structure. We confirmed that EBs are located close to the temperature minimum or in the lower chromosphere. Two spectral features (lines in our case), observed simultaneously, significantly strengthen the constraints on a realistic model.

Impact of Active Metabolism on Chlamydia trachomatis Elementary Body Transcript Profile and Infectivity.

PubMed

Grieshaber, Scott; Grieshaber, Nicole; Yang, Hong; Baxter, Briana; Hackstadt, Ted; Omsland, Anders

2018-07-15

Bacteria of the genus Chlamydia include the significant human pathogens Chlamydia trachomatis and C. pneumoniae All chlamydiae are obligate intracellular parasites that depend on infection of a host cell and transition through a biphasic developmental cycle. Following host cell invasion by the infectious elementary body (EB), the pathogen transitions to the replicative but noninfectious reticulate body (RB). Differentiation of the RB back to the EB is essential to generate infectious progeny. While the EB form has historically been regarded as metabolically inert, maintenance of infectivity during incubation with specific nutrients has revealed active maintenance of the infectious phenotype. Using transcriptome sequencing, we show that the transcriptome of extracellular EBs incubated under metabolically stimulating conditions does not cluster with germinating EBs but rather with the transcriptome of EBs isolated directly from infected cells. In addition, the transcriptional profile of the extracellular metabolizing EBs more closely resembled that of EB production than germination. Maintenance of infectivity of extracellular EBs was achieved by metabolizing chemically diverse compounds, including glucose 6-phosphate, ATP, and amino acids, all of which can be found in extracellular environments, including mucosal secretions. We further show that the EB cell type actively maintains infectivity in the inclusion after terminal differentiation. Overall, these findings contribute to the emerging understanding that the EB cell form is actively maintained through metabolic processes after terminal differentiation to facilitate prolonged infectivity within the inclusion and under host cell free conditions, for example, following deposition at mucosal surfaces. IMPORTANCE Chlamydiae are obligate intracellular Gram-negative bacteria that are responsible for a wide range of diseases in both animal and human hosts. According to the Centers for Disease Control and Prevention, C. trachomatis is the most frequently reported sexually transmitted infection in the United States, costing the American health care system nearly $2.4 billion annually. Every year, there are over 4 million new cases of Chlamydia infections in the United States and an estimated 100 million cases worldwide. To cause disease, Chlamydia must successfully complete its complex biphasic developmental cycle, alternating between an infectious cell form (EB) specialized for initiating entry into target cells and a replicative form (RB) specialized for creating and maintaining the intracellular replication niche. The EB cell form has historically been considered metabolically quiescent, a passive entity simply waiting for contact with a host cell to initiate the next round of infection. Recent studies and data presented here demonstrate that the EB maintains its infectious phenotype by actively metabolizing a variety of nutrients. Therefore, the EB appears to have an active role in chlamydial biology, possibly within multiple environments, such as mucosal surfaces, fomites, and inside the host cell after formation. Copyright © 2018 American Society for Microbiology.

Identification of the IGF-1 processing product human Ec/rodent Eb peptide in various tissues: Evidence for its differential regulation after exercise-induced muscle damage in humans.

PubMed

Vassilakos, George; Philippou, Anastassios; Koutsilieris, Michael

2017-02-01

Insulin-like growth factor-1 (IGF-1) is a pleiotropic factor expressed in various tissues and plays a critical role in skeletal muscle physiology. Alternative splicing of the IGF-1 gene gives rise to different precursor polypeptides (isoforms) which could undergo post-translational cleavage, generating the common mature IGF-1 peptide and different carboxyl terminal extension (E-) peptides, with the fate of the latter being, so far, unknown. The objective if this study was to identify the IGF-1Ec forms or processing product(s), other than mature IGF-1, generated in different human and rodent tissues and particularly in human skeletal muscle after exercise-induced damage. Protein lysates from a wide range of human and rodent tissues were immunoblotted with a rabbit anti-human Ec polyclonal antibody raised against the last 24 amino acids of the C-terminal of the Ec peptide. This antibody can recognize the Ec peptide, both as part of IGF-1Ec and alone, and also the corresponding rodent forms, due to the high homology that the human Ec shares with the rodent Eb. We were able to confirm, for the first time, that the human Ec peptide and its rodent homologous Eb peptide are produced simultaneously with their precursor protein (pro-IGF-1Ec/Eb) in vivo, in a wide range of tissues (e.g. muscle, liver, heart). Proprotein convertase furin digestion of human muscle and liver protein lysates confirmed that the higher molecular form, pro-IGF-1Ec, can be cleaved to produce the free Ec peptide. Furthermore, initial evidence is provided that Ec peptide is differentially regulated during the process of muscle regeneration after exercise-induced damage in humans. The findings of this study possibly imply that the post-translational modification of the IGF-1Ec pro-peptide may regulate the bioavailability and activity of the processing product(s). Copyright © 2016. Published by Elsevier Ltd.

Loss of heme oxygenase-1 accelerates mesodermal gene expressions during embryoid body development from mouse embryonic stem cells.

PubMed

Lai, Yan-Liang; Lin, Chen-Yu; Jiang, Wei-Cheng; Ho, Yen-Chun; Chen, Chung-Huang; Yet, Shaw-Fang

2018-05-01

Heme oxygenase (HO)-1 is an inducible stress response protein and well known to protect cells and tissues against injury. Despite its important function in cytoprotection against physiological stress, the role of HO-1 in embryonic stem cell (ESC) differentiation remains largely unknown. We showed previously that induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant stress-induced cell death and more prone to lose pluripotent markers upon LIF withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out the controversy of potential gene flaws in iPS cells, we derived and established mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts. Using wild type D3 and HO-1 knockout ESCs in the 3-dimensional embryoid body (EB) differentiation model, we showed that at an early time point during EB development, an absence of HO-1 led to enhanced ROS level, concomitant with increased expressions of master mesodermal regulator brachyury and endodermal marker GATA6. In addition, critical smooth muscle cell (SMC) transcription factor serum response factor and its coactivator myocardin were enhanced. Furthermore, HO-1 deficiency increased Smad2 in ESCs and EBs, revealing a role of HO-1 in controlling Smad2 level. Smad2 not only mediates mesendoderm differentiation of mouse ESCs but also SMC development. Collectively, loss of HO-1 resulted in higher level of mesodermal and SMC regulators, leading to accelerated and enhanced SMC marker SM α-actin expression. Our results reveal a previously unrecognized function of HO-1 in regulating SMC gene expressions during ESC-EB development. More importantly, our findings may provide a novel strategy in enhancing ESC differentiation toward SMC lineage. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Regulated expression and role of c-Myb in the cardiovascular-directed differentiation of mouse embryonic stem cells.

PubMed

Ishida, Masayoshi; El-Mounayri, Omar; Kattman, Steven; Zandstra, Peter; Sakamoto, Hiroshi; Ogawa, Minetaro; Keller, Gordon; Husain, Mansoor

2012-01-20

c-myb null (knockout) embryonic stem cells (ESC) can differentiate into cardiomyocytes but not contractile smooth muscle cells (SMC) in embryoid bodies (EB). To define the role of c-Myb in SMC differentiation from ESC. In wild-type (WT) EB, high c-Myb levels on days 0-2 of differentiation undergo ubiquitin-mediated proteosomal degradation on days 2.5-3, resurging on days 4-6, without changing c-myb mRNA levels. Activin-A and bone morphogenetic protein 4-induced cardiovascular progenitors were isolated by FACS for expression of vascular endothelial growth factor receptor (VEGFR)2 and platelet-derived growth factor receptor (PDGFR)α. By day 3.75, hematopoesis-capable VEGFR2+ cells were fewer, whereas cardiomyocyte-directed VEGFR2+/PDGFRα+ cells did not differ in abundance in knockout versus WT EB. Importantly, highest and lowest levels of c-Myb were observed in VEGFR2+ and VEGFR2+/PDGFRα+ cells, respectively. Proteosome inhibitor MG132 and lentiviruses enabling inducible expression or knockdown of c-myb were used to regulate c-Myb in WT and knockout EB. These experiments showed that c-Myb promotes expression of VEGFR2 over PDGFRα, with chromatin immunopreciptation and promoter-reporter assays defining specific c-Myb-responsive binding sites in the VEGFR2 promoter. Next, FACS-sorted VEGFR2+ cells expressed highest and lowest levels of SMC- and fibroblast-specific markers, respectively, at days 7-14 after retinoic acid (RA) as compared with VEGFR2+/PDGFRα+ cells. By contrast, VEGFR2+/PDGFRα+ cells cultured without RA beat spontaneously, like cardiomyocytes between days 7 and 14, and expressed cardiac troponin. Notably, RA was required to more fully differentiate SMC from VEGFR2+ cells and completely blocked differentiation of cardiomyocytes from VEGFR2+/PDGFRα+ cells. c-Myb is tightly regulated by proteosomal degradation during cardiovascular-directed differentiation of ESC, expanding early-stage VEGFR2+ progenitors capable of RA-responsive SMC formation.

The EB factory project. II. Validation with the Kepler field in preparation for K2 and TESS

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

Parvizi, Mahmoud; Paegert, Martin; Stassun, Keivan G., E-mail: mahmoud.parvizi@vanderbilt.edu

Large repositories of high precision light curve data, such as the Kepler data set, provide the opportunity to identify astrophysically important eclipsing binary (EB) systems in large quantities. However, the rate of classical “by eye” human analysis restricts complete and efficient mining of EBs from these data using classical techniques. To prepare for mining EBs from the upcoming K2 mission as well as other current missions, we developed an automated end-to-end computational pipeline—the Eclipsing Binary Factory (EBF)—that automatically identifies EBs and classifies them into morphological types. The EBF has been previously tested on ground-based light curves. To assess the performancemore » of the EBF in the context of space-based data, we apply the EBF to the full set of light curves in the Kepler “Q3” Data Release. We compare the EBs identified from this automated approach against the human generated Kepler EB Catalog of ∼2600 EBs. When we require EB classification with ⩾90% confidence, we find that the EBF correctly identifies and classifies eclipsing contact (EC), eclipsing semi-detached (ESD), and eclipsing detached (ED) systems with a false positive rate of only 4%, 4%, and 8%, while complete to 64%, 46%, and 32%, respectively. When classification confidence is relaxed, the EBF identifies and classifies ECs, ESDs, and EDs with a slightly higher false positive rate of 6%, 16%, and 8%, while much more complete to 86%, 74%, and 62%, respectively. Through our processing of the entire Kepler “Q3” data set, we also identify 68 new candidate EBs that may have been missed by the human generated Kepler EB Catalog. We discuss the EBF's potential application to light curve classification for periodic variable stars more generally for current and upcoming surveys like K2 and the Transiting Exoplanet Survey Satellite.« less

The Eb Factory Project. Ii. Validation With the Kepler Field in Preparation for K2 and Tess

NASA Astrophysics Data System (ADS)

Parvizi, Mahmoud; Paegert, Martin; Stassun, Keivan G.

2014-12-01

Large repositories of high precision light curve data, such as the Kepler data set, provide the opportunity to identify astrophysically important eclipsing binary (EB) systems in large quantities. However, the rate of classical “by eye” human analysis restricts complete and efficient mining of EBs from these data using classical techniques. To prepare for mining EBs from the upcoming K2 mission as well as other current missions, we developed an automated end-to-end computational pipeline—the Eclipsing Binary Factory (EBF)—that automatically identifies EBs and classifies them into morphological types. The EBF has been previously tested on ground-based light curves. To assess the performance of the EBF in the context of space-based data, we apply the EBF to the full set of light curves in the Kepler “Q3” Data Release. We compare the EBs identified from this automated approach against the human generated Kepler EB Catalog of ˜ 2600 EBs. When we require EB classification with ≥slant 90% confidence, we find that the EBF correctly identifies and classifies eclipsing contact (EC), eclipsing semi-detached (ESD), and eclipsing detached (ED) systems with a false positive rate of only 4%, 4%, and 8%, while complete to 64%, 46%, and 32%, respectively. When classification confidence is relaxed, the EBF identifies and classifies ECs, ESDs, and EDs with a slightly higher false positive rate of 6%, 16%, and 8%, while much more complete to 86%, 74%, and 62%, respectively. Through our processing of the entire Kepler “Q3” data set, we also identify 68 new candidate EBs that may have been missed by the human generated Kepler EB Catalog. We discuss the EBF's potential application to light curve classification for periodic variable stars more generally for current and upcoming surveys like K2 and the Transiting Exoplanet Survey Satellite.

Dosimetric impact of tumor bed delineation variability based on 4DCT scan for external-beam partial breast irradiation.

PubMed

Guo, Bing; Li, Jianbin; Wang, Wei; Li, Fengxiang; Guo, Yanluan; Li, Yankang; Liu, Tonghai

2015-01-01

This study sought to evaluate the dosimetric impact of tumor bed delineation variability (based on clips, seroma or both clips and seroma) during external-beam partial breast irradiation (EB-PBI) planned utilizing four-dimensional computed tomography (4DCT) scans. 4DCT scans of 20 patients with a seroma clarity score (SCS) 3~5 and ≥5 surgical clips were included in this study. The combined volume of the tumor bed formed using clips, seroma, or both clips and seroma on the 10 phases of 4DCT was defined as the internal gross target volume (termed IGTVC, IGTVS and IGTVC+S, respectively). A 1.5-cm margin was added by defining the planning target volume (termed PTVC, PTVS and PTVC+S, respectively). Three treatment plans were established using the 4DCT images (termed EB-PBIC, EB-PBIS, EB-PBIC+S, respectively). The results showed that the volume of IGTVC+S was significantly larger than that of IGTVCand IGTVS. Similarly, the volume of PTVC+S was markedly larger than that of PTVC and PTVS. However, the PTV coverage for EB-PBIC+S was similar to that of EB-PBIC and EB-PBIS, and there were no significant differences in the homogeneity index or conformity index between the three treatment plans (P=0.878, 0.086). The EB-PBIS plan resulted in the lowest ipsilateral normal breast and ipsilateral lung doses compared with the EB-PBIC and EB-PBIC+S plans. To conclude, the volume variability delineated based on clips, seroma or both clips and seroma resulted in dosimetric variability for organs at risk, but did not show a marked influence on the dosimetric distribution.

Dosimetric impact of tumor bed delineation variability based on 4DCT scan for external-beam partial breast irradiation

PubMed Central

Guo, Bing; Li, Jianbin; Wang, Wei; Li, Fengxiang; Guo, Yanluan; Li, Yankang; Liu, Tonghai

2015-01-01

This study sought to evaluate the dosimetric impact of tumor bed delineation variability (based on clips, seroma or both clips and seroma) during external-beam partial breast irradiation (EB-PBI) planned utilizing four-dimensional computed tomography (4DCT) scans. 4DCT scans of 20 patients with a seroma clarity score (SCS) 3~5 and ≥5 surgical clips were included in this study. The combined volume of the tumor bed formed using clips, seroma, or both clips and seroma on the 10 phases of 4DCT was defined as the internal gross target volume (termed IGTVC, IGTVS and IGTVC+S, respectively). A 1.5-cm margin was added by defining the planning target volume (termed PTVC, PTVS and PTVC+S, respectively). Three treatment plans were established using the 4DCT images (termed EB-PBIC, EB-PBIS, EB-PBIC+S, respectively). The results showed that the volume of IGTVC+S was significantly larger than that of IGTVCand IGTVS. Similarly, the volume of PTVC+S was markedly larger than that of PTVC and PTVS. However, the PTV coverage for EB-PBIC+S was similar to that of EB-PBIC and EB-PBIS, and there were no significant differences in the homogeneity index or conformity index between the three treatment plans (P=0.878, 0.086). The EB-PBIS plan resulted in the lowest ipsilateral normal breast and ipsilateral lung doses compared with the EB-PBIC and EB-PBIC+S plans. To conclude, the volume variability delineated based on clips, seroma or both clips and seroma resulted in dosimetric variability for organs at risk, but did not show a marked influence on the dosimetric distribution. PMID:26885108

Observations of Ellerman bomb emission features in He I D3 and He I 10 830 Å

NASA Astrophysics Data System (ADS)

Libbrecht, Tine; Joshi, Jayant; Rodríguez, Jaime de la Cruz; Leenaarts, Jorrit; Ramos, Andrés Asensio

2017-02-01

Context. Ellerman bombs (EBs) are short-lived emission features, characterised by extended wing emission in hydrogen Balmer lines. Until now, no distinct signature of EBs has been found in the He I 10 830 Å line, and conclusive observations of EBs in He I D3 have never been reported. Aims: We aim to study the signature of EBs in neutral helium triplet lines. Methods: The observations consisted of ten consecutive SST/TRIPPEL raster scans close to the limb, featuring the Hβ, He I D3 and He I 10 830 Å spectral regions. We also obtained raster scans with IRIS and made use of the SDO/AIA 1700 Å channel. We used Hazel to invert the neutral helium triplet lines. Results: Three EBs in our data show distinct emission signatures in neutral helium triplet lines, most prominently visible in the He I D3 line. The helium lines have two components: a broad and blueshifted emission component associated with the EB, and a narrower absorption component formed in the overlying chromosphere. One of the EBs in our data shows evidence of strong velocity gradients in its emission component. The emission component of the other two EBs could be fitted using a constant slab. Our analysis hints towards thermal Doppler motions having a large contribution to the broadening for helium and IRIS lines. We conclude that the EBs must have high temperatures to exhibit emission signals in neutral helium triplet lines. An order of magnitude estimate places our observed EBs in the range of T 2 × 104-105 K. Movies associated to Figs. 3-5 are available at http://www.aanda.org

Phosphoproteomic analysis of the Chlamydia caviae elementary body and reticulate body forms

PubMed Central

Adams, Nancy E.; Maurelli, Anthony T.

2015-01-01

Chlamydia are Gram-negative, obligate intracellular bacteria responsible for significant diseases in humans and economically important domestic animals. These pathogens undergo a unique biphasic developmental cycle transitioning between the environmentally stable elementary body (EB) and the replicative intracellular reticulate body (RB), a conversion that appears to require extensive regulation of protein synthesis and function. However, Chlamydia possess a limited number of canonical mechanisms of transcriptional regulation. Ser/Thr/Tyr phosphorylation of proteins in bacteria has been increasingly recognized as an important mechanism of post-translational control of protein function. We utilized 2D gel electrophoresis coupled with phosphoprotein staining and MALDI-TOF/TOF analysis to map the phosphoproteome of the EB and RB forms of Chlamydia caviae. Forty-two non-redundant phosphorylated proteins were identified (some proteins were present in multiple locations within the gels). Thirty-four phosphorylated proteins were identified in EBs, including proteins found in central metabolism and protein synthesis, Chlamydia-specific hypothetical proteins and virulence-related proteins. Eleven phosphorylated proteins were identified in RBs, mostly involved in protein synthesis and folding and a single virulence-related protein. Only three phosphoproteins were found in both EB and RB phosphoproteomes. Collectively, 41 of 42 C. caviae phosphoproteins were present across Chlamydia species, consistent with the existence of a conserved chlamydial phosphoproteome. The abundance of stage-specific phosphoproteins suggests that protein phosphorylation may play a role in regulating the function of developmental-stage-specific proteins and/or may function in concert with other factors in directing EB–RB transitions. PMID:25998263

Epidermolysis bullosa care in Germany.

PubMed

Bruckner-Tuderman, Leena

2010-04-01

Until 2003, no structures existed in Germany for special care of patients with rare diseases, such as epidermolysis bullosa (EB). At that point, the Federal Ministry of Education and Research announced a clinical research program-networks for rare diseases. The Network Epidermolysis Bullosa (EB Network), coordinated from the Department of Dermatology, University Medical Center Freiburg, has operated since October 2003 with the goal of improving diagnostics and clinical management, elucidating disease mechanisms, and development of novel therapies for EB (www.netzwerk-eb.de). Future goals of the EB Network include securing the clinical-diagnostic and IT structures established with grant support and focusing research on molecular disease mechanisms in EB and novel biologically valid therapies. Intensive collaborations with other networks for rare genetic diseases will generate durable structures in Germany and form a basis for future international consortia. Copyright 2010 Elsevier Inc. All rights reserved.

Ellerman bombs observed with the new vacuum solar telescope and the atmospheric imaging assembly onboard the solar dynamics observatory

NASA Astrophysics Data System (ADS)

Chen, Yajie; Tian, Hui; Xu, Zhi; Xiang, Yongyuan; Fang, Yuliang; Yang, Zihao

2017-12-01

Ellerman bombs (EBs) are believed to be small-scale reconnection events occurring around the temperature minimum region in the solar atmosphere. They are often identified as significant enhancements in the extended Hα wings without obvious signatures in the Hα core. Here we explore the possibility of using the 1700 Å images taken by the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO) to study EBs. From the Hα wing images obtained with the New Vacuum Solar Telescope (NVST) on 2015 May 2, we have identified 145 EBs and 51% of them clearly correspond to the bright points (BPs) in the AIA 1700 Å images. If we resize the NVST images using a linear interpolation to make the pixel sizes of the AIA and NVST images the same, some previously identified EBs disappear and about 71% of the remaining EBs are associated with BPs. Meanwhile, 66% of the compact brightenings in the AIA 1700 Å images can be identified as EBs in the Hα wings. The intensity enhancements of the EBs in the Hα wing images reveal a linear correlation with those of the BPs in the AIA 1700 Å images. Our study suggests that a significant fraction of EBs can be observed with the AIA 1700 Å filter, which is promising for large-sample statistical study of EBs as the seeing-free and full-disk SDO/AIA data are routinely available.

Electric bicycle cost calculation models and analysis based on the social perspective in China.

PubMed

Yan, Xuetong; He, Jie; King, Mark; Hang, Wen; Zhou, Bojian

2018-05-10

Electric bicycles (EBs) are increasingly popular around the world. In April 2014, EB ownership in China reached 181 million. While some aspects of the impact of EBs have been studied, most of the literature analyzing the cost of EBs has been conducted from the buyer's point of view and the perspective of social cost has not been covered, which is therefore the focus of this paper. From the consumer's point of view, only the costs paid from purchase until retirement are included in the cost of EBs, i.e., the EB acquisition cost, battery replacement cost, charging cost, and repair and maintenance cost are included. Considered from the perspective of the social cost (including impact on the environment), costs that are not paid directly by consumers should also be included in the cost of EBs, i.e., the lead-acid battery scrap processing cost, the cost of pollution caused by wastewater, and the traffic-related costs. Data are obtained from secondary sources and surveys, and calculations demonstrate that in the life cycle of an EB, the consumer cost is 6386.2 CNY, the social cost is 10,771.2 CNY, and the ratio of consumer to social cost is 1:1.69. By comparison, the ratio for motor vehicles is 1:1.06, so that the share of the life cycle cost of EBs that is not borne by the consumer is much higher than that for motor vehicles, which needs to be addressed.

Prior minimal endoscopic sphincterotomy to prevent pancreatitis related to endoscopic balloon sphincteroplasty

PubMed Central

Kanazawa, Ryo; Sai, Jin Kan; Ito, Tomoyasu; Miura, Hiroko; Ishii, Shigeto; Saito, Hiroaki; Tomishima, Ko; Shimizu, Ryo; Sato, Koki; Hayashi, Manabu; Watanabe, Sumio; Shiina, Shuichiro

2016-01-01

AIM To investigate the efficacy of prior minimal endoscopic sphincterotomy (EST) to prevent pancreatitis related to endoscopic balloon sphincteroplasty (EBS). METHODS After bile duct access was gained and cholangiogram confirmed the presence of stones < 8 mm in the common bile duct at endoscopic retrograde cholangiography, patients were subjected to minimal EST (up to one-third of the size the papilla) plus 8 mm EBS (EST-EBS group). The incidence of pancreatitis and the difference in serum amylase level after the procedure were examined and compared with those associated with 8-mm EBS alone in 32 patients of historical control (control group). RESULTS One hundred and five patients were included in the EST-EBS group, and complete stone removal was accomplished in all of them. The difference in serum amylase level after the procedure was - 25.0 (217.9) IU/L in the EST-EBS group and this value was significantly lower than the 365.5 (576.3) IU/L observed in the control group (P < 0.001). The incidence of post-procedure pancreatitis was 0% (0/105) in the EST-EBS group and 15.6% (5/32) in the control group (P < 0.001). CONCLUSION Prior minimal EST might be useful to prevent the elevation of serum amylase level and the occurrence of pancreatitis related to EBS. PMID:27803773

Ethidium bromide as a marker of mtDNA replication in living cells

NASA Astrophysics Data System (ADS)

Villa, Anna Maria; Fusi, Paola; Pastori, Valentina; Amicarelli, Giulia; Pozzi, Chiara; Adlerstein, Daniel; Doglia, Silvia Maria

2012-04-01

Mitochondrial DNA (mtDNA) in tumor cells was found to play an important role in maintaining the malignant phenotype. Using laser scanning confocal fluorescence microscopy (LSCFM) in a recent work, we reported a variable fluorescence intensity of ethidium bromide (EB) in mitochondria nucleoids of living carcinoma cells. Since when EB is bound to nucleic acids its fluorescence is intensified; a higher EB fluorescence intensity could reflect a higher DNA accessibility to EB, suggesting a higher mtDNA replication activity. To prove this hypothesis, in the present work we studied, by LSCFM, the EB fluorescence in mitochondria nucleoids of living neuroblastoma cells, a model system in which differentiation affects the level of mtDNA replication. A drastic decrease of fluorescence was observed after differentiation. To correlate EB fluorescence intensity to the mtDNA replication state, we evaluated the mtDNA nascent strands content by ligation-mediated real-time PCR, and we found a halved amount of replicating mtDNA molecules in differentiating cells. A similar result was obtained by BrdU incorporation. These results indicate that the low EB fluorescence of nucleoids in differentiated cells is correlated to a low content of replicating mtDNA, suggesting that EB may be used as a marker of mtDNA replication in living cells.

The microtubule-associated protein EB1 maintains cell polarity through activation of protein kinase C.

PubMed

Schober, Joseph M; Kwon, Guim; Jayne, Debbie; Cain, Jeanine M

2012-01-06

The plus-ends of microtubules target the cell cortex to modulate actin protrusion dynamics and polarity, but little is known of the molecular mechanism that couples the interaction. EB1 protein associates with the plus-ends of microtubules, placing EB1 in an ideal spatial position to mediate microtubule-actin cross talk. The objective of the current study was to further understand intracellular signaling involved in EB1-dependent cell polarity and motility. B16F10 mouse melanoma cells were depleted of EB1 protein using short hair-pin RNA interference. Correlative live cell-immunofluorescence microscopy was performed to determine localization of WAVE2 and IQGAP1 to protruding versus retracting edges. EB1 knock down caused poor subcellular separation of WAVE2 and IQGAP1, and overall decreased localization. Activation of PKC corrected defects in WAVE2 and IQGAP1 localization, cell spreading and cell shape to levels observed in control cells, but did not correct defects in cell migration. Consistent with these findings, decreased PKC phosphorylation was observed in EB1 knock down cells. These findings support a model where EB1 protein links microtubules to actin protrusion and cell polarity through signaling pathways involving PKC. Copyright © 2011 Elsevier Inc. All rights reserved.

Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults.

PubMed

Karl, J Philip; Smith, Tracey J; Wilson, Marques A; Bukhari, Asma S; Pasiakos, Stefan M; McClung, Holly L; McClung, James P; Lieberman, Harris R

2016-04-01

Military personnel frequently endure intermittent periods of severe energy deficit which can compromise health and performance. Physiologic factors contributing to underconsumption, and the subsequent drive to overeat, are not fully characterized. This study aimed to identify associations between appetite, metabolic homeostasis and endocrine responses during and following severe, short-term energy deprivation. Twenty-three young adults (17M/6F, 21±3years, BMI 25±3kg/m(2)) participated in a randomized, controlled, crossover trial. During separate 48-h periods, participants increased habitual energy expenditure by 1647±345kcal/d (mean±SD) through prescribed exercise at 40-65% VO2peak, and consumed provided isovolumetric diets designed to maintain energy balance at the elevated energy expenditure (EB; 36±93kcal/d energy deficit) or to produce a severe energy deficit (ED; 3681±716kcal/d energy deficit). Appetite, markers of metabolic homeostasis and endocrine mediators of appetite and substrate availability were periodically measured. Ad libitum energy intake was measured over 36h following both experimental periods. Appetite increased during ED and was greater than during EB despite maintenance of diet volume (P=0.004). Ad libitum energy intake was 907kcal/36h [95% CI: 321, 1493kcal/36h, P=0.004] higher following ED compared to following EB. Serum beta-hydroxybutyrate, free fatty acids, branched-chain amino acids, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol concentrations were higher (P<0.001 for all), whereas whole-body protein balance was more negative (P<0.001), and serum glucose, insulin, and leptin concentrations were lower (P<0.001 for all) during ED relative to during EB. Cortisol concentrations, but not any other hormone or metabolic substrate, were inversely associated with satiety during EB (R(2)=0.23, P=0.04). In contrast, serum glucose and DHEA-S concentrations were inversely associated with satiety during ED (R(2)=0.68, P<0.001). No associations between physiologic variables measured during EB and ad libitum energy intake following EB were observed. However, serum leptin and net protein balance measured during ED were inversely associated with ad libitum energy intake following ED (R(2)=0.48, P=0.01). These findings suggest that changes in metabolic homeostasis during energy deprivation modulate appetite independent of reductions in diet volume. Following energy deprivation, physiologic signals of adipose and lean tissue loss may drive restoration of energy balance. www.clinicaltrials.gov #NCT01603550. Published by Elsevier Inc.

[Influence of high-voltage electric burn on the microcirculation of heart in rabbit].

PubMed

Zhang, Qing-fu; Zhou, Hui-min; Wang, Che-jiang; Shao, Hong-bo

2012-06-01

To study the influence of high-voltage electric burn on the microcirculation of heart in rabbit. One-hundred and twenty New Zealand rabbits of clean grade were divided into control group (C) and electric burn group (EB) according to the random number table, with 60 rabbits in each group. Rabbits in EB group were subjected to high-voltage electric burn (the electrical current flow into the left foreleg at the lateral side of proximal end and out from the corresponding site of the right hind leg) with voltage regulator and experimental transformer. Rabbits in C group were sham injured with the same devices without electrification. At 15 minutes before injury, and 5 minutes, 1, 2, 4, 8 hour (s) post injury (PIM or PIH), ten rabbits in each group were chosen to examine the cardiac apex microcirculation hemoperfusion (CAMH) with laser Doppler hemoperfusion image instrument. The morphologic changes of microvessels of left ventricular wall tissues of 2 rabbits from each of the 10 rabbits collected at above-mentioned time points were observed with light microscope and transmission electron microscope. Auricular vein blood of rabbit was harvested at above-mentioned time points for the determination of aspartate amino transferase (AST), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK), and creatine kinase isozyme MB (CK-MB) by full-automatic biochemical analyzer. Data were processed with two-factor analysis of variance and LSD test. (1) The differences between C group and EB group in detection results were statistically significant, with F values from 425.991 to 3046.834, P values all below 0.01. Only the data within EB group were comparable. (2) At PIM 5, the CAMH value of rabbits in EB group was (1.96 ± 0.09) V, which was lower than that at 15 minutes before injury [(4.34 ± 0.35) V, P < 0.01]. The CAMH value of rabbits in EB group was increased at PIH 1 [(3.43 ± 0.30) V], and then it showed a tendency of decrease. (3) Bleeding and microthrombus formation were observed in venule and capillary vessel of rabbits in EB group at PIH 8. Breakage of basement membrane of capillary endothelial cells, mitochondrial swelling, and severe degranulation from damaged endoplasmic reticulum were observed in rabbits of EB group at PIH 8. (4) Levels of AST, LDH, HBDH, CK, and CK-MB in rabbits of EB group were significantly higher at PIH 1, 2, 4, 8 than at 15 minutes before injury (with P values all below 0.01). The AST level peaked at PIH 2 [(164 ± 39) U/L]. Levels of LDH and HBDH peaked at PIH 4, which were respectively (1016 ± 246) U/L and (487 ± 54) U/L. The CK level peaked at PIH 8 [(7799 ± 738) U/L]. The CK-MB level peaked at PIH 2 [(1848 ± 65) U/L]. High-voltage electric burn can bring damage to the microvessels of heart in rabbits and change blood flow of microcirculation, which should be given adequate attention during the treatment.

Studies of interaction of emodin and DNA in the presence of ethidium bromide by spectroscopic method

NASA Astrophysics Data System (ADS)

Bi, Shuyun; Zhang, Hanqi; Qiao, Chunyu; Sun, Ying; Liu, Chunming

2008-01-01

Emodin interacting with deoxyribonucleic acid (DNA) has been studied by different spectroscopic techniques, such as fluorescence, ultraviolet and visible (UV-vis), and fourier transform infared (FT-IR) spectroscopies, using ethidium bromide (EB) as a fluorescence probe of DNA. The decrease in the fluorescence of DNA-EB system on addition of emodin shows that the fluorescence quenching of DNA-EB complex by emodin occurs. The binding constants of emodin with DNA in the presence of EB are 6.02 × 10 4, 9.20 × 10 4 and 1.17 × 10 5 L mol -1 at 20, 35 and 50 °C, respectively. FT-IR spectrum further suggests that both the phosphate groups and the bases of DNA react with emodin. The reaction of DNA with emodin in the presence of EB is affected by ionic strength and temperature. The values of melting temperature ( Tm) of DNA-EB complex and emodin-DNA-EB complexes were determined, respectively. From the experiment evidences, the major binding mode of emodin with DNA should be the groove binding.

Progress Towards Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015

PubMed Central

Uitto, Jouni; Tuderman, Leena Bruckner; Christiano, Angela M.; McGrath, John A.; Has, Cristina; South, Andrew P.; Kopelan, Brett; Robinson, E. Clare

2015-01-01

Epidermolysis bullosa (EB), a group of complex heritable blistering diseases, is the topic of triennial research meetings organized by DEBRA International, the umbrella of patient advocacy organizations. The DEBRA 2015 Research Conference, held in May 2015, brought together investigators and clinicians from around the world working at the forefront of EB research. Discussing the state-of-the-art approaches from a wide range of disciplines, there was a palpable excitement at this conference brought about by the optimism about applying new sequencing techniques, genome editing, protein replacement, autologous and allogeneic stem cell therapy, innovations in cancer biology, revertant mosaicism and iPSC techniques, all of which are aimed at developing new therapies for EB. Many in the field who have participated in EB research for many years were especially enthusiastic and felt that, possibly for the first time, the field seems uniquely poised to bring these new tools to effectively tackle EB using multiple complementary approaches towards improved quality of life and eventually a cure for patients suffering from EB, a currently intractable disease. PMID:26802230

Engineered Barrier System performance requirements systems study report. Revision 02

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

Balady, M.A.

This study evaluates the current design concept for the Engineered Barrier System (EBS), in concert with the current understanding of the geologic setting to assess whether enhancements to the required performance of the EBS are necessary. The performance assessment calculations are performed by coupling the EBS with the geologic setting based on the models (some of which were updated for this study) and assumptions used for the 1995 Total System Performance Assessment (TSPA). The need for enhancements is determined by comparing the performance assessment results against the EBS related performance requirements. Subsystem quantitative performance requirements related to the EBS includemore » the requirement to allow no more than 1% of the waste packages (WPs) to fail before 1,000 years after permanent closure of the repository, as well as a requirement to control the release rate of radionuclides from the EBS. The EBS performance enhancements considered included additional engineered components as well as evaluating additional performance available from existing design features but for which no performance credit is currently being taken.« less

An experimental investigation of wastewater treatment using electron beam irradiation

NASA Astrophysics Data System (ADS)

Emami-Meibodi, M.; Parsaeian, M. R.; Amraei, R.; Banaei, M.; Anvari, F.; Tahami, S. M. R.; Vakhshoor, B.; Mehdizadeh, A.; Fallah Nejad, N.; Shirmardi, S. P.; Mostafavi, S. J.; Mousavi, S. M. J.

2016-08-01

Electron beam (EB) is used for disinfection and treatment of different types of sewage and industrial wastewater. However, high capital investment required and the abundant energy consumed by this process raise doubts about its cost-effectiveness. In this paper, different wastewaters, including two textile sewages and one municipal wastewater are experimentally studied under different irradiation strategies (i.e. batch, 60 l/min and 1000 m3/day) in order to establish the reliability and the optimum conditions for the treatment process. According to the results, EB improves the efficiency of traditional wastewater treatment methods, but, for textile samples, coagulation before EB irradiation is recommended. The cost estimation of EB treatment compared to conventional methods shows that EB has been more expensive than chlorination and less expensive than activated sludge. Therefore, EB irradiation is advisable if and only if conventional methods of textile wastewater treatment are insufficient or chlorination of municipal wastewater is not allowed for health reasons. Nevertheless, among the advanced oxidation processes (AOP), EB irradiation process may be the most suitable one in industrial scale operations.

The laminar organization of the Drosophila ellipsoid body is semaphorin-dependent and prevents the formation of ectopic synaptic connections

PubMed Central

Xie, Xiaojun; Tabuchi, Masashi; Brown, Matthew P; Mitchell, Sarah P; Wu, Mark N; Kolodkin, Alex L

2017-01-01

The ellipsoid body (EB) in the Drosophila brain is a central complex (CX) substructure that harbors circumferentially laminated ring (R) neuron axons and mediates multifaceted sensory integration and motor coordination functions. However, what regulates R axon lamination and how lamination affects R neuron function remain unknown. We show here that the EB is sequentially innervated by small-field and large-field neurons and that early developing EB neurons play an important regulatory role in EB laminae formation. The transmembrane proteins semaphorin-1a (Sema-1a) and plexin A function together to regulate R axon lamination. R neurons recruit both GABA and GABA-A receptors to their axon terminals in the EB, and optogenetic stimulation coupled with electrophysiological recordings show that Sema-1a-dependent R axon lamination is required for preventing the spread of synaptic inhibition between adjacent EB lamina. These results provide direct evidence that EB lamination is critical for local pre-synaptic inhibitory circuit organization. DOI: http://dx.doi.org/10.7554/eLife.25328.001 PMID:28632130

A novel single walled carbon nanotube (SWCNT) functionalization agent facilitating in vivo combined chemo/thermo therapy

NASA Astrophysics Data System (ADS)

Zhang, Liwen; Rong, Pengfei; Chen, Minglong; Gao, Shi; Zhu, Lei

2015-10-01

Carbon nanotubes (CNTs) have shown intriguing applications in biotechnological and biomedical fields due to their unique shape and properties. However, the fact that unmodified CNTs are prone to aggregation, stunts CNTs applications under physiological conditions. In this research, we found that as little as 1/5th the single walled carbon nanotube (SWCNT) weight of Evans Blue (EB) is capable of dispersing SWCNT as well as facilitating SWCNT functionalization. In view of the binding between EB and albumin, the yielding product (SWCNT/EB) demonstrated extreme stability for weeks under physiological conditions and it can be endowed with a therapeutic ability by simply mixing SWCNT/EB with an albumin based drug. Specifically, the formed SWCNT/EB/albumin/PTX nanocomplex exhibits strong near-infrared (NIR) absorbance, and can serve as an agent for chemo/thermal therapeutic purposes. Our in vivo result reveals that SWCNT/EB/albumin/PTX after being administered into the MDA-MB-435 tumor would effectively ablate the tumor by chemo and photothermal therapy. Such a combined treatment strategy provides remarkable therapeutic outcomes in restraining tumor growth compared to chemo or photothermal therapy alone. Overall, our strategy of dispersing SWCNTs by EB can be used as a platform for carrying other drugs or functional genes with the aid of albumin to treat diseases. The present study opens new opportunities in surface modification of SWCNTs for future clinical disease treatment.Carbon nanotubes (CNTs) have shown intriguing applications in biotechnological and biomedical fields due to their unique shape and properties. However, the fact that unmodified CNTs are prone to aggregation, stunts CNTs applications under physiological conditions. In this research, we found that as little as 1/5th the single walled carbon nanotube (SWCNT) weight of Evans Blue (EB) is capable of dispersing SWCNT as well as facilitating SWCNT functionalization. In view of the binding between EB and albumin, the yielding product (SWCNT/EB) demonstrated extreme stability for weeks under physiological conditions and it can be endowed with a therapeutic ability by simply mixing SWCNT/EB with an albumin based drug. Specifically, the formed SWCNT/EB/albumin/PTX nanocomplex exhibits strong near-infrared (NIR) absorbance, and can serve as an agent for chemo/thermal therapeutic purposes. Our in vivo result reveals that SWCNT/EB/albumin/PTX after being administered into the MDA-MB-435 tumor would effectively ablate the tumor by chemo and photothermal therapy. Such a combined treatment strategy provides remarkable therapeutic outcomes in restraining tumor growth compared to chemo or photothermal therapy alone. Overall, our strategy of dispersing SWCNTs by EB can be used as a platform for carrying other drugs or functional genes with the aid of albumin to treat diseases. The present study opens new opportunities in surface modification of SWCNTs for future clinical disease treatment. Electronic supplementary information (ESI) available: Characterization of EB dispersed SWCNT; chemical structures of dyes applied for SWCNT dispersion; spectrum of EB/albumin; PTX loading efficiency onto albumin at different ratios. See DOI: 10.1039/c5nr03752b

Identification and characterization of OsEBS, a gene involved in enhanced plant biomass and spikelet number in rice.

PubMed

Dong, Xianxin; Wang, Xiaoyan; Zhang, Liangsheng; Yang, Zhengting; Xin, Xiaoyun; Wu, Shuang; Sun, Chuanqing; Liu, Jianxiang; Yang, Jinshui; Luo, Xiaojin

2013-12-01

Common wild rice (Oryza rufipogon Griff.) is an important genetic reservoir for rice improvement. We investigated a quantitative trait locus (QTL), qGP5-1, which is related to plant height, leaf size and panicle architecture, using a set of introgression lines of O. rufipogon in the background of the Indica cultivar Guichao2 (Oryza sativa L.). We cloned and characterized qGP5-1 and confirmed that the newly identified gene OsEBS (enhancing biomass and spikelet number) increased plant height, leaf size and spikelet number per panicle, leading to an increase in total grain yield per plant. Our results showed that the increased size of vegetative organs in OsEBS-expressed plants was enormously caused by increasing cell number. Sequence alignment showed that OsEBS protein contains a region with high similarity to the N-terminal conserved ATPase domain of Hsp70, but it lacks the C-terminal regions of the peptide-binding domain and the C-terminal lid. More results indicated that OsEBS gene did not have typical characteristics of Hsp70 in this study. Furthermore, Arabidopsis (Arabidopsis thaliana) transformed with OsEBS showed a similar phenotype to OsEBS-transgenic rice, indicating a conserved function of OsEBS among plant species. Together, we report the cloning and characterization of OsEBS, a new QTL that controls rice biomass and spikelet number, through map-based cloning, and it may have utility in improving grain yield in rice. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Current Status of Early Blight Resistance in Tomato: An Update

PubMed Central

Adhikari, Pragya; Oh, Yeonyee; Panthee, Dilip R.

2017-01-01

Early blight (EB) is one of the dreadful diseases of tomato caused by several species of Alternaria including Alternaria linariae (which includes A. solani and A. tomatophila), as well as A. alternata. In some instances, annual economic yield losses due to EB have been estimated at 79%. Alternaria are known only to reproduce asexually, but a highly-virulent isolate has the potential to overcome existing resistance genes. Currently, cultural practices and fungicide applications are employed for the management of EB due to the lack of strong resistant cultivars. Resistance sources have been identified in wild species of tomato; some breeding lines and cultivars with moderate resistance have been developed through conventional breeding methods. Polygenic inheritance of EB resistance, insufficient resistance in cultivated species and the association of EB resistance with undesirable horticultural traits have thwarted the effective breeding of EB resistance in tomato. Several quantitative trait loci (QTL) conferring EB resistance have been detected in the populations derived from different wild species including Solanum habrochaites, Solanum arcanum and S. pimpinellifolium, but none of them could be used in EB resistance breeding due to low individual QTL effects. Pyramiding of those QTLs would provide strong resistance. More research is needed to identify additional sources of useful resistance, to incorporate resistant QTLs into breeding lines through marker-assisted selection (MAS) and to develop resistant cultivars with desirable horticultural traits including high yielding potential and early maturity. This paper will review the current understanding of causal agents of EB of tomato, resistance genetics and breeding, problems associated with breeding and future prospects. PMID:28934121

Metabolic Features of Protochlamydia amoebophila Elementary Bodies – A Link between Activity and Infectivity in Chlamydiae

PubMed Central

Watzka, Margarete; Wultsch, Anna; Tziotis, Dimitrios; Montanaro, Jacqueline; Richter, Andreas; Schmitt-Kopplin, Philippe; Horn, Matthias

2013-01-01

The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from 13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide evidence that metabolic activity in the extracellular stage of chlamydiae is of major biological relevance as it is a critical factor affecting maintenance of infectivity. PMID:23950718

On-farm estimation of energy balance in dairy cows using only frequent body weight measurements and body condition score.

PubMed

Thorup, V M; Edwards, D; Friggens, N C

2012-04-01

Precise energy balance estimates for individual cows are of great importance to monitor health, reproduction, and feed management. Energy balance is usually calculated as energy input minus output (EB(inout)), requiring measurements of feed intake and energy output sources (milk, maintenance, activity, growth, and pregnancy). Except for milk yield, direct measurements of the other sources are difficult to obtain in practice, and estimates contain considerable error sources, limiting on-farm use. Alternatively, energy balance can be estimated from body reserve changes (EB(body)) using body weight (BW) and body condition score (BCS). Automated weighing systems exist and new technology performing semi-automated body condition scoring has emerged, so frequent automated BW and BCS measurements are feasible. We present a method to derive individual EB(body) estimates from frequently measured BW and BCS and evaluate the performance of the estimated EB(body) against the traditional EB(inout) method. From 76 Danish Holstein and Jersey cows, parity 1 or 2+, on a glycerol-rich or a whole grain-rich total mixed ration, BW was measured automatically at each milking. The BW was corrected for the weight of milk produced and for gutfill. Changes in BW and BCS were used to calculate changes in body protein, body lipid, and EB(body) during the first 150 d in milk. The EB(body) was compared with the traditional EB(inout) by isolating the term within EB(inout) associated with most uncertainty; that is, feed energy content (FEC); FEC=(EB(body)+EMilk+EMaintenance+Eactivity)/dry matter intake, where the energy requirements are for milk produced (EMilk), maintenance (EMaintenance), and activity (EActivity). Estimated FEC agreed well with FEC values derived from tables (the mean estimate was 0.21 MJ of effective energy/kg of dry matter or 2.2% higher than the mean table value). Further, the FEC profile did not suggest systematic bias in EB(body) with stage of lactation. The EB(body) estimated from daily BW, adjusted for milk and meal-related gutfill and combined with frequent BCS, can provide a successful tool. This offers a pragmatic solution to on-farm calculation of energy balance with the perspective of improved precision under commercial conditions. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Meeting Children's Needs.

ERIC Educational Resources Information Center

Keniston, Kenneth

1979-01-01

Until government policy puts greater emphasis on changing the social and economic factors that contribute so massively to family problems, our social programs will remain directed at healing wounds, not preventing them. More resources of money and authority are needed to strengthen parents' abilities to do their jobs. (Author/EB)

Nesprin provides elastic properties to muscle nuclei by cooperating with spectraplakin and EB1

PubMed Central

Wang, Shuoshuo; Reuveny, Adriana

2015-01-01

Muscle nuclei are exposed to variable cytoplasmic strain produced by muscle contraction and relaxation, but their morphology remains stable. Still, the mechanism responsible for maintaining myonuclear architecture, and its importance, is currently elusive. Herein, we uncovered a unique myonuclear scaffold in Drosophila melanogaster larval muscles, exhibiting both elastic features contributed by the stretching capacity of MSP300 (nesprin) and rigidity provided by a perinuclear network of microtubules stabilized by Shot (spectraplakin) and EB1. Together, they form a flexible perinuclear shield that protects myonuclei from intrinsic or extrinsic forces. The loss of this scaffold resulted in significantly aberrant nuclear morphology and subsequently reduced levels of essential nuclear factors such as lamin A/C, lamin B, and HP1. Overall, we propose a novel mechanism for maintaining myonuclear morphology and reveal its critical link to correct levels of nuclear factors in differentiated muscle fibers. These findings may shed light on the underlying mechanism of various muscular dystrophies. PMID:26008743

Enhanced backscatter of optical beams reflected in atmospheric turbulence

NASA Astrophysics Data System (ADS)

Nelson, W.; Palastro, J. P.; Wu, C.; Davis, C. C.

2014-10-01

Optical beams propagating through the atmosphere acquire phase distortions from turbulent fluctuations in the refractive index. While these distortions are usually deleterious to propagation, beams reflected in a turbulent medium can undergo a local recovery of spatial coherence and intensity enhancement referred to as enhanced backscatter (EBS). Using simulations, we investigate the EBS of optical beams reflected from mirrors, corner cubes, and rough surfaces, and identify the regimes in which EBS is most distinctly observed. Standard EBS detection requires averaging the reflected intensity over many passes through uncorrelated turbulence. Here we present an algorithm called the "tilt-shift method" which allows detection of EBS in static turbulence, improving its suitability for potential applications.

Photometric analysis of Ellerman bombs .

NASA Astrophysics Data System (ADS)

Berlicki, A.; Heinzel, P.; Avrett, E. H.

Observations of Ellerman bombs (EBs) show them as short-lived, compact, and spatially localized emissions that are well observable in the wings of the Halpha hydrogen line. The Halpha line profiles of EBs are characterized by deep absorption at the line center and enhanced emission in the wings with maximum around ± 1 Å from the line center, fading beyond ± 5 Å. EBs may also be observed in the chromospheric Ca II lines and in the UV as bright points often located within active regions. Previous work suggests that EBs may be considered as micro-flares and may contribute significantly to the heating of the lower chromosphere in newly emerging magnetic flux regions. However, it is still not clear at what height in the solar atmosphere the emission of EBs originates. In our analysis we used observations of EBs obtained in the Halpha line with the Dutch Open Telescope (DOT) and in the UV range with the TRACE 1600 Å channel. These one-hour long simultaneous sequences obtained with high temporal and spatial resolution were used to analyze the relation between the emission in the Halpha line and at 1600 Å. The observations show fast variations of EB emission in both channels. Comparison between the observed emission in Halpha and at 1600 Å and theoretical calculations allowed us to draw conclusions about the vertical structure of EBs.

Akap350 Recruits Eb1 to The Spindle Poles, Ensuring Proper Spindle Orientation and Lumen Formation in 3d Epithelial Cell Cultures.

PubMed

Almada, Evangelina; Tonucci, Facundo M; Hidalgo, Florencia; Ferretti, Anabela; Ibarra, Solange; Pariani, Alejandro; Vena, Rodrigo; Favre, Cristián; Girardini, Javier; Kierbel, Arlinet; Larocca, M Cecilia

2017-11-02

The organization of epithelial cells to form hollow organs with a single lumen requires the accurate three-dimensional arrangement of cell divisions. Mitotic spindle orientation is defined by signaling pathways that provide molecular links between specific spots at the cell cortex and astral microtubules, which have not been fully elucidated. AKAP350 is a centrosomal/Golgi scaffold protein, implicated in the regulation of microtubule dynamics. Using 3D epithelial cell cultures, we found that cells with decreased AKAP350 expression (AKAP350KD) formed polarized cysts with abnormal lumen morphology. Analysis of mitotic cells in AKAP350KD cysts indicated defective spindle alignment. We established that AKAP350 interacts with EB1, a microtubule associated protein that regulates spindle orientation, at the spindle poles. Decrease of AKAP350 expression lead to a significant reduction of EB1 levels at spindle poles and astral microtubules. Conversely, overexpression of EB1 rescued the defective spindle orientation induced by deficient AKAP350 expression. The specific delocalization of the AKAP350/EB1complex from the centrosome decreased EB1 levels at astral microtubules and lead to the formation of 3D-organotypic structures which resembled AKAP350KD cysts. We conclude that AKAP350 recruits EB1 to the spindle poles, ensuring EB1 presence at astral microtubules and proper spindle orientation during epithelial morphogenesis.

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases.

PubMed

Lee, Brendon W H; Tan, Jeremy C K; Radjenovic, Melissa; Coroneo, Minas T; Murrell, Dedee F

2018-05-22

Epidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surface disease (OSD) may occur in both and require ophthalmological assessment. Disease scoring systems have a critical role in providing objective and accurate assessment of disease severity. The objectives of this report were, firstly, to document the prevalence and severity of ocular involvement in EB/AIBD. Secondly, to review and evaluate existing ocular and systemic scoring systems for EB/AIBD. Finally, to identify areas where further development of ocular specific tools in EB/AIBD could be pursued. A literature search was performed in October 2017 utilising Medline, Embase, and Scopus databases. The results were restricted by date of publication, between 01.01.1950 and 31.10.2017. The reference lists of these articles were then reviewed for additional relevant publications. Articles of all languages were included if an English translation was available. Articles were excluded if they were duplicates, had no reference to ocular involvement in EB/AIBD or described ocular involvement in other diseases. Descriptions of ocular involvement in EB/AIBD were identified in 88 peer-reviewed journal articles. Findings reported include but are not limited to: cicatrising conjunctivitis, meibomian gland dysfunction, dry eye disease, trichiasis, symblepharon, fornix fibrosis, keratopathy, ectropion/entropion, ankyloblepharon, corneal ulceration, visual impairment and blindness. Although scoring systems exist for assessment of OSD in mucous membrane pemphigoid, no such tools exist for the other AIBD subtypes or for EB. Several systemic scoring systems exist in the dermatological literature that are efficacious in grading overall EB/AIBD severity, but have limited inclusion of ocular features. To the best of our knowledge, there is no recognised or validated scoring systems which comprehensively stages or grades the spectrum of ocular manifestations in EB/AIBD. There are a range of ocular complications documented in EB and AIBD. Development of a comprehensive ocular scoring system for EB/AIBD which incorporates the delineation between 'activity' and 'damage' would facilitate more objective patient assessment, improved longitudinal monitoring, comparison of intervention outcomes, and provide commonality for discussion of these patients due to the multidisciplinary nature of their care.

47 CFR 27.1203 - EBS programming requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false EBS programming requirements. 27.1203 Section 27.1203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES....1203 EBS programming requirements. (a) Except as provided in paragraphs (b), (c), and (d) of this...

Shewanella canadensis sp. nov. and Shewanella atlantica sp. nov., manganese dioxide- and hexahydro-1,3,5-trinitro-1,3,5-triazine-reducing, psychrophilic marine bacteria.

PubMed

Zhao, Jian-Shen; Manno, Dominic; Thiboutot, Sonia; Ampleman, Guy; Hawari, Jalal

2007-09-01

Two strains belonging to the genus Shewanella, HAW-EB2(T) and HAW-EB5(T), were isolated previously from marine sediment sampled from the Atlantic Ocean, near Halifax harbour in Canada, for their potential to degrade explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). In the present study, strains HAW-EB2(T) and HAW-EB5(T) were found to display high 16S rRNA gene sequence similarity (90-99.5 %) to species of Shewanella, but their gyrB sequences were significantly different from each other and from species of Shewanella (79-87.6 %). Furthermore, DNA-DNA hybridization showed that the genomic DNA of the two strains was only 22 % related and showed less than 41 % relatedness to closely related species of Shewanella. In comparison to other species of Shewanella, strains HAW-EB2(T) and HAW-EB5(T) were also unique in some phenotypic properties such as activities of beta-galactosidase and tyrosine arylamidase and the ability to metabolize certain organic acids and sugars. Both strains HAW-EB2(T) and HAW-EB5(T) utilize malate, valerate, peptone and yeast extract as sole carbon and energy sources. The major membrane fatty acids of the two strains were C(14 : 0), iso-C(15 : 0), C(16 : 0), C(16 : 1)omega7, C(18 : 1)omega7 and C(20 : 5)omega3 and their major quinones were Q-7, Q-8 and MK-7. On the basis of these results, strain HAW-EB2(T) (=NCIMB 14238(T) =CCUG 54553(T)) is proposed as the type strain of Shewanella canadensis sp. nov. and strain HAW-EB5(T) (=NCIMB 14239(T) =CCUG 54554(T)) is proposed as the type strain of Shewanella atlantica sp. nov.

Quantitation of DNA Adducts Induced by 1,3-Butadiene

NASA Astrophysics Data System (ADS)

Sangaraju, Dewakar; Villalta, Peter W.; Wickramaratne, Susith; Swenberg, James; Tretyakova, Natalia

2014-07-01

Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI+-HRMS3 analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub-ppm concentrations of BD (0.5-1.5 ppm). EB-GII concentrations increased linearly from 1.15 ± 0.23 to 10.11 ± 0.45 adducts per 106 nucleotides in HT1080 cells treated with 0.5-10 μM DEB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17 ± 0.05, 0.33 ± 0.08, and 0.50 ± 0.04 adducts per 106 nucleotides, respectively. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20 ± 0.12 d) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI+-HRMS3 Orbitrap methodology to quantitative analysis of DNA adducts in vivo.

Application of a non-hazardous vital dye for cell counting with automated cell counters.

PubMed

Kim, Soo In; Kim, Hyun Jeong; Lee, Ho-Jae; Lee, Kiwon; Hong, Dongpyo; Lim, Hyunchang; Cho, Keunchang; Jung, Neoncheol; Yi, Yong Weon

2016-01-01

Recent advances in automated cell counters enable us to count cells more easily with consistency. However, the wide use of the traditional vital dye trypan blue (TB) raises environmental and health concerns due to its potential teratogenic effects. To avoid this chemical hazard, it is of importance to introduce an alternative non-hazardous vital dye that is compatible with automated cell counters. Erythrosin B (EB) is a vital dye that is impermeable to biological membranes and is used as a food additive. Similarly to TB, EB stains only nonviable cells with disintegrated membranes. However, EB is less popular than TB and is seldom used with automated cell counters. We found that cell counting accuracy with EB was comparable to that with TB. EB was found to be an effective dye for accurate counting of cells with different viabilities across three different automated cell counters. In contrast to TB, EB was less toxic to cultured HL-60 cells during the cell counting process. These results indicate that replacing TB with EB for use with automated cell counters will significantly reduce the hazardous risk while producing comparable results. Copyright © 2015 Logos Biosystems, Inc. Published by Elsevier Inc. All rights reserved.

Restrictions in oral functions caused by oral manifestations of epidermolysis bullosa.

PubMed

Stellingsma, Cornelis; Dijkstra, Pieter U; Dijkstra, Janke; Duipmans, José C; Jonkman, Marcel F; Dekker, Rienk

2011-01-01

Several forms of epidermolysis bullosa (EB) present oral manifestations. Blistering of the (peri)oral mucosa affects the opening of the mouth, the mobility of the tongue and lips, thereby restricting oral functions. We describe the prevalence and characteristics of oral manifestations of EB in relation to loss of oral functions in a cross-sectional study of different types of EB patients using standardized measurement techniques. Twenty-two patients were included. The mobility of the mandible, lips and tongue was measured, the mandibular function impairment questionnaire (MFIQ) was filled out and additional questions regarding hindrance of EB during oral hygiene and intelligibility of speech (being understood) were asked in structured interviews. The median age was 11.8 yrs. Mobility of the mandible, tongue and lip was restricted, oral hygiene procedures were hindered in most patients. A data comparison was made between the recessive dystrophic EB (RDEB) and junctional EB (JEB) groups. Mandibular function was impaired in both groups but more severely in the RDEB-population. Intelligibility in both groups was almost unaffected. Restrictions in mobility of the mouth, tongue and lips are frequently present in EB patients. These are most severe in the RDEB group and support the clinical relevance of optimizing symptomatic treatment.

Induction of cytoplasmic petite in yeast by guanidine hydrochloride: combined treatment with other inducing agents.

PubMed

Villa, L L; Juliani, M H

1980-06-01

We have studied the induction of rho- mutants by guanidine hydrochloride (GuHCl) in combination with other known inducers: ethidium bromide (EB), berenil and ultraviolet light. Competition was observed when cells were simultaneously treated with optimal concentrations of EB and GuHCl; on the other hand, treatment of cells with EB in the presence of non-inducing concentrations of GuHCl resulted in the stimulation of rho- induction of EB. Furthermore, using a strain which upon treatment with high EB concentrations shows recovery of respiratory competence, the presence of GuHCl did not interfere either with the early phase of induction or with the recovery phase, but it did interfere in a competitive fashion with the final irreversible phase of EB induction. In the case of berenil, a synergistic effect was seen when cells were pretreated with GuHCl. A synergistic induction was also observed when cells were submitted to UV prior to GuHCl treatment. These results suggest that GuHCl, EB and berenil act via some common step in their rho- induction pathways. Moreover, GuHCl may somehow be decreasing the efficiency of dark repair of ultraviolet lesions on mitochondrial DNA.

Quantitative Glycoproteomics Analysis Reveals Changes in N-Glycosylation Level Associated with Pancreatic Ductal Adenocarcinoma

PubMed Central

2015-01-01

Glycosylation plays an important role in epithelial cancers, including pancreatic ductal adenocarcinoma. However, little is known about the glycoproteome of the human pancreas or its alterations associated with pancreatic tumorigenesis. Using quantitative glycoproteomics approach, we investigated protein N-glycosylation in pancreatic tumor tissue in comparison with normal pancreas and chronic pancreatitis tissue. The study lead to the discovery of a roster of glycoproteins with aberrant N-glycosylation level associated with pancreatic cancer, including mucin-5AC (MUC5AC), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), insulin-like growth factor binding protein (IGFBP3), and galectin-3-binding protein (LGALS3BP). Pathway analysis of cancer-associated aberrant glycoproteins revealed an emerging phenomenon that increased activity of N-glycosylation was implicated in several pancreatic cancer pathways, including TGF-β, TNF, NF-kappa-B, and TFEB-related lysosomal changes. In addition, the study provided evidence that specific N-glycosylation sites within certain individual proteins can have significantly altered glycosylation occupancy in pancreatic cancer, reflecting the complexity of the molecular mechanisms underlying cancer-associated glycosylation events. PMID:24471499

Quantitative glycoproteomics analysis reveals changes in N-glycosylation level associated with pancreatic ductal adenocarcinoma.

PubMed

Pan, Sheng; Chen, Ru; Tamura, Yasuko; Crispin, David A; Lai, Lisa A; May, Damon H; McIntosh, Martin W; Goodlett, David R; Brentnall, Teresa A

2014-03-07

Glycosylation plays an important role in epithelial cancers, including pancreatic ductal adenocarcinoma. However, little is known about the glycoproteome of the human pancreas or its alterations associated with pancreatic tumorigenesis. Using quantitative glycoproteomics approach, we investigated protein N-glycosylation in pancreatic tumor tissue in comparison with normal pancreas and chronic pancreatitis tissue. The study lead to the discovery of a roster of glycoproteins with aberrant N-glycosylation level associated with pancreatic cancer, including mucin-5AC (MUC5AC), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), insulin-like growth factor binding protein (IGFBP3), and galectin-3-binding protein (LGALS3BP). Pathway analysis of cancer-associated aberrant glycoproteins revealed an emerging phenomenon that increased activity of N-glycosylation was implicated in several pancreatic cancer pathways, including TGF-β, TNF, NF-kappa-B, and TFEB-related lysosomal changes. In addition, the study provided evidence that specific N-glycosylation sites within certain individual proteins can have significantly altered glycosylation occupancy in pancreatic cancer, reflecting the complexity of the molecular mechanisms underlying cancer-associated glycosylation events.

Transcriptional control of the autophagy-lysosome system in pancreatic cancer

PubMed Central

Perera, Rushika M.; Stoykova, Svetlana; Nicolay, Brandon N.; Ross, Kenneth N.; Fitamant, Julien; Boukhali, Myriam; Lengrand, Justine; Deshpande, Vikram; Selig, Martin K.; Ferrone, Cristina R.; Settleman, Jeff; Stephanopoulos, Gregory; Dyson, Nicholas J.; Zoncu, Roberto; Ramaswamy, Sridhar; Haas, Wilhelm; Bardeesy, Nabeel

2016-01-01

Activation of cellular stress response pathways to maintain metabolic homeostasis is emerging as a critical growth and survival mechanism in many cancers1. The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy2–4, a conserved self-degradative process5. However, the regulatory circuits that activate autophagy and reprogram PDA cell metabolism are unknown. We now show that autophagy induction in PDA occurs as part of a broader transcriptional program that coordinates activation of lysosome biogenesis and function, and nutrient scavenging, mediated by the MiT/TFE family transcription factors. In PDA cells, the MiT/TFE proteins6 – MITF, TFE3 and TFEB – are decoupled from regulatory mechanisms that control their cytoplasmic retention. Increased nuclear import in turn drives the expression of a coherent network of genes that induce high levels of lysosomal catabolic function essential for PDA growth. Unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosomal activation is specifically required to maintain intracellular amino acid (AA) pools. These results identify the MiT/TFE transcription factors as master regulators of metabolic reprogramming in pancreatic cancer and demonstrate activation of clearance pathways converging on the lysosome as a novel hallmark of aggressive malignancy. PMID:26168401

Distinct retroelement classes define evolutionary breakpoints demarcating sites of evolutionary novelty

PubMed Central

Longo, Mark S; Carone, Dawn M; Green, Eric D; O'Neill, Michael J; O'Neill, Rachel J

2009-01-01

Background Large-scale genome rearrangements brought about by chromosome breaks underlie numerous inherited diseases, initiate or promote many cancers and are also associated with karyotype diversification during species evolution. Recent research has shown that these breakpoints are nonrandomly distributed throughout the mammalian genome and many, termed "evolutionary breakpoints" (EB), are specific genomic locations that are "reused" during karyotypic evolution. When the phylogenetic trajectory of orthologous chromosome segments is considered, many of these EB are coincident with ancient centromere activity as well as new centromere formation. While EB have been characterized as repeat-rich regions, it has not been determined whether specific sequences have been retained during evolution that would indicate previous centromere activity or a propensity for new centromere formation. Likewise, the conservation of specific sequence motifs or classes at EBs among divergent mammalian taxa has not been determined. Results To define conserved sequence features of EBs associated with centromere evolution, we performed comparative sequence analysis of more than 4.8 Mb within the tammar wallaby, Macropus eugenii, derived from centromeric regions (CEN), euchromatic regions (EU), and an evolutionary breakpoint (EB) that has undergone convergent breakpoint reuse and past centromere activity in marsupials. We found a dramatic enrichment for long interspersed nucleotide elements (LINE1s) and endogenous retroviruses (ERVs) and a depletion of short interspersed nucleotide elements (SINEs) shared between CEN and EBs. We analyzed the orthologous human EB (14q32.33), known to be associated with translocations in many cancers including multiple myelomas and plasma cell leukemias, and found a conserved distribution of similar repetitive elements. Conclusion Our data indicate that EBs tracked within the class Mammalia harbor sequence features retained since the divergence of marsupials and eutherians that may have predisposed these genomic regions to large-scale chromosomal instability. PMID:19630942

Diversity of Endophytic Bacteria in a Fern Species Dryopteris uniformis (Makino) Makino and Evaluation of Their Antibacterial Potential Against Five Foodborne Pathogenic Bacteria.

PubMed

Das, Gitishree; Park, Seonjoo; Baek, Kwang-Hyun

2017-05-01

The fern plant Dryopteris uniformis has traditionally been used in herbal medicine and possesses many biological activities. This study was conducted to explore the endophytic bacterial diversity associated with D. uniformis and evaluate their antibacterial potential against foodborne pathogenic bacteria (FPB). Among 51 isolated endophytic bacteria (EB), 26 EB were selected based on their morphological characteristics and identified by 16S rRNA gene analysis. The distribution of EB was diverse in the leaf and the stem/root tissues. When the EB were screened for antibacterial activity against five FPB, Listeria monocytogenes, Salmonella Typhimurium, Bacillus cereus, Staphylococcus aureus, and Escherichia coli O157:H7, four EB Bacillus sp. cryopeg, Paenibacillus sp. rif200865, Staphylococcus warneri, and Bacillus psychrodurans had a broad spectrum of antibacterial activity (9.58 ± 0.66 to 21.47 ± 0.27 mm inhibition zone). The butanol solvent extract of B. sp. cryopeg and P. sp. rif200865 displayed effective antibacterial activity against the five FPB, which was evident from the scanning electron microscopy with irregular or burst cell morphology in the EB-treated bacteria compared to smooth and regular cells in case of the control bacteria. The minimum inhibitory concentration and minimum bactericidal concentration values ranged between 250-500 μg/mL and 500-100 μg/mL, respectively. The above outcomes signify the huge prospective of the selected EB in the food industry. Overall, the above results suggested that D. uniformis contains several culturable EB that possess effective antibacterial compounds, and that EB can be utilized as a source of natural antibacterial agents for their practical application in food industry to control the spread of FPB as a natural antibacterial agent.

Producing and marketing a specialty egg.

PubMed

Michella, S M; Slaugh, B T

2000-07-01

Eggland's Best, Inc. markets premium quality shell eggs under the Eggland's Best (EB) brand name. The company, started in 1988, is comprised of a franchise network of established egg producers and covers most of the United States. Eggland's Best provides its franchisees with marketing and technical support. The franchisees produce, process, and distribute EB eggs according to the strict program established and monitored by EB. Production follows the all-natural vegetarian feed program in accordance with the company's US patent entitled "Eggs Compatible with a Cholesterol Reducing Diet and Method of Producing the Same." The EB program excludes animal fat and other animal byproducts. Eggland's Best eggs have seven times the generic level of vitamin E, nearly three times more omega-3 fatty acids and iodine, and 25% less saturated fat than regular generic eggs. Eggland's Best has one of the finest shell egg quality assurance programs anywhere. Eggland's Best franchisees submit weekly egg samples that are analyzed for shell quality, interior quality, vitamin E, iodine, cholesterol and fatty acids. Samples of feed and the EB-patented feed supplement are also analyzed. Approximately 28,000 total laboratory tests are conducted annually. Nationwide product and display retail evaluations are contracted through an outside audit company (40 to 50 cities evaluated four times per year). All EB eggs are USDA graded according to EB's strict quality standards. Producers must follow a food safety quality assurance program (United Egg Producers Association 5-Star or equivalent state or company program). Each egg is stamped "EB" as assurance of meeting EB's highest standards of flavor, quality, and nutrition. Eggland's Best has enjoyed record sales growth for the past 3 yr.

Self-organization phenomena in embryonic stem cell-derived embryoid bodies: axis formation and breaking of symmetry during cardiomyogenesis.

PubMed

Fuchs, Christiane; Scheinast, Matthias; Pasteiner, Waltraud; Lagger, Sabine; Hofner, Manuela; Hoellrigl, Alexandra; Schultheis, Martina; Weitzer, Georg

2012-01-01

Aggregation of embryonic stem cells gives rise to embryoid bodies (EBs) which undergo developmental processes reminiscent of early eutherian embryonic development. Development of the three germ layers suggests that gastrulation takes place. In vivo, gastrulation is a highly ordered process but in EBs only few data support the hypothesis that self-organization of differentiating cells leads to morphology, reminiscent of the early gastrula. Here we demonstrate that a timely implantation-like process is a prerequisite for the breaking of the radial symmetry of suspended EBs. Attached to a surface, EBs develop a bilateral symmetry and presumptive mesodermal cells emerge between the center of the EBs and a horseshoe-shaped ridge of cells. The development of an epithelial sheet of cells on one side of the EBs allows us to define an 'anterior' and a 'posterior' end of the EBs. In the mesodermal area, first cardiomyocytes (CMCs) develop mainly next to this epithelial sheet of cells. Development of twice as many CMCs at the 'left' side of the EBs breaks the bilateral symmetry and suggests that cardiomyogenesis reflects a local or temporal asymmetry in EBs. The asymmetric appearance of CMCs but not the development of mesoderm can be disturbed by ectopic expression of the muscle-specific protein Desmin. Later, the bilateral morphology becomes blurred by an apparently chaotic differentiation of many cell types. The absence of comparable structures in aggregates of cardiovascular progenitor cells isolated from the heart demonstrates that the self-organization of cells during a gastrulation-like process is a unique feature of embryonic stem cells. Copyright © 2011 S. Karger AG, Basel.

Photoacoustic imaging of intravenously injected photosensitizer in rat burn models for efficient antibacterial photodynamic therapy

NASA Astrophysics Data System (ADS)

Tsunoi, Yasuyuki; Sato, Shunichi; Ashida, Hiroshi; Terakawa, Mitsuhiro

2012-02-01

For efficient photodynamic treatment of wound infection, a photosensitizer must be distributed in the whole infected tissue region. To ensure this, depth profiling of a photosensitizer is necessary in vivo. In this study, we applied photoacoustic (PA) imaging to visualize the depth profile of an intravenously injected photosensitizer in rat burn models. In burned tissue, pharmacokinetics is complicated; vascular occlusion takes place in the injured tissue, while vascular permeability increases due to thermal invasion. In this study, we first used Evans Blue (EB) as a test drug to examine the feasibility of photosensitizer dosimetry based on PA imaging. On the basis of the results, an actual photosensitizer, talaporfin sodium was used. An EB solution was intravenously injected into a rat deep dermal burn model. PA imaging was performed on the wound with 532 nm and 610 nm nanosecond light pulses for visualizing vasculatures (blood) and EB, respectively. Two hours after injection, the distribution of EB-originated signal spatially coincided well with that of blood-originated signal measured after injury, indicating that EB molecules leaked out from the blood vessels due to increased permeability. Afterwards, the distribution of EB signal was broadened in the depth direction due to diffusion. At 12 hours after injection, clear EB signals were observed even in the zone of stasis, demonstrating that the leaked EB molecules were delivered to the injured tissue layer. The level and time course of talaporfin sodium-originated signals were different compared with those of EB-originated signals, showing animal-dependent and/or drug-dependent permeabilization and diffusion in the tissue. Thus, photosensitizer dosimetry should be needed before every treatment to achieve desirable outcome of photodynamic treatment, for which PA imaging can be concluded to be valid and useful.

Icariin promotes expression of junctophilin 2 and Ca2+ related function during cardiomyocyte differentiation of murine embryonic stem cells.

PubMed

Liang, Xingguang; Hong, Dongsheng; Huang, Yujie; Rao, Yuefeng; Ma, Kuifen; Huang, Mingzhu; Zhang, Xingguo; Lou, Yijia; Zhao, Qingwei

2015-12-01

Junctophilin2 (JP2) is a critical protein associated with cardiogenesis. Icariin (ICA) facilitated the directional differentiation of murine embryonic stem (ES) cells into cardiomyocytes. However, little is known about the effects of ICA on JP2 during cardiac differentiation. Here, we explored whether ICA has effects on the expression and Ca2+ related function of JP2 during cardiomyocyte differentiation of ES cells in vitro. Embryonid bodies (EBs) formed by hanging drop were treated with 10(-7) mol/L ICA from day 5 to promote the cardiac differentiation. Percentage of beating EBs and number of beating area within EBs were monitored. Cardiomyocytes were purified by discontinuous percoll gradient centrifugation from EBs. The expression of JP2, α-actinin and troponin-T within EBs or isolated cardiomyocytes were analyzed by immunocytochemistry, western blot and flow cytometry. The transient Ca2+ release was characterized in cardiomyocytes treated with/without 10 mmol/L caffeine and 8 mmol/L Ca2+. Our results showed that ES cell-derived cardiomyocytes were well characterized with JP2 proteins. ICA promoted cardiomyocyte differentiation as indicated by an increased percentage of beating EBs and number of beating area within EBs. The expression of JP2, α-actinin and troponin-T were up-regulated both in EBs and isolated cardiomyocytes from EBs. Furthermore, ICA-induced JP2 expression was accompanied by a remarkable increase of the amplitude of Ca2+ transients in cardiomyocytes before/after caffeine and Ca2+ stimulating. In conclusion, ICA promotes in cardiac differentiation partly through regulating JP2 and improved the Ca2+ modulatory function of cardiomyocytes.

RNA Regulation of Estrogen

DTIC Science & Technology

2010-08-01

microtubule-associated protein, RP/EB family, member 3 6.06 211668_s_at PLAU plasminogen activator, urokinase 6.06 207403_at IRS4 insulin receptor...polypeptide 3.48 202410_x_at INS-IGF2 insulin -like growth factor 2 (somatomedin A); insulin ; INS-IGF2 readthrough transcript 3.48 202410_x_at INS insulin -like...growth factor 2 (somatomedin A); insulin ; INS-IGF2 readthrough transcript 3.48 202410_x_at IGF2 insulin -like growth factor 2 (somatomedin A); insulin

Agricultural burning smoke in Eastern Washington: Part II. Exposure assessment

NASA Astrophysics Data System (ADS)

Wu, Chang-Fu; Jimenez, Jorge; Claiborn, Candis; Gould, Tim; Simpson, Christopher D.; Larson, Tim; Sally Liu, L.-J.

Several studies have documented potential health effects due to agricultural burning smoke. However, there is a paucity of literature characterizing community residents' exposure to agricultural burning smoke. This study assesses personal exposures to particulate matter (PM) with aerodynamic diameters <2.5 μm (PM 2.5) from agriculture burning smoke ( Eb) for 33 asthmatic adults in Pullman, WA. PM 2.5 concentrations were measured on 16 subjects, inside of all but four residences, outside of 6 residences, and at a central site. The mean±standard deviation of personal exposure to PM 2.5 was 13.8±11.1 μg m -3, which was on average 8.0 μg m -3 higher during the agricultural burning episodes (19.0±11.8 μg m -3) than non-episodes (11.0±9.7 μg m -3). The levoglucosan (LG, a unique marker for biomass burning PM) on personal filter samples also was higher during the episodes than non-episodes (0.026±0.030 vs. 0.010±0.012 μg m -3). We applied the random component superposition model on central-site and home indoor PM measurements, and estimated a central-site infiltration factor between 0.21 and 2.05 for residences with good modeling performance. We combined the source apportionment and total exposure modeling results to estimate individual Eb, which ranged from 1.2 to 6.7 μg m -3 and correlated with personal LG with an r of 0.51. The sensitivity analysis of applying the infiltration efficiency estimated from the recursive model showed that the Eb (range: 1.3-4.3 μg m -3) obtained from this approach have a higher correlation with personal LG ( r=0.75). Nevertheless, the small sample size of personal LG measurements prevents a comparative and conclusive assessment of the model performance. We found a significant between-subject variation between episodes and non-episodes in both the Eb estimates and subjects' activity patterns. This suggests that the LG measurements at the central site may not always represent individual exposures to agricultural burning smoke. We recommend collecting more microenvironmental samples to model the Eb and more personal samples to validate the Eb estimates.

Evans blue dye-enhanced capillary-resolution photoacoustic microscopy in vivo

NASA Astrophysics Data System (ADS)

Yao, Junjie; Maslov, Konstantin; Hu, Song; Wang, Lihong V.

2009-09-01

Complete and continuous imaging of microvascular networks is crucial for a wide variety of biomedical applications. Photoacoustic tomography can provide high resolution microvascular imaging using hemoglobin within red blood cells (RBCs) as an endogenic contrast agent. However, intermittent RBC flow in capillaries results in discontinuous and fragmentary capillary images. To overcome this problem, we use Evans blue (EB) dye as a contrast agent for in vivo photoacoustic imaging. EB has strong optical absorption and distributes uniformly in the blood stream by chemically binding to albumin. With the help of EB, complete and continuous microvascular networks--especially capillaries--are imaged. The diffusion dynamics of EB leaving the blood stream and the clearance dynamics of the EB-albumin complex are also quantitatively investigated.

47 CFR 27.58 - Interference to BRS/EBS receivers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Interference to BRS/EBS receivers. 27.58 Section 27.58 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Technical Standards § 27.58 Interference to BRS/EBS receivers. (a...

PSD-95 alters microtubule dynamics via an association with EB3

PubMed Central

Sweet, Eric S.; Previtera, Michelle L.; Fernández, Jose R.; Charych, Erik I.; Tseng, Chia-Yi; Kwon, Munjin; Starovoytov, Valentin; Zheng, James Q.; Firestein, Bonnie L.

2011-01-01

Little is known about how the neuronal cytoskeleton is regulated when a dendrite decides whether to branch or not. Previously, we reported that postsynaptic density protein 95 (PSD-95) acts as a stop signal for dendrite branching. It is yet to be elucidated how PSD-95 affects the cytoskeleton and how this regulation relates to the dendritic arbor. Here, we show that the SH3 (src homology 3) domain of PSD-95 interacts with a proline-rich region within the microtubule end-binding protein EB3. Overexpression of PSD-95 or mutant EB3 results in a decreased lifetime of EB3 comets in dendrites. In line with these data, transfected rat neurons show that overexpression of PSD-95 results in less organized microtubules at dendritic branch points and decreased dendritogensis. The interaction between PSD-95 and EB3 elucidates a function for a novel region of EB3 and provides a new and important mechanism for the regulation of microtubules in determining dendritic morphology. PMID:21248129

Etched beam splitters in InP/InGaAsP.

PubMed

Norberg, Erik J; Parker, John S; Nicholes, Steven C; Kim, Byungchae; Krishnamachari, Uppiliappan; Coldren, Larry A

2011-01-17

An etched beam splitter (EBS) photonic coupler based on frustrated total internal reflection (FTIR) is designed, fabricated and characterized in the InP/InGaAsP material system. The EBS offers an ultra compact footprint (8x11 μm) and a complete range of bar/cross coupling ratio designs. A novel pre-etching process is developed to achieve sufficient depth of the etched coupling gaps. Fabricated EBS couplers demonstrate insertion loss between 1 and 2.6 dB with transmission (cross-coupling) ≤ 10%. The results show excellent agreement with 3D finite-difference time-domain (FDTD) modeling. The coupling of EBS has weak wavelength dependence in the C-band, making it suitable for wavelength division multiplexing (WDM) or other wide bandwidth applications. Finally, the EBS is integrated with active semiconductor optical amplifier (SOA) and phase-modulator components; using a flattened ring resonator structure, a channelizing filter tunable in both amplitude and center frequency is demonstrated, as well as an EBS coupled ring laser.

Evaluation of substituted ebselen derivatives as potential trypanocidal agents.

PubMed

Gordhan, Heeren M; Patrick, Stephen L; Swasy, Maria I; Hackler, Amber L; Anayee, Mark; Golden, Jennifer E; Morris, James C; Whitehead, Daniel C

2017-02-01

Human African trypanosomiasis is a disease of sub-Saharan Africa, where millions are at risk for the illness. The disease, commonly referred to as African sleeping sickness, is caused by an infection by the eukaryotic pathogen, Trypanosoma brucei. Previously, a target-based high throughput screen revealed ebselen (EbSe), and its sulfur analog, EbS, to be potent in vitro inhibitors of the T. brucei hexokinase 1 (TbHK1). These molecules also exhibited potent trypanocidal activity in vivo. In this manuscript, we synthesized a series of sixteen EbSe and EbS derivatives bearing electron-withdrawing carboxylic acid and methyl ester functional groups, and evaluated the influence of these substituents on the biological efficacy of the parent scaffold. With the exception of one methyl ester derivative, these modifications ablated or blunted the potent TbHK1 inhibition of the parent scaffold. Nonetheless, a few of the methyl ester derivatives still exhibited trypanocidal effects with single-digit micromolar or high nanomolar EC 50 values. Copyright © 2016 Elsevier Ltd. All rights reserved.

Photoacoustic microscopy using Evans Blue dye as a contrast agent

NASA Astrophysics Data System (ADS)

Yao, Junjie; Maslov, Konstantin I.; Hu, Song; Wang, Lihong V.

2010-02-01

Complete and continuous imaging of microvascular networks is crucial for a wide variety of biomedical applications. Photoacoustic tomography can provide high resolution microvascular imaging using hemoglobin within red blood cells (RBC) as an endogenous contrast agent. However, intermittent RBC flow in capillaries results in discontinuous and fragmentary capillary images. To overcome this problem, we used Evans Blue (EB) dye as a contrast agent for in vivo photoacoustic imaging. EB has strong optical absorption at 610 nm and distributes uniformly in the blood stream by chemically binding to albumin. By intravenous injection of EB (6%, 200 μL), complete and continuous microvascular networks-especially capillaries-of the ears of nude mice were imaged. The diffusion of EB (3%, 100 μL) leaving the blood stream was monitored for 2 hours. At lower administration dose of EB (3%, 50 μL), the clearance of the EB-albumin complex was imaged for 10 days and quantitatively investigated using a two-compartment model.

Application of the unified mask data format based on OASIS for VSB EB writers

NASA Astrophysics Data System (ADS)

Suzuki, Toshio; Hirumi, Junji; Suga, Osamu

2005-11-01

Mask data preparation (MDP) for modern mask manufacturing becomes a complex process because many kinds of EB data formats are used in mask makers and EB data files continue to become bigger by the application of RET. Therefore we developed a unified mask pattern data format named "OASIS.VSB1" and a job deck format named "MALY2" for Variable-Shaped-Beam (VSB) EB writers. OASIS.VSB is the mask pattern data format based on OASISTM 3 (Open Artwork System Interchange Standard) released as a successive format to GDSII by SEMI. We defined restrictions on OASIS for VSB EB writers to input OASIS.VSB data directly to VSB EB writers just like the native EB data. OASIS.VSB specification and MALY specification have been disclosed to the public and will become a SEMI standard in the near future. We started to promote the spread activities of OASIS.VSB and MALY. For practical use of OASIS.VSB and MALY, we are discussing the infrastructure system of MDP processing using OASIS.VSB and MALY with mask makers, VSB EB makers, and device makers. We are also discussing the tools for the infrastructure system with EDA vendors. The infrastructure system will enable TAT, the man-hour, and the cost in MDP to be reduced. In this paper, we propose the plan of the infrastructure system of MDP processing using OASIS.VSB and MALY as an application of OASIS.VSB and MALY.

Sex and Authority in the Workplace: The Causes of Sexual Inequality.

ERIC Educational Resources Information Center

Wolf, Wendy C.; Fligstein, Neil D.

1979-01-01

Assessed in this paper is the relative importance of three factors that partially account for the unequal distribution of men and women in positions of authority: (1) women's qualifications; (2) the behaviors and policies of employers; and (3) the attitudes and behaviors of the women themselves. (Author/EB)

Teacher Preparation for Emergent Bilingual Students: Implications of Evidence for Policy

ERIC Educational Resources Information Center

López, Francesca; Santibañez, Lucrecia

2018-01-01

Failure to adequately prepare teachers of emergent bilingual (EB) students could have devastating consequences for student achievement, EB reclassification, and eventually, high school and college completion. To enhance the policy discourse, we explore how teacher certification requirements relate to both EB student achievement and teacher…

The Beaverdam Group: Archaeological Investigations at 9EB92, 9EB207, 9EB208 and 9EB219 Richard B. Russell Multiple Resource Area, Elbert County, Georgia.

DTIC Science & Technology

1984-01-01

soapstone (steatite) for both vessels and 0 cooking stones, basin mortars, phyllite and slate knives, round or stemmed scrapers, three-quarter or full...gneissic rock, and soapstone . During sub- sequent review, it was pointed out that the use of quartzite for tool manufacture is without precedent in the...fashioned from non-local materials. Quartz, meta-igneous rock and soapstone could be found within 10 km of the Beaverdain Group, whereas other lithic

Electron beam irradiated polymer electrolyte film: Morphology, dielectric and AC conductivity studies

NASA Astrophysics Data System (ADS)

Yesappa, L.; Niranjana, M.; Ashokkumar, S. P.; Vijeth, H.; Ganesh, S.; Devendrappa, H.

2018-05-01

The polymer (PVdF-co-HFP: LiClO4=90:10, PHL10) electrolyte films prepared by solution casting method and studied morphology, dielectric properties and ac conductivity before and after electron beam (EB) irradiation. The polarized optical micrographs reveals size of spherulite reduced with increasing EB dose represents increase in amorphousity. The dielectric measurements were studied at different temperatures and observed increase with frequency at different temperatures upon EB irradiation. The ac conductivity increases with frequency due to effect of EB dose.

End-binding protein 1 controls signal propagation from the T cell receptor

PubMed Central

Martín-Cófreces, Noa B; Baixauli, Francesc; López, María J; Gil, Diana; Monjas, Alicia; Alarcón, Balbino; Sánchez-Madrid, Francisco

2012-01-01

The role of microtubules (MTs) in the control and dynamics of the immune synapse (IS) remains unresolved. Here, we show that T cell activation requires the growth of MTs mediated by the plus-end specific protein end-binding 1 (EB1). A direct interaction of the T cell receptor (TCR) complex with EB1 provides the molecular basis for EB1 activity promoting TCR encounter with signalling vesicles at the IS. EB1 knockdown alters TCR dynamics at the IS and prevents propagation of the TCR activation signal to LAT, thus inhibiting activation of PLCγ1 and its localization to the IS. These results identify a role for EB1 interaction with the TCR in controlling TCR sorting and its connection with the LAT/PLCγ1 signalosome. PMID:22922463

Electron beam machining using rotating and shaped beam power distribution

DOEpatents

Elmer, John W.; O'Brien, Dennis W.

1996-01-01

An apparatus and method for electron beam (EB) machining (drilling, cutting and welding) that uses conventional EB guns, power supplies, and welding machine technology without the need for fast bias pulsing technology. The invention involves a magnetic lensing (EB optics) system and electronic controls to: 1) concurrently bend, focus, shape, scan, and rotate the beam to protect the EB gun and to create a desired effective power-density distribution, and 2) rotate or scan this shaped beam in a controlled way. The shaped beam power-density distribution can be measured using a tomographic imaging system. For example, the EB apparatus of this invention has the ability to drill holes in metal having a diameter up to 1000 .mu.m (1 mm or larger), compared to the 250 .mu.m diameter of laser drilling.

Evaluation of emamectin benzoate and substance EX against salmon lice in sea-ranched Atlantic salmon smolts.

PubMed

Skilbrei, Ove Tommy; Espedal, Per Gunnar; Nilsen, Frank; Garcia, Enrique Perez; Glover, Kevin A

2015-04-08

Experimental releases of Atlantic salmon smolts treated with emamectin benzoate (EB) against salmon lice have previously been used to estimate the significance of salmon lice on the survival of migrating smolts. In recent years, the salmon louse has developed reduced sensitivity to EB, which may influence the results of such release experiments. We therefore tested the use of 2 anti-lice drugs: EB was administered to salmon smolts in high doses by intra-peritoneal injection and the prophylactic substance EX (SubEX) was administered by bathing. A third, untreated control group was also established. Salmon were challenged with copepodids of 2 strains of salmon lice (1 EB-sensitive strain and 1 with reduced EB-sensitivity) in mixed-group experimental tanks. At 31 d post-challenge, the numbers of pre-adult lice on treated fish were around 20% compared with the control fish, with minor or no differences between the 2 treatments and lice strains. Both treatments therefore appeared to give the smolts a high degree of protection against infestation of copepodids of salmon lice. However, significantly lower growth of the EB-treatment group indicates that bathing the fish in SubEX is less stressful for smolts than intra-peritoneal injection of EB.

FINE-SCALE PHOTOSPHERIC CONNECTIONS OF ELLERMAN BOMBS

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

Yang, Heesu; Chae, Jongchul; Song, Donguk

2016-10-01

We investigate the photospheric and magnetic field structures associated with Ellerman bombs (EBs) using the 1.6 m New Solar Telescope at Big Bear Solar Observatory. The nine observed EBs were accompanied by elongated granule-like features (EGFs) that showed transverse motions prior to the EBs with an average speed of about 3.8 km s{sup −1}. Each EGF consisted of a sub-arcsecond bright core encircled by a dark lane around its moving front. The bright core appeared in the TiO broadband filter images and in the far wings of the H α and Ca ii 8542 Å lines. In four EBs, themore » bi-directional expanding motion of the EGFs was identified in the TiO images. In those cases, the EGFs were found to be accompanied by an emerging flux (EF). In four other EBs, the EGF developed at the edge of a penumbra and traveled in the sunspot’s radial direction. The EGFs in these cases were identified as a moving magnetic feature (MMF). Our results show a clear connection among the magnetic elements, photospheric features, and EBs. This result suggests that the EBs result from magnetic reconnection forced by EFs or MMFs that are frequently manifested by EGFs.« less

Isotope Dilution nanoLC/ESI+-HRMS3 Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene.

PubMed

Sangaraju, Dewakar; Boldry, Emily J; Patel, Yesha M; Walker, Vernon; Stepanov, Irina; Stram, Daniel; Hatsukami, Dorothy; Tretyakova, Natalia

2017-02-20

1,3-Butadiene (BD) is an important industrial and environmental chemical classified as a known human carcinogen. Occupational exposure to BD in the polymer and monomer industries is associated with an increased incidence of lymphoma. BD is present in automobile exhaust, cigarette smoke, and forest fires, raising concern about potential exposure of the general population to this carcinogen. Following inhalation exposure, BD is bioactivated to 3,4-epoxy-1-butene (EB). If not detoxified, EB is capable of modifying guanine and adenine bases of DNA to form nucleobase adducts, which interfere with accurate DNA replication and cause cancer-initiating mutations. We have developed a nanoLC/ESI + -HRMS 3 methodology for N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts in human urine (limit of detection: 0.25 fmol/mL urine; limit of quantitation: 1.0 fmol/mL urine). This new method was successfully used to quantify EB-GII in urine of F344 rats treated with 0-200 ppm of BD, occupationally exposed workers, and smokers belonging to two different ethnic groups. EB-GII amounts increased in a dose-dependent manner in urine of laboratory rats exposed to 0, 62.5, or 200 ppm of BD. Urinary EB-GII levels were significantly increased in workers occupationally exposed to 0.1-2.2 ppm of BD (1.25 ± 0.51 pg/mg of creatinine) as compared to administrative controls exposed to <0.01 ppm of BD (0.22 ± 0.08 and pg/mg of creatinine) (p = 0.0024), validating the use of EB-GII as a biomarker of human exposure to BD. EB-GII was also detected in smokers' urine with European American smokers excreting significantly higher amounts of EB-GII than African American smokers (0.48 ± 0.09 vs 0.12 ± 0.02 pg/mg of creatinine, p = 3.1 × 10 -7 ). Interestingly, small amounts of EB-GII were observed in animals and humans with no known exposure to BD, providing preliminary evidence for its endogenous formation. Urinary EB-GII adduct levels and urinary mercapturic acids of BD (MHBMA, DHBMA) were compared in a genotyped multiethnic smoker cohort.

Contouring and Constraining Bowel on a Full-Bladder Computed Tomography Scan May Not Reflect Treatment Bowel Position and Dose Certainty in Gynecologic External Beam Radiation Therapy

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

Yaparpalvi, Ravindra, E-mail: ryaparpa@montefiore.org; Mehta, Keyur J.; Bernstein, Michael B.

Purpose: To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials: Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined.more » Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results: Average (±SD) planned bladder volume was 299.7 ± 68.5 cm{sup 3}. Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm{sup 3} (range, 74.3-251.4 cm{sup 3}). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm{sup 3}; P=.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions: Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV{sub B}owel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient.« less

Diabetes-related distress and its associated factors among patients with type 2 diabetes mellitus in China.

PubMed

Zhou, Huanhuan; Zhu, Junya; Liu, Lin; Li, Fan; Fish, Anne F; Chen, Tao; Lou, Qingqing

2017-06-01

Diabetes-related distress is one of the psychological disorders affecting patients with diabetes, yet there are few studies about diabetes-related distress in Chinese patients. To assess the level of psychological distress and examine its associated factors, we conducted a cross-sectional analysis of patients with type 2 diabetes mellitus from a Chinese tertiary hospital. The Diabetes Distress Scale (DDS) and the General Self-Efficacy Scale (GSES) were administered. There were 210 (57.85%) patients with little or no diabetes-related distress, 84 (23.14%) with moderate diabetes-related distress and 69 (19.01%) with high diabetes-related distress. Stepwise multiple linear regression showed that sleep time was significantly related to the DDS total score and the subscale scores of emotional burden (EB) (β=-0.190, -0.379), respectively. GSES was associated with the DDS total score (β=-0.128) and the EB score (β=-0.153). Oral medication plus insulin was significantly related to regimen-related distress (RD) (β=0.137), physician-related distress (PD) (β=0.152) and interpersonal distress (ID) (β=0.103). Physical activity (β=-0.185) and making meal plan with health care professionals(HCP) (β=-0.169) were associated with RD. The prevalence of diabetes-related distress among patients with type 2 diabetes mellitus was high in China. DDS and EB were associated with poorer sleep time and lower self-efficacy. Interventions to improve sleep are needed. Qualitative and longitudinal studies are required to understand why type 2 diabetic patients are not getting enough sleep. Copyright © 2017. Published by Elsevier B.V.

Vertically aligned double wall carbon nanotube arrays adsorbent for pure and mixture adsorption of H2S, ethylbenzene and carbon monoxide, grand canonical Monte Carlo simulation.

PubMed

Tasharrofi, Saeideh; Taghdisian, Hossein; Golchoobi, Abdollah

2018-05-01

In this study, pure and ternary adsorption of hydrogen sulfide (H 2 S), ethylbenzene (EB), and carbon monoxide (CO) on different arrays of zigzag double wall carbon nanotube was investigated using grand canonical Monte Carlo simulations. The internal diameters of nanotube were fixed at 2r = 50.17 Å while nanotube wall distances were different values from d = 0 Å to d = 150 Å. Pure simulation results indicated that adsorption quantity of H 2 S and EB in low pressure ranges of P = 1.9 bar to P = 3.1 bar was at least 100% more than CO adsorption quantities. At high pressure ranges of P = 23.1 bar to P = 38.2 bar H 2 S adsorption was greater than EB and CO by about 200 molecules per unit cell (UC) at low nanotube distances. This was related to smaller kinetic diameter and greater dipole moment of H 2 S compared to EB and CO. At higher nanotube distance the effect of size however disappears and all three gases approach to adsorption quantity of about 800 molecules/UC. Graphical representation of adsorption areas showed that H 2 S and CO form multilayer adsorption around nanotube inner and outer walls while EB fill the whole space uniformly without any congestion around the walls. Ternary adsorption results EB/CO and H 2 S/CO selectivity are greater than EB/H 2 S selectivity. In addition, at smaller nanotube distances H 2 S/CO selectivity is generally higher than EB/CO selectivity, which at higher nanotube distance the order becomes revers suggesting that size dependent effects on adsorption vanishes. Isosteric heat of adsorption shows that the order of EB > H 2 S > CO suggesting that ethylbenzene interaction with nanotube arrays was strongest. Although H 2 S has a greater dipole moment and smaller molecular dimension, EB adsorption at higher nanotube distance is greater than H 2 S by at least 50% probably because EB is less volatile. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of endoscopic papillary balloon dilation and sphincterotomy in young patients with CBD stones and gallstones.

PubMed

Seo, Yu Ri; Moon, Jong Ho; Choi, Hyun Jong; Kim, Dong Choon; Ha, Ji Su; Lee, Tae Hoon; Cha, Sang-Woo; Cho, Young Deok; Park, Sang-Heum; Kim, Sun-Joo

2014-05-01

Endoscopic biliary sphincterotomy (EBS) results in permanent loss of sphincter function and its long-term complications are unknown. Endoscopic papillary balloon dilation (EPBD) is an alternative procedure that preserves sphincter function, although it is associated with a higher risk of pancreatitis than is EBS. The aim of this study was to evaluate the safety and outcomes of EPBD with limited indications for removal of common bile duct (CBD) stones combined with gallstones in patients younger than 40 years. Young (age < 40 years) patients who had CBD stones combined with gallstones on imaging studies were enrolled in this study. A total of 132 patients were randomly divided into the EPBD group (n = 62) or the EBS group (n = 70) for extraction of CBD stones. The ballooning size of EPBD ranged from 6 to 10 mm. Complete bile duct clearance was achieved in 98.4 % (61/62) of the EPBD group and 100 % (70/70) of the EBS group. Mechanical lithotripsy was required in 8.1 % (5/62) of the EPBD group and 8.6 % (6/70) of the EBS group. The early complication rates were 8.1 % (5/62) (five pancreatitis) in the EPBD group and 11.4 % (8/70) (five [7.1 %] pancreatitis, two bleeding and one perforation) in the EBS group. The recurrence rates of CBD stones were 1.6 % (1/62) in the EPBD group and 5.7 % (4/70) in the EBS group. EPBD with limited indications was safe and effective as EBS for removal of CBD stones combined with gallstones in young patients who had a longer life expectancy.

Composite of PAH-degrading endophytic bacteria reduces contamination and health risks caused by PAHs in vegetables.

PubMed

Wang, Jian; Liu, Juan; Ling, Wanting; Huang, Qingguo; Gao, Yanzheng

2017-11-15

Vegetables accumulate polycyclic aromatic hydrocarbons (PAHs) at high concentrations when grown in contaminated sites. Inoculation with PAH-degrading endophytic bacteria (EB PAH ) has been recognized as one of the most promising ways to remove PAHs from plant bodies; however, the performance of single endophytic bacteria is generally limited. This investigation used a composite of eight EB PAH to reduce the contamination and health risk posed by 16 EPA priority PAHs in vegetables including Chinese cabbage (Brassica chinensis L.) and pakchoi (Brassica campestris L.). Composite EB PAH have strong PAH degradation abilities, and more than 65% of ∑PAH were degraded after 10-day insuspension with composite EB PAH . Vegetable were contacted with composite EB PAH by seed soaking (SS) and leaf painting (LP) with an EB PAH cell incubation at OD 600nm =0.2-1.5. Compared with those in non-inoculated controls, the ∑PAH concentrations in edible parts of Chinese cabbage and pakchoi colonized by composite EB PAH via SS and LP with bacterial suspension at OD 600nm =0.2-1.5 were 42.07-70.77% and 15.79-53.20% lower, and the incremental lifetime cancer risk (ILCR) values for males and females were 31.78-84.08% and 26.60-83.40% smaller, respectively. SS was the optimal inoculation method for reducing PAH concentrations and ILCR values. Our results indicate that inoculating plants with composite EB PAH can lower the health risk posed by vegetables contaminated with PAHs, and may be used to mitigate plant PAH contamination. Copyright © 2017 Elsevier B.V. All rights reserved.

Transforming growth factor (TGF)beta, fibroblast growth factor (FGF) and retinoid signalling pathways promote pancreatic exocrine gene expression in mouse embryonic stem cells.

PubMed Central

Skoudy, Anouchka; Rovira, Meritxell; Savatier, Pierre; Martin, Franz; León-Quinto, Trinidad; Soria, Bernat; Real, Francisco X

2004-01-01

Extracellular signalling cues play a major role in the activation of differentiation programmes. Mouse embryonic stem (ES) cells are pluripotent and can differentiate into a wide variety of specialized cells. Recently, protocols designed to induce endocrine pancreatic differentiation in vitro have been designed but little information is currently available concerning the potential of ES cells to differentiate into acinar pancreatic cells. By using conditioned media of cultured foetal pancreatic rudiments, we demonstrate that ES cells can respond in vitro to signalling pathways involved in exocrine development and differentiation. In particular, modulation of the hedgehog, transforming growth factor beta, retinoid, and fibroblast growth factor pathways in ES cell-derived embryoid bodies (EB) resulted in increased levels of transcripts encoding pancreatic transcription factors and cytodifferentiation markers, as demonstrated by RT-PCR. In EB undergoing spontaneous differentiation, expression of the majority of the acinar genes (i.e. amylase, carboxypeptidase A and elastase) was induced after the expression of endocrine genes, as occurs in vivo during development. These data indicate that ES cells can undergo exocrine pancreatic differentiation with a kinetic pattern of expression reminiscent of pancreas development in vivo and that ES cells can be coaxed to express an acinar phenotype by activation of signalling pathways known to play a role in pancreatic development and differentiation. PMID:14733613

77 FR 7603 - Notice of a Change in Status of an Extended Benefit (EB) Period for Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... Extended Benefit (EB) Period for Alaska AGENCY: Employment and Training Administration, Labor. ACTION... Extended Benefits program began January 22, 2012. The trigger notice covering state eligibility for the EB... governed by the Federal- State Extended Unemployment Compensation Act of 1970, as amended, and the...

Trends for Electron Beam Accelerator Applications in Industry

NASA Astrophysics Data System (ADS)

Machi, Sueo

2011-02-01

Electron beam (EB) accelerators are major pieces of industrial equipment used for many commercial radiation processing applications. The industrial use of EB accelerators has a history of more than 50 years and is still growing in terms of both its economic scale and new applications. Major applications involve the modification of polymeric materials to create value-added products, such as heat-resistant wires, heat-shrinkable sheets, automobile tires, foamed plastics, battery separators and hydrogel wound dressing. The surface curing of coatings and printing inks is a growing application for low energy electron accelerators, resulting in an environmentally friendly and an energy-saving process. Recently there has been the acceptance of the use of EB accelerators in lieu of the radioactive isotope cobalt-60 as a source for sterilizing disposable medical products. Environmental protection by the use of EB accelerators is a new and important field of application. A commercial plant for the cleaning flue gases from a coal-burning power plant is in operation in Poland, employing high power EB accelerators. In Korea, a commercial plant uses EB to clean waste water from a dye factory.

Cresting the wave: proper motions of the Eastern Banded Structure

NASA Astrophysics Data System (ADS)

Deason, Alis J.; Belokurov, Vasily; Koposov, Sergey E.

2018-01-01

We study the kinematic properties of the Eastern Banded Structure (EBS) and Hydra I overdensity using exquisite proper motions derived from the Sloan Digital Sky Survey (SDSS) and Gaia source catalogue. Main sequence turn-off stars in the vicinity of the EBS are identified from SDSS photometry; we use the proper motions and, where applicable, spectroscopic measurements of these stars to probe the kinematics of this apparent stream. We find that the EBS and Hydra I share common kinematic and chemical properties with the nearby Monoceros Ring. In particular, the proper motions of the EBS, like Monoceros, are indicative of prograde rotation (Vϕ ∼ 180-220 km s-1), which is similar to the Galactic thick disc. The kinematic structure of stars in the vicinity of the EBS suggests that it is not a distinct stellar stream, but rather marks the 'edge' of the Monoceros Ring. The EBS and Hydra I are the latest substructures to be linked with Monoceros, leaving the Galactic anti-centre a mess of interlinked overdensities which likely share a unified, Galactic disc origin.

A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa - case report and literature review.

PubMed

Michalak, Agata; Cichoż-Lach, Halina; Prozorow-Król, Beata; Buk, Leszek; Dzida, Monika

2018-04-13

Epidermolysis bullosa (EB) constitutes a heterogenous group of rare multisystem genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EB manifestation is not only limited to the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract and upper gastrointestinal tract. The presence of particular symptoms is directly determined by a type of altered skin protein. Gastrointestinal manifestation of EB is most commonly reflected by esophageal stenosis due to recurrent esophageal blistering, followed by consequent scarring. Here we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland. Management of an esophageal stricture in such circumstances is based on endoscopic dilatation. However, in most severe cases, placement of a gastrostomy tube is required. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.

Memory scrutinized through electrical brain stimulation: A review of 80 years of experiential phenomena.

PubMed

Curot, Jonathan; Busigny, Thomas; Valton, Luc; Denuelle, Marie; Vignal, Jean-Pierre; Maillard, Louis; Chauvel, Patrick; Pariente, Jérémie; Trebuchon, Agnès; Bartolomei, Fabrice; Barbeau, Emmanuel J

2017-07-01

Electrical brain stimulations (EBS) sometimes induce reminiscences, but it is largely unknown what type of memories they can trigger. We reviewed 80 years of literature on reminiscences induced by EBS and added our own database. We classified them according to modern conceptions of memory. We observed a surprisingly large variety of reminiscences covering all aspects of declarative memory. However, most were poorly detailed and only a few were episodic. This result does not support theories of a highly stable and detailed memory, as initially postulated, and still widely believed as true by the general public. Moreover, memory networks could only be activated by some of their nodes: 94.1% of EBS were temporal, although the parietal and frontal lobes, also involved in memory networks, were stimulated. The qualitative nature of memories largely depended on the site of stimulation: EBS to rhinal cortex mostly induced personal semantic reminiscences, while only hippocampal EBS induced episodic memories. This result supports the view that EBS can activate memory in predictable ways in humans. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multi-wavelength analysis of Ellerman Bomb Light Curves

NASA Astrophysics Data System (ADS)

Herlender, M.; Berlicki, A.

We present the results of a multi-wavelength photometric analysis of Ellerman Bomb (EB) observations obtained from the Dutch Open Telescope. In our data we have found 6 EBs located in the super-penumbra of the main spot in the active region NOAA 10781. We present light curves of EB observed in the Hα line centre and wing +0.7 Å, in the Ca II H line centre and wing~+2.35 Å, in the G-band and in the TRACE 1600 Å filter. We have shown that EBs were visible in the G-band and moreover, there was a good correlation between the light curves in the G-band and in the Hα line wings. We also found quasi-periodic oscillations of EBs brightness in the G-band, CaII H line and TRACE 1600 Å filter.

Electron beam machining using rotating and shaped beam power distribution

DOEpatents

Elmer, J.W.; O`Brien, D.W.

1996-07-09

An apparatus and method are disclosed for electron beam (EB) machining (drilling, cutting and welding) that uses conventional EB guns, power supplies, and welding machine technology without the need for fast bias pulsing technology. The invention involves a magnetic lensing (EB optics) system and electronic controls to: (1) concurrently bend, focus, shape, scan, and rotate the beam to protect the EB gun and to create a desired effective power-density distribution, and (2) rotate or scan this shaped beam in a controlled way. The shaped beam power-density distribution can be measured using a tomographic imaging system. For example, the EB apparatus of this invention has the ability to drill holes in metal having a diameter up to 1,000 {micro}m (1 mm or larger), compared to the 250 {micro}m diameter of laser drilling. 5 figs.

Can ill-structured problems reveal beliefs about medical knowledge and knowing? A focus-group approach

PubMed Central

Roex, Ann; Clarebout, Geraldine; Dory, Valerie; Degryse, Jan

2009-01-01

Background Epistemological beliefs (EB) are an individual's cognitions about knowledge and knowing. In several non-medical domains, EB have been found to contribute to the way individuals reason when faced with ill-structured problems (i.e. problems with no clear-cut, right or wrong solutions). Such problems are very common in medical practice. Determining whether EB are also influential in reasoning processes with regard to medical issues to which there is no straightforward answer, could have implications for medical education. This study focused on 2 research questions: 1. Can ill-structured problems be used to elicit general practice trainees' and trainers' EB? and 2. What are the views of general practice trainees and trainers about knowledge and how do they justify knowing? Methods 2 focus groups of trainees (n = 18) were convened on 3 occasions during their 1st year of postgraduate GP training. 2 groups of GP trainers (n = 11) met on one occasion. Based on the methodology of the Reflective Judgement Interview (RJI), participants were asked to comment on 11 ill-structured problems. The sessions were audio taped and transcribed and an adapted version of the RJI scoring rules was used to assess the trainees' reasoning about ill-structured problems. Results Participants made a number of statements illustrating their EB and their importance in clinical reasoning. The level of EB varied widely form one meeting to another and depending on the problem addressed. Overall, the EB expressed by trainees did not differ from those of trainers except on a particular ill-structured problem regarding shoulder pain. Conclusion The use of focus groups has entailed some difficulties in the interpretation of the results, but a number of preliminary conclusions can be drawn. Ill-structured medical problems can be used to elicit EB. Most trainees and trainers displayed pre-reflective and quasi-reflective EB. The way trainees and doctors view and justify knowledge are likely to be involved in medical reasoning processes. PMID:19775425

Collagen-IV supported embryoid bodies formation and differentiation from buffalo (Bubalus bubalis) embryonic stem cells

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

Taru Sharma, G., E-mail: gts553@gmail.com; Dubey, Pawan K.; Verma, Om Prakash

Graphical abstract: EBs formation, characterization and expression of germinal layers marker genes of in vivo developed teratoma using four different types of extracellular matrices. Highlights: Black-Right-Pointing-Pointer Collagen-IV matrix is found cytocompatible for EBs formation and differentiation. Black-Right-Pointing-Pointer Established 3D microenvironment for ES cells development and differentiation into three germ layers. Black-Right-Pointing-Pointer Collagen-IV may be useful as promising candidate for ES cells based therapeutic applications. -- Abstract: Embryoid bodies (EBs) are used as in vitro model to study early extraembryonic tissue formation and differentiation. In this study, a novel method using three dimensional extracellular matrices for in vitro generation of EBsmore » from buffalo embryonic stem (ES) cells and its differentiation potential by teratoma formation was successfully established. In vitro derived inner cell masses (ICMs) of hatched buffalo blastocyst were cultured on buffalo fetal fibroblast feeder layer for primary cell colony formation. For generation of EBs, pluripotent ES cells were seeded onto four different types of extracellular matrices viz; collagen-IV, laminin, fibronectin and matrigel using undifferentiating ES cell culture medium. After 5 days of culture, ESCs gradually grew into aggregates and formed simple EBs having circular structures. Twenty-six days later, they formed cystic EBs over collagen matrix with higher EBs formation and greater proliferation rate as compared to other extracellular matrices. Studies involving histological observations, fluorescence microscopy and RT-PCR analysis of the in vivo developed teratoma revealed that presence of all the three germ layer derivatives viz. ectoderm (NCAM), mesoderm (Flk-1) and endoderm (AFP). In conclusion, the method described here demonstrates a simple and cost-effective way of generating EBs from buffalo ES cells. Collagen-IV matrix was found cytocompatible as it supported buffalo EBs formation, their subsequent differentiation could prove to be useful as promising candidate for ES cells based therapeutic applications.« less

SMALL-SCALE STRUCTURING OF ELLERMAN BOMBS AT THE SOLAR LIMB

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

Nelson, C. J.; Doyle, J. G.; Scullion, E. M.

2015-01-01

Ellerman bombs (EBs) have been widely studied in recent years due to their dynamic, explosive nature and apparent links to the underlying photospheric magnetic field implying that they may be formed by magnetic reconnection in the photosphere. Despite a plethora of researches discussing the morphologies of EBs, there has been a limited investigation of how these events appear at the limb, specifically, whether they manifest as vertical extensions away from the disk. In this article, we make use of high-resolution, high-cadence observations of an Active Region at the solar limb, collected by the CRisp Imaging SpectroPolarimeter (CRISP) instrument, to identifymore » EBs and infer their physical properties. The upper atmosphere is also probed using the Solar Dynamic Observatory's Atmospheric Imaging Assembly (SDO/AIA). We analyze 22 EB events evident within these data, finding that 20 appear to follow a parabolic path away from the solar surface at an average speed of 9 km s{sup –1}, extending away from their source by 580 km, before retreating back at a similar speed. These results show strong evidence of vertical motions associated with EBs, possibly explaining the dynamical ''flaring'' (changing in area and intensity) observed in on-disk events. Two in-depth case studies are also presented that highlight the unique dynamical nature of EBs within the lower solar atmosphere. The viewing angle of these observations allows for a direct linkage between these EBs and other small-scale events in the Hα line wings, including a potential flux emergence scenario. The findings presented here suggest that EBs could have a wider-reaching influence on the solar atmosphere than previously thought, as we reveal a direct linkage between EBs and an emerging small-scale loop, and other near-by small-scale explosive events. However, as previous research found, these extensions do not appear to impact upon the Hα line core, and are not observed by the SDO/AIA EUV filters.« less

Multiwavelength spectropolarimetric observations of an Ellerman bomb

NASA Astrophysics Data System (ADS)

Rezaei, R.; Beck, C.

2015-10-01

Context. Ellerman bombs (EBs) are enhanced emission in the wings of the Hα line in the solar spectrum. Aims: We study the structure of an EB in the photosphere and chromosphere. Methods: We analyze simultaneous observations of four chromospheric lines (Hα, Ca ii H, Ca ii IR 854 nm, and He i 1083 nm) as well as two photospheric lines (Fe i 630 and Si i 1082.7 nm) along with high-cadence 160 and 170 nm ultraviolet (UV) continuum filtergrams. Full Stokes data from the Helioseismic and Magnetic Imager (HMI) are used to trace the temporal evolution of the magnetic structure. Results: We identify the EB by excess emission in the wings of the Hα line, a brightening in the UV continuum, and large emission peaks in the core of the two Ca ii lines. The EB shows a blueshift in all chromospheric lines, while no shifts are observed in the photospheric lines. The blueshift in the chromospheric layer causes very asymmetric emission peaks in the Ca ii H line. The photospheric Si i spectral line shows a shallower line depth at the location of the EB. The UV continuum maps show that the EB was substantially brighter than its surroundings for about 30 min. The continuum contrast of the EB from 170 nm to 1080 nm shows a power-law dependency on the wavelength. The temperature enhancement amounts to 130 K in the low photosphere and 400 K at the temperature minimum level. This temperature excess is also seen in an LTE inversion of the Ca ii spectra. The total thermal and radiative energy content of the EB is about 1020 J and 1018 J in the photosphere and chromosphere, respectively. The HMI data hints at a photospheric magnetic flux cancellation as the driver of the EB. Conclusions: Ellerman bombs release the energy in a height range of several pressure scale heights around the temperature minimum such that they affect both the photosphere and the lower chromosphere.

Microtubule plus-end tracking of end-binding protein 1 (EB1) is regulated by CDK5 regulatory subunit-associated protein 2

PubMed Central

Fong, Ka-Wing; Au, Franco K. C.; Jia, Yue; Yang, Shaozhong; Zhou, Liying; Qi, Robert Z.

2017-01-01

Microtubules are polar cytoskeleton filaments that extend via growth at their plus ends. Microtubule plus-end-tracking proteins (+TIPs) accumulate at these growing plus ends to control microtubule dynamics and attachment. The +TIP end-binding protein 1 (EB1) and its homologs possess an autonomous plus-end-tracking mechanism and interact with other known +TIPs, which then recruit those +TIPs to the growing plus ends. A major +TIP class contains the SXIP (Ser-X-Ile-Pro, with X denoting any amino acid residue) motif, known to interact with EB1 and its homologs for plus-end tracking, but the role of SXIP in regulating EB1 activities is unclear. We show here that an interaction of EB1 with the SXIP-containing +TIP CDK5 regulatory subunit-associated protein 2 (CDK5RAP2) regulates several EB1 activities, including microtubule plus-end tracking, dynamics at microtubule plus ends, microtubule and α/β-tubulin binding, and microtubule polymerization. The SXIP motif fused with a dimerization domain from CDK5RAP2 significantly enhanced EB1 plus-end-tracking and microtubule-polymerizing and bundling activities, but the SXIP motif alone failed to do so. An SXIP-binding-deficient EB1 mutant displayed significantly lower microtubule plus-end tracking than the wild-type protein in transfected cells. These results suggest that EB1 cooperates with CDK5RAP2 and perhaps other SXIP-containing +TIPs in tracking growing microtubule tips. We also generated plus-end-tracking chimeras of CDK5RAP2 and the adenomatous polyposis coli protein (APC) and found that overexpression of the dimerization domains interfered with microtubule plus-end tracking of their respective SXIP-containing chimeras. Our results suggest that disruption of SXIP dimerization enables detailed investigations of microtubule plus-end-associated functions of individual SXIP-containing +TIPs. PMID:28320860

EB welding of launch vehicles

NASA Astrophysics Data System (ADS)

Szabo, Attila

While large structural components can be electron beam (EB) welded, equipment and operating costs increase with the requisite vacuum chamber's size. Attention is presently given to cost-effective ways of EB welding launch-vehicle assemblies without compromise of weld quality in such alloys as 2219, 2090, Weldalite, and HP9-4-30/20. Weld strengths at both room and cryogenic temperatures that were 50 percent higher than those obtainable for such materials with arc welding have been demonstrated. Fracture toughnesses were also 40-50 percent higher than arc-welded values. Attention is given to EB joint fit-up allowables for 2219-T87 Al alloy.

Combined effects of microwaves, electron beams and polyfunctional monomers on rubber vulcanization.

PubMed

Manaila, Elena; Martin, Diana; Stelescu, Daniela Zuga; Craciun, Gabriela; Ighigeanu, Daniel; Matei, Constantin

2009-01-01

This paper presents comparative results obtained by conventional vulcanization with benzoyl peroxide (CV-BP), separate electron beam vulcanization (EB-V) and simultaneous electron beam and microwave vulcanization (EB+MW-V) applied to two kind of rubber samples: EVA (ethylene vinyl acetate) rubber-sample (EVA-sample) and EPDM (ethylene-propylene terpolymer) rubber-sample (EPDM-sample). The EVA-samples contain 61.54% EVA Elvax 260, 30.77% carbon black, 1.85% TAC (triallylcyanurate) polyfunctional monomer and 5.84% filler (zinc oxide, stearic acid, polyethylene glycol and antioxidant). The EPDM-samples contain 61.54% EPDM Nordel 4760, 30.77% carbon black, 1.85% TMPT (trimethylopropane trimethacrylate) polyfunctional monomer and 5.84% filler (zinc oxide, stearic acid, polyethylene glycol and antioxidant). The rubber samples designed for different vulcanization methods were obtained from raw rubber mixtures, as compressed sheets of 2 mm in the polyethylene foils to minimize oxidation. For EB and EB + MW treatments the sheets were cut in rectangular shape 0.15 x 0.15 m2. The physical properties of samples obtained by CV-BP EV-Vand EB + MW-V methods were evaluated by measuring the tearing strength, residual elongation, elongation at break, tensile strength, 300% modulus, 100% modulus, elasticity and hardness. The obtained results demonstrate an improvement of rubber several properties obtained by EB and EB + MW processing as compared to classical procedure using benzoyl peroxide.

Suppression of the PI3K subunit p85α delays embryoid body development and inhibits cell adhesion.

PubMed

Gurney, Susan M R; Forster, Peter; Just, Ursula; Schwanbeck, Ralf

2011-12-01

Phosphatidylinositol-3-kinases (PI3Ks) exert a variety of signaling functions in eukaryotes. We suppressed the PI3K regulatory subunit p85α using a small interfering RNA (Pik3r1 siRNA) and examined the effects on embryoid body (EB) development in hanging drop culture. We observed a 150% increase in the volume of the treated EBs within 24 h, compared to the negative controls. Fluorescence Activated Cell Sorting (FACS) assays showed that this increase in volume is not due to increased cellular proliferation. Instead, the increase in volume appears to be due to reduced cellular aggregation and adherence. This is further shown by our observation that 40% of treated EBs form twin instead of single EBs, and that they have a significantly reduced ability to adhere to culture dishes when plated. A time course over the first 96 h reveals that the impaired adherence is transient and explained by an initial 12-hour delay in EB development. Quantitative PCR expression analysis suggests that the adhesion molecule integrin-β1 (ITGB1) is transiently downregulated by the p85α suppression. In conclusion we found that suppressing p85α leads to a delay in forming compact EBs, accompanied by a transient inability of the EBs to undergo normal cell-cell and cell-substrate adhesion. Copyright © 2011 Wiley Periodicals, Inc.

Multi-wavelength Spectral Analysis of Ellerman Bombs Observed by FISS and IRIS

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

Hong, Jie; Ding, M. D.; Cao, Wenda, E-mail: dmd@nju.edu.cn

Ellerman bombs (EBs) are a kind of solar activity that is suggested to occur in the lower solar atmosphere. Recent observations using the Interface Region Imaging Spectrograph (IRIS) show connections between EBs and IRIS bombs (IBs), which imply that EBs might be heated to a much higher temperature (8 × 10{sup 4} K) than previous results. Here we perform a spectral analysis of EBs simultaneously observed by the Fast Imaging Solar Spectrograph and IRIS. The observational results show clear evidence of heating in the lower atmosphere, indicated by the wing enhancement in H α , Ca ii 8542 Å, andmore » Mg ii triplet lines and also by brightenings in images of the 1700 Å and 2832 Å ultraviolet continuum channels. Additionally, the intensity of the Mg ii triplet line is correlated with that of H α when an EB occurs, suggesting the possibility of using the triplet as an alternative way to identify EBs. However, we do not find any signal in IRIS hotter lines (C ii and Si iv). For further analysis, we employ a two-cloud model to fit the two chromospheric lines (H α and Ca ii 8542 Å) simultaneously, and obtain a temperature enhancement of 2300 K for a strong EB. This temperature is among the highest of previous modeling results, albeit still insufficient to produce IB signatures at ultraviolet wavelengths.« less

Diagnosis of Inherited Epidermolysis Bullosa in Resource-Limited Settings: Immunohistochemistry Revisited.

PubMed

Yenamandra, Vamsi Krishna; Bhari, Neetu; Ray, Subrata Basu; Sreenivas, Vishnubhatla; Dinda, Amit Kumar; Scaria, Vinod; Sharma, Vinod Kumar; Sethuraman, Gomathy

2017-01-01

Immunofluorescence (IFM) antigen mapping is the most commonly used technique to diagnose and differentiate epidermolysis bullosa (EB). In India, IFM is limited to few research laboratories and is not readily available, making the diagnosis largely clinical and often inaccurate. Ob jective of the Study: To examine the diagnostic usefulness of immunohistochemistry (IHC) as compared to IFM in resource-limited settings. Forty-four consecutive EB patients were included in this study. IHC and IFM were performed on 7-µm frozen tissue sections using standard laboratory protocols with a limited panel of antibodies. The kappa coefficient of agreement was calculated with genetic analysis as the gold standard. IFM and IHC accurately identified the subtype of EB in 80.9% (p < 0.001) of the cases, when a clear blister cavity was evident on biopsy. The sensitivities and specificities of IHC and IFM for diagnosing EB simplex, junctional EB, and dystrophic EB were 100, 100, and 60% and 82.4, 100, and 100%, respectively. IHC was equally effective (p < 0.001) in establishing the type of EB as IFM. IHC staining and its interpretation were simple and comparable to IFM. IHC had an advantage of showing subtle changes in the epidermal architecture that could not be appreciated on IFM and hence can be considered useful in resource-limited settings. © 2017 S. Karger AG, Basel.

ELLERMAN BOMBS WITH JETS: CAUSE AND EFFECT

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

Reid, A.; Mathioudakis, M.; Scullion, E.

2015-05-20

Ellerman Bombs (EBs) are thought to arise as a result of photospheric magnetic reconnection. We use data from the Swedish 1 m Solar Telescope to study EB events on the solar disk and at the limb. Both data sets show that EBs are connected to the foot points of forming chromospheric jets. The limb observations show that a bright structure in the Hα blue wing connects to the EB initially fueling it, leading to the ejection of material upwards. The material moves along a loop structure where a newly formed jet is subsequently observed in the red wing of Hα.more » In the disk data set, an EB initiates a jet which propagates away from the apparent reconnection site within the EB flame. The EB then splits into two, with associated brightenings in the inter-granular lanes. Micro-jets are then observed, extending to 500 km with a lifetime of a few minutes. Observed velocities of the micro-jets are approximately 5–10 km s{sup −1}, while their chromospheric counterparts range from 50 to 80 km s{sup −1}. MURaM simulations of quiet Sun reconnection show that micro-jets with properties similar to those of the observations follow the line of reconnection in the photosphere, with associated Hα brightening at the location of increased temperature.« less

Retarded germination of Nicotiana tabacum seeds following insertion of exogenous DNA mimics the seed persistent behavior

PubMed Central

Gagliardi, Assunta; Zaninelli, Mauro; Bini, Luca; Baldi, Antonella; Caccianiga, Marco; Reggi, Serena; Rossi, Luciana

2017-01-01

Tobacco seeds show a coat-imposed dormancy in which the seed envelope tissues (testa and endosperm) impose a physical constraint on the radicle protrusion. The germination-limiting process is represented by the endosperm rupture which is induced by cell-wall weakening. Transgenic tobacco seeds, obtained by insertion of exogenous genes codifying for seed-based oral vaccines (F18 and VT2eB), showed retarded germination with respect to the wild type and modified the expression of endogenous proteins. Morphological and proteomic analyses of wild type and transgenic seeds revealed new insights into factors influencing seed germination. Our data showed that the interference of exogenous DNA influences the germination rather than the dormancy release, by modifying the maturation process. Dry seeds of F18 and VT2eB transgenic lines accumulated a higher amount of reserve and stress–related proteins with respect to the wild type. Moreover, the storage proteins accumulated in tobacco F18 and VT2eB dry seeds have structural properties that do not enable the early limited proteolysis observed in the wild type. Morphological observations by electron and light microscopy revealed a retarded mobilization of the storage material from protein and lipid bodies in transgenic seeds, thus impairing water imbibition and embryo elongation. In addition, both F18 and VT2eB dry seeds are more rounded than the wild type. Both the morphological and biochemical characteristics of transgenic seeds mimic the seed persistent profile, in which their roundness enables them to be buried in the soil, while the higher content of storage material enables the hypocotyl to elongate more and the cotyledons to emerge. PMID:29216220

Comparison of Four Protocols to Generate Chondrocyte-Like Cells from Human Induced Pluripotent Stem Cells (hiPSCs).

PubMed

Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Richter, Magdalena; Trzeciak, Tomasz

2017-04-01

Stem cells (SCs) are a promising approach to regenerative medicine, with the potential to treat numerous orthopedic disorders, including osteo-degenerative diseases. The development of human-induced pluripotent stem cells (hiPSCs) has increased the potential of SCs for new treatments. However, current methods of differentiating hiPSCs into chondrocyte-like cells are suboptimal and better methods are needed. The aim of the present study was to assess four different chondrogenic differentiation protocols to identify the most efficient method of generating hiPSC-derived chondrocytes. For this study, hiPSCs were obtained from primary human dermal fibroblasts (PHDFs) and differentiated into chondrocyte-like cells using four different protocols: 1) monolayer culture with defined growth factors (GF); 2) embryoid bodies (EBs) in a chondrogenic medium with TGF-β3 cells; 3) EBs in chondrogenic medium conditioned with human chondrocytes (HC-402-05a cell line) and 4) EBs in chondrogenic medium conditioned with human chondrocytes and supplemented with TGF-β3. The cells obtained through these four protocols were evaluated and compared at the mRNA and protein levels. Although chondrogenic differentiation of hiPSCs was successfully achieved with all of these protocols, the two fastest and most cost-effective methods were the monolayer culture with GFs and the medium conditioned with human chondrocytes. Both of these methods are superior to other available techniques. The main advantage of the conditioned medium is that the technique is relatively simple and inexpensive while the directed method (i.e., monolayer culture with GFs) is faster than any protocol described to date because it is does not require additional steps such as EB formation.

Daily rhythms in locomotor circuits in Drosophila involve PDF

PubMed Central

Pírez, Nicolás; Christmann, Bethany L.

2013-01-01

The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep. PMID:23678016

Daily rhythms in locomotor circuits in Drosophila involve PDF.

PubMed

Pírez, Nicolás; Christmann, Bethany L; Griffith, Leslie C

2013-08-01

The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep.

Retarded germination of Nicotiana tabacum seeds following insertion of exogenous DNA mimics the seed persistent behavior.

PubMed

Onelli, Elisabetta; Moscatelli, Alessandra; Gagliardi, Assunta; Zaninelli, Mauro; Bini, Luca; Baldi, Antonella; Caccianiga, Marco; Reggi, Serena; Rossi, Luciana

2017-01-01

Tobacco seeds show a coat-imposed dormancy in which the seed envelope tissues (testa and endosperm) impose a physical constraint on the radicle protrusion. The germination-limiting process is represented by the endosperm rupture which is induced by cell-wall weakening. Transgenic tobacco seeds, obtained by insertion of exogenous genes codifying for seed-based oral vaccines (F18 and VT2eB), showed retarded germination with respect to the wild type and modified the expression of endogenous proteins. Morphological and proteomic analyses of wild type and transgenic seeds revealed new insights into factors influencing seed germination. Our data showed that the interference of exogenous DNA influences the germination rather than the dormancy release, by modifying the maturation process. Dry seeds of F18 and VT2eB transgenic lines accumulated a higher amount of reserve and stress-related proteins with respect to the wild type. Moreover, the storage proteins accumulated in tobacco F18 and VT2eB dry seeds have structural properties that do not enable the early limited proteolysis observed in the wild type. Morphological observations by electron and light microscopy revealed a retarded mobilization of the storage material from protein and lipid bodies in transgenic seeds, thus impairing water imbibition and embryo elongation. In addition, both F18 and VT2eB dry seeds are more rounded than the wild type. Both the morphological and biochemical characteristics of transgenic seeds mimic the seed persistent profile, in which their roundness enables them to be buried in the soil, while the higher content of storage material enables the hypocotyl to elongate more and the cotyledons to emerge.

Electron beam technologies in Poland state of the art and possibilities of development

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

Wojcicki, S.

1994-12-31

The recent state of high energy electron beam /EB/ used for metals melting and welding in Poland has been presented. Some typical construction of EB furnaces and EB welding machines designed and constructed in Institute of Vacuum Technology in Warsaw are shown. The examples of their application has also been described.

Error-Based Simulation for Error-Awareness in Learning Mechanics: An Evaluation

ERIC Educational Resources Information Center

Horiguchi, Tomoya; Imai, Isao; Toumoto, Takahito; Hirashima, Tsukasa

2014-01-01

Error-based simulation (EBS) has been developed to generate phenomena by using students' erroneous ideas and also offers promise for promoting students' awareness of errors. In this paper, we report the evaluation of EBS used in learning "normal reaction" in a junior high school. An EBS class, where students learned the concept…

77 FR 8901 - Notice of a Change in Status of an Extended Benefit (EB) Period for New Mexico

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

... Extended Benefit (EB) Period for New Mexico AGENCY: Employment and Training Administration, Labor. ACTION... State's EB status: The Federal authorization to have a three year look-back was recently extended to... governed by the Federal- State Extended Unemployment Compensation Act of 1970, as amended, and the...

24 CFR 954.4 - Other Federal requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 7(b) of the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450e(b)). Section 7...) Definitions. (i) The Indian Self-Determination and Education Assistance Act (25 U.S.C. 450e(b)) defines... Section 7(b) of the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450e(b)) (Indian Act...

Collateral Information for Equating in Small Samples: A Preliminary Investigation

ERIC Educational Resources Information Center

Kim, Sooyeon; Livingston, Samuel A.; Lewis, Charles

2011-01-01

This article describes a preliminary investigation of an empirical Bayes (EB) procedure for using collateral information to improve equating of scores on test forms taken by small numbers of examinees. Resampling studies were done on two different forms of the same test. In each study, EB and non-EB versions of two equating methods--chained linear…

Conditions of Employment and Income Distribution in Mexico as Incentives for Mexican Migration to the United States: Prospects to the End of the Century.

ERIC Educational Resources Information Center

James, Dilmus D.; Evans, John S.

1979-01-01

This paper examines factors contributing to the flow of undocumented migrants from Mexico, demonstrating the problem to be both massive and enduring. Focused on are the inadequate growth of productive employment, income inequality, and rapid population growth. (Author/EB)

Patterns of Sensitivity to Parenting and Peer Environments: Early Temperament and Adolescent Externalizing Behavior.

PubMed

Tung, Irene; Noroña, Amanda N; Morgan, Julia E; Caplan, Barbara; Lee, Steve S; Baker, Bruce L

2018-03-14

Although parenting behavior and friendship quality predict adolescent externalizing behaviors (EBs), individual differences in temperament may differentially affect susceptibility to these factors over time. In a multi-method and multi-informant study of 141 children followed prospectively from toddlerhood to adolescence, we tested the independent and interactive associations of age 3 reactive temperament (e.g., negative emotionality) and age 13 observed parenting (i.e., positive and negative behavior) and friendship (i.e., conflict and warmth), with multi-informant ratings of age 15 aggression and rule-breaking behavior. Negative parenting predicted growth in parent-rated EB, but only for adolescents with early reactive temperament. Temperament did not affect sensitivity to positive parenting or friendship. Results are discussed in the context of differential susceptibility theory and intervention implications for adolescents. © 2018 Society for Research on Adolescence.

Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging.

PubMed

Koehler, Christopher L; Perkins, Guy A; Ellisman, Mark H; Jones, D Leanne

2017-08-07

Intestinal stem cells (ISCs) maintain the midgut epithelium in Drosophila melanogaster Proper cellular turnover and tissue function rely on tightly regulated rates of ISC division and appropriate differentiation of daughter cells. However, aging and epithelial injury cause elevated ISC proliferation and decreased capacity for terminal differentiation of daughter enteroblasts (EBs). The mechanisms causing functional decline of stem cells with age remain elusive; however, recent findings suggest that stem cell metabolism plays an important role in the regulation of stem cell activity. Here, we investigate how alterations in mitochondrial homeostasis modulate stem cell behavior in vivo via RNA interference-mediated knockdown of factors involved in mitochondrial dynamics. ISC/EB-specific knockdown of the mitophagy-related genes Pink1 or Parkin suppresses the age-related loss of tissue homeostasis, despite dramatic changes in mitochondrial ultrastructure and mitochondrial damage in ISCs/EBs. Maintenance of tissue homeostasis upon reduction of Pink1 or Parkin appears to result from reduction of age- and stress-induced ISC proliferation, in part, through induction of ISC senescence. Our results indicate an uncoupling of cellular, tissue, and organismal aging through inhibition of ISC proliferation and provide insight into strategies used by stem cells to maintain tissue homeostasis despite severe damage to organelles. © 2017 Koehler et al.

Biological effects of the anti-parasitic chemotherapeutant emamectin benzoate on a non-target crustacean, the spot prawn (Pandalus platyceros Brandt, 1851) under laboratory conditions.

PubMed

Veldhoen, Nik; Ikonomou, Michael G; Buday, Craig; Jordan, Jameson; Rehaume, Vicki; Cabecinha, Melissa; Dubetz, Cory; Chamberlain, Jon; Pittroff, Sabrina; Vallée, Kurtis; van Aggelen, Graham; Helbing, Caren C

2012-02-01

The potential impact of commercial salmon aquaculture along the coast of British Columbia on the health of non-target marine wildlife is of growing concern. In the current initiative, the biological effects on gene expression within spot prawn (Pandalus platyceros) exposed to the sea lice controlling agent, emamectin benzoate (EB; 0.1-4.8 mg/kg sediment), were investigated. A mean sediment/water partitioning coefficient (K(p)) was determined to be 21.81 and significant levels of EB were detected in the tail muscle tissue in all exposed animals. Animals selected for the experiment did not have eggs and were of similar weight. Significant mortality was observed within 8 days of EB treatment at concentrations between 0.1 and 0.8 mg/kg and there was no effect of EB on molting. Twelve spot prawn cDNA sequences were isolated from the tail muscle either by directed cloning or subtractive hybridization of control versus EB exposed tissues. Three of the transcripts most affected by EB exposure matched sequences encoding the 60S ribosomal protein L22, spliceosome RNA helicase WM6/UAP56, and the intracellular signal mediator histidine triad nucleotide binding protein 1 suggesting that translation, transcription regulation, and apoptosis pathways were impacted. The mRNA encoding the molting enzyme, β-N-acetylglucosaminidase, was not affected by EB treatment. However, the expression of this transcript was extremely variable making it unsuitable for effects assessment. The results suggest that short-term exposure to EB can impact biological processes within this non-target crustacean. Copyright © 2011 Elsevier B.V. All rights reserved.

Secure fixation of femoral bone plug with a suspensory button in anatomical anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft

PubMed Central

TAKETOMI, SHUJI; INUI, HIROSHI; NAKAMURA, KENSUKE; YAMAGAMI, RYOTA; TAHARA, KEITARO; SANADA, TAKAKI; MASUDA, HIRONARI; TANAKA, SAKAE; NAKAGAWA, TAKUMI

2015-01-01

Purpose the efficacy and safety of using a suspensory button for femoral fixation in anatomical anterior cruciate ligament (ACL) reconstruction with bone-patellar tendon-bone (BPTB) graft have not been established. The purpose of the current study was to evaluate bone plug integration onto the femoral socket and migration of the bone plug and the EndoButton (EB) (Smith & Nephew, Andover, MA, USA) after rectangular tunnel ACL reconstruction with BPTB autograft. Methods thirty-four patients who underwent anatomical rectangular ACL reconstruction with BPTB graft using EB for femoral fixation and in whom three-dimensional (3D) computed tomography (CT) was performed one week and one year after surgery were included in this study. Bone plug integration onto the femoral socket, bone plug migration, soft tissue interposition, EB migration and EB rotation were evaluated on 3D CT. The clinical outcome was also assessed and correlated with the imaging outcomes. Results the bone plug was integrated onto the femoral socket in all cases. The incidence of bone plug migration, soft tissue interposition, EB migration and EB rotation was 15, 15, 9 and 56%, respectively. No significant association was observed between the imaging outcomes. The postoperative mean Lysholm score was 97.1 ± 5.0 points. The postoperative side-to-side difference, evaluated using a KT-2000 arthrometer, averaged 0.5 ± 1.3 mm. There were no complications associated with EB use. Imaging outcomes did not affect the postoperative KT side-to-side difference. Conclusions the EB is considered a reliable device for femoral fixation in anatomical rectangular tunnel ACL reconstruction with BPTB autograft. Level of evidence Level IV, therapeutic case series. PMID:26889465

Vaginocervical stimulation attenuates the sensitization of appetitive sexual behaviors by estradiol benzoate in the ovariectomized rat.

PubMed

Jones, Sherri Lee; Germé, Katuschia; Graham, M Dean; Roy, Patrick; Gardner Gregory, James; Rosenbaum, Stephanie; Parada, Mayte; Pfaus, James G

2015-09-01

The acute administration of estradiol benzoate (EB) to the ovariectomized (OVX) rat induces low levels of lordosis while sexually appetitive behaviors (e.g., hops, darts, solicitations) are absent, yet the repeated administration of EB results in a behavioral sensitization in which lordosis is potentiated and sexually appetitive behaviors are induced. We have shown that repeated copulation attenuates the sensitization of appetitive sexual behaviors. Here, we assessed which component of male stimulation during copulation is involved in the attenuation. On 8 occasions, sexually experienced OVX Long-Evans rats were treated with 10μgEB and 48h later assigned to one of six groups that differed in their experience on intermediates tests (2-7). One was given repeated access to a male (EB/Male), and another was placed in the copulation chamber alone (EB/Alone) on intermediate tests. Three groups were given one of three somatosensory stimuli by the experimenter: manual flank stimulation (FLS), clitoral stimulation (CLS), or vaginocervical stimulation (VCS). Finally, the control group was left undisturbed in the animal care facility (ACF). Sexual behaviors were measured on Tests 1 and 8. VCS received from the experimenter (VCS) or from the male during copulation (EB/Male) attenuated the magnitude of the sensitization of appetitive sexual behaviors compared with those that were not brought to the testing rooms (ACF), and the effect was most pronounced on sexual solicitations. These results suggest that VCS received during penile intromission inhibits the sensitization of sexually appetitive behaviors by repeated administration of EB. As such, repeated administration of EB may oppose those mechanisms that induce estrous termination, perhaps by sensitizing inhibitory processes within the ventromedial hypothalamus that typically prevent the display of sexual behaviors (i.e., by facilitating disinhibition). Copyright © 2015 Elsevier Inc. All rights reserved.

Imprinted expression in cystic embryoid bodies shows an embryonic and not an extra-embryonic pattern

PubMed Central

Kulinski, Tomasz M.; Casari, M. Rita T.; Guenzl, Philipp M.; Wenzel, Daniel; Andergassen, Daniel; Hladik, Anastasiya; Datlinger, Paul; Farlik, Matthias; Theussl, H. -Christian; Penninger, Josef M.; Knapp, Sylvia; Bock, Christoph; Barlow, Denise P.; Hudson, Quanah J.

2015-01-01

A large subset of mammalian imprinted genes show extra-embryonic lineage (EXEL) specific imprinted expression that is restricted to placental trophectoderm lineages and to visceral yolk sac endoderm (ysE). Isolated ysE provides a homogenous in vivo model of a mid-gestation extra-embryonic tissue to examine the mechanism of EXEL-specific imprinted gene silencing, but an in vitro model of ysE to facilitate more rapid and cost-effective experiments is not available. Reports indicate that ES cells differentiated into cystic embryoid bodies (EBs) contain ysE, so here we investigate if cystic EBs model ysE imprinted expression. The imprinted expression pattern of cystic EBs is shown to resemble fetal liver and not ysE. To investigate the reason for this we characterized the methylome and transcriptome of cystic EBs in comparison to fetal liver and ysE, by whole genome bisulphite sequencing and RNA-seq. Cystic EBs show a fetal liver pattern of global hypermethylation and low expression of repeats, while ysE shows global hypomethylation and high expression of IAPEz retroviral repeats, as reported for placenta. Transcriptome analysis confirmed that cystic EBs are more similar to fetal liver than ysE and express markers of early embryonic endoderm. Genome-wide analysis shows that ysE shares epigenetic and repeat expression features with placenta. Contrary to previous reports, we show that cystic EBs do not contain ysE, but are more similar to the embryonic endoderm of fetal liver. This explains why cystic EBs reproduce the imprinted expression seen in the embryo but not that seen in the ysE. PMID:25912690

Genetic parameter estimation for milk β-hydroxybutyrate and acetone in early lactation and its association with fat to protein ratio and energy balance in Korean Holstein cattle.

PubMed

Ranaraja, Umanthi; Cho, KwangHyun; Park, MiNa; Kim, SiDong; Lee, SeokHyun; Do, ChangHee

2018-06-01

The objective of this study was to estimate the genetic parameters for milk β-hydroxybutyrate (BHBA), acetone (Ac), fat protein ratio (FPR), and energy balance (EB) using milk test day records and investigate the effect of early lactation FPR and EB on milk ketone body concentrations. Total 262,940 test-day records collected from Korea Animal Improvement Association during the period of 2012 to 2016 were used in this study. BHBA and Ac concentrations in milk were measured by Fourier transform infrared spectroscopy (FTIR). FPR values were obtained using test day records of fat and protein percentage. EB was calculated using previously developed equation based on parity, lactation week, and milk composition data. Genetic parameters were estimated by restricted maximum likelihood procedure based on repeatability model using Wombat program. Elevated milk BHBA and Ac concentrations were observed during the early lactation under the negative energy balance. Milk FPR tends to decrease with the decreasing ketone body concentrations. Heritability estimates for milk BHBA, Ac, EB, and FPR ranged from 0.09 to 0.14, 0.23 to 0.31, 0.19 to 0.52, and 0.16 to 0.42 respectively at parity 1, 2, 3, and 4. The overall heritability for BHBA, Ac, EB and FPR were 0.29, 0.32, 0.58, and 0.38 respectively. A common pattern was observed in heritability of EB and FPR along with parities. FPR and EB can be suggested as potential predictors for risk of hyperketonemia. The heritability estimates of milk BHBA, Ac, EB, and FPR indicate that the selective breeding may contribute to maintaining the milk ketone bodies at optimum level during early lactation.

Efficiency of Core Biopsy for BI-RADS-5 Breast Lesions.

PubMed

Wolf, Ronald; Quan, Glenda; Calhoun, Kris; Soot, Laurel; Skokan, Laurie

2008-01-01

Stereotactic biopsy has proven more cost effective for biopsy of lesions associated with moderately suspicious mammograms. Data regarding selection of stereotactic biopsy (CORE) instead of excisional biopsy (EB) as the first diagnostic procedure in patients with nonpalpable breast lesions and highest suspicion breast imaging-reporting and data system (BI-RADS)-5 mammograms are sparse. Records from a regional health system radiology database were screened for mammograms associated with image-guided biopsy. A total of 182 nonpalpable BI-RADS-5 lesions were sampled in 178 patients over 5 years, using CORE or EB. Initial surgical margins, number of surgeries, time from initial procedure to last related surgical procedure, and hospital and professional charges for related admissions were compared using chi-squared, t-test, and Wilcoxon Mann-Whitney tests. A total of 108 CORE and 74 EB were performed as the first diagnostic procedure. Invasive or in situ carcinoma was diagnosed in 156 (86%) of all biopsies, 95 in CORE and 61 in EB groups. Negative margins of the first surgical procedure were more frequent in CORE (n = 70, 74%) versus EB (n = 17, 28%), p < 0.05. Use of CORE was associated with fewer total surgical procedures per lesion (1.29 +/- 0.05 versus 1.8 +/- 0.05, p < 0.05). Time of initial diagnostic procedure to final treatment did not vary significantly according to group (27 +/- 2 days versus 22 +/- 2 days, CORE versus EB). Mean charges including the diagnostic procedure and all subsequent surgeries were not different between CORE and EB groups ($10,500 +/- 300 versus $11,500 +/- 500, p = 0.08). Use of CORE as the first procedure in patients with highly suspicious mammograms is associated with improved pathologic margins and need for fewer surgical procedures than EB, and should be considered the preferred initial diagnostic approach.

Comparison of early morphological and molecular changes induced by 17-alpha-methyltestosterone and estradiol benzoate in the rat ovary.

PubMed

Ferre, Céline; Belluco, Sara; Tinwell, Helen; Bars, Rémi; Benahmed, Mohamed; Rouquie, David; Schorsch, Frédéric

2013-05-01

Repeated exposure to 17-α-methyltestosterone (17MT) and estradiol benzoate (EB) for 28 or 90 days in rats induce similar ovarian atrophy. The objective of the present work was to identify and compare the early effects induced by 17MT and EB on the ovary using molecular and histopathological tools. Female rats were evaluated after 1, 3 or 7 days following an oral exposure by gavage at a daily dose of 600 mg/kg/day for 17MT and 5 mg/kg/day for EB. All animals were found to be acyclic after 3 or 7 days of treatment with 17MT and EB. Histopathological changes were present in the ovary, uterus, vagina and mammary gland after both treatments. Ovarian atrophy known as the long term effect of 17MT and EB was not yet detected after 7 days of treatment. But non regressive corpora lutea and cystic follicles were identically observed in the ovary of 17MT and EB treated females. Both compounds induced a decrease of LH transcripts together with an increase of plasma progesterone and prolactin levels. Differences in the profile of regulation of the aromatase were noted after 1 and 3 days of treatment in 17MT treated animals (upregulated) when compared to EB treated animals (downregulated). In summary, we have shown that despite the different nature of hormonal activity, EB and 17MT induce very early endocrine perturbation which presents several similarities. Our work indicated that the detection of early key hormonal markers in short term studies can help to predict the adverse long term effects on target tissues. Copyright © 2012 Elsevier GmbH. All rights reserved.

The Spatial Distribution of Adult Obesity Prevalence in Denver County, Colorado: An Empirical Bayes Approach to Adjust EHR-Derived Small Area Estimates.

PubMed

Tabano, David C; Bol, Kirk; Newcomer, Sophia R; Barrow, Jennifer C; Daley, Matthew F

2017-12-06

Measuring obesity prevalence across geographic areas should account for environmental and socioeconomic factors that contribute to spatial autocorrelation, the dependency of values in estimates across neighboring areas, to mitigate the bias in measures and risk of type I errors in hypothesis testing. Dependency among observations across geographic areas violates statistical independence assumptions and may result in biased estimates. Empirical Bayes (EB) estimators reduce the variability of estimates with spatial autocorrelation, which limits the overall mean square-error and controls for sample bias. Using the Colorado Body Mass Index (BMI) Monitoring System, we modeled the spatial autocorrelation of adult (≥ 18 years old) obesity (BMI ≥ 30 kg m 2 ) measurements using patient-level electronic health record data from encounters between January 1, 2009, and December 31, 2011. Obesity prevalence was estimated among census tracts with >=10 observations in Denver County census tracts during the study period. We calculated the Moran's I statistic to test for spatial autocorrelation across census tracts, and mapped crude and EB obesity prevalence across geographic areas. In Denver County, there were 143 census tracts with 10 or more observations, representing a total of 97,710 adults with a valid BMI. The crude obesity prevalence for adults in Denver County was 29.8 percent (95% CI 28.4-31.1%) and ranged from 12.8 to 45.2 percent across individual census tracts. EB obesity prevalence was 30.2 percent (95% CI 28.9-31.5%) and ranged from 15.3 to 44.3 percent across census tracts. Statistical tests using the Moran's I statistic suggest adult obesity prevalence in Denver County was distributed in a non-random pattern. Clusters of EB obesity estimates were highly significant (alpha=0.05) in neighboring census tracts. Concentrations of obesity estimates were primarily in the west and north in Denver County. Statistical tests reveal adult obesity prevalence exhibit spatial autocorrelation in Denver County at the census tract level. EB estimates for obesity prevalence can be used to control for spatial autocorrelation between neighboring census tracts and may produce less biased estimates of obesity prevalence.

The Modified Selenenyl Amide, M-hydroxy Ebselen, Attenuates Diabetic Nephropathy and Diabetes-Associated Atherosclerosis in ApoE/GPx1 Double Knockout Mice

PubMed Central

Tan, Sih Min; Sharma, Arpeeta; Yuen, Derek Y. C.; Stefanovic, Nada; Krippner, Guy; Mugesh, Govindasamy; Chai, Zhonglin; de Haan, Judy B.

2013-01-01

Seleno-organic glutathione peroxidase (GPx) mimetics, including ebselen (Eb), have been tested in in vitro studies for their ability to scavenge reactive oxygen and nitrogen species, including hydrogen peroxide and peroxynitrite. In this study, we investigated the efficacies of two Eb analogues, m-hydroxy ebselen (ME) and ethanol-ebselen (EtE) and compared these with Eb in cell based assays. We found that ME is superior in attenuating the activation of hydrogen peroxide-induced pro-inflammatory mediators, ERK and P38 in human aortic endothelial cells. Consequently, we investigated the effects of ME in an in vivo model of diabetes, the ApoE/GPx1 double knockout (dKO) mouse. We found that ME attenuates plaque formation in the aorta and lesion deposition within the aortic sinus of diabetic dKO mice. Oxidative stress as assessed by 8-OHdG in urine and nitrotyrosine immunostaining in the aortic sinus and kidney tubules, was reduced by ME in diabetic dKO mice. ME also attenuated diabetes-associated renal injury which included tubulointerstitial fibrosis and glomerulosclerosis. Furthermore, the bioactivity of the pro-fibrotic cytokine transforming growth factor-β (TGF-β) as assessed by phospho-Smad2/3 immunostaining was attenuated after treatment with ME. TGF-β-stimulated increases in collagen I and IV gene expression and protein levels were attenuated by ME in rat kidney tubular cells. However, in contrast to the superior activity of ME in in vitro and cell based assays, ME did not further augment the attenuation of diabetes-associated atherosclerosis and renal injury in our in vivo model when compared with Eb. In conclusion, this study strengthens the notion that bolstering GPx-like activity using synthetic mimetics may be a useful therapeutic strategy in lessening the burden of diabetic complications. However, these studies highlight the importance of in vivo analyses to test the efficacies of novel Eb analogues, as in vitro and cell based assays are only partly predictive of the in vivo situation. PMID:23874911

High-sensitivity green resist material with organic solvent-free spin-coating and tetramethylammonium hydroxide-free water-developable processes for EB and EUV lithography

NASA Astrophysics Data System (ADS)

Takei, Satoshi; Hanabata, Makoto; Oshima, Akihiro; Kashiwakura, Miki; Kozawa, Takahiro; Tagawa, Seiichi

2015-03-01

We investigated the eco-friendly electron beam (EB) and extreme-ultraviolet (EUV) lithography using a high-sensitive negative type of green resist material derived from biomass to take advantage of organic solvent-free water spin-coating and tetramethylammonium hydroxide(TMAH)-free water-developable techniques. A water developable, non-chemically amplified, high sensitive, and negative tone resist material in EB lithography was developed for environmental affair, safety, easiness of handling, and health of the working people, instead of the common developable process of TMAH. The material design concept to use the water-soluble resist material with acceptable properties such as pillar patterns with less than 100 nm in high EB sensitivity of 10 μC/cm2 and etch selectivity with a silicon-based middle layer in CF4 plasma treatment was demonstrated for EB and EUV lithography.

Modeling electric bicycle's lane-changing and retrograde behaviors

NASA Astrophysics Data System (ADS)

Tang, Tie-Qiao; Luo, Xiao-Feng; Zhang, Jian; Chen, Liang

2018-01-01

Recently, electric bicycle (EB) has been one important traffic tool due to its own merits. However, EB's motion behaviors (especially at a signalized/non-signalized intersection) are more complex than those of vehicle since it always has lane-changing and retrograde behaviors. In this paper, we propose a model to explore EB's lane-changing and retrograde behaviors on a road with a signalized intersection. The numerical results indicate that the proposed model can qualitatively describe each EB's lane-changing and retrograde behaviors near a signalized intersection, and that lane-changing and retrograde behaviors have prominent impacts on the signalized intersection (i.e., prominent jams and congestions occur). The above results show that EB should be controlled as a vehicle, i.e., lane-changing and retrograde behaviors at a signalized intersection should strictly be prohibited to improve the operational efficiency and traffic safety at the signalized intersection.

Decomposition of 2,4-dichlorophenoxyacetic acid by ozonation, ionizing radiation as well as ozonation combined with ionizing radiation

NASA Astrophysics Data System (ADS)

Drzewicz, Przemyslaw; Trojanowicz, Marek; Zona, Robert; Solar, Sonja; Gehringer, Peter

2004-03-01

Electron beam (EB), ozone (O 3) and the combination EB/O 3 were used to study the oxidative decomposition of 2,4-dichlorophenoxyacetic acid (2,4-D) in local tap water. Using an EB treatment, a dose of 10 kGy was required for complete 2,4-D degradation, and a 90% conversion of organic chlorine into chloride ions. Using additionally 1.33 mmol dm -3 O 3 during irradiation, the same result was achieved with a dose of 2.7 kGy. The yields of products acetate and formate were almost doubled by the combined EB/O 3 treatment, compared to those obtained with the same dose by EB irradiation. Gamma radiolysis showed that the degradation dose was proportional to the initial concentration of 2,4-D in the range of 50-2260 μmol dm -3.

Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

PubMed

Noujima-Harada, Mai; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sakurai, Hiroaki; Igarashi, Kazuhiko; Ito, Etsuro; Nagakita, Keina; Taniguchi, Kohei; Ohnishi, Nobuhiko; Omote, Shizuma; Tabata, Tetsuya; Sato, Yasuharu; Yoshino, Tadashi

2017-05-01

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-β-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

An Evaluation of Empirical Bayes's Estimation of Value-Added Teacher Performance Measures

ERIC Educational Resources Information Center

Guarino, Cassandra M.; Maxfield, Michelle; Reckase, Mark D.; Thompson, Paul N.; Wooldridge, Jeffrey M.

2015-01-01

Empirical Bayes's (EB) estimation has become a popular procedure used to calculate teacher value added, often as a way to make imprecise estimates more reliable. In this article, we review the theory of EB estimation and use simulated and real student achievement data to study the ability of EB estimators to properly rank teachers. We compare the…

Enhanced backscatter of optical beams reflected in turbulent air.

PubMed

Nelson, W; Palastro, J P; Wu, C; Davis, C C

2015-07-01

Optical beams propagating through air acquire phase distortions from turbulent fluctuations in the refractive index. While these distortions are usually deleterious to propagation, beams reflected in a turbulent medium can undergo a local recovery of spatial coherence and intensity enhancement referred to as enhanced backscatter (EBS). Here we validate the commonly used phase screen simulation with experimental results obtained from lab-scale experiments. We also verify theoretical predictions of the dependence of the turbulence strength on EBS. Finally, we present a novel algorithm called the "tilt-shift method" which allows detection of EBS in frozen turbulence, reducing the time required to detect the EBS signal.

Endoscopic Biliary Stenting Versus Percutaneous Transhepatic Biliary Stenting in Advanced Malignant Biliary Obstruction: Cost-effectiveness Analysis.

PubMed

Sun, Xin Rong; Tang, Cheng Wu; Lu, Wen Ming; Xu, Yong Qiang; Feng, Wen Ming; Bao, Yin; Zheng, Yin Yuan

2014-05-01

This study aims to compare the clinical outcomes and costs between endoscopic biliary stenting (EBS) and percutaneous transhepatic biliary stenting (PTBS). We randomly assigned 112 patients with unresectable malignant biliary obstruction 2006 and 2011 to receive EBS or PTBS with self-expandable metal stent (SEMS) as palliative treatment. PTBS was successfully performed in 55 patients who formed the PTBS group (failed in 2 patients). EBS was successfully performed in 52 patients who formed the EBS group (failed in 3 patients). The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the BBS group (P < 0.05). There was no significant difference in effectiveness of biliary drainage (P = 0.9357) or survival time between two groups (P = 0.6733). Early complications occurred in PTBS group was significantly lower than in EBS group (3/55 vs 11/52, P = 0.0343). Late complications in the EBS group did not differ significantly from PTBS group (7/55 vs 9/52, P = 0.6922). The survival curves in the two groups showed no significant difference (P = 0.5294). Conclusions: 3.

A novel KRT5 mutation associated with generalized severe epidermolysis bullosa simplex in a 2-year-old Chinese boy

PubMed Central

Zhang, Jia; Yan, Ming; Liang, Jianying; Li, Ming; Yao, Zhirong

2016-01-01

Mutations in keratin 5 (KRT5) or KRT14 genes are responsible for the most severe form of epidermolysis bullosa simplex (EBS), which is EBS generalized severe (EBS-gen sev). To date, only four pathogenic mutations (p.Arg165Ser and p.Lys199Asn in KRT5; p.Arg125Cys and p.Arg125His in KRT14) have been reported to be responsible for EBS-gen sev in the Chinese population. In the present study, a 2-year-old Chinese boy was clinically suspected to suffer from EBS, and thus Sanger sequencing was performed in the extracted genomic DNA samples from the patient, his parents and 100 healthy controls. A novel de novo heterozygous missense mutation c.503A>G (p.Glu168Gly) located at the N-terminal end segment of the 1A domain in KRT5 was identified by molecular analysis. In silico analysis tools were used to predict the pathogenicity of the novel missense mutation. A diagnosis of EBS-gen sev was thus confirmed according to the clinical presentations and molecular results. PMID:27882080

Effectiveness of training in evidence-based medicine skills for healthcare professionals: a systematic review.

PubMed

Hecht, Lars; Buhse, Susanne; Meyer, Gabriele

2016-04-04

Basic skills in evidence-based medicine (EbM) are indispensable for healthcare professionals to promote consumer-centred, evidence-based treatment. EbM training courses are complex interventions - a fact that has not been methodologically reflected by previous systematic reviews. This review evaluates the effects of EbM training for healthcare professionals as well as the quality of reporting of such training interventions. We searched PubMed, EMBASE, CINAHL, Cochrane Library, ERIC, Campbell Library and PsycINFO up to 9/2014. Randomised controlled trials, controlled clinical trials as well as before-after trials were included. Authors were contacted in order to obtain missing data. Two independent reviewers extracted data and assessed risk of bias. We reviewed 14.507 articles; n = 61 appeared potentially eligible; n = 13 involving 1,120 participants were included. EbM training shows some impact on knowledge and skills, whereas the impact on practical EbM application remains unclear. Risk of bias of included trials raises uncertainty about the effects. Description of complex interventions was poor. EbM training has some positive effects on knowledge and skills of healthcare professionals. Appropriate methods for development, piloting, evaluation, reporting and implementation of the training should be applied.

Ebselen induces mitochondrial permeability transition because of its interaction with adenine nucleotide translocase.

PubMed

Pavón, Natalia; Correa, Francisco; Buelna-Chontal, Mabel; Hernández-Esquivel, Luz; Chávez, Edmundo

2015-10-15

Mitochondrial permeability transition is a process established through massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an antioxidant seleno compound, has been introduced as a reagent which inhibits mitochondrial dysfunction induced by permeability transition. Paradoxically enough, it has been shown that Ebs may also be able to induce the opening of the mitochondrial non-selective pores. This study was performed with the purpose of establishing the membrane system involved in Ebs-induced pore opening. Permeability transition was appraised by analyzing the following: i) matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c, and iii) the inhibition of superoxide dismutase. All of these adverse reactions were inhibited by N-ethylmaleimide and cyclosporin A. At concentrations from 5 to 20 μM, we found that Ebs induces non-specific membrane permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin-5-maleimide to the thiol groups of the adenine nucleotide translocase. Based on the above, it is tempting to hypothesize that Ebs induces pore opening through its binding to the ADP/ATP carrier. Copyright © 2015 Elsevier Inc. All rights reserved.

In vitro assessment of the growth and plasma membrane H+ -ATPase inhibitory activity of ebselen and structurally related selenium- and sulfur-containing compounds in Candida albicans.

PubMed

Orie, Natalie N; Warren, Andrew R; Basaric, Jovana; Lau-Cam, Cesar; Piętka-Ottlik, Magdalena; Młochowski, Jacek; Billack, Blase

2017-06-01

Ebselen (EB, compound 1) is an investigational organoselenium compound that reduces fungal growth, in part, through inhibition of the fungal plasma membrane H + -ATPase (Pma1p). In the present study, the growth inhibitory activity of EB and of five structural analogs was assessed in a fluconazole (FLU)-resistant strain of Candida albicans (S2). While none of the compounds were more effective than EB at inhibiting fungal growth (IC 50  ∼ 18 μM), two compounds, compounds 5 and 6, were similar in potency. Medium acidification assays performed with S2 yeast cells revealed that compounds 4 and 6, but not compounds 2, 3, or 5, exerted an inhibitory activity comparable to EB (IC 50  ∼ 14 μM). Using a partially purified Pma1p preparation obtained from S2 yeast cells, EB and all the analogs demonstrated a similar inhibitory activity. Taken together, these results indicate that EB analogs are worth exploring further for use as growth inhibitors of FLU-resistant fungi. © 2017 Wiley Periodicals, Inc.

Differentiating Mouse Embryonic Stem Cells into Embryoid Bodies by Hanging-Drop Cultures.

PubMed

Behringer, Richard; Gertsenstein, Marina; Nagy, Kristina Vintersten; Nagy, Andras

2016-12-01

Embryonic stem (ES) cells can develop into many types of differentiated tissues if they are placed into a differentiating environment. This can occur in vivo when the ES cells are injected into or aggregated with an embryo, or in vitro if their culture conditions are modified to induce differentiation. There are an increasing number of differentiating culture conditions that can bias the differentiation of ES cells into desired cell types. Determining the mechanisms that control ES cell differentiation into therapeutically important cell types is a quickly growing area of research. Knowledge gained from these studies may eventually lead to the use of stem cells to repair specific damaged tissues. Many times ES cell differentiation proceeds through an intermediate stage called the embryoid body (EB). EBs are round structures composed of ES cells that have undergone some of the initial stages of differentiation. EBs can then be manipulated further to generate more specific cell types. This protocol describes a method to differentiate ES cells into EBs. It produces EBs of comparable size. This aspect is important because the differentiation processes taking place inside an EB are influenced by its size. © 2016 Cold Spring Harbor Laboratory Press.

Electron-Beam Atomic Spectroscopy for In Situ Measurements of Melt Composition for Refractory Metals: Analysis of Fundamental Physics and Plasma Models

NASA Astrophysics Data System (ADS)

Gasper, Paul Joseph; Apelian, Diran

2015-04-01

Electron-beam (EB) melting is used for the processing of refractory metals, such as Ta, Nb, Mo, and W. These metals have high value and are critical to many industries, including the semiconductor, aerospace, and nuclear industries. EB melting can also purify secondary feedstock, enabling the recovery and recycling of these materials. Currently, there is no method for measuring melt composition in situ during EB melting. Optical emission spectroscopy of the plasma generated by EB impact with vapor above the melt, a technique here termed electron-beam atomic spectroscopy, can be used to measure melt composition in situ, allowing for analysis of melt dynamics, facilitating improvement of EB melting processes and aiding recycling and recovery of these critical and high-value metals. This paper reviews the physics of the plasma generation by EB impact by characterizing the densities and energies of electrons, ions, and neutrals, and describing the interactions between them. Then several plasma models are introduced and their suitability to this application analyzed. Lastly, a potential method for calibration-free composition measurement is described and the challenges for implementation addressed.

Distribution and permeability of capillaries at the skin of the conception vessel and the governor vessel in healthy rabbits.

PubMed

Zhou, Dan; Guo, Yi; Guo, Yong-Ming; Zhang, Sai; Pan, Ping

2011-12-01

To investigate the distribution and permeability of blood vessels on the Conception Vessel and the Governor Vessel in the physiological state. Evans blue (EB) solution was injected into the marginal ear vein of healthy rabbits. Three hours after injection, the rabbits were sacrificed and the skin on the Conception Vessel and the Governor Vessel and the corresponding bilateral non-channels was collected. EB was extracted with 7:3 acetone: physiological saline, and the absorbance of EB at each skin tissue was measured with a spectrophotometer. The A value of EB absorbance at the Conception Vessel on the abdominal skin was lower than that of the corresponding bilateral non-channels with a statistically significant difference (P< 0.01). The A value of EB absorbance at the Governor Vessel on the back was higher than that of the corresponding bilateral non-channels (P < 0.05). There was no statistical difference in the A value of EB absorbance between the bilateral non-channels of the abdomen and the back (P > 0.05). There were differences in capillary distribution and permeability between the Conception Vessel, the Governor Vessel and the corresponding bilateral non-meridians.

Evaluation of different methods to detect microbial hygiene indicators relevant in the dairy industry.

PubMed

Hervert, C J; Alles, A S; Martin, N H; Boor, K J; Wiedmann, M

2016-09-01

It is estimated that 19% of the total food loss from retail, food service, and households comes from dairy products. A portion of this loss may be attributed to premature spoilage of products due to lapses in sanitation and postpasteurization contamination at the processing level. Bacterial groups including coliforms, Enterobacteriaceae (EB), and total gram-negative organisms represent indicators of poor sanitation or postpasteurization contamination in dairy products worldwide. Although Petrifilms (3M, St. Paul, MN) and traditional selective media are commonly used for the testing of these indicator organism groups throughout the US dairy industry, new rapid methods are also being developed. This project was designed to evaluate the ability of different methods to detect coliforms, EB, and other gram-negative organisms isolated from various dairy products and dairy processing environments. Using the Food Microbe Tracker database, a collection of 211 coliform, EB, and gram-negative bacterial isolates representing 25 genera associated with dairy products was assembled for this study. We tested the selected isolates in pure culture (at levels of approximately 15 to 300 cells/test) to evaluate the ability of 3M Coliform Petrifilm to detect coliforms, 3M Enterobacteriaceae Petrifilm, violet red bile glucose agar, and an alternative flow cytometry-based method (bioMérieux D-Count, Marcy-l'Étoile, France) to detect EB, and crystal violet tetrazolium agar to detect total gram-negative organisms. Of the 211 gram-negative isolates tested, 82% (174/211) had characteristic growth on crystal violet tetrazolium agar. Within this set of 211 gram-negative organisms, 175 isolates representing 19 EB genera were screened for detection using EB selective/differential testing methods. We observed positive results for 96% (168/175), 90% (158/175), and 86% (151/175) of EB isolates when tested on EB Petrifilm, violet red bile glucose agar, and D-Count, respectively; optimization of the cut-off thresholds for the D-Count may further improve its sensitivity and specificity, but will require additional data and may vary in food matrices. Additionally, 74% (129/175) of the EB isolates tested positive as coliforms. The data obtained from this study identify differences in detection between 5 microbial hygiene indicator tests and highlight the benefits of EB and total gram-negative testing methods. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Chromogranin A derived peptide CGA47-66 inhibits hyper-permeability of blood brain barrier in mice with sepsis].

PubMed

Zeng, Yan; Zhang, Dan; Jiang, Liping; Wei, Fu; Xu, Shan

2016-02-01

To explore the effect of chromofungin (CHR), a chromogranin A (CGA) derived peptide CGA47-66, on hyper-permeability of blood brain barrier in septic mice. 120 healthy male C57BL/6 mice were randomly divided into groups, with 12 mice in each group. Seventy-two mice were used for dynamic observation of the contents of water and Evan blue (EB) in brain tissue after being treated with lipopolysaccharide (LPS). Another 48 mice were divided into normal saline control group (NS group), LPS induced sepsis model group (LPS group), low-dose CHR pretreatment group (CL+LPS group), and high-dose CHR pretreatment group (CH+LPS group). The septic model was reproduced by intraperitoneal injection of 10 mg/kg LPS 0.1 mL, and the mice in NS group was given equal volume of normal saline. The mice in CL+LPS group and CH+LPS group were intraperitoneally injected with 15.5 μg/kg and 77.5 μg/kg CHR 10 minutes before LPS injection. Six hours after LPS injection, 4 mL/kg of 2% EB was injected via caudal vein, the contents of water and EB in brain tissue were determined, and EB immune fluorescence in brain tissue was determined to assess the changes in permeability of blood brain barrier. Brain pathology was observed with hematoxylin and eosin (HE) staining. With the extension of time after LPS injection, the contents of water and EB in brain tissue were gradually increased, and the time of difference with statistical significance appeared earlier when compared with that of control group in the contents of water than that in EB contents (3 hours and 6 hours, respectively). The contents of water and EB in brain tissue in LPS group were significantly increased as compared with NS group [water content: (79.77±0.62)% vs. (78.28±0.44)%, P < 0.01; EB content (μg/g): 13.87±4.50 vs. 7.13±1.76, P < 0.05]. CHR pretreatment with either of two dosages could reverse the increase in water and EB contents in brain tissue induced by LPS, and the effect was more significant in CH+LPS group [water content: (78.15±0.73)% vs. (79.77±0.62)%, EB (μg/g): 7.09±2.59 vs. 13.87±4.50, both P < 0.05]. It was shown by EB fluorescence observation that the fluorescence signal displayed only in the meninges in NS group, and EB fluorescence was widely distributed in brain parenchyma in LPS group, indicating that the EB leakage in LPS group was more marked than that of NS group. In CHR pretreatment groups, EB fluorescence was decreased in brain parenchyma, indicating that EB leakage was significantly less marked, while it was more obvious in high dose CHR group. It was shown by HE staining that cerebral blood vessel structure was intact in NS group, and the gap around blood vessel was not significant increased. On the other hand, brain structure in LPS group appeared loose, with widening of small perivascular spaces and obvious edema. Brain edema in CHR pretreatment groups was improved as compared with that of the LPS group, and it was more apparent in high dose CHR group. LPS induced change in blood brain barrier permeability in mice in a time-dependent manner. Exogenous CGA derived peptides CHR can inhibit LPS induced hyper-permeability of blood brain barrier in septic mice, thus reduces brain edema, protects the brain tissue, and the effect is more obvious with a high dose of CHR (77.5 μg/kg).

Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

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

Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt; Lucas, Rui L.; Andrade, Vanda

2012-02-01

Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared tomore » rats treated with Mn alone), concomitant with reduced brain E{sub 2} prostaglandin (PGE{sub 2}) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ► Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.« less

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

Caporuscio, Florie Andre; Norskog, Katherine Elizabeth; Maner, James

Over the past five years the Used Fuel Campaign has investigated Engineered Barrier Systems (EBS) at higher heat loads (up to 300°C) and pressure (150 bar). This past year experimental work was hindered due to a revamping of the hydrothermal lab. Regardless, two experiments were run this past year, EBS-18 and EBS-19. EBS-18 was run using Low Carbon Steel (LCS) and opalinus clay in addition to the bentonite and opalinus brine. Many of the past results were confirmed in EBS-18, such as the restriction of illite formation due to the bulk chemistry, pyrite degradation, and zeolite formation dependent on themore » bentonite and opalinus clay. The LCS show vast amounts of pit corrosion (over 100μm of corrosion in six weeks), leading a corrosion rate of 1083 μm/year. In addition, a mineral goethite, an iron-bearing hydroxide, formed in the pits of the LCS. Preliminary results from EBS-19 water chemistry are included but SEM imaging, micro probe and XRD are still needed for further results. Copper corrosion was investigated further and over 850 measurements were taken. It was concluded that pitting and pyrite degradation drastically increase the corrosion rate from 0.12 to 0.39 μm/day. However, the growth of a layer of the mineral chalcocite is thought to subdue the corrosion rate to 0.024 μm/day as observed in the EBS-13, a sixth month experiment. This document presents the findings of this past year.« less

Ultrastructural characteristics of three undifferentiated mouse embryonic stem cell lines and their differentiated three-dimensional derivatives: a comparative study.

PubMed

Alharbi, Suzan; Elsafadi, Mona; Mobarak, Mohammed; Alrwili, Ali; Vishnubalaji, Radhakrishnan; Manikandan, Muthurangan; Al-Qudsi, Fatma; Karim, Saleh; Al-Nabaheen, May; Aldahmash, Abdullah; Mahmood, Amer

2014-04-01

The fine structures of mouse embryonic stem cells (mESCs) grown as colonies and differentiated in three-dimensional (3D) culture as embryoid bodies (EBs) were analyzed by transmission electron microscopy. Undifferentiated mESCs expressed markers that proved their pluripotency. Differentiated EBs expressed different differentiation marker proteins from the three germ layers. The ultrastructure of mESCs revealed the presence of microvilli on the cell surfaces, large and deep infolded nuclei, low cytoplasm-to-nuclear ratios, frequent lipid droplets, nonprominent Golgi apparatus, and smooth endoplasmic reticulum. In addition, we found prominent juvenile mitochondria and free ribosomes-rich cytoplasm in mESCs. Ultrastructure of the differentiated mESCs as EBs showed different cell arrangements, which indicate the different stages of EB development and differentiation. The morphologies of BALB/c and 129 W9.5 EBs were very similar at day 4, whereas C57BL/6 EBs were distinct from the others at day 4. This finding suggested that differentiation of EBs from different cell lines occurs in the same pattern but not at the same rate. Conversely, the ultrastructure results of BALB/c and 129 W9.5 ESCs revealed differentiating features, such as the dilated profile of a rough endoplasmic reticulum. In addition, we found low expression levels of undifferentiated markers on the outer cells of BALB/c and 129 W9.5 mESC colonies, which suggests a faster differentiation potential.

The microtubule associated protein END BINDING 1 represses root responses to mechanical cues.

PubMed

Gleeson, Laura; Squires, Shannon; Bisgrove, Sherryl R

2012-05-01

The ability of roots to navigate around rocks and other debris as they grow through the soil requires a mechanism for detecting and responding to input from both touch and gravity sensing systems. The microtubule associated protein END BINDING 1b (EB1b) is involved in this process as mutants have defects responding to combinations of touch and gravity cues. This study investigates the role of EB1b in root responses to mechanical cues. We find that eb1b-1 mutant roots exhibit an increase over wild type in their response to touch and that the expression of EB1b genes in transgenic mutants restores the response to wild type levels, indicating that EB1b is an inhibitor of the response. Mutant roots are also hypersensitive to increased levels of mechanical stimulation, revealing the presence of another process that activates the response. These findings are supported by analyses of double mutants between eb1b-1 and seedlings carrying mutations in PHOSPHOGLUCOMUTASE (PGM), ALTERED RESPONSE TO GRAVITY1 (ARG1), or TOUCH3 (TCH3), genes that encode proteins involved in gravity sensing, signaling, or touch responses, respectively. A model is proposed in which root responses to mechanical cues are modulated by at least two competing regulatory processes, one that promotes touch-mediated growth and another, regulated by EB1b, which dampens root responses to touch and enhances gravitropism. © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

VEGF induces differentiation of functional endothelium from human embryonic stem cells: implications for tissue engineering

PubMed Central

Nourse, Marilyn B.; Halpin, Daniel E.; Scatena, Marta; Mortisen, Derek J.; Tulloch, Nathaniel L.; Hauch, Kip D.; Torok-Storb, Beverly; Ratner, Buddy D.; Pabon, Lil; Murry, Charles E.

2010-01-01

Objective Human embryonic stem cells (hESCs) offer a sustainable source of endothelial cells for therapeutic vascularization and tissue engineering, but current techniques for generating these cells remain inefficient. We endeavored to induce and isolate functional endothelial cells from differentiating hESCs. Methods and Results To enhance endothelial cell differentiation above a baseline of ∼2% in embryoid body (EB) spontaneous differentiation, three alternate culture conditions were compared. Vascular endothelial growth factor (VEGF) treatment of EBs showed the best induction, with markedly increased expression of endothelial cell proteins CD31, VE-Cadherin, and von Willebrand Factor, but not the hematopoietic cell marker CD45. CD31 expression peaked around days 10-14. Continuous VEGF treatment resulted in a four- to five-fold enrichment of CD31+ cells but did not increase endothelial proliferation rates, suggesting a primary effect on differentiation. CD31+ cells purified from differentiating EBs upregulated ICAM-1 and VCAM-1 in response to TNFα, confirming their ability to function as endothelial cells. These cells also expressed multiple endothelial genes and formed lumenized vessels when seeded onto porous poly(2-hydroxyethyl methacrylate) scaffolds and implanted in vivo subcutaneously in athymic rats. Collagen gel constructs containing hESC-derived endothelial cells and implanted into infarcted nude rat hearts formed robust networks of patent vessels filled with host blood cells. Conclusions VEGF induces functional endothelial cells from hESCs independent of endothelial cell proliferation. These enrichment methods increase endothelial cell yield, enabling applications for revascularization as well as basic studies of human endothelial biology. We demonstrate the ability of hESC-derived endothelial cells to facilitate vascularization of tissue-engineered implants. PMID:19875721

[Conception and implementation of a novel E-learning module with EbM learning contents in operative dentistry].

PubMed

Gerhardt-Szép, Susanne; Dreher, Stefanie; Rüttermann, Stefan; Weberschock, Tobias

2017-11-01

Computer-assisted learning (CAL) programs are becoming more widely used in medical and dental training. However, the combination of CAL programs and evidence-based education in dentistry has not been described previously. The aim was to determine the acceptance and user-friendliness of a CAL program combined with evidence-based training. The didactic concept of the module includes the case-oriented, problem-based embedding of a total of 32 EbM learning assignments, which can be completed interactively and self-determinedly in an interdisciplinary context using focus patients with different diseases. The present study was conducted at the Dental School of the Goethe University in Frankfurt/Main. Data on acceptance and user-friendliness were collected from three consecutive cohorts of 114 dental students attending their first clinical semester. They used the "Toothache Walk-in Clinic: FOCUS" CAL, which can be downloaded via the Internet. The instrument consisted of 64 statements. The first part addressed general information about the user. The second part contained 43 specific statements on the CAL program. These included factors A (handling and technical aspects), B (content and functional range), and C (didactics and suitability for education). Possible responses ranged from 0 to 3 (0 = strongly disagree, 3 = strongly agree). All of the 114 questionnaires distributed were returned (response rate 100%). Most users (90.1%) considered the topics of evidence-based dentistry important for their training. They rated the program by using German school grades, and the overall rating was 2.26 (SD = 0.64). Most students (88.6%) considered the program useful for their clinical training in the treatment of patients. The mean scores for the 43 specific items amounted to 1.90 (factor A, SD = 0.63), 1.55 (factor B, SD = 1.93), and 2.23 (factor C, SD = 0.79). The CAL program with dental medicine vignettes and learning elements for evidence-based medicine received a primarily positive assessment. Students welcome that EbM contents are offered as part of their dental studies curriculum. Copyright © 2017. Published by Elsevier GmbH.

76 FR 73684 - Notice of a Change in Status of an Extended Benefit (EB) Period for New York and Maryland

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... the last notice regarding the States EB status: Based on the data released by the Bureau of Labor Statistics on September 16, 2011, the seasonally-adjusted total unemployment rate for New York rose to meet... began October 2. The trigger notice covering state eligibility for the EB program can be found at: http...

Pain care for patients with epidermolysis bullosa: best care practice guidelines.

PubMed

Goldschneider, Kenneth R; Good, Julie; Harrop, Emily; Liossi, Christina; Lynch-Jordan, Anne; Martinez, Anna E; Maxwell, Lynne G; Stanko-Lopp, Danette

2014-10-09

Inherited epidermolysis bullosa (EB) comprises a group of rare disorders that have multi-system effects and patients present with a number of both acute and chronic pain care needs. Effects on quality of life are substantial. Pain and itching are burdensome daily problems. Experience with, and knowledge of, the best pain and itch care for these patients is minimal. Evidence-based best care practice guidelines are needed to establish a base of knowledge and practice for practitioners of many disciplines to improve the quality of life for both adult and pediatric patients with EB. The process was begun at the request of Dystrophic Epidermolysis Bullosa Research Association International (DEBRA International), an organization dedicated to improvement of care, research and dissemination of knowledge for EB patients worldwide. An international panel of experts in pain and palliative care who have extensive experience caring for patients with EB was assembled. Literature was reviewed and systematically evaluated. For areas of care without direct evidence, clinically relevant literature was assessed, and rounds of consensus building were conducted. The process involved a face-to-face consensus meeting that involved a family representative and methodologist, as well as the panel of clinical experts. During development, EB family input was obtained and the document was reviewed by a wide variety of experts representing several disciplines related to the care of patients with EB. The first evidence-based care guidelines for the care of pain in EB were produced. The guidelines are clinically relevant for care of patients of all subtypes and ages, and apply to practitioners of all disciplines involved in the care of patients with EB. When the evidence suggests that the diagnosis or treatment of painful conditions differs between adults and children, it will be so noted. Evidence-based care guidelines are a means of standardizing optimal care for EB patients, whose disease is often times horrific in its effects on quality of life, and whose care is resource-intensive and difficult. The guideline development process also highlighted areas for research in order to improve further the evidence base for future care.

Photometric Follow-up of Eclipsing Binary Candidates from KELT and Kepler

NASA Astrophysics Data System (ADS)

Garcia Soto, Aylin; Rodriguez, Joseph E.; Bieryla, Allyson; KELT survey

2018-01-01

Eclipsing binaries (EBs) are incredibly valuable, as they provide the opportunity to precisely measure fundamental stellar parameters without the need for stellar models. Therefore, we can use EBs to directly test stellar evolution models. Constraining the stellar properties of stars is important since they directly influence our understanding of any planets orbiting them. Using the Harvard University's Clay 0.4m telescope and Fred Lawrence Whipple Observatory’s 1.2m telescope on Mount Hopkins, Arizona, we conducted follow-up multi-band photometric observations of EB candidates from the Kilodegree Extremely Little Telescope (KELT) survey and the Kepler mission. We will present our follow-up observations and AstroImageJ analysis on these 5 EB systems.

Phosphorescent quantum dots/ethidium bromide nanohybrids based on photoinduced electron transfer for DNA detection.

PubMed

Bi, Lin; Yu, Yuan-Hua

2015-04-05

Mercaptopropionic acid-capped Mn-doped ZnS quantum dots/ethidium bromide (EB) nanohybrids were constructed for photoinduced electron transfer (PIET) and then used as a room-temperature phosphorescence (RTP) probe for DNA detection. EB could quench the RTP of Mn-doped ZnS QDs by PIET, thereby forming Mn-doped ZnS QDs/EB nanohybrids and storing RTP. Meanwhile, EB could be inserted into DNA and EB could be competitively desorbed from the surface of Mn-doped ZnS QDs by DNA, thereby releasing the RTP of Mn-doped ZnS QDs. Based on this mechanism, a RTP sensor for DNA detection was developed. Under optimal conditions, the detection limit for DNA was 0.045 mg L(-1), the relative standard deviation was 1.7%, and the method linear ranged from 0.2 to 20 mg L(-1). The proposed method was applied to biological fluids, in which satisfactory results were obtained. Copyright © 2015 Elsevier B.V. All rights reserved.

EB and EUV lithography using inedible cellulose-based biomass resist material

NASA Astrophysics Data System (ADS)

Takei, Satoshi; Hanabata, Makoto; Oshima, Akihiro; Kashiwakura, Miki; Kozawa, Takahiro; Tagawa, Seiichi

2016-03-01

The validity of our approach of inedible cellulose-based resist material derived from woody biomass has been confirmed experimentally for the use of pure water in organic solvent-free water spin-coating and tetramethylammonium hydroxide(TMAH)-free water-developable techniques of eco-conscious electron beam (EB) and extreme-ultraviolet (EUV) lithography. The water developable, non-chemically amplified, high sensitive, and negative tone resist material in EB and EUV lithography was developed for environmental affair, safety, easiness of handling, and health of the working people. The inedible cellulose-based biomass resist material was developed by replacing the hydroxyl groups in the beta-linked disaccharides with EB and EUV sensitive groups. The 50-100 nm line and space width, and little footing profiles of cellulose-based biomass resist material on hardmask and layer were resolved at the doses of 10-30 μC/cm2. The eco-conscious lithography techniques was referred to as green EB and EUV lithography using inedible cellulose-based biomass resist material.

Perioperative care of patients with epidermolysis bullosa: proceedings of the 5th international symposium on epidermolysis bullosa, Santiago Chile, December 4-6, 2008.

PubMed

Goldschneider, Kenneth; Lucky, Anne W; Mellerio, Jemima E; Palisson, Francis; del Carmen Viñuela Miranda, Maria; Azizkhan, Richard G

2010-09-01

Epidermolysis bullosa (EB) has become recognized as a multisystem disorder that poses a number of pre-, intra-, and postoperative challenges. While anesthesiologists have long appreciated the potential difficult intubation in patients with EB, other systems can be affected by this disorder. Hematologic, cardiac, skeletal, gastrointestinal, nutritional, and metabolic deficiencies are foci of preoperative medical care, in addition to the airway concerns. Therefore, multidisciplinary planning for operative care is imperative. A multinational, interdisciplinary panel of experts assembled in Santiagio, Chile to review the best practices for perioperative care of patients with EB. This paper presents guidelines that represent a synthesis of evidence-based approaches and the expert consensus of this panel and are intended to aid physicians new to caring for patients with EB when operative management is indicated. With proper medical optimization and attention to detail in the operating room, patients with EB can have an uneventful perioperative course.

Microstructural, mechanical and oxidation features of NiCoCrAlY coating produced by plasma activated EB-PVD

NASA Astrophysics Data System (ADS)

He, Jian; Guo, Hongbo; Peng, Hui; Gong, Shengkai

2013-06-01

NiCoCrAlY coatings produced by electron beam-physical vapor deposition (EB-PVD) have been extensively used as the oxidation resistance coatings or suitable bond coats in thermal barrier coating (TBC) system. However, the inherent imperfections caused by EB-PVD process degrade the oxidation resistance of the coatings. In the present work, NiCoCrAlY coatings were creatively produced by plasma activated electron beam-physical vapor deposition (PA EB-PVD). The novel coatings showed a terraced substructure on the surface of each grain due to the increased energy of metal ions and enhanced mobility of adatoms. Also a strong (1 1 1) crystallographic texture of γ/γ' grains was observed. The toughness of the coatings got remarkably improved compared with the coatings deposited by conventional EB-PVD and the oxidation behavior at 1373 K showed that the novel coatings had excellent oxidation resistance. The possible mechanism was finally discussed.

Characterization of electrolyte-binder mixes for use in thermal batteries

NASA Astrophysics Data System (ADS)

Guidotti, R. A.; Reinhardt, F. W.

1991-03-01

A number of metal oxides were evaluated for their ability to immobilize molten LiCl-KCl eutectic in electrolyte-binder (EB) mixes used in thermally activated batteries. These metal oxides included fumed silicas, alumina, and a titania (all prepared by steam hydrolysis of the halides), floated silicas, MgO, and an alumina molecular sieve. The characteristics of the EB powders that were used as metrics were flow properties, homogeneity, BET surface area, particle-size distribution, and moisture content. The characteristics of EB pellets used as metrics were deformation at 530 C under an applied pressure and tendency for electrolyte leakage at 400 C. Many of the same characterization techniques used for EB powders were applied to the LiCl-KCl eutectic, its component halides, and the metal oxides as well. The reproducibility of the properties of several of the standard Sandia EB mixes was evaluated for materials prepared at a number of thermal-battery manufacturing facilities following the same processing procedures.

Neuronal populations in the occipital cortex of the blind synchronize to the temporal dynamics of speech

PubMed Central

Van Ackeren, Markus Johannes; Barbero, Francesca M; Mattioni, Stefania; Bottini, Roberto

2018-01-01

The occipital cortex of early blind individuals (EB) activates during speech processing, challenging the notion of a hard-wired neurobiology of language. But, at what stage of speech processing do occipital regions participate in EB? Here we demonstrate that parieto-occipital regions in EB enhance their synchronization to acoustic fluctuations in human speech in the theta-range (corresponding to syllabic rate), irrespective of speech intelligibility. Crucially, enhanced synchronization to the intelligibility of speech was selectively observed in primary visual cortex in EB, suggesting that this region is at the interface between speech perception and comprehension. Moreover, EB showed overall enhanced functional connectivity between temporal and occipital cortices that are sensitive to speech intelligibility and altered directionality when compared to the sighted group. These findings suggest that the occipital cortex of the blind adopts an architecture that allows the tracking of speech material, and therefore does not fully abstract from the reorganized sensory inputs it receives. PMID:29338838

Formation and hematopoietic differentiation of human embryoid bodies by suspension and hanging drop cultures.

PubMed

Cerdan, Chantal; Hong, Seok Ho; Bhatia, Mickie

2007-10-01

The in vitro aggregation of human embryonic stem cells (hESCs) into clusters termed embryoid bodies (EBs) allows for the spontaneous differentiation of cells representing endoderm, mesoderm, and ectoderm lineages. This stochastic process results however, in the generation of low numbers of differentiated cells, and can be enhanced to some extent by the addition of exogenous growth factors or overexpression of regulatory genes. In the authors' laboratory, the use of hematopoietic cytokines in combination with the mesoderm inducer bone morphogenetic protein-4 (BMP-4) was able to generate up to 90% of CD45(+) hematopoietic cells with colony-forming unit (CFU) activity. This unit describes two protocols that have been successfully applied in the authors' laboratory for the generation of EBs in (1) suspension and (2) hanging drop (HD) cultures from enzymatically digested clumps of undifferentiated hESC colonies.

Epidemiology of cough in relation to China

PubMed Central

2013-01-01

Cough is one of the most common complaints for which patients seek medical attention. Misdiagnosis and mistreatment of cough exist commonly in China. The prevalence of acute cough caused by upper airway infection fluctuates between 9% and 64% in the community, for chronic cough, the prevalence >10% in most surveys, ranging from 7.2%-33%. The common causes of chronic cough are upper airway cough syndrome (previously called as post nasal drip syndrome [PNDS]), cough variant asthma (CVA), gastroesophageal reflux related cough (GERD) and eosinophilic bronchitis (EB). There is a regional discrepancy regarding the prevalence of common causes of cough and distribution of gender among China, UK, USA, the most common cause of chronic cough in China are CVA, followed by UACS, EB and atopic cough (AC), the male is almost equal to female in numbers in China. The risk factors for cough includes cold air, smoking, environmental pollutants, noxious substances and allergens, and unreasonable diet habits. PMID:23835047

Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

PubMed

Moruno-Manchon, Jose F; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

2018-01-01

Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general. Copyright © 2017 Elsevier Inc. All rights reserved.

An Evaluation of Empirical Bayes' Estimation of Value- Added Teacher Performance Measures. Working Paper #31. Revised

ERIC Educational Resources Information Center

Guarino, Cassandra M.; Maxfield, Michelle; Reckase, Mark D.; Thompson, Paul; Wooldridge, Jeffrey M.

2014-01-01

Empirical Bayes' (EB) estimation is a widely used procedure to calculate teacher value-added. It is primarily viewed as a way to make imprecise estimates more reliable. In this paper we review the theory of EB estimation and use simulated data to study its ability to properly rank teachers. We compare the performance of EB estimators with that of…

Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview

PubMed Central

Pereira, Jorge; Porto-Figueira, Priscilla; Cavaco, Carina; Taunk, Khushman; Rapole, Srikanth; Dhakne, Rahul; Nagarajaram, Hampapathalu; Câmara, José S.

2015-01-01

Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases. PMID:25584743

[Epidermolysis bullosa in peru: clinical and epidemiological study of patients treated in a national reference pediatric hospital, 1993-2015].

PubMed

Torres-Iberico, Rosario; Palomo-Luck, Patricia; Torres-Ramos, Gilmer; Lipa-Chancolla, Roxana

2017-01-01

To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%), union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

International Collaborations on Engineered Barrier Systems: Brief Overview of SKB-EBS Activities.

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

Jove-Colon, Carlos F.

2015-10-01

Research collaborations with international partners on the behavior and performance of engineered barrier systems (EBS) are an important aspect of the DOE-NE Used Fuel Disposition Campaign strategy in the evaluation of disposal design concepts. These international partnerships are a cost-effective way of engaging in key R&D activities with common goals resulting in effective scientific knowledge exchanges thus enhancing existing and future research programs in the USA. This report provides a brief description of the activities covered by the Swedish Nuclear Fuel and Waste Management Company (SKB) EBS Task Force (TF) (referred hereafter as SKB EBS TF) and potential future directionsmore » for engagement of the DOE-NE UFDC program in relevant R&D activities. Emphasis is given to SKB EBS TF activities that are still ongoing and aligned to the UFDC R&D program. This include utilization of data collected in the bentonite rock interaction experiment (BRIE) and data sets from benchmark experiments produced by the chemistry or “C” part of the SKB EBS TF. Potential applications of information generated by this program include comparisons/tests between model and data (e.g., reactive diffusion), development and implementation of coupled-process models (e.g., HM), and code/model benchmarking.« less

Room temperature exchange bias in multiferroic BiFeO3 nano- and microcrystals with antiferromagnetic core and two-dimensional diluted antiferromagnetic shell

NASA Astrophysics Data System (ADS)

Zhang, Chuang; Wang, Shou Yu; Liu, Wei Fang; Xu, Xun Ling; Li, Xiu; Zhang, Hong; Gao, Ju; Li, De Jun

2017-05-01

Exchange bias (EB) of multiferroics presents many potential opportunities for magnetic devices. However, instead of using low-temperature field cooling in the hysteresis loop measurement, which usually shows an effective approach to obtain obvious EB phenomenon, there are few room temperature EB. In this article, extensive studies on room temperature EB without field cooling were observed in BiFeO3 nano- and microcrystals. Moreover, with increasing size the hysteresis loops shift from horizontal negative exchange bias (NEB) to positive exchange bias (PEB). In order to explain the tunable EB behaviors with size dependence, a phenomenological qualitative model based on the framework of antiferromagnetic (AFM) core-two-dimensional diluted antiferromagnet in a field (2D-DAFF) shell structure was proposed. The training effect (TE) ascertained the validity of model and the presence of unstable magnetic structure using Binek's model. Experimental results show that the tunable EB effect can be explained by the competition of ferromagnetic (FM) exchange coupling and AFM exchange coupling interaction between AFM core and 2D-DAFF shell. Additionally, the local distortion of lattice fringes was observed in hexagonal-shaped BiFeO3 nanocrystals with well-dispersed behavior. The electrical conduction properties agreed well with the space charge-limited conduction mechanism.

Analysis of Hydrogen Atom Abstraction from Ethylbenzene by an FeVO(TAML) Complex.

PubMed

Shen, Longzhu Q; Kundu, Soumen; Collins, Terrence J; Bominaar, Emile L

2017-04-17

It was shown previously (Chem. Eur. J. 2015, 21, 1803) that the rate of hydrogen atom abstraction, k, from ethylbenzene (EB) by TAML complex [Fe V (O)B*] - (1) in acetonitrile exhibits a large kinetic isotope effect (KIE ∼ 26) in the experimental range 233-243 K. The extrapolated tangents of ln(k/T) vs T -1 plots for EB-d 10 and EB gave a large, negative intercept difference, Int(EB) - Int(EB-d 10 ) = -34.5 J mol -1 K -1 for T -1 → 0, which is shown to be exclusively due to an isotopic mass effect on tunneling. A decomposition of the apparent activation barrier in terms of electronic, ZPE, thermal enthalpic, tunneling, and entropic contributions is presented. Tunneling corrections to ΔH ⧧ and ΔS ⧧ are estimated to be large. The DFT prediction, using functional B3LYP and basis set 6-311G, for the electronic contribution is significantly smaller than suggested by experiment. However, the agreement improves after correction for the basis set superposition error in the interaction between EB and 1. The kinetic model employed has been used to predict rate constants outside the experimental temperature range, which enabled us to compare the reactivity of 1 with those of other hydrogen abstracting complexes.

In Vivo and In Vitro Nitinol Corrosion Properties

NASA Astrophysics Data System (ADS)

Lonn, Melissa K.; Metcalf, Justin M.; Choules, Brian D.

2015-09-01

Regulatory authorities often require in vitro testing on medical devices prior to approval. Current standardized corrosion testing methods (ASTM F2129) require testing in a non-physiologic, de-oxygenated solution for a pre-exposure time of ≤1 h; however, no correlations between the prescribed simulated environment and whole blood conditions have been elucidated. This study compared open circuit potential (OCP), breakdown potentials (Eb), Eb - OCP, and cyclic polarization curves tested in vivo (OCP only) and in vitro in whole blood to those tested in phosphate-buffered saline (PBS). Two oxide thicknesses of Nitinol, two solution oxygen contents (deaerated and aerated solutions), and two pre-exposure durations (acute and chronic) were investigated. The in vitro OCP in whole blood was not significantly different than the in vivo OCP, suggesting that whole blood in vitro can be used to determine baseline corrosion behavior of medical implants. Eb - OCP tested per ASTM F2129 was comparable to acute whole blood and was conservative compared to chronic whole blood for both oxide thicknesses. However, OCP, Eb, and cyclic polarization curves were not always comparable to whole blood. Testing in aerated PBS achieved Eb, Eb - OCP, and cyclic polarization curves that were comparable to or more conservative than whole blood testing, regardless of pre-exposure duration and oxide thickness.

Embryoid bodies formation and differentiation from mouse embryonic stem cells in collagen/Matrigel scaffolds.

PubMed

Zhou, Jin; Zhang, Ye; Lin, Qiuxia; Liu, Zhiqiang; Wang, Haibin; Duan, Cuimi; Wang, Yanmeng; Hao, Tong; Wu, Kuiwu; Wang, Changyong

2010-07-01

Embryonic stem (ES) cells have the potential to develop into any type of tissue and are considered as a promising source of seeding cells for tissue engineering and transplantation therapy. The main catalyst for ES cells differentiation is the growth into embryoid bodies (EBs), which are utilized widely as the trigger of in vitro differentiation. In this study, a novel method for generating EBs from mouse ES cells through culture in collagen/Matrigel scaffolds was successfully established. When single ES cells were seeded in three dimensional collagen/Matrigel scaffolds, they grew into aggregates gradually and formed simple EBs with circular structures. After 7 days' culture, they formed into cystic EBs that would eventually differentiate into the three embryonic germ layers. Evaluation of the EBs in terms of morphology and potential to differentiate indicated that they were typical in structure and could generate various cell types; they were also able to form into tissue-like structures. Moreover, with introduction of ascorbic acid, ES cells differentiated into cardiomyocytes efficiently and started contracting synchronously at day 19. The results demonstrated that collagen/Matrigel scaffolds supported EBs formation and their subsequent differentiation in a single three dimensional environment. Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Annealing behavior of the EB-centers and M-center in low-energy electron irradiated n-type 4H-SiC

NASA Astrophysics Data System (ADS)

Beyer, F. C.; Hemmingsson, C.; Pedersen, H.; Henry, A.; Janzén, E.; Isoya, J.; Morishita, N.; Ohshima, T.

2011-05-01

After low-energy electron irradiation of epitaxial n-type 4H-SiC with a dose of 5×1016 cm-2, the bistable M-center, previously reported in high-energy proton implanted 4H-SiC, is detected in the deep level transient spectroscopy (DLTS) spectrum. The annealing behavior of the M-center is confirmed, and an enhanced recombination process is suggested. The annihilation process is coincidental with the evolvement of the bistable EB-centers in the low temperature range of the DLTS spectrum. The annealing energy of the M-center is similar to the generation energy of the EB-centers, thus partial transformation of the M-center to the EB-centers is suggested. The EB-centers completely disappeared after annealing temperatures higher than 700 ∘C without the formation of new defects in the observed DLTS scanning range. The threshold energy for moving Si atom in SiC is higher than the applied irradiation energy, and the annihilation temperatures are relatively low, therefore the M-center, EH1 and EH3, as well as the EB-centers are attributed to defects related to the C atom in SiC, most probably to carbon interstitials and their complexes.

Tidal Synchronization and Differential Rotation of Kepler Eclipsing Binaries

NASA Astrophysics Data System (ADS)

Lurie, John C.; Vyhmeister, Karl; Hawley, Suzanne L.; Adilia, Jamel; Chen, Andrea; Davenport, James R. A.; Jurić, Mario; Puig-Holzman, Michael; Weisenburger, Kolby L.

2017-12-01

Few observational constraints exist for the tidal synchronization rate of late-type stars, despite its fundamental role in binary evolution. We visually inspected the light curves of 2278 eclipsing binaries (EBs) from the Kepler Eclipsing Binary Catalog to identify those with starspot modulations, as well as other types of out-of-eclipse variability. We report rotation periods for 816 EBs with starspot modulations, and find that 79% of EBs with orbital periods of less than 10 days are synchronized. However, a population of short-period EBs exists, with rotation periods typically 13% slower than synchronous, which we attribute to the differential rotation of high-latitude starspots. At 10 days, there is a transition from predominantly circular, synchronized EBs to predominantly eccentric, pseudosynchronized EBs. This transition period is in good agreement with the predicted and observed circularization period for Milky Way field binaries. At orbital periods greater than about 30 days, the amount of tidal synchronization decreases. We also report 12 previously unidentified candidate δ Scuti and γ Doradus pulsators, as well as a candidate RS CVn system with an evolved primary that exhibits starspot occultations. For short-period contact binaries, we observe a period-color relation and compare it to previous studies. As a whole, these results represent the largest homogeneous study of tidal synchronization of late-type stars.

Breath analysis as a potential and non-invasive frontier in disease diagnosis: an overview.

PubMed

Pereira, Jorge; Porto-Figueira, Priscilla; Cavaco, Carina; Taunk, Khushman; Rapole, Srikanth; Dhakne, Rahul; Nagarajaram, Hampapathalu; Câmara, José S

2015-01-09

Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases.

Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis

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

Gonzalez-Gay, M.A.; Zanelli, E.; Krco, C.J.

1995-05-01

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E{beta}{sup d} molecule prevents CIA development in susceptible H2{sup q} mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F{sub 1} mice, only H2Eb{sup d} and H2Eb{sup s} molecules showed protection. Using recombinant B10.RDD (Eb{sup d/b}) mice, we found that CIA protection was mediated bymore » the first domain of the E{beta}{sup d} molecule. Using peptides covering the third hypervariable region of the E{beta} chain, we found a perfect correlation between presentation of E{beta} peptides by the H2A{sup q} molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E{beta} peptides for the H2A{sup q} molecule. 35 refs., 2 figs., 3 tabs.« less

Treatment of toluene and its by-products using an electron beam/ultra-fine bubble hybrid system

NASA Astrophysics Data System (ADS)

Son, Youn-Suk; Kim, Tae-Hun; Choi, Chang Yong; Park, Jun-Hyeong; Ahn, Ji-Won; Dinh, Trieu-Vuong

2018-03-01

Although, until quite recently, many technologies (electron beam (EB), plasma, and ultraviolet) have been studied to overcome disadvantages of conventional methods (such as absorption, adsorption, biofiltration and incineration) for treatment of volatile organic compounds (VOCs), their techniques still have some problems such as formation of a by-product. Generally, it is reported that various by-products are generated from the EB irradiation process to remove VOCs. Therefore, we developed an electron beam/ultra-fine bubble (EB/UB) hybrid system to enhance removal efficiency of a VOC (toluene) and to reduce its by-products formed by electron beam irradiation. As a result, the removal efficiency of toluene (30 ppm) by only EB (10 kGy) was 80.1%. However, the removal efficiency of toluene using the hybrid system (water temperature: 5 ℃) was increased up to 17% when compared to only EB (10 kGy). Additionally, the 65.2% of ozone formed from the EB process was removed in UB reactor. In case of other trace by-products such as undesired VOCs and aldehydes, the levels were lowered down to the below detection limit by the subsequent UB reactor. We also found that the amount of toluene collected and solubilized into water is affected by the water temperature in the UB reactor.

Changes in the DNA methylation profile of the rat H19 gene upstream region during development and transgenic hepatocarcinogenesis and its role in the imprinted transcriptional regulation of the H19 gene.

PubMed

Manoharan, Herbert; Babcock, Karlee; Pitot, Henry C

2004-09-01

Monoallelic expression of the imprinted H19 and insulin-like growth factor-2 (Igf2) genes depends on the hypomethylation of the maternal allele and hypermethylation of the paternal allele of the H19 upstream region. Previous studies from our laboratory on liver carcinogenesis in the F1 hybrid of Fischer 344 (F344) and Sprague-Dawley Alb SV40 T Ag transgenic rat (SD) strains revealed the biallelic expression of H19 in hepatomas. We undertook a comparative study of the DNA methylation status of the upstream region of H19 in fetal, adult, and neoplastic liver. Bisulfite DNA sequencing analysis of a 3.745-kb DNA segment extending from 2950 to 6695 bp of the H19 upstream region revealed marked variations in the methylation patterns in fetal, adult, and neoplastic liver. In the fetal liver, equal proportions of hyper- and hypomethylated strands revealed the differentially methylated status of the parental alleles, but in neoplastic liver a pronounced change in the pattern of methylation was observed with a distinct change to hypomethylation in the short segments between 2984 and 3301 bp, 6033-6123 bp, and 6518-6548 bp. These results indicated that methylation of all cytosines in this region may contribute to the imprinting status of the rat H19 gene. This phenomenon of differential methylation-related epigenetic alteration in the key cis-regulatory domains of the H19 promoter influences switching to biallelic expression in hepatocellular carcinogenesis. Similar to mouse and human, we showed that the zinc-finger CCTCC binding factor (CTCF) binds to the unmethylated CTCF binding site in the upstream region to influence monoallelic imprinted expression in fetal liver. CTCF does not appear to be rate limiting in fetal, normal, and neoplastic liver. 3' to the CTCF binding sites, another DNA region exhibits methylation of CpG's in both DNA strands in adult liver, retention of the imprint in fetal liver, and complete demethylation in neoplastic liver. In this region is also a putative binding site for a basic helix-loop-helix leucine-zipper transcription factor, TFEB. The differential CpG methylation seen in the adult that involves the TFEB binding site may explain the lack of expression of the H19 gene in adult normal liver. Furthermore, these findings demonstrate that the loss of imprinting of the H19 gene in hepatic neoplasms of the SD Alb SV40 T Ag transgenic rat is directly correlated with and probably the result of differential methylation of CpG dinucleotides in two distinct regions of the gene that are within 4 kb 5' of the transcription start site. Cytogenetic analysis of hepatocytes in the transgenic animal prior to the appearance of nodules or neoplasms indicates a role of such loss of imprinting in the very early period of neoplastic development, possibly the transition from the stage of promotion to that of progression. Copyright 2004 Wiley-Liss, Inc.

Pharmacokinetics and transcriptional effects of the anti-salmon lice drug emamectin benzoate in Atlantic salmon (Salmo salar L.)

PubMed Central

Olsvik, Pål A; Lie, Kai K; Mykkeltvedt, Eva; Samuelsen, Ole B; Petersen, Kjell; Stavrum, Anne-Kristin; Lunestad, Bjørn T

2008-01-01

Background Emamectin benzoate (EB) is a dominating pharmaceutical drug used for the treatment and control of infections by sea lice (Lepeophtheirus salmonis) on Atlantic salmon (Salmo salar L). Fish with an initial mean weight of 132 g were experimentally medicated by a standard seven-day EB treatment, and the concentrations of drug in liver, muscle and skin were examined. To investigate how EB affects Atlantic salmon transcription in liver, tissues were assessed by microarray and qPCR at 7, 14 and 35 days after the initiation of medication. Results The pharmacokinetic examination revealed highest EB concentrations in all three tissues at day 14, seven days after the end of the medication period. Only modest effects were seen on the transcriptional levels in liver, with small fold-change alterations in transcription throughout the experimental period. Gene set enrichment analysis (GSEA) indicated that EB treatment induced oxidative stress at day 7 and inflammation at day 14. The qPCR examinations showed that medication by EB significantly increased the transcription of both HSP70 and glutathione-S-transferase (GST) in liver during a period of 35 days, compared to un-treated fish, possibly via activation of enzymes involved in phase II conjugation of metabolism in the liver. Conclusion This study has shown that a standard seven-day EB treatment has only a modest effect on the transcription of genes in liver of Atlantic salmon. Based on GSEA, the medication seems to have produced a temporary oxidative stress response that might have affected protein stability and folding, followed by a secondary inflammatory response. PMID:18786259

Pharmacokinetics and transcriptional effects of the anti-salmon lice drug emamectin benzoate in Atlantic salmon (Salmo salar L.).

PubMed

Olsvik, Pål A; Lie, Kai K; Mykkeltvedt, Eva; Samuelsen, Ole B; Petersen, Kjell; Stavrum, Anne-Kristin; Lunestad, Bjørn T

2008-09-11

Emamectin benzoate (EB) is a dominating pharmaceutical drug used for the treatment and control of infections by sea lice (Lepeophtheirus salmonis) on Atlantic salmon (Salmo salar L). Fish with an initial mean weight of 132 g were experimentally medicated by a standard seven-day EB treatment, and the concentrations of drug in liver, muscle and skin were examined. To investigate how EB affects Atlantic salmon transcription in liver, tissues were assessed by microarray and qPCR at 7, 14 and 35 days after the initiation of medication. The pharmacokinetic examination revealed highest EB concentrations in all three tissues at day 14, seven days after the end of the medication period. Only modest effects were seen on the transcriptional levels in liver, with small fold-change alterations in transcription throughout the experimental period. Gene set enrichment analysis (GSEA) indicated that EB treatment induced oxidative stress at day 7 and inflammation at day 14. The qPCR examinations showed that medication by EB significantly increased the transcription of both HSP70 and glutathione-S-transferase (GST) in liver during a period of 35 days, compared to un-treated fish, possibly via activation of enzymes involved in phase II conjugation of metabolism in the liver. This study has shown that a standard seven-day EB treatment has only a modest effect on the transcription of genes in liver of Atlantic salmon. Based on GSEA, the medication seems to have produced a temporary oxidative stress response that might have affected protein stability and folding, followed by a secondary inflammatory response.

Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis

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

Caldwell, H.D.; Kromhout, J.; Schachter, J.

1981-03-01

Elementary bodies (EB) of Chlamydia trachomatis serotypes C, E, and L2 were extrinsically radioiodinated, and whole-cell lysates of these serotypes were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Autoradiography of the polypeptide profiles identified a major surface protein with an apparent subunit molecular weight of 39,500 that was common to each C. trachomatis serotype. The abilities of nonionic (Triton X-100), dipolar ionic (Zwittergent TM-314), mild (sodium deoxycholate and sodium N-lauroyl sarcosine), and strongly anionic (SDS) detergents to extract this protein from intact EB of the L2 serotype were investigated by SDS-PAGE analysis of the soluble and insoluble fractions obtainedmore » after each detergent treatment. Only SDS readily extracted this protein from intact EB. Sarkosyl treatment selectively solubilized the majority of other EB proteins, leaving the 39,500-dalton protein associated with the Sarkosyl-insoluble fraction. Ultrastructural studies of the Sarkosyl-insoluble EB pellet showed it to consist of empty EB particles possessing an apparently intact outer membrane. No structural evidence for a peptidoglycan-like cell wall was found. Morphologically these chlamydial outer membrane complexes (COMC) resembled intact chlamydial EB outer membranes. The 39,500-dalton outer membrane protein was quantitatively extracted from COMC by treating them with 2% SDS at 60 degrees C. This protein accounted for 61% of the total COMC-associated protein, and its extraction resulted in a concomitant loss of the COMC membrane structure and morphology. The 39,500-dalton major outer membrane protein is a serogroup antigen of C. trachomatis organisms.« less

Mouse embryonic stem cell-derived cells reveal niches that support neuronal differentiation in the adult rat brain.

PubMed

Maya-Espinosa, Guadalupe; Collazo-Navarrete, Omar; Millán-Aldaco, Diana; Palomero-Rivero, Marcela; Guerrero-Flores, Gilda; Drucker-Colín, René; Covarrubias, Luis; Guerra-Crespo, Magdalena

2015-02-01

A neurogenic niche can be identified by the proliferation and differentiation of its naturally residing neural stem cells. However, it remains unclear whether "silent" neurogenic niches or regions suitable for neural differentiation, other than the areas of active neurogenesis, exist in the adult brain. Embryoid body (EB) cells derived from embryonic stem cells (ESCs) are endowed with a high potential to respond to specification and neuralization signals of the embryo. Hence, to identify microenvironments in the postnatal and adult rat brain with the capacity to support neuronal differentiation, we transplanted dissociated EB cells to conventional neurogenic and non-neurogenic regions. Our results show a neuronal differentiation pattern of EB cells that was dependent on the host region. Efficient neuronal differentiation of EB cells occurred within an adjacent region to the rostral migratory stream. EB cell differentiation was initially patchy and progressed toward an even distribution along the graft by 15-21 days post-transplantation, giving rise mostly to GABAergic neurons. EB cells in the striatum displayed a lower level of neuronal differentiation and derived into a significant number of astrocytes. Remarkably, when EB cells were transplanted to the striatum of adult rats after a local ischemic stroke, increased number of neuroblasts and neurons were observed. Unexpectedly, we determined that the adult substantia nigra pars compacta, considered a non-neurogenic area, harbors a robust neurogenic environment. Therefore, neurally uncommitted cells derived from ESCs can detect regions that support neuronal differentiation within the adult brain, a fundamental step for the development of stem cell-based replacement therapies. © 2014 AlphaMed Press.

Development of a clinical diagnostic matrix for characterizing inherited epidermolysis bullosa.

PubMed

Yenamandra, V K; Moss, C; Sreenivas, V; Khan, M; Sivasubbu, S; Sharma, V K; Sethuraman, G

2017-06-01

Accurately diagnosing the subtype of epidermolysis bullosa (EB) is critical for management and genetic counselling. Modern laboratory techniques are largely inaccessible in developing countries, where the diagnosis remains clinical and often inaccurate. To develop a simple clinical diagnostic tool to aid in the diagnosis and subtyping of EB. We developed a matrix indicating presence or absence of a set of distinctive clinical features (as rows) for the nine most prevalent EB subtypes (as columns). To test an individual patient, presence or absence of these features was compared with the findings expected in each of the nine subtypes to see which corresponded best. If two or more diagnoses scored equally, the diagnosis with the greatest number of specific features was selected. The matrix was tested using findings from 74 genetically characterized patients with EB aged > 6 months by an investigator blinded to molecular diagnosis. For concordance, matrix diagnoses were compared with molecular diagnoses. Overall, concordance between the matrix and molecular diagnoses for the four major types of EB was 91·9%, with a kappa coefficient of 0·88 [95% confidence interval (CI) 0·81-0·95; P < 0·001]. The matrix achieved a 75·7% agreement in classifying EB into its nine subtypes, with a kappa coefficient of 0·73 (95% CI 0·69-0·77; P < 0·001). The matrix appears to be simple, valid and useful in predicting the type and subtype of EB. An electronic version will facilitate further testing. © 2016 British Association of Dermatologists.

Characterization of the biochemical, physiological, and medicinal properties of Streptomyces hygroscopicus ACTMS-9H isolated from the Amazon (Brazil).

PubMed

Lima, Sandrine M A; Melo, Janaína G S; Militão, Gardênia C G; Lima, Gláucia M S; do Carmo A Lima, Maria; Aguiar, Jaciana S; Araújo, Renata M; Braz-Filho, Raimundo; Marchand, Pascal; Araújo, Janete M; Silva, Teresinha G

2017-01-01

Actinomycetes are known to produce numerous secondary bioactive metabolites of pharmaceutical interest. The purpose of this study was to isolate, characterize, and investigate the antibacterial, antifungal, and anticancer activities of metabolites produced by Actinobacteria isolated from the rhizosphere of Paullinia cupana. The Actinobacteria was identified as Streptomyces hygroscopicus ACTMS-9H. Based on a bioguided study, the methanolic biomass extract obtained from submerged cultivation had the most potent antibacterial, antifungal, and cytotoxic activities. This extract was partitioned with n-hexane, ethyl acetate, and 2-butanol. Elaiophylin was isolated from the methanolic biomass extract, and its molecular formula was determined (C 54 H 88 O 18 ) based on 1 H and 13 C NMR, IR and MS analyses. The 2-butanol phase was fractionated into four fractions (EB1, EB2A, EB2B, and EB3M). Chemical prospecting indicated the presence of alkaloids, saponins, and reducing sugars in the methanolic extract and 2-butanol phase. The elaiophylin displayed anticancer activity in HEp-2 and HL-60 cells with an IC 50 of 1 μg/mL. The EB1 fraction was selectively toxic to HL-60 cells with IC 50 of 9 ng/mL. Bioautography showed that the EB1 fraction contained an alkaloid with antibacterial and antifungal activities (MIC values ≤1.9 and <3.9 μg/mL, respectively). In conclusion, the EB1 fraction and elaiophylin of S. hygroscopicus have potent antimicrobial, antifungal, and anticancer activities.

Effect of antioxidants on the dentin interface bond stability of adhesives exposed to hydrolytic degradation.

PubMed

Gotti, Valéria B; Feitosa, Victor P; Sauro, Salvatore; Correr-Sobrinho, Lourenço; Leal, Fernanda B; Stansbury, Jeffrey W; Correr, Américo B

2015-02-01

This study assessed the effect of antioxidants vitamin C (Vit. C), vitamin E (Vit. E) and quercetin (Querc) on the dentin bonding performance, degree of conversion, and rate of polymerization of three commercial adhesive systems (Adper Single Bond 2 [SB], Clearfil SE Bond [CSE], Adper Easy Bond [EB]). Human premolars were restored using antioxidant-doped adhesives. The samples were stored for 24 h in distilled water or 6 months under simulated pulpal pressure. Teeth were cut into sticks and the microtensile bond strength (μTBS) to dentin was tested in a universal testing machine. Qualitative nanoleakage analysis was performed from a central stick of each restored tooth. Degree of conversion and rate of polymerization of adhesive systems were evaluated in triplicate using real-time FT-IR. Although the inclusion of the antioxidants negatively affected the μTBS over 24 h, the antioxidant-doped adhesives maintained (SB-Vit. C, SB-Vit. E, CSE-Vit. C, EB-Querc) or increased (SB-Querc, CSE-Vit. E, CSE-Querc, EB-Vit. E, and EB-Vit. C) their μTBS during 6 months of storage. Only the μTBS of Adper Single Bond 2 dropped significantly after 6 months among the control groups. Slight changes in the nanoleakage pattern after aging were observed in all groups, except for the EB-control group, which showed a noteworthy increase in nanoleakage after 6 months, and for EB-Vit. C, which presented a remarkable decrease. A lower degree of conversion was obtained with all antioxidants in SB and EB, except for the EB-Vit. E group. Similar degrees of conversion were attained in control and experimental groups for CSE. The rate of polymerization was reduced in antioxidant-doped adhesives. The performance of antioxidants changed according to the adhesive system to which they were added, and antioxidant-doped adhesives appear to have a positive effect on the adhesive interface durability, since their bond strength obtained after 24 h was maintained or increased over time.

A common-garden experiment to quantify evolutionary processes in copepods: the case of emamectin benzoate resistance in the parasitic sea louse Lepeophtheirus salmonis.

PubMed

Ljungfeldt, Lina Eva Robin; Espedal, Per Gunnar; Nilsen, Frank; Skern-Mauritzen, Mette; Glover, Kevin Alan

2014-05-19

The development of pesticide resistance represents a global challenge to food production. Specifically for the Atlantic salmon aquaculture industry, parasitic sea lice and their developing resistance to delousing chemicals is challenging production. In this study, seventeen full sibling families, established from three strains of Lepeophtheirus salmonis displaying differing backgrounds in emamectin benzoate (EB) tolerance were produced and quantitatively compared under a common-garden experimental design. Lice surviving to the preadult stage were then exposed to EB and finally identified through the application of DNA parentage testing. With the exception of two families (19 and 29%), survival from the infectious copepod to preadult stage was very similar among families (40-50%). In contrast, very large differences in survival following EB exposure were observed among the families (7.9-74%). Family survival post EB exposure was consistent with the EB tolerance characteristics of the strains from which they were established and no negative effect on infection success were detected in association with increased EB tolerance. Two of the lice families that displayed reduced sensitivity to EB were established from a commercial farm that had previously used this chemical. This demonstrates that resistant alleles were present on this farm even though the farm had not reported treatment failure. To our knowledge, this represents the first study where families of any multi-cellular parasite have been established and compared in performance under communal rearing conditions in a common-garden experiment. The system performed in a predictable manner and permitted, for the first time, elucidation of quantitative traits among sea lice families. While this experiment concentrated on, and provided a unique insight into EB sensitivity among lice families, the experimental design represents a novel methodology to experimentally address both resistance development and other evolutionary questions in parasitic copepods.

A common-garden experiment to quantify evolutionary processes in copepods: the case of emamectin benzoate resistance in the parasitic sea louse Lepeophtheirus salmonis

PubMed Central

2014-01-01

Background The development of pesticide resistance represents a global challenge to food production. Specifically for the Atlantic salmon aquaculture industry, parasitic sea lice and their developing resistance to delousing chemicals is challenging production. In this study, seventeen full sibling families, established from three strains of Lepeophtheirus salmonis displaying differing backgrounds in emamectin benzoate (EB) tolerance were produced and quantitatively compared under a common-garden experimental design. Lice surviving to the preadult stage were then exposed to EB and finally identified through the application of DNA parentage testing. Results With the exception of two families (19 and 29%), survival from the infectious copepod to preadult stage was very similar among families (40-50%). In contrast, very large differences in survival following EB exposure were observed among the families (7.9-74%). Family survival post EB exposure was consistent with the EB tolerance characteristics of the strains from which they were established and no negative effect on infection success were detected in association with increased EB tolerance. Two of the lice families that displayed reduced sensitivity to EB were established from a commercial farm that had previously used this chemical. This demonstrates that resistant alleles were present on this farm even though the farm had not reported treatment failure. Conclusions To our knowledge, this represents the first study where families of any multi-cellular parasite have been established and compared in performance under communal rearing conditions in a common-garden experiment. The system performed in a predictable manner and permitted, for the first time, elucidation of quantitative traits among sea lice families. While this experiment concentrated on, and provided a unique insight into EB sensitivity among lice families, the experimental design represents a novel methodology to experimentally address both resistance development and other evolutionary questions in parasitic copepods. PMID:24885085

Solubility and disintegration of new calcium aluminate cement (EndoBinder) containing different radiopacifying agents.

PubMed

Garcia, Lucas da Fonseca Roberti; Chinelatti, Michelle Alexandra; Rossetto, Hebert Luis; Pires-de-Souza, Fernanda de Carvalho Panzeri

2014-02-01

The aim of this study was to evaluate the solubility and disintegration of EndoBinder (EB) containing 3 different radiopacifying agents, bismuth oxide (Bi2O3), zinc oxide (ZnO), or zirconium oxide (ZrO2), in comparison with gray mineral trioxide aggregate (GMTA) and white MTA (WMTA). Ten specimens of each cement were made in a stainless steel matrix (20 × 1.5 mm) according to Specification no. 57 of American National Standards Institute/American Dental Association: EB + Bi2O3, EB + ZrO, EB + ZnO, WMTA, and GMTA. The specimens were weighed on an accurate analytical scale and immersed in 50 mL distilled and deionized water at 37°C for 7 days. Afterwards, specimens were dried and weighed again to determine mass loss (%). Resulting solutions were analyzed in an atomic absorption spectrophotometer for identification and quantification of chemical elements released. All cements presented mean values of solubility and disintegration above the American National Standards Institute/American Dental Association Specification no. 57. EB + Bi2O3 presented the lowest mass loss (5.08%) and WMTA (6.65%) the highest, with no statistically significant difference (P > .05). The release of several chemical elements was observed, mostly metal ions. Only GMTA and EB + Bi2O3 showed the presence of Cr, with significant difference (P < .05). EB + ZnO presented the highest levels of Pb, followed by WMTA (P < .05). For As, the cements presented different release levels, with EB + ZnO showing the highest and GMTA the lowest levels (P < .05). However, the amounts of As and Pb released were lower than the safe limit proposed by ISO 9917-1. Irrespective of the radiopacifying agents used, EndoBinder presented similar behavior to MTA. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Effects of chlorogenic acid on adenine nucleotides hydrolyzing enzyme activities and expression in platelets of rats experimentally demyelinated with ethidium bromide.

PubMed

Leal, Claudio A M; Leal, Daniela B R; Adefegha, Stephen A; Morsch, Vera M; Beckmann, Diego V; Castilhos, Lívia G; Thorstenberg, Maria L P; Jaques, Jeandre A Dos S; Souza, Viviane do C G; Farias, Júlia G; Martins, Caroline C; Schetinger, Maria R C

2016-07-01

The effects of chlorogenic acid (one of the major phenolic acid found in human diets) were investigated on the adenine nucleotides hydrolyzing enzymes; ecto-nucleotide pyrophosphatase/phophodiesterase (E-NPP), ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), E-5'- nucleotidase and ecto-adenosine deaminase (E-ADA) activities and expression in platelets of rats experimentally demyelinated with ethidium bromide. Rats were divided into four groups of eight animals each. Group I rats were control rats; injected with saline (CT), group II rats were injected with saline and treated with chlorogenic acid (AC), group III rats were injected with 0.1% ethidium bromide (EB) and group IV rats were injected with 0.1% EB and treated with chlorogenic acid (EB+AC). The activities of the enzymes were analyzed using colorimetric methods, and the gene expression of NTPDase 1, 2 and 3 were analyzed using the polymerase chain reaction (PCR). The results revealed that there was a significant (P<0.01) reduction in E-NPP activity in EB group (1.63±0.10nmol p-nitrophenol released/min/mg protein) when compared to CT group (2.33±0.14nmol p-nitrophenol released/min/mg protein). However, treatment with chlorogenic acid significantly (P<0.05) increased E-NPP activity in EB group. Furthermore, no significant (P>0.05) change was observed in the E-NPP activity of EB+AC group (2.19±0.08nmol p-nitrophenol released/min/mg protein) when compared to CT group (2.33±0.14nmol p-nitrophenol released/min/mg protein). In addition, there was a significant (P<0.05) increase in AMP hydrolysis in EB rat group when compared to CT group. No significant (P>0.05) difference was observed in AMP hydrolysis between AC, AC+EB and CT groups. Conversely, there were no significant (P>0.05) differences in ATP and ADP hydrolyses between all the groups (AC, EB, AC+EB and CT groups). Likewise, there were no significant (P>0.05) changes in E-ADA activity and percentage platelet aggregation among all groups studied. Similarly, no significant (P>0.05) change was observed in the expression of E-NTPDase 1, 2 and 3 in all the groups tested. Our study revealed that chlorogenic acid may modulate the hydrolysis of adenine nucleotides in platelets of rats demyelinated and treated with chlorogenic acid via alteration of E-NPP and ecto-5'-nucleotidase activities. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Persistence of blood changes associated with alteration of the dietary electrolyte balance in commercial pigs after feed withdrawal, transportation, and lairage, and the effects on performance and carcass quality.

PubMed

Edwards, L N; Engle, T E; Paradis, M A; Correa, J A; Anderson, D B

2010-12-01

Increasing dietary electrolyte balance (dEB) has previously been shown to reduce the incidence of nonambulatory and noninjured swine, improve meat quality, and reduce the incidence of gastric ulcers. The objective of this study was to evaluate the effect of dEB under commercial conditions. Due to the variability in feed withdrawal, transport, and lairage conditions in the swine industry, it was necessary to determine first the persistence of blood changes during the marketing process after alteration of dEB. Sixteen pens of 8 crossbred barrows were assigned to a low (121 mEq/kg) or high (375 mEq/kg) dEB diet, calculated as Na(+) + K(+) - Cl(-), to determine the persistence of blood changes associated with the alteration of dEB. Diets were formulated to meet or exceed NRC (1998) requirements for energy, protein, vitamins, and minerals. Dietary treatments were provided for ad libitum intake for 3 d before slaughter. Before transport, animals were fasted in the barn for approximately 10 h. After fasting, animals were shipped to the packing plant, rested for 8 h, and subsequently slaughtered. Initial and final BW of the animals were obtained. Blood was sampled at baseline (2 d before administration of diets), before feed withdrawal (0 h), after feed withdrawal (10 h), and at exsanguination (20 h). Consumption of the high dEB diet for 3 d resulted in an increase in blood TCO(2) (P = 0.001), HCO(3)(-) (P = 0.001), and base excess (P = 0.0003) and a decrease in Cl(-) (P = 0.0002) and anion gap (P = 0.01). These differences, however, were not maintained for any of the blood components after the 10-h feed withdrawal (P > 0.22). Increasing dEB had no adverse effects (P > 0.18) on growth performance, meat quality, or carcass yield and did not decrease pars esophageal ulcer scores. This study demonstrated that the effect of dEB on blood components was not maintained after a 10-h feed withdrawal. Therefore, it is likely that the ability of the animal to withstand any increased metabolic acid load associated with the stress of transport was lost after feed withdrawal. Further research is needed to determine the effects of dEB alteration in animals that have not been fasted before shipment and using diets with a larger difference in dEB.

Evidence-based medicine in daily surgical decision making: a survey-based comparison between the UK and Germany.

PubMed

Schnitzbauer, Andreas A; Proneth, Andrea; Pengel, Liset; Ansorg, Jörg; Anthuber, Matthias; Bechstein, Wolf O; Schlitt, Hans J; Geissler, Edward K

2015-01-01

Evidence-based medicine (EbM) is a vital part of reasonable and conclusive decision making for clinicians in daily clinical work. To analyze the knowledge and the attitude of surgeons towards EbM, a survey was performed in the UK and Germany. A web-based questionnaire was distributed via mailing lists from the Royal College of Surgeons of England (RCSE) and the Berufsverband Deutscher Chirurgen (BDC). Our primary aim was to get information about knowledge of EbM amongst German and British surgeons. A total of 549 individuals opened the questionnaire, but only 198 questionnaires were complete and valid for analysis. In total, 40,000 recipients were approached via the mailing lists of the BDC and RCSE. The response rate was equally low in both countries. On a scale from 1 (unimportant) to 10 (very important), all participants rated EbM as very important for daily clinical decision making (7.3 ± 1.9) as well as for patients (7.8 ± 1.9) and the national health system (7.8 ± 1.9). On a scale from 1 (unimportant) to 5 (very important), systematic reviews (4.6 ± 0.6) and randomized controlled trials (4.6 ± 0.6) were identified as the highest levels of study designs to enhance evidence in medicine. British surgeons considered EbM to be more important in daily clinical work when compared to data from German surgeons (7.9 ± 1.6 vs. 6.7 ± 2.1, p < 0.001). Subgroup analysis showed different results in some categories; however, a pattern to explain the differences was not evident. Personal requirements expressed in a free text field emphasized the results and reflected concerns such as broad unwillingness and lack of interdisciplinary approaches for patients (n = 59: 25 in the UK and 34 in Germany). The overall results show that EbM is believed to be important by surgeons in the UK and Germany. However, perception of EbM in the respective health system (UK vs. Germany) may be different. Nonetheless, EbM is an important tool to navigate through daily clinical problems although a discrepancy between the knowledge of theoretical abstract terms and difficulties in implementing EbM in daily clinical work has been detected. The provision of infrastructure, courses and structured education as a permanent instrument will advance the knowledge, application and improvement of EbM in the future. © 2014 S. Karger AG, Basel.

Defense Logistics Agency Did Not Fully Implement the Business Enterprise Architecture Procure-to-Pay Business Process in the Enterprise Business System

DTIC Science & Technology

2014-10-28

change. Enterprise Business System In August 2000, DLA began developing its Enterprise Resource Planning ( ERP ) system by initiating the Business...the EBS core system. EBS became the ERP system solution supporting DLA nonenergy commodity activities. DLA subsequently enhanced its EBS...capabilities by adding SAP software that supported DLA Enterprise Operational Accounting, real property, and inventory management functions. As part of the

Fetal bovine serum enables cardiac differentiation of human embryonic stem cells.

PubMed

Bettiol, Esther; Sartiani, Laura; Chicha, Laurie; Krause, Karl Heinz; Cerbai, Elisabetta; Jaconi, Marisa E

2007-10-01

During development, cardiac commitment within the mesoderm requires endoderm-secreted factors. Differentiation of embryonic stem cells into the three germ layers in vitro recapitulates developmental processes and can be influenced by supplements added to culture medium. Hence, we investigated the effect of fetal bovine serum (FBS) and KnockOut serum replacement (SR) on germ layers specification and cardiac differentiation of H1 human embryonic stem cells (hESC) within embryoid bodies (EB). At the time of EB formation, FBS triggered an increased apoptosis. As assessed by quantitative PCR on 4-, 10-, and 20-day-old EB, FBS promoted a faster down-regulation of pluripotency marker Oct4 and an increased expression of endodermal (Sox17, alpha-fetoprotein, AFP) and mesodermal genes (Brachyury, CSX). While neuronal and hematopoietic differentiation occurred in both supplements, spontaneously beating cardiomyocytes were only observed in FBS. Action potential (AP) morphology of hESC-derived cardiomyocytes indicated that ventricular cells were present only after 2 months of culture. However, quantification of myosin light chain 2 ventricular (mlc2v)-positive areas revealed that mlc2v-expressing cardiomyocytes could be detected already after 2 weeks of differentiation, but not in all beating clusters. In conclusion, FBS enabled cardiac differentiation of hESC, likely in an endodermal-dependent pathway. Among cardiac cells, ventricular cardiomyocytes differentiated over time, but not as the predominant cardiac cell subtype.

Nanoplasmonic Phenomena at Electronic Boundaries in Graphene

DOE PAGES

Fei, Zhe; Ni, Guang -Xin; Jiang, Bor -Yuan; ...

2017-06-30

Here, we review recent discoveries of the intriguing plasmonic phenomena at a variety of electronic boundaries (EBs) in graphene including a line of charges in graphene induced by a carbon nanotube gate, grain boundaries in chemical vapor deposited graphene films, an interface between graphene and moiré patterned graphene, an interface between graphene and bilayer graphene, and others. All these and other EBs cause plasmonic impedance mismatch at the two sides of the boundaries. Manifestations of this effect include plasmonic fringes that stem from plasmon reflections and interference. Quantitative analysis and modeling of these plasmonic fringes uncovered intriguing properties and underlyingmore » physics of the EBs. Potential plasmonic applications associated with these EBs are also briefly discussed.« less

Nanoplasmonic Phenomena at Electronic Boundaries in Graphene

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

Fei, Zhe; Ni, Guang -Xin; Jiang, Bor -Yuan

Here, we review recent discoveries of the intriguing plasmonic phenomena at a variety of electronic boundaries (EBs) in graphene including a line of charges in graphene induced by a carbon nanotube gate, grain boundaries in chemical vapor deposited graphene films, an interface between graphene and moiré patterned graphene, an interface between graphene and bilayer graphene, and others. All these and other EBs cause plasmonic impedance mismatch at the two sides of the boundaries. Manifestations of this effect include plasmonic fringes that stem from plasmon reflections and interference. Quantitative analysis and modeling of these plasmonic fringes uncovered intriguing properties and underlyingmore » physics of the EBs. Potential plasmonic applications associated with these EBs are also briefly discussed.« less

Supramolecular Assembly of Tripodal Trisamides

NASA Astrophysics Data System (ADS)

Feng, Li

2010-03-01

A series of tripodal trisamide compounds have been synthesized from tris(2-aminoethyl)amine (TREN) by condensation with different acid chlorides. Gelation of organic solvents with these compounds was investigated as a function of concentration and solvent solubility parameter. Compounds made with linear acid chlorides were poor gelators. A gelator made with 2-ethylbutyryl chloride (TREN-EB) was an excellent gelator for many organic solvents. It was found that the minimum gelation concentration of TREN-EB increased with increasing solubility parameter of the solvent. Thin films samples were prepared by spin-coating mixtures of TREN-EB and a poly(acrylate). Scanning force microscopy measurements showed that TREN-EB formed nanofibrillar network structures. In addition a dependence of the network morphology on the casting solvent was found.

Integrating clinicians, knowledge and data: expert-based cooperative analysis in healthcare decision support

PubMed Central

2010-01-01

Background Decision support in health systems is a highly difficult task, due to the inherent complexity of the process and structures involved. Method This paper introduces a new hybrid methodology Expert-based Cooperative Analysis (EbCA), which incorporates explicit prior expert knowledge in data analysis methods, and elicits implicit or tacit expert knowledge (IK) to improve decision support in healthcare systems. EbCA has been applied to two different case studies, showing its usability and versatility: 1) Bench-marking of small mental health areas based on technical efficiency estimated by EbCA-Data Envelopment Analysis (EbCA-DEA), and 2) Case-mix of schizophrenia based on functional dependency using Clustering Based on Rules (ClBR). In both cases comparisons towards classical procedures using qualitative explicit prior knowledge were made. Bayesian predictive validity measures were used for comparison with expert panels results. Overall agreement was tested by Intraclass Correlation Coefficient in case "1" and kappa in both cases. Results EbCA is a new methodology composed by 6 steps:. 1) Data collection and data preparation; 2) acquisition of "Prior Expert Knowledge" (PEK) and design of the "Prior Knowledge Base" (PKB); 3) PKB-guided analysis; 4) support-interpretation tools to evaluate results and detect inconsistencies (here Implicit Knowledg -IK- might be elicited); 5) incorporation of elicited IK in PKB and repeat till a satisfactory solution; 6) post-processing results for decision support. EbCA has been useful for incorporating PEK in two different analysis methods (DEA and Clustering), applied respectively to assess technical efficiency of small mental health areas and for case-mix of schizophrenia based on functional dependency. Differences in results obtained with classical approaches were mainly related to the IK which could be elicited by using EbCA and had major implications for the decision making in both cases. Discussion This paper presents EbCA and shows the convenience of completing classical data analysis with PEK as a mean to extract relevant knowledge in complex health domains. One of the major benefits of EbCA is iterative elicitation of IK.. Both explicit and tacit or implicit expert knowledge are critical to guide the scientific analysis of very complex decisional problems as those found in health system research. PMID:20920289

Integrating clinicians, knowledge and data: expert-based cooperative analysis in healthcare decision support.

PubMed

Gibert, Karina; García-Alonso, Carlos; Salvador-Carulla, Luis

2010-09-30

Decision support in health systems is a highly difficult task, due to the inherent complexity of the process and structures involved. This paper introduces a new hybrid methodology Expert-based Cooperative Analysis (EbCA), which incorporates explicit prior expert knowledge in data analysis methods, and elicits implicit or tacit expert knowledge (IK) to improve decision support in healthcare systems. EbCA has been applied to two different case studies, showing its usability and versatility: 1) Bench-marking of small mental health areas based on technical efficiency estimated by EbCA-Data Envelopment Analysis (EbCA-DEA), and 2) Case-mix of schizophrenia based on functional dependency using Clustering Based on Rules (ClBR). In both cases comparisons towards classical procedures using qualitative explicit prior knowledge were made. Bayesian predictive validity measures were used for comparison with expert panels results. Overall agreement was tested by Intraclass Correlation Coefficient in case "1" and kappa in both cases. EbCA is a new methodology composed by 6 steps:. 1) Data collection and data preparation; 2) acquisition of "Prior Expert Knowledge" (PEK) and design of the "Prior Knowledge Base" (PKB); 3) PKB-guided analysis; 4) support-interpretation tools to evaluate results and detect inconsistencies (here Implicit Knowledg -IK- might be elicited); 5) incorporation of elicited IK in PKB and repeat till a satisfactory solution; 6) post-processing results for decision support. EbCA has been useful for incorporating PEK in two different analysis methods (DEA and Clustering), applied respectively to assess technical efficiency of small mental health areas and for case-mix of schizophrenia based on functional dependency. Differences in results obtained with classical approaches were mainly related to the IK which could be elicited by using EbCA and had major implications for the decision making in both cases. This paper presents EbCA and shows the convenience of completing classical data analysis with PEK as a mean to extract relevant knowledge in complex health domains. One of the major benefits of EbCA is iterative elicitation of IK.. Both explicit and tacit or implicit expert knowledge are critical to guide the scientific analysis of very complex decisional problems as those found in health system research.

Kinematics of mechanical and adhesional micromanipulation under a scanning electron microscope

NASA Astrophysics Data System (ADS)

Saito, Shigeki; Miyazaki, Hideki T.; Sato, Tomomasa; Takahashi, Kunio

2002-11-01

In this paper, the kinematics of mechanical and adhesional micromanipulation using a needle-shaped tool under a scanning electron microscope is analyzed. A mode diagram is derived to indicate the possible micro-object behavior for the specified operational conditions. Based on the diagram, a reasonable method for pick and place operation is proposed. The keys to successful analysis are to introduce adhesional and rolling-resistance factors into the kinematic system consisting of a sphere, a needle-shaped tool, and a substrate, and to consider the time dependence of these factors due to the electron-beam (EB) irradiation. Adhesional force and the lower limit of maximum rolling resistance are evaluated quantitatively in theoretical and experimental ways. This analysis shows that it is possible to control the fracture of either the tool-sphere or substrate-sphere interface of the system selectively by the tool-loading angle and that such a selective fracture of the interfaces enables reliable pick or place operation even under EB irradiation. Although the conventional micromanipulation was not repeatable because the technique was based on an empirically effective method, this analysis should provide us with a guideline to reliable micromanipulation.

Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells.

PubMed

Kim, Gi Dae; Oh, Jedo; Park, Hyen-Joo; Bae, Kihwan; Lee, Sang Kook

2013-08-01

Magnolol, a neolignan from the traditional medicinal plant Magnolia obovata, has been shown to possess neuroprotective, anti-inflammatory, anticancer and anti-angiogenic activities. However, the precise mechanism of the anti-angiogenic activity of magnolol remains to be elucidated. In the present study, the anti-angiogenic effect of magnolol was evaluated in mouse embryonic stem (mES)/embryoid body (EB)-derived endothelial-like cells. The endothelial-like cells were obtained by differentiation from mES/EB cells. Magnolol (20 µM) significantly suppressed the transcriptional and translational expression of platelet endothelial cell adhesion molecule (PECAM), an endothelial biomarker, in mES/EB-derived endothelial-like cells. To further understand the molecular mechanism of the suppression of PECAM expression, signaling pathways were analyzed in the mES/EB-derived endothelial-like cells. Magnolol induced the generation of reactive oxygen species (ROS) by mitochondria, a process that was associated with the induction of apoptosis as determined by positive Annexin V staining and the activation of cleaved caspase-3. The involvement of ROS generation by magnolol was confirmed by treatment with an antioxidant, N-acetyl-cysteine (NAC). NAC inhibited the magnolol-mediated induction of ROS generation and suppression of PECAM expression. In addition, magnolol suppressed the activation of MAPKs (ERK, JNK and p38) and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Taken together, these findings demonstrate for the first time that the anti-angiogenic activity of magnolol may be associated with ROS-mediated apoptosis and the suppression of the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells.

A case of IgG4-related lung disease complicated by asymptomatic chronic Epstein-Barr virus infection.

PubMed

Kotetsu, Yasuaki; Ikegame, Satoshi; Takebe-Akazawa, Keiko; Koga, Takaomi; Okabayashi, Kan; Takata, Shohei

2017-11-01

IgG4-related disease is characterized by IgG4-positive plasmacyte infiltration into various organs, but its etiology is not unknown. To elucidate the etiology of IgG4-related disease. We experienced an interesting case of IgG4-related lung disease complicated by chronic EB virus infection. A 70-year-old male visited our hospital due to failure of pneumonia treatment. Chest computed tomography (CT) showed consolidation in the right middle field and slight mediastinal lymphadenopathy in the subcarinal region. Lung consolidation improved with antibiotics; subcarinal lymphadenopathy progressed after 4 months. Malignant lymphoma was suspected given elevated sIL2-R levels (1862 U/mL). Patchy ground glass opacities appeared in the bilateral lung field just before surgical biopsy. He was diagnosed with IgG4-related lung disease after inspection of a pathological specimen obtained from the right upper lung and right hilar lymph node. EB virus-infected cells were also detected in the lymph node. Blood examination revealed EB virus viremia, but the patient did not present with symptoms or organ involvement. This led to a diagnosis of asymptomatic chronic EB virus infection. Recent studies have suggested an association between EB virus infection and IgG4-related diseases in the pathological exploration of surgically resected lymph nodes. Our case is the first case of IgG4-related lung disease in which EB virus infection was both pathologically and clinically proved. The present case is of particular interest in view of this newly reported association, and may serve as a fundamental report for future studies connecting EB virus infection with IgG4-related diseases. © 2016 John Wiley & Sons Ltd.

Effect of dietary manipulation on substrate flux and energy balance in obese women taking the appetite suppressant dexfenfluramine.

PubMed

Poppitt, S D; Swann, D L; Murgatroyd, P R; Elia, M; McDevitt, R M; Prentice, A M

1998-11-01

Studies in lean men show poor regulation of energy (EB) and fat balance (FB) during manipulation of dietary ratios of fat to carbohydrate. High-fat (HF), high-energy diets cause hyperphagia and a positive EB and FB. The protocol was designed to measure substrate flux and EB in obese women taking dexfenfluramine (DF) or placebo (PL) during an HF (50% of energy) or low-fat (25% of energy; LF) diet. We hypothesized that alterations in dietary fat would not be regulated and would lead to a positive EB and FB. The study was double-blind, randomized, and placebo-controlled, with 4 treatments (LF/DF, HF/DF, LF/PL, and HF/PL) and a crossover. Five days of continuous, whole-body calorimetry measurements were made in 6 subjects after 8 d of home DF/PL treatment. Macronutrient balance and EB were measured within the chamber as the cumulative difference between ad libitum intake and oxidation. The HF diet increased energy (HF, 10.50 MJ/d; LF, 8.13 MJ/d; P < 0.0001) and fat intakes (HF, 5.34 MJ/d; LF, 2.06 MJ/d; P < 0.0001), leading to a positive EB (delta = 2.37 MJ/d) and FB (delta = 2.31 MJ/d). DF reduced energy (DF, 8.96 MJ/d; PL, 9.66 MJ/d; P < 0.01) and macronutrient intakes, but did not increase energy expenditure (delta = -0.31 MJ/d; P < 0.01), or 24-h fat oxidation (delta = 0.03 MJ/d; P = 0.46). EB and FB are poorly regulated with HF, energy-dense diets in obese women, which leads to fat deposition and weight gain.

Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide.

PubMed

Beckmann, Diego V; Carvalho, Fabiano B; Mazzanti, Cinthia M; Dos Santos, Rosmarini P; Andrades, Amanda O; Aiello, Graciane; Rippilinger, Angel; Graça, Dominguita L; Abdalla, Fátima H; Oliveira, Lizielle S; Gutierres, Jessié M; Schetinger, Maria Rosa C; Mazzanti, Alexandre

2014-05-17

The purpose of this study was to investigate whether the flavonoid quercetin can prevent alterations in the behavioral tests and of cholinergic neurotransmission in rats submitted to the ethidium bromide (EB) experimental demyelination model during events of demyelination and remyelination. Wistar rats were randomly distributed into four groups (20 animals per group): Control (pontine saline injection and treatment with ethanol), Querc (pontine saline injection and treatment with quercetin), EB (pontine 0.1% EB injection and treatment with ethanol), and EB+Querc (pontine 0.1% EB injection and treatment with quercetin). The groups Querc and Querc+EB were treated once daily with quercetin (50mg/kg) diluted in 25% ethanol solution (1ml/kg) and the animals of the control and EB groups were treated once daily with 25% ethanol solution (1ml/kg). Two stages were observed: phase of demyelination (peak on day 7) and phase of remyelination (peak on day 21 post-injection). Behavioral tests (beam walking, foot fault and inclined plane test), acetylcholinesterase (AChE) activity and lipid peroxidation in pons, cerebellum, hippocampus, hypothalamus, striatum and cerebral cortex were measured. The quercetin promoted earlier locomotor recovery, suggesting that there was demyelination prevention or further remyelination velocity as well as it was able to prevent the inhibition of AChE activity and the increase of lipidic peroxidation, suggesting that this compound can protect cholinergic neurotransmission. These results may contribute to a better understanding of the neuroprotective role of quercetin and the importance of an antioxidant diet in humans to provide benefits in neurodegenerative diseases such as MS. Copyright © 2014. Published by Elsevier Inc.

Free-Weight Augmentation With Elastic Bands Improves Bench Press Kinematics in Professional Rugby Players.

PubMed

García-López, David; Hernández-Sánchez, Sonsoles; Martín, Esperanza; Marín, Pedro J; Zarzosa, Fernando; Herrero, Azael J

2016-09-01

García-López, D, Hernández-Sánchez, S, Martín, E, Marín, PJ, Zarzosa, F, and Herrero, AJ. Free-weight augmentation with elastic bands improves bench press kinematics in professional rugby players. J Strength Cond Res 30(9): 2493-2499, 2016-This study aimed to investigate the effects of combining elastic bands to free weight resistance (EB + FWR) on the acceleration-deceleration and velocity profiles of the bench press in professional rugby players and recreationally trained subjects. Sixteen male subjects (8 rugby players and 8 recreationally trained subjects) were randomly assigned to complete 2 experimental conditions in a crossover fashion: EB + FWR and FWR. In both conditions, subjects performed 1 bench press set to volitional exhaustion with a load equivalent to the 85% of 1 repetition maximum (1RM). In the EB + FWR condition, the contribution of elastic resistance was approximately 20% of the selected load (85% 1RM). Results indicate that EB + FWR condition increased significantly the range of concentric movement in which the barbell is accelerated. This increase was significantly higher in rugby players (35%) in comparison with recreationally trained subjects (13%). Maximal velocity was also increased in EB + FWR (17%), when compared with FWR condition. These results suggest that when combined with variable resistance (i.e., EB), the external resistance seems to be more evenly distributed over the full range of motion, decreasing the need for dramatic deceleration at the end of the concentric phase. The present data also indicate that the kinematic benefits of an EB + FWR approach seems to be more prominent in athletes from modalities in which high level of strength and power are required (i.e., rugby players).

The evolution of and challenges for industrial radiation processing—2012

NASA Astrophysics Data System (ADS)

Berejka, A. J.; Cleland, M. R.; Walo, M.

2014-01-01

The evolution of industrial radiation processing is traced from Roentgen's discovery of X-radiation in 1895 by following the development of high current, electron beam accelerators (EB) throughout the twentieth century. Although Becquerel soon followed Roentgen with his discovery of what became to be known as radioactivity, electrical sources for ionizing radiation dominate industrial processing with there being more than ten times as many industrial installations using high current EB equipment than the facilities relying upon large concentrations of radioactive isotopes. In the 1950s, the discovery that ionizing radiation would enhance the value of what has become the world's largest volume commodity plastic, polyethylene (PE), opened the way for full scale commercial use of high current EB equipment. While the crosslinking of the PE insulation on wire became one of the first major industrial applications, other uses of EB processing soon followed. In the 1970s, low-energy, self-shielded EB equipment made the surface curing of inks, coatings and adhesives more industrially viable. In the early part of the twenty-first century, new market applications involving the low-energy EB surface decontamination of packaging materials emerged. This new area poses challenges for the metrology needed to control industrial processes, in that there is limited EB penetration into what have been used as dosimeters by industry. Major industrial use of radiation process is now over 50 years old. Because of the diversity of end-uses and the fact that the use of ionizing radiation in industry is a process technique, it is hard to quantify the value-added to numerous commercial products that benefit from this energy efficient process. It may be in excess of a trillion Euros in value-added to articles of commerce. In this milieu, there are some broad-based opportunities for research which are noted.

Differential skeletal responses of hindlimb unloaded rats on a vitamin D-deficient diet to 1,25-dihydroxyvitamin D3 and its analog, seocalcitol (EB1089)

NASA Technical Reports Server (NTRS)

Narayanan, Ramesh; Allen, Matthew R.; Gaddy, Dana; Bloomfield, Susan A.; Smith, Carolyn L.; Weigel, Nancy L.

2004-01-01

Conditions of disuse in bed rest patients, as well as microgravity experienced by astronauts are accompanied by reduced mechanical loading, reduced calcium absorption, and lower serum levels of 1,25(OH)2D3 (1,25-D), the active metabolite of vitamin D, all contributing to bone loss. To determine whether 1,25-D or a less calcemic analog, Seocalcitol or EB1089 (1 alpha,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D3) can alleviate bone loss in a rat hindlimb unloading model of disuse osteopenia, mature male rats originally on a vitamin D replete diet containing 1.01% calcium were transferred to a vitamin D-deficient diet containing 0.48% calcium and then tail suspended and treated for 28 days with vehicle, 0.05 microg/kg 1,25-D, or 0.05 microg/kg EB1089. The vitamin D-deficient diet caused a substantial decrease in bone mineral density (-8%), which may be compounded by hindlimb unloading (-10%). Exogenous 1,25-D not only prevented the bone loss but also increased the bone mineral density to greater than the baseline level (+7%). EB1089 was less effective in preventing bone loss. Analysis of site and cell-specific effects of 1,25-D and EB1089 revealed that 1,25-D was more active than EB1089 in the intestine, the site of calcium absorption, and in inducing osteoclastogenesis and bone resorption whereas EB1089 was more effective in inducing osteoblast differentiation. These studies suggest that elevating circulating 1,25-D levels presumably increasing calcium absorption can counteract bone loss induced by disuse or microgravity with its associated reductions in circulating 1,25-D and decreased calcium absorption.

Use of a novel laparoscopic gastrostomy technique in children with severe epidermolysis bullosa.

PubMed

Patel, Kamlesh; Wells, Jonathan; Jones, Rosie; Browne, Fiona; Moss, Celia; Parikh, Dakshesh

2014-05-01

Supplementing nutrition in children with severe epidermolysis bullosa (EB) is challenging because of skin and mucosal fragility. Percutaneous endoscopic gastrostomy is contraindicated in EB, whereas more invasive open surgical gastrostomy placement can be complicated by chronic leakage. The aim of the study was to review the efficacy and acceptability, in children with severe EB, of our modified 2-port laparoscopic approach using the Seldinger technique with serial dilatation and tube insertion through a peel-away sheath. Retrospective review of children with EB who underwent laparoscopic feeding gastrostomy at our centre since 2009. Seven children (6 severe generalised recessive dystrophic EB, 1 non-Herlitz junctional EB; 2 girls, 5 boys) underwent modified laparoscopic gastrostomy placement at median age 4.85 years (range 1.0-8.8), with fundoplication for gastro-oesophageal reflux in 1 case, with follow-up for 0.3 to 3.9 years. The procedure was well tolerated with oral feeds usually given after 4 hours and whole protein gastrostomy feeds within 24 hours in 6 patients. Improved growth was reflected in mean weight and height z scores: -1.36 (range -2.6 to 0.5) to -0.61 (range -2.34 to 2.0) and -1.09 (range -2.42 to 1.0) to 0.71 (range -1.86 to 1.0), respectively. Postoperatively, 5 patients experienced minor local complications: minimal leakage without skin damage in 3 and transient peristomal granulation rapidly responsive to topical treatment in 2; this followed acute gastrostomy site infection in 1. There was no leakage after the immediate postoperative period. We conclude that our less-invasive laparoscopic gastrostomy technique is effective and better tolerated in children with severe EB, at least in the medium term, than open gastrostomy placement. Longer follow-up is required.

Adopting a Sustainable Community of Practice Model when Developing a Service to Support Patients with Epidermolysis Bullosa (EB): A Stakeholder-Centered Approach.

PubMed

Gowran, Rosemary Joan; Kennan, Avril; Marshall, Siobhán; Mulcahy, Irene; Ní Mhaille, Sile; Beasley, Sarah; Devlin, Mark

2015-02-01

Epidermolysis bullosa (EB) is a rare, genetic skin condition that is complicated, distressing, and painful and permeates every aspect of patients' lives. Support services are essential for meeting the primary needs of patients and families living with EB; however, provision is challenged by many complex issues. In collaboration with the patient organization DEBRA Ireland, this research conducted an in-depth analysis of Irish healthcare support services for EB, with a view to moving towards an improved and sustainable care pathway. A sustainable community of practice model (SCOP), as a core construct provided a simplified framework when studying this complex system. The research utilized mixed methods, comprising individual interviews, questionnaires, and a participatory action research workshop based on a soft systems approach. The study engaged patients, family members, service providers, and policy developers. Findings emphasized that the complexities of life with EB are more than 'skin deep'. The lived experience of stakeholders revealed many levels of emotion, both positive and heart-rending. Despite the positive efforts of specialists in this field, inadequacies to meet the primary needs of people with EB, such as bandages-fundamental for survival-were highlighted. Participants reported challenges relating to understanding patients' needs, access to consistent services within hospitals and the community, time constraints, and the strong emotions evoked by this severe and rare disease. The study identified several areas that can be targeted to bring about improvements in meeting primary needs. Education and research at public, policy, and practice levels need to be prioritized. It is imperative that citizens move beyond an awareness that EB exists and demonstrate a consciousness about the importance of advocating and enabling seamless and sustainable support services through collective action.

Radioligand Therapy of Prostate Cancer with a Long-Lasting Prostate-Specific Membrane Antigen Targeting Agent 90Y-DOTA-EB-MCG.

PubMed

Wang, Zhantong; Jacobson, Orit; Tian, Rui; Mease, Ronnie C; Kiesewetter, Dale O; Niu, Gang; Pomper, Martin G; Chen, Xiaoyuan

2018-06-15

Several radioligands targeting prostate-specific membrane antigen (PSMA) have been clinically introduced as a new class of radiotheranostics for the treatment of prostate cancer. Among them, ((( R)-1-carboxy-2-mcercaptoethyl)carbamoyl)-l-glutamic acid (MCG) has been successfully labeled with radioisotopes for prostate cancer imaging. The aim of this study is to conjugate MCG with an albumin binding moiety to further improve the in vivo pharmacokinetics. MCG was conjugated with an Evans blue (EB) derivative for albumin binding and a DOTA chelator. PSMA positive (PC3-PIP) and PSMA negative (PC3) cells were used for both in vitro and in vivo studies. Longitudinal PET imaging was performed at 1, 4, 24, and 48 h post-injection to evaluate the biodistribution and tumor uptake of 86 Y-DOTA-EB-MCG. DOTA-EB-MCG was also labeled with 90 Y for radionuclide therapy. Besides tumor growth measurement, tumor response to escalating therapeutic doses were also evaluated by immunohistochemistry and fluorescence microscopy. Based on quantification from 86 Y-DOTA-EB-MCG PET images, the tracer uptake in PC3-PIP tumors increased from 22.33 ± 2.39%ID/g at 1 h post-injection (p.i.), to the peak of 40.40 ± 4.79%ID/g at 24 h p.i. Administration of 7.4 MBq of 90 Y-DOTA-EB-MCG resulted in significant regression of tumor growth in PSMA positive xenografts. No apparent toxicity or body weight loss was observed in all treated mice. Modification of MCG with an Evans blue derivative resulted in a highly efficient prostate cancer targeting agent (EB-MCG), which showed great potential in prostate cancer treatment after being labeled with therapeutic radioisotopes.

The Functional Role of eL19 and eB12 Intersubunit Bridge in the Eukaryotic Ribosome.

PubMed

Kisly, Ivan; Gulay, Suna P; Mäeorg, Uno; Dinman, Jonathan D; Remme, Jaanus; Tamm, Tiina

2016-05-22

During translation, the two eukaryotic ribosomal subunits remain associated through 17 intersubunit bridges, five of which are eukaryote specific. These are mainly localized to the peripheral regions and are believed to stabilize the structure of the ribosome. The functional importance of these bridges remains largely unknown. Here, the essentiality of the eukaryote-specific bridge eB12 has been investigated. The main component of this bridge is ribosomal protein eL19 that is composed of an N-terminal globular domain, a middle region, and a long C-terminal α-helix. The analysis of deletion mutants demonstrated that the globular domain and middle region of eL19 are essential for cell viability, most likely functioning in ribosome assembly. The eB12 bridge, formed by contacts between the C-terminal α-helix of eL19 and 18S rRNA in concert with additional stabilizing interactions involving either eS7 or uS17, is dispensable for viability. Nevertheless, eL19 mutants impaired in eB12 bridge formation displayed slow growth phenotypes, altered sensitivity/resistance to translational inhibitors, and enhanced hyperosmotic stress tolerance. Biochemical analyses determined that the eB12 bridge contributes to the stability of ribosome subunit interactions in vitro. 60S subunits containing eL19 variants defective in eB12 bridge formation failed to form 80S ribosomes regardless of Mg(2+) concentration. The reassociation of 40S and mutant 60S subunits was markedly improved in the presence of deacetylated tRNA, emphasizing the importance of tRNAs during the subunit association. We propose that the eB12 bridge plays an important role in subunit joining and in optimizing ribosome functionality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nonsense variant in COL7A1 causes recessive dystrophic epidermolysis bullosa in Central Asian Shepherd dogs.

PubMed

Niskanen, Julia; Dillard, Kati; Arumilli, Meharji; Salmela, Elina; Anttila, Marjukka; Lohi, Hannes; Hytönen, Marjo K

2017-01-01

A rare hereditary mechanobullous disorder called epidermolysis bullosa (EB) causes blistering in the skin and the mucosal membranes. To date, nineteen EB-related genes have been discovered in human and other species. We describe here a novel EB variant in dogs. Two newborn littermates of Central Asian Shepherd dogs with severe signs of skin blistering were brought to a veterinary clinic and euthanized due to poor prognosis. In post-mortem examination, the puppies were shown to have findings in the skin and the mucosal membranes characteristic of EB. A whole-genome sequencing of one of the affected puppies was performed to identify the genetic cause. The resequencing data were filtered under a recessive model against variants from 31 other dog genomes, revealing a homozygous case-specific nonsense variant in one of the known EB-causing genes, COL7A1 (c.4579C>T, p.R1527*). The variant results in a premature stop codon and likely absence of the functional protein in the basement membrane of the skin in the affected dogs. This was confirmed by immunohistochemistry using a COL7A1 antibody. Additional screening of the variant indicated full penetrance and breed specificity at ~28% carrier frequency. In summary, this study reveals a novel COL7A1 variant causing recessive dystrophic EB and provides a genetic test for the eradication of the disease from the breed.

Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle.

PubMed

Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

2015-01-01

The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. Prospective randomized control study. Tertiary care center. A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). Clinical pregnancy rate (CPR). Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle.

ELMO Bumpy Square proposal

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

Dory, R.A.; Uckan, N.A.; Ard, W.B.

The ELMO Bumpy Square (EBS) concept consists of four straight magnetic mirror arrays linked by four high-field corner coils. Extensive calculations show that this configuration offers major improvements over the ELMO Bumpy Torus (EBT) in particle confinement, heating, transport, ring production, and stability. The components of the EBT device at Oak Ridge National Laboratory can be reconfigured into a square arrangement having straight sides composed of EBT coils, with new microwave cavities and high-field corners designed and built for this application. The elimination of neoclassical convection, identified as the dominant mechanism for the limited confinement in EBT, will give themore » EBS device substantially improved confinement and the flexibility to explore the concepts that produce this improvement. The primary goals of the EBS program are twofold: first, to improve the physics of confinement in toroidal systems by developing the concepts of plasma stabilization using the effects of energetic electrons and confinement optimization using magnetic field shaping and electrostatic potential control to limit particle drift, and second, to develop bumpy toroid devices as attractive candidates for fusion reactors. This report presents a brief review of the physics analyses that support the EBS concept, discussions of the design and expected performance of the EBS device, a description of the EBS experimental program, and a review of the reactor potential of bumpy toroid configurations. Detailed information is presented in the appendices.« less

Internal Fine Structure of Ellerman Bombs

NASA Astrophysics Data System (ADS)

Hashimoto, Yuki; Kitai, Reizaburo; Ichimoto, Kiyoshi; Ueno, Satoru; Nagata, Shin'ichi; Ishii, Takako T.; Hagino, Masaoki; Komori, Hiroyuki; Nishida, Keisuke; Matsumoto, Takuma; Otsuji, Kenichi; Nakamura, Tahei; Kawate, Tomoko; Watanabe, Hiroko; Shibata, Kazunari

2010-08-01

We conducted coordinated observations of Ellerman bombs (EBs) between Hinode Satellite and Hida Observatory (HOP12). CaII H broad-band filter images of NOAA 10966 on 2007 August 9 and 10 were obtained with the Solar Optical Telescope (SOT) aboard the Hinode Satellite, and many bright points were observed. We identified a total of 4 bright points as EBs, and studied the temporal variation of their morphological fine structures and spectroscopic characteristics. With high-resolution CaII H images of SOT, we found that the EBs, thus far thought of as single bright features, are composed of a few of fine subcomponents. Also, by using Stokes I/V filtergrams with Hinode/SOT, and CaII H spectroheliograms with Hida/Domeless Solar Telescope (DST), our observation showed: (1) The mean duration, the mean width, the mean length, and the mean aspect ratio of the subcomponents were 390 s, 170 km, 450 km, and 2.7, respectively. (2) Subcomponents started to appear on the magnetic neutral lines, and extended their lengths from the original locations. (3) When the CaII H line of EBs showed the characteristic blue asymmetry, they are associated with the appearance or re-brightening of subcomponents. Summarizing our results, we obtained an observational view that elementary magnetic reconnections take place one by one successively and intermittently in EBs, and that their manifestation is the fine subcomponents of the EB phenomena.

Control of natural microorganisms in chamomile (Chamomilla recutita L.) by gamma ray and electron beam irradiation.

PubMed

Al-Bachir, Mahfouz

2017-01-01

Microbial contamination levels and corresponding sensitivities to gamma rays (GR) and elec- tron beam (EB) irradiation were tested in chamomile (Chamomile recutta L.). Chamomile powders were treated with 10 and 20 kGy by GR and EB, respectively. Microbiological and chemical analyses were performed on controls and treated samples immediately after irradiation, and after 12 months of storage. The control samples of chamomile exhibited rather high microbiological contamination, exceeding the levels of 4 log10 CFU g-1   (CFU - colony forming units) reported by national and international authorities as the maximum permissible total count level. Irradiation with GR and EB was found to cause a reduction in microbial contamination proportionate to the dose delivered. The sterilizing effect of EB on microorganisms was higher than the GR one. A dose of 10 kGy of GR and EB significantly (p < 0.05) reduced the total bacte- rial, total coliform and total fungal contamination. A dose of 20 kGy of GR significantly (p < 0.05) reduced the total bacterial and total fungal contamination, while a 20 kGy dose of EB reduced the initial bacterial, total coliform and total fungal contamination to below detection level when the analysis was carried out im- mediately after irradiation treatment or after 12 months of storage. The comparative study demonstrated that electron beam was more effective for decontamination of chamomile powder than gamma irradiation.

Inversion polymorphism and extra bristles in Indian natural populations of Drosophila ananassae: joint variation.

PubMed

Das, A; Mohanty, S; Parida, B B

1994-10-01

Five Indian natural populations of Drosophila ananassae were analysed for chromosome inversions and the presence of individuals with extra scutellar bristles in the F1 progeny of isofemale lines initiated from naturally impregnated females. Three commonly occurring inversions were found in these populations with varying frequencies as was the number of individuals with extra bristles (e.b.). Female individuals were more often found to carry extra scutellar bristles than were males. This result reveals that polygenic loci responsible for the determination of e.b. are widespread in Indian natural populations of D. ananassae. A significant positive correlation between the inversion frequency and the number of individuals with e.b. was detected in the isofemale lines of all the five populations. The 2L inversion, alpha, was found to be closely associated with individuals with the e.b. phenotype. The observed results are compared with earlier results obtained for D. melanogaster. The association of the alpha inversion with the e.b. phenotype is discussed in relation to chromosomal evolution in the melanogaster species group.

Seafood-like flavour obtained from the enzymatic hydrolysis of the protein by-products of seaweed (Gracilaria sp.).

PubMed

Laohakunjit, Natta; Selamassakul, Orrapun; Kerdchoechuen, Orapin

2014-09-01

An enzymatic bromelain seaweed protein hydrolysate (eb-SWPH) was characterised as the precursor for thermally processed seafood flavour. Seaweed (Gracilaria fisheri) protein after agar extraction was hydrolysed using bromelain (enzyme activity=119,325 U/g) at 0-20% (w/w) for 0.5-24 h. Optimal hydrolysis conditions were determined using response surface methodology. The proposed model took into account the interaction effect of the enzyme concentration and hydrolysis time on the physicochemical properties and volatile components of eb-SWPH. The optimal hydrolysis conditions for the production of eb-SWPH were 10% bromelain for 3h, which resulted in a 38.15% yield and a 62.91% degree of hydrolysis value. Three free amino acids, arginine, lysine, and leucine, were abundant in the best hydrolysate. Ten volatile flavours of the best eb-SWPH were identified using gas chromatography/mass spectrometry. The predominant odourants were hexanal, hexanoic acid, nonanoic acid, and dihydroactinidiolide. The thermally processed seafood flavour produced from eb-SWPH exhibited a roasted seafood-like flavouring. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems

DOE PAGES

Phan, Manh-Huong; Alonso, Javier; Khurshid, Hafsa; ...

2016-11-23

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and relatedmore » phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications.« less

Measurement of oxytetracycline and emamectin benzoate in freshwater sediments downstream of land based aquaculture facilities in the Atlantic Region of Canada.

PubMed

Lalonde, Benoit A; Ernst, William; Greenwood, Lyndsay

2012-09-01

This study investigated the occurrence of oxytetracycline (OTC) and emamectin benzoate (EB) in sediments located near the effluent outfall from four freshwater aquaculture facilities in Atlantic Canada. While two facilities had no detectable concentrations of EB or OTC, two facilities had detectable concentrations of one or both of these chemicals. Concentrations ranged from <0.05-18 mg/kg to <0.01-2.5 mg/kg for OTC and EB respectively. Although these values could not be compared with freshwater toxicant values, some of the concentrations of EB and OTC detected were higher than LC(50) values calculated for marine invertebrates. OTC concentrations measured in this study are also of a magnitude which has been known to produce resistant bacteria.

Radiation curing progress in Hungary

NASA Astrophysics Data System (ADS)

Czvikovszky, T.

Radiation chemistry and radiation processing is an actively cultivated field of chemical technology and of applied research in several Central/Eastern European countries. Hungary, with his synthetic polymer production over 50 kg/capita/year, with his strong commitment in nuclear power production /almost 40 % of total electric power/, with his pioneering activity in food irradiation, radiation sterilization as well as EB processing of polymer — performs an iniciating role in this region. Actually four industrial EB machines are working in Hungary on plastics converting. Two of these accelerators, manufactured in SU are producing heat-shrinkable products. Two other, low-energy EB machines from FRG are working on industrial-scale surface-coating. An ELECTROCURTAIN /USA/ is serving R/D. Some actual problems of the applied radiation chemistry of EB-curing will be discussed.

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems

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

Phan, Manh-Huong; Alonso, Javier; Khurshid, Hafsa

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and relatedmore » phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications.« less

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems

PubMed Central

Phan, Manh-Huong; Alonso, Javier; Khurshid, Hafsa; Lampen-Kelley, Paula; Chandra, Sayan; Stojak Repa, Kristen; Nemati, Zohreh; Das, Raja; Iglesias, Óscar; Srikanth, Hariharan

2016-01-01

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and related phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications. PMID:28335349

Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats

PubMed Central

Allen, Patricia J.; DeBold, Joseph F.; Rios, Maribel; Kanarek, Robin B.

2015-01-01

Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine + T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine + EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy metabolism, whereas combined creatine and sex steroids acted in a neuroprotective manner in gonadectomized rats, potentially by reducing metabolic complications associated with castration or ovariectomy. PMID:25560941

SFPQ/PSF-TFE3 renal cell carcinoma: a clinicopathologic study emphasizing extended morphology and reviewing the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite an identical gene fusion.

PubMed

Wang, Xiao-Tong; Xia, Qiu-Yuan; Ni, Hao; Ye, Sheng-Bing; Li, Rui; Wang, Xuan; Shi, Shan-Shan; Zhou, Xiao-Jun; Rao, Qiu

2017-05-01

Xp11 translocation renal cell carcinoma (RCC) with SFPQ/PSF-TFE3 gene fusion is a rare epithelial tumor. Of note, the appearance of the gene fusion does not necessarily mean that it is renal cell carcinoma. The corresponding mesenchymal neoplasms, including Xp11 neoplasm with melanocytic differentiation, TFE3 rearrangement-associated perivascular epithelioid cell tumor (PEComa) and melanotic Xp11 translocation renal cancer, can also harbor the identical gene fusion. However, the differences between Xp11 translocation RCC and the corresponding mesenchymal neoplasm have only recently been described. Herein, we examined 5 additional cases of SFPQ-TFE3 RCCs using clinicopathologic, immunohistochemical, and molecular analyses. One tumor had the typical morphologic features of SFPQ-TFE3 RCC, whereas other 3 cases demonstrated the unusual morphologic features associated with pseudorosettes formation or clusters of smaller cells, mimicking TFEB RCC. The remaining one showed branching tubules and papillary structure composed of clear and eosinophilic tumor cells. Immunohistochemically, all 5 cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, PAX-8 and CD10, whereas no cases demonstrated TFEB, Cathepsin K, CA-IX, CK7, Melan-A, or HMB-45 expression. Genetically, the fusion transcripts were identified in 3 cases by reverse-transcription polymerase chain reaction (RT-PCR). On the basis of fluorescence in situ hybridization (FISH) analysis, all the cases were detected with SFPQ-TFE3 gene fusion. Clinical follow-up data were available for all the patients, and no one developed tumor recurrence, progression, or metastasis. We also review the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite the identical gene fusion. The presence of pseudorosettes also expands the known histological features of SFPQ-TFE3 RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Recognition memory for vibrotactile rhythms: an fMRI study in blind and sighted individuals.

PubMed

Sinclair, Robert J; Dixit, Sachin; Burton, Harold

2011-01-01

Calcarine sulcal cortex possibly contributes to semantic recognition memory in early blind (EB). We assessed a recognition memory role using vibrotactile rhythms and a retrieval success paradigm involving learned "old" and "new" rhythms in EB and sighted. EB showed no activation differences in occipital cortex indicating retrieval success but replicated findings of somatosensory processing. Both groups showed retrieval success in primary somatosensory, precuneus, and orbitofrontal cortex. The S1 activity might indicate generic sensory memory processes.

Recognition memory for vibrotactile rhythms: An fMRI study in blind and sighted individuals

PubMed Central

SINCLAIR, ROBERT J.; DIXIT, SACHIN; BURTON, HAROLD

2014-01-01

Calcarine sulcal cortex possibly contributes to semantic recognition memory in early blind (EB). We assessed a recognition memory role using vibrotactile rhythms and a retrieval success paradigm involving learned “old” and “new” rhythms in EB and sighted. EB showed no activation differences in occipital cortex indicating retrieval success but replicated findings of somatosensory processing. Both groups showed retrieval success in primary somatosensory, precuneus, and orbitofrontal cortex. The S1 activity might indicate generic sensory memory processes. PMID:21846300

Enhanced backscatter of optical beams reflected in turbulent air

NASA Astrophysics Data System (ADS)

Nelson, W.; Palastro, J. P.; Wu, C.; Davis, C. C.

2015-07-01

Optical beams propagating through air acquire phase distortions from turbulent fluctuations in the refractive index. While these distortions are usually deleterious to propagation, beams reflected in a turbulent medium can undergo a local recovery of spatial coherence and intensity enhancement referred to as enhanced backscatter (EBS). Using a combination of lab-scale experiments and simulations, we investigate the EBS of optical beams reflected from corner cubes and rough surfaces, and identify the regimes in which EBS is most distinctly observed.

Evaluation of the accuracy of estimated baseline serum creatinine for acute kidney injury diagnosis.

PubMed

Hatakeyama, Yutaka; Horino, Taro; Nagata, Keitaro; Kataoka, Hiromi; Matsumoto, Tatsuki; Terada, Yoshio; Okuhara, Yoshiyasu

2018-04-01

Modern epidemiologic studies of acute kidney injury (AKI) have been facilitated by the increasing availability of electronic medical records. However, pre-morbid reference serum creatinine (SCr) data are often unavailable in such records. Investigators substitute estimated baseline SCr with the eGFR 75 approach, instead of using actually measured baseline SCr. Here, we evaluated the accuracy of estimated baseline SCr for AKI diagnosis in the Japanese population. Inpatients and outpatients aged 18-80 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using SCr levels. The non-AKI and AKI groups were selected using the following criteria: increase 1.5 times greater than baseline SCr ("baseline SCr") or increase 0.3 mg/dL greater than baseline SCr in 48 h ("increase in 48 h"). AKI accuracy defined by the estimated reference SCr, the average SCr value of the non-AKI population (eb-GFR-A approach), or the back-calculated SCr from fixed eGFR = 75 mL/min/1.73 m 2 (eGFR 75 approach, or, eb-GFR-B approach in this study), was evaluated. We analyzed data from 131,358 Japanese patients. The number of patients with reference baseline SCr in the non-AKI and AKI patients were 29,834 and 8952, respectively. For AKI patients diagnosed using "baseline SCr", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 63.5 and 57.7%, respectively, while in AKI diagnosed using "increase in 48 h", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 78.7 and 75.1%, respectively. In non-AKI patients, false-positive rates of AKI misdiagnosed via eb-GFR-A and eb-GFR-B were 7.4 and 6.8%, respectively. AKI diagnosis using the average SCr value of the general population may yield more accurate results than diagnosis using the eGFR 75 approach when the reference SCr is unavailable.

Epidemiology of Inherited Epidermolysis Bullosa Based on Incidence and Prevalence Estimates From the National Epidermolysis Bullosa Registry.

PubMed

Fine, Jo-David

2016-11-01

Accurate estimation of the incidence and prevalence of each subtype of epidermolysis bullosa (EB) is essential before clinical trials can be designed and sufficient funding allocated by government agencies and third-party insurers for the care of these individuals. To determine the incidence and prevalence of inherited EB stratified by subtype in the United States during a 16-year period. Prospective cross-sectional and longitudinal study. Data were obtained from 3271 patients consecutively enrolled in the National Epidermolysis Bullosa Registry from January 1, 1986, through December 31, 2002, using a detailed instrument created with the assistance of the National Institutes of Health. Analyses were performed in January 1999 and April 2015. Participants were patients of all ages with EB. Extensive clinical and laboratory data were collected on patients who were subclassified and serially revalidated based on published diagnostic recommendations by an international panel of experts. Pertinent to this report, estimates were made of the incidence and prevalence during 2 time frames. During the first 5 years of funding of the registry, the overall incidence and prevalence of inherited EB were 19.60 and 8.22 per 1 million live births, respectively. When reassessed over the entire 16 years of the study, the prevalence rose to 11.07, whereas the overall incidence remained unchanged at 19.57 cases. Changes were also observed within some disease subsets as increased numbers of patients were identified, recruited, followed up longitudinally, and resubclassified as needed over time. For example, in 2002, the prevalence of EBS overall and localized EBS had increased considerably by 30.4% and 25.5%, respectively, whereas the prevalence of generalized intermediate EBS declined by 76.7% as a result of later subclassification of some of those patients into other subtypes. In contrast, no significant change was noted in the overall prevalence of JEB or generalized severe JEB, although there was a 73.0% decline in the prevalence of generalized intermediate JEB. Precise estimates of the incidence and prevalence of each major subtype of inherited EB in the United States are now available that should assist investigators in choosing which subtypes are amenable to properly designed, large-scale, clinical trials.

Gene expression profile in human induced pluripotent stem cells: Chondrogenic differentiation in vitro, part A

PubMed Central

Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Richter, Magdalena; Trzeciak, Tomasz

2017-01-01

Human induced pluripotent stem cells (hiPSCs) offer promise in regenerative medicine, however more data are required to improve understanding of key aspects of the cell differentiation process, including how specific chondrogenic processes affect the gene expression profile of chondrocyte-like cells and the relative value of cell differentiation markers. The main aims of the present study were as follows: To determine the gene expression profile of chondrogenic-like cells derived from hiPSCs cultured in mediums conditioned with HC-402-05a cells or supplemented with transforming growth factor β3 (TGF-β3), and to assess the relative utility of the most commonly used chondrogenic markers as indicators of cell differentiation. These issues are relevant with regard to the use of human fibroblasts in the reprogramming process to obtain hiPSCs. Human fibroblasts are derived from the mesoderm and thus share a wide range of properties with chondrocytes, which also originate from the mesenchyme. Thus, the exclusion of dedifferentiation instead of chondrogenic differentiation is crucial. The hiPSCs were obtained from human primary dermal fibroblasts during a reprogramming process. Two methods, both involving embryoid bodies (EB), were used to obtain chondrocytes from the hiPSCs: EBs formed in a chondrogenic medium supplemented with TGF-β3 (10 ng/ml) and EBs formed in a medium conditioned with growth factors from HC-402-05a cells. Based on immunofluorescence and reverse transcription-quantiative polymerase chain reaction analysis, the results indicated that hiPSCs have the capacity for effective chondrogenic differentiation, in particular cells differentiated in the HC-402-05a-conditioned medium, which present morphological features and markers that are characteristic of mature human chondrocytes. By contrast, cells differentiated in the presence of TGF-β3 may demonstrate hypertrophic characteristics. Several genes [paired box 9, sex determining region Y-box (SOX) 5, SOX6, SOX9 and cartilage oligomeric matrix protein] were demonstrated to be good markers of early hiPSC chondrogenic differentiation: Insulin-like growth factor 1, Tenascin-C, and β-catenin were less valuable. These observations provide valuable data on the use of hiPSCs in cartilage tissue regeneration. PMID:28447755

Electron Beam Technology for Environmental Pollution Control.

PubMed

Chmielewski, Andrzej G; Han, Bumsoo

2016-10-01

Worldwide, there are over 1700 electron beam (EB) units in commercial use, providing an estimated added value to numerous products, amounting to 100 billion USD or more. High-current electron accelerators are used in diverse industries to enhance the physical and chemical properties of materials and to reduce undesirable contaminants such as pathogens, toxic byproducts, or emissions. Over the past few decades, EB technologies have been developed aimed at ensuring the safety of gaseous and liquid effluents discharged to the environment. It has been demonstrated that EB technologies for flue gas treatment (SO x and NO x removal), wastewater purification, and sludge hygienization can be effectively deployed to mitigate environmental degradation. Recently, extensive work has been carried out on the use of EB for environmental remediation, which also includes the removal of emerging contaminants such as VOCs, endocrine disrupting chemicals (EDCs), and potential EDCs.

The fluorescence resonance energy transfer (FRET) gate: a time-resolved study.

PubMed

Xu, Qing-Hua; Wang, Shu; Korystov, Dmitry; Mikhailovsky, Alexander; Bazan, Guillermo C; Moses, Daniel; Heeger, Alan J

2005-01-18

The two-step energy-transfer process in a self-assembled complex comprising a cationic conjugated polymer (CCP) and a dsDNA is investigated by using pump-dump-emission spectroscopy and time-correlated single-photon counting; energy is transferred from the CCP to an ethidium bromide (EB) molecule intercalated into the dsDNA through a fluorescein molecule linked to one terminus of the DNA. Time-dependent anisotropy measurements indicate that the inefficient direct energy transfer from the CCP to the intercalated EB results from the near orthogonality of their transition moments. These measurements also show that the transition moment of the fluorescein spans a range of angular distributions and lies between that of the CCP and EB. Consequently, the fluorescein acts as a fluorescence resonance energy-transfer gate to relay the excitation energy from the CCP to the EB.

The fluorescence resonance energy transfer (FRET) gate: A time-resolved study

PubMed Central

Xu, Qing-Hua; Wang, Shu; Korystov, Dmitry; Mikhailovsky, Alexander; Bazan, Guillermo C.; Moses, Daniel; Heeger, Alan J.

2005-01-01

The two-step energy-transfer process in a self-assembled complex comprising a cationic conjugated polymer (CCP) and a dsDNA is investigated by using pump-dump-emission spectroscopy and time-correlated single-photon counting; energy is transferred from the CCP to an ethidium bromide (EB) molecule intercalated into the dsDNA through a fluorescein molecule linked to one terminus of the DNA. Time-dependent anisotropy measurements indicate that the inefficient direct energy transfer from the CCP to the intercalated EB results from the near orthogonality of their transition moments. These measurements also show that the transition moment of the fluorescein spans a range of angular distributions and lies between that of the CCP and EB. Consequently, the fluorescein acts as a fluorescence resonance energy-transfer gate to relay the excitation energy from the CCP to the EB. PMID:15642946

A mutation in the LAMC2 gene causes the Herlitz junctional epidermolysis bullosa (H-JEB) in two French draft horse breeds.

PubMed

Milenkovic, Dragan; Chaffaux, Stéphane; Taourit, Sead; Guérin, Gérard

2003-01-01

Epidermolysis bullosa (EB) is a heterogeneous group of inherited diseases characterised by skin blistering and fragility. In humans, one of the most severe forms of EB known as Herlitz-junctional EB (H-JEB), is caused by mutations in the laminin 5 genes. EB has been described in several species, like cattle, sheep, dogs, cats and horses where the mutation, a cytosine insertion in exon 10 of the LAMC2 gene, was very recently identified in Belgian horses as the mutation responsible for JEB. In this study, the same mutation was found to be totally associated with the JEB phenotype in two French draft horse breeds, Trait Breton and Trait Comtois. This result provides breeders a molecular test to better manage their breeding strategies by genetic counselling.

Optimal Battery Charging, Part 1: Minimizing Time-to-Charge, Energy Loss, and Temperature Rise for OCV-Resistance Battery Model

DTIC Science & Technology

2015-02-18

vi½k ¼ 0 (17) l½k ¼ vH½k vs ½k (18) s½kþ 1 ¼ vH½k vl½kþ 1 (19) From (17) we have i½k ¼ chl½kþ 1 2R0D k ¼ 0;1;…k1 1 (20) From (18), we...resistance R0 in model I. The batteries are Samsung EB575152 (four cells), Samsung EB504465 (four cells), Samsung AB463651 (two cells), Nokia BP-4L (four cells...commercial batteries. Make Model Cell# R0 (mU) R1 (mU) C1 (F) a Cbatt (Ah) Samsung EB575152 1 253 106 4581 0.997934 1.1875 Samsung EB575152 2 209 94 5203

Impurity segregation behavior in polycrystalline silicon ingot grown with variation of electron-beam power

NASA Astrophysics Data System (ADS)

Lee, Jun-Kyu; Lee, Jin-Seok; Jang, Bo-Yun; Kim, Joon-Soo; Ahn, Young-Soo; Cho, Churl-Hee

2014-08-01

Electron beam melting (EBM) systems have been used to improve the purity of metallurgical grade silicon feedstock for photovoltaic application. Our advanced EBM system is able to effectively remove volatile impurities using a heat source with high energy from an electron gun and to continuously allow impurities to segregate at the top of an ingot solidified in a directional solidification (DS) zone in a vacuum chamber. Heat in the silicon melt should move toward the ingot bottom for the desired DS. However, heat flux though the ingot is changed as the ingot becomes longer due to low thermal conductivity of silicon. This causes a non-uniform microstructure of the ingot, finally leading to impurity segregation at its middle. In this research, EB power irradiated on the silicon melt was controlled during the ingot growth in order to suppress the change of heat flux. EB power was reduced from 12 to 6.6 kW during the growth period of 45 min with a drop rate of 0.125 kW/min. Also, the silicon ingot was grown under a constant EB power of 12 kW to estimate the effect of the drop rate of EB power. When the EB power was reduced, the grains with columnar shape were much larger at the middle of the ingot compared to the case of constant EB power. Also, the present research reports a possible reason for the improvement of ingot purity by considering heat flux behaviors.

Superior Red Blood Cell Generation from Human Pluripotent Stem Cells Through a Novel Microcarrier-Based Embryoid Body Platform.

PubMed

Sivalingam, Jaichandran; Lam, Alan Tin-Lun; Chen, Hong Yu; Yang, Bin Xia; Chen, Allen Kuan-Liang; Reuveny, Shaul; Loh, Yuin-Han; Oh, Steve Kah-Weng

2016-08-01

In vitro generation of red blood cells (RBCs) from human embryonic stem cells and human induced pluripotent stem cells appears to be a promising alternate approach to circumvent shortages in donor-derived blood supplies for clinical applications. Conventional methods for hematopoietic differentiation of human pluripotent stem cells (hPSC) rely on embryoid body (EB) formation and/or coculture with xenogeneic cell lines. However, most current methods for hPSC expansion and EB formation are not amenable for scale-up to levels required for large-scale RBC generation. Moreover, differentiation methods that rely on xenogenic cell lines would face obstacles for future clinical translation. In this study, we report the development of a serum-free and chemically defined microcarrier-based suspension culture platform for scalable hPSC expansion and EB formation. Improved survival and better quality EBs generated with the microcarrier-based method resulted in significantly improved mesoderm induction and, when combined with hematopoietic differentiation, resulted in at least a 6-fold improvement in hematopoietic precursor expansion, potentially culminating in a 80-fold improvement in the yield of RBC generation compared to a conventional EB-based differentiation method. In addition, we report efficient terminal maturation and generation of mature enucleated RBCs using a coculture system that comprised primary human mesenchymal stromal cells. The microcarrier-based platform could prove to be an appealing strategy for future scale-up of hPSC culture, EB generation, and large-scale generation of RBCs under defined and xeno-free conditions.

Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle

PubMed Central

Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

2015-01-01

OBJECTIVE: The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. DESIGN: Prospective randomized control study. SETTING: Tertiary care center. MATERIALS AND METHODS: A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). MAIN OUTCOME MEASURE: Clinical pregnancy rate (CPR). RESULTS: Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). CONCLUSIONS: Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle. PMID:26538858

Cell responses to titanium treated by a sandblast-free method for implant applications.

PubMed

Zhang, Jie; Xie, Youneng; Zuo, Jun; Li, Jiaxin; Wei, Qiuping; Yu, Zhiming; Tang, Zhangui

2017-09-01

Sandblast and acid-etching (SLA) is the most prevalent treatment to titanium implants, while residual sand particles are inevitably introduced on SLA titanium surfaces. NH 4 OH and H 2 O 2 mixture was used to etch titanium plates (E) and titanium bars (EB), aiming at substituting sandblast procedure. To study the effects of different scale rough structures on cell response of Human osteoblast-like cells (MG63), traditional H 2 SO 4 and HCl mixture was also used to further etch the titanium plates above (DE). Holes of 10-20μm were obtained on E and DE surfaces, which are very close to the size of osteoblasts. Surfaces with micro/nano and micro/submicro hierarchical structures were obtained on the treated titanium. As-prepared E, DE and EB surfaces are hydrophilic, while only EB stayed hydrophilic after 5days' exposure to air. MG63 cultured on E and EB surfaces showed higher proliferation rate and attachment area than on DE and P surfaces. E and DE showed higher alkaline phosphatases (ALP) activity after 7 and 14days of osteoinduction, while EB showed the highest osteopontin (OPN) and bone sialoprotein (BSP) production after 21days of osteoinduction. These results indicate that E and EB surfaces boost the proliferation and osteogenic differentiation of MG63 without introducing sand particles. This is a promising treatment to titanium implant. Copyright © 2017. Published by Elsevier B.V.

EBS7 is a plant-specific component of a highly conserved endoplasmic reticulum-associated degradation system in Arabidopsis

PubMed Central

Liu, Yidan; Zhang, Congcong; Wang, Dinghe; Su, Wei; Liu, Linchuan; Wang, Muyang; Li, Jianming

2015-01-01

Endoplasmic reticulum (ER)-associated degradation (ERAD) is an essential part of an ER-localized protein quality-control system for eliminating terminally misfolded proteins. Recent studies have demonstrated that the ERAD machinery is conserved among yeast, animals, and plants; however, it remains unknown if the plant ERAD system involves plant-specific components. Here we report that the Arabidopsis ethyl methanesulfonate-mutagenized brassinosteroid-insensitive 1 suppressor 7 (EBS7) gene encodes an ER membrane-localized ERAD component that is highly conserved in land plants. Loss-of-function ebs7 mutations prevent ERAD of brassinosteroid insensitive 1-9 (bri1-9) and bri1-5, two ER-retained mutant variants of the cell-surface receptor for brassinosteroids (BRs). As a result, the two mutant receptors accumulate in the ER and consequently leak to the plasma membrane, resulting in the restoration of BR sensitivity and phenotypic suppression of the bri1-9 and bri1-5 mutants. EBS7 accumulates under ER stress, and its mutations lead to hypersensitivity to ER and salt stresses. EBS7 interacts with the ER membrane-anchored ubiquitin ligase Arabidopsis thaliana HMG-CoA reductase degradation 1a (AtHrd1a), one of the central components of the Arabidopsis ERAD machinery, and an ebs7 mutation destabilizes AtHrd1a to reduce polyubiquitination of bri1-9. Taken together, our results uncover a plant-specific component of a plant ERAD pathway and also suggest its likely biochemical function. PMID:26371323

Disease characterization using LQTS-specific induced pluripotent stem cells.

PubMed

Egashira, Toru; Yuasa, Shinsuke; Suzuki, Tomoyuki; Aizawa, Yoshiyasu; Yamakawa, Hiroyuki; Matsuhashi, Tomohiro; Ohno, Yohei; Tohyama, Shugo; Okata, Shinichiro; Seki, Tomohisa; Kuroda, Yusuke; Yae, Kojiro; Hashimoto, Hisayuki; Tanaka, Tomofumi; Hattori, Fumiyuki; Sato, Toshiaki; Miyoshi, Shunichiro; Takatsuki, Seiji; Murata, Mitsushige; Kurokawa, Junko; Furukawa, Tetsushi; Makita, Naomasa; Aiba, Takeshi; Shimizu, Wataru; Horie, Minoru; Kamiya, Kaichiro; Kodama, Itsuo; Ogawa, Satoshi; Fukuda, Keiichi

2012-09-01

Long QT syndrome (LQTS) is an inheritable and life-threatening disease; however, it is often difficult to determine disease characteristics in sporadic cases with novel mutations, and more precise analysis is necessary for the successful development of evidence-based clinical therapies. This study thus sought to better characterize ion channel cardiac disorders using induced pluripotent stem cells (iPSCs). We reprogrammed somatic cells from a patient with sporadic LQTS and from controls, and differentiated them into cardiomyocytes through embryoid body (EB) formation. Electrophysiological analysis of the LQTS-iPSC-derived EBs using a multi-electrode array (MEA) system revealed a markedly prolonged field potential duration (FPD). The IKr blocker E4031 significantly prolonged FPD in control- and LQTS-iPSC-derived EBs and induced frequent severe arrhythmia only in LQTS-iPSC-derived EBs. The IKs blocker chromanol 293B did not prolong FPD in the LQTS-iPSC-derived EBs, but significantly prolonged FPD in the control EBs, suggesting the involvement of IKs disturbance in the patient. Patch-clamp analysis and immunostaining confirmed a dominant-negative role for 1893delC in IKs channels due to a trafficking deficiency in iPSC-derived cardiomyocytes and human embryonic kidney (HEK) cells. This study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation. Such analyses may in turn lead to future progress in personalized medicine.

Spectraplakins promote microtubule-mediated axonal growth by functioning as structural MAPs and EB1-dependent +TIPs

PubMed Central

Alves-Silva, J.; Sánchez-Soriano, N.; Beaven, R.; Klein, M.; Parkin, J.; Millard, T.H.; Bellen, H. J; Venken, K. J.T.; Ballestrem, C.; Kammerer, R.A.; Prokop, A.

2013-01-01

The correct outgrowth of axons is essential for the development and regeneration of nervous systems. Axon growth is primarily driven by microtubules. Key regulators of microtubules in this context are the spectraplakins, a family of evolutionarily conserved actin-microtubule linkers. Loss of function of the mouse spectraplakin ACF7 or of its close Drosophila homologue Short stop/Shot similarly cause severe axon shortening and microtubule disorganisation. How spectraplakins perform these functions is not known. Here we show that axonal growth promoting roles of Shot require interaction with EB1 (End binding protein) at polymerising plus ends of microtubules. We show that binding of Shot to EB1 requires SxIP motifs in Shot’s carboxyterminal tail (Ctail), mutations of these motifs abolish Shot functions in axonal growth, loss of EB1 function phenocopies Shot loss, and genetic interaction studies reveal strong functional links between Shot and EB1 in axonal growth and microtubule organisation. In addition, we report that Shot localises along microtubule shafts and stabilises them against pharmacologically induced depolymerisation. This function is EB1-independent but requires net positive charges within Ctail which essentially contribute to the microtubule shaft association of Shot. Therefore, spectraplakins are true members of two important classes of neuronal microtubule regulating proteins: +TIPs (plus end regulators) and structural MAPs (microtubule associated proteins). From our data we deduce a model that relates the different features of the spectraplakin carboxy-terminus to the two functions of Shot during axonal growth. PMID:22764224

Distributed Wireless Power Transfer With Energy Feedback

NASA Astrophysics Data System (ADS)

Lee, Seunghyun; Zhang, Rui

2017-04-01

Energy beamforming (EB) is a key technique for achieving efficient radio-frequency (RF) transmission enabled wireless energy transfer (WET). By optimally designing the waveforms from multiple energy transmitters (ETs) over the wireless channels, they can be constructively combined at the energy receiver (ER) to achieve an EB gain that scales with the number of ETs. However, the optimal design of EB waveforms requires accurate channel state information (CSI) at the ETs, which is challenging to obtain practically, especially in a distributed system with ETs at separate locations. In this paper, we study practical and efficient channel training methods to achieve optimal EB in a distributed WET system. We propose two protocols with and without centralized coordination, respectively, where distributed ETs either sequentially or in parallel adapt their transmit phases based on a low-complexity energy feedback from the ER. The energy feedback only depends on the received power level at the ER, where each feedback indicates one particular transmit phase that results in the maximum harvested power over a set of previously used phases. Simulation results show that the two proposed training protocols converge very fast in practical WET systems even with a large number of distributed ETs, while the protocol with sequential ET phase adaptation is also analytically shown to converge to the optimal EB design with perfect CSI by increasing the training time. Numerical results are also provided to evaluate the performance of the proposed distributed EB and training designs as compared to other benchmark schemes.

Fusion welding of a modern borated stainless steel

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

Robino, C.V.; Cieslak, M.J.

1997-01-01

Experiments designed to assess the fabrication and service weldability of 304B4A borated stainless steel were conducted. Welding procedures and parameters for manual gas tungsten arc (GTA) welding, autogenous electron beam (EB) welding and filler-added EB welding were developed and found to be similar to those for austenitic stainless steels. Following the procedure development, four test welds were produced and evaluated by microstructural analysis and Charpy impact testing. Further samples were used for determination of the postweld heat treatment (PWHT) response of the welds. The fusion zone structure of welds in this alloy consists of primary austenite dendrites with an interdendriticmore » eutectic-like austenite/boride constituent. Welds also show an appreciable partially molten zone that consists of the austenite/boride eutectic surrounding unmelted austenite islands. The microstructure of the EB welds was substantially finer than that of the GTA welds, and boride coarsening was not observed in the solid state heat-affected zone (HAZ) of either weld type. The impact toughness of as-welded samples was found to be relatively poor, averaging less than 10 J for both GTA and EB welds. For fusion zone notched GTA and EB samples and centerline notched EB samples, fracture generally occurred along the boundary between the partially molten and solid-state regions of the HAZ. The results of the PWHT study were very encouraging, with typical values of the impact energy for HAZ notched samples approaching 40 J, or twice the minimum code-acceptable value.« less

Ethylbenzene induces microsomal oxygen free radical generation: antibody-directed characterization of the responsible cytochrome P450 enzymes.

PubMed

Serron, S C; Dwivedi, N; Backes, W L

2000-05-01

Small aromatic hydrocarbons cause changes in oxidative metabolism by modulating the levels of cytochrome P450 enzymes, with the changes in these enzymes being responsible for qualitative changes in aromatic hydrocarbon metabolism. The goal of this study was to determine if exposure to the small alkylbenzene ethylbenzene (EB) leads to an increase in hepatic free radical production. Male F344 rats were treated with ip injections of EB (10 mmol/kg) and compared to corn oil controls. Hepatic free radical production was examined by measuring the conversion of 2',7'-dichlorofluorescin diacetate (DCFH-DA) to its fluorescent product 2',7'-dichlorofluorescein (DCF). A significant elevation of fluorescent DCF production was observed after treatment with EB, despite the lack of effect on overall cytochrome P450 levels. This process was shown to be inhibitable by metyrapone, an inhibitor of P450. DCF production was also inhibited by catalase, suggesting that hydrogen peroxide (H(2)O(2)) is one of the reactive oxygen intermediates involved in EB-mediated reactive oxygen species (ROS) formation. Interestingly, superoxide dismutase (SOD) did not inhibit DCF production in corn oil-treated rats but was an effective inhibitor in the EB-treated groups. In an effort to determine if the increase in ROS production was related to changes in specific P450 enzymes, DCF production was measured in the presence of anti-CYP2B, anti-CYP2C11, anti-CYP2E1, and anti-CYP3A2 inhibitory antibodies. Anti-CYP2B antibodies inhibited DCF production in EB-treated, but not corn oil groups, which is consistent with the low constitutive levels of this enzyme and its induction by EB. The data also demonstrate that CYP2B contributes to ROS production. Anti-CYP2C11 did not influence DCF production in either group. ROS formation in corn oil-treated rats as well as in ethylbenzene-treated rats was also inhibited with antibodies to anti-CYP2E1 and anti-CYP3A2. These results suggest that CYP2C11 does not appear to influence free radical production and that the increase in free radical production in EB treated rats is consistent with the EB-mediated elevation of CYP2B, CYP 2E1, and CYP3A2. Such alterations in free radical generation in response to hydrocarbon treatment may contribute to the toxicity of these compounds. Copyright 2000 Academic Press.

Single vs dual (en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience

PubMed Central

Al-Shraideh, Yousef; Farooq, Umar; El-Hennawy, Hany; Farney, Alan C; Palanisamy, Amudha; Rogers, Jeffrey; Orlando, Giuseppe; Khan, Muhammad; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; Stratta, Robert J

2016-01-01

AIM: To compare outcomes between single and dual en bloc (EB) kidney transplants (KT) from small pediatric donors. METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached to the inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients. RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors (17 mo vs 38 mo, P < 0.001), mean weight (11.0 kg vs 17.4 kg, P = 0.046) and male donors (50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time (21 h), kidney donor profile index (KDPI; 73% vs 62%) and levels of serum creatinine (SCr, 0.37 mg/dL vs 0.49 mg/dL, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence (12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay (mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection (6% vs 16%), operative complications (3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively (all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/dL vs 1.35 mg/dL and 72.5 mL/min per 1.73 m2 vs 60.5 mL/min per 1.73 m2 (both P = NS) in the dual EB and single KT groups, respectively. CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes. PMID:27011923

Diffusion Tensor Imaging of Incentive Effects in Prospective Memory after Pediatric Traumatic Brain Injury

PubMed Central

Wilde, Elisabeth A.; Bigler, Erin D.; Chu, Zili; Yallampalli, Ragini; Oni, Margaret B.; Wu, Trevor C.; Ramos, Marco A.; Pedroza, Claudia; Vásquez, Ana C.; Hunter, Jill V.; Levin, Harvey S.

2011-01-01

Abstract Few studies exist investigating the brain-behavior relations of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, children with moderate-to-severe TBI performed an EB-PM test with two motivational enhancement conditions and underwent concurrent diffusion tensor imaging (DTI) at 3 months post-injury. Children with orthopedic injuries (OI; n = 37) or moderate-to-severe TBI (n = 40) were contrasted. Significant group differences were found for fractional anisotropy (FA) and apparent diffusion coefficient for orbitofrontal white matter (WM), cingulum bundles, and uncinate fasciculi. The FA of these WM structures in children with TBI significantly correlated with EB-PM performance in the high, but not the low motivation condition. Regression analyses within the TBI group indicated that the FA of the left cingulum bundle (p = 0.003), left orbitofrontal WM (p < 0.02), and left (p < 0.02) and right (p < 0.008) uncinate fasciculi significantly predicted EB-PM performance in the high motivation condition. We infer that the cingulum bundles, orbitofrontal WM, and uncinate fasciculi are important WM structures mediating motivation-based EB-PM responses following moderate-to-severe TBI in children. PMID:21250917

The effect of matrix composition of 3D constructs on embryonic stem cell differentiation.

PubMed

Battista, Sabrina; Guarnieri, Daniela; Borselli, Cristina; Zeppetelli, Stefania; Borzacchiello, Assunta; Mayol, Laura; Gerbasio, Diego; Keene, Douglas R; Ambrosio, Luigi; Netti, Paolo A

2005-11-01

The use of embryonic stem (ES) cells as unlimited cell source in tissue engineering has ignited the hope of regenerating any kind of tissue in vitro. However, the role of the material in control and guidance of their development and commitment into complex and viable three-dimensional (3D) tissues is still poorly understood. In this work, we investigate the role of material composition and structure on promoting ES cells growth and differentiation, by culturing mouse ES cell-derived embryoid bodies (EBs) in various semi-interpenetrating polymer networks (SIPNs), made of collagen, fibronectin (FN) and laminin (LM). We show that both composition and strength of the supportive matrix play an important role in EBs development. High collagen concentrations inhibit EBs cavitation and hence the following EBs differentiation, by inhibiting apoptosis. The presence of FN in 3D collagen constructs strongly stimulates endothelial cell differentiation and vascularization. Conversely, LM increases the ability of ES cells to differentiate into beating cardiomyocytes. Our data suggest that matrix composition has an important role in EBs development and that it is possible to influence stem cell differentiation toward preferential pattern, by modulating the physical and biochemical properties of the scaffold.

Apparent isotropic electrical property for electrical brain stimulation (EBS) using magnetic resonance diffusion weighted imaging (MR-DWI)

NASA Astrophysics Data System (ADS)

Lee, Mun Bae; Kwon, Oh-In

2018-04-01

Electrical brain stimulation (EBS) is an invasive electrotherapy and technique used in brain neurological disorders through direct or indirect stimulation using a small electric current. EBS has relied on computational modeling to achieve optimal stimulation effects and investigate the internal activations. Magnetic resonance diffusion weighted imaging (DWI) is commonly useful for diagnosis and investigation of tissue functions in various organs. The apparent diffusion coefficient (ADC) measures the intensity of water diffusion within biological tissues using DWI. By measuring trace ADC and magnetic flux density induced by the EBS, we propose a method to extract electrical properties including the effective extracellular ion-concentration (EEIC) and the apparent isotropic conductivity without any auxiliary additional current injection. First, the internal current density due to EBS is recovered using the measured one component of magnetic flux density. We update the EEIC by introducing a repetitive scheme called the diffusion weighting J-substitution algorithm using the recovered current density and the trace ADC. To verify the proposed method, we study an anesthetized canine brain to visualize electrical properties including electrical current density, effective extracellular ion-concentration, and effective isotropic conductivity by applying electrical stimulation of the brain.

E-beam direct write is free

NASA Astrophysics Data System (ADS)

Glasser, Lance A.

2007-10-01

In this paper we discuss four business concepts that will impact the adoption of e-beam direct write (EbDW). They are: (1) The economically advantageous region for EbDW. At what costs and volumes EbDW is economically advantageous is controlled by a two-sided constraint involving the cost of reticles on one hand and the cost of design on the other. (2) The important role of product derivatives and other markets that can be satisfied by designs with heavy IP reuse. The natural long tail in demand for differentiated products is today chopped off by the high costs of reticles. We show data on the elasticity of the product derivative market with respect to certain costs. (3) That because reticle prices typically decline at a 30% per year for the first few years after a new node is introduced, delaying the fabrication of that first reticle set for a new product can save millions, more than paying for EbDW. The applicability of this technique is, however, limited by the need for product requalifaction. (4) Finally, we introduce the business concept of the virtual reticle as a possible component in EbDW pricing.

Structural, optical, and transport properties of nanocrystalline bismuth telluride thin films treated with homogeneous electron beam irradiation and thermal annealing.

PubMed

Takashiri, Masayuki; Asai, Yuki; Yamauchi, Kazuki

2016-08-19

We investigated the effects of homogeneous electron beam (EB) irradiation and thermal annealing treatments on the structural, optical, and transport properties of bismuth telluride thin films. Bismuth telluride thin films were prepared by an RF magnetron sputtering method at room temperature. After deposition, the films were treated with homogeneous EB irradiation, thermal annealing, or a combination of both the treatments (two-step treatment). We employed Williamson-Hall analysis for separating the strain contribution from the crystallite domain contribution in the x-ray diffraction data of the films. We found that strain was induced in the thin films by EB irradiation and was relieved by thermal annealing. The crystal orientation along c-axis was significantly enhanced by the two-step treatment. Scanning electron microscopy indicated the melting and aggregation of nano-sized grains on the film surface by the two-step treatment. Optical analysis indicated that the interband transition of all the thin films was possibly of the indirect type, and that thermal annealing and two-step treatment methods increased the band gap of the films due to relaxation of the strain. Thermoelectric performance was significantly improved by the two-step treatment. The power factor reached a value of 17.2 μW (cm(-1) K(-2)), approximately 10 times higher than that of the as-deposited thin films. We conclude that improving the crystal orientation and relaxing the strain resulted in enhanced thermoelectric performance.

Drosophila Mitf regulates the V-ATPase and the lysosomal-autophagic pathway.

PubMed

Bouché, Valentina; Espinosa, Alma Perez; Leone, Luigi; Sardiello, Marco; Ballabio, Andrea; Botas, Juan

2016-01-01

An evolutionarily conserved gene network regulates the expression of genes involved in lysosome biogenesis, autophagy, and lipid metabolism. In mammals, TFEB and other members of the MiTF-TFE family of transcription factors control this network. Here we report that the lysosomal-autophagy pathway is controlled by Mitf gene in Drosophila melanogaster. Mitf is the single MiTF-TFE family member in Drosophila and prior to this work was known only for its function in eye development. We show that Mitf regulates the expression of genes encoding V-ATPase subunits as well as many additional genes involved in the lysosomal-autophagy pathway. Reduction of Mitf function leads to abnormal lysosomes and impairs autophagosome fusion and lipid breakdown during the response to starvation. In contrast, elevated Mitf levels increase the number of lysosomes, autophagosomes and autolysosomes, and decrease the size of lipid droplets. Inhibition of Drosophila MTORC1 induces Mitf translocation to the nucleus, underscoring conserved regulatory mechanisms between Drosophila and mammalian systems. Furthermore, we show Mitf-mediated clearance of cytosolic and nuclear expanded ATXN1 (ataxin 1) in a cellular model of spinocerebellar ataxia type 1 (SCA1). This remarkable observation illustrates the potential of the lysosomal-autophagy system to prevent toxic protein aggregation in both the cytoplasmic and nuclear compartments. We anticipate that the genetics of the Drosophila model and the absence of redundant MIT transcription factors will be exploited to investigate the regulation and function of the lysosomal-autophagy gene network.

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

Saunders, C.B.; Carmichael, A.A.; Kremers, W.

The mechanical and physical properties of electron-beam (EB) curable carbon-fiber-reinforced composites were investigated, using a resin matrix made from a mixture of 50 percent of an epoxy diacrylate oligomer, 30 percent of a polybutadiene diacrylate oligomer, and 20 percent of dipentaerythritol monohydroxypentaacrylate monomer, and applying varying EB doses for curing the mixture. It was found that the gel content in the cured prepreg polymer depended upon the total EB dose below 50 kGy, the dose rate, and, at a low dose of 16 kGy/hr, on the atmosphere and pressure during irradiation. 14 refs.

Three New Pierce's Disease Pathogenicity Effectors Identified Using Xylella fastidiosa Biocontrol Strain EB92-1.

PubMed

Zhang, Shujian; Chakrabarty, Pranjib K; Fleites, Laura A; Rayside, Patricia A; Hopkins, Donald L; Gabriel, Dean W

2015-01-01

Xylella fastidiosa (X. fastidiosa) infects a wide range of plant hosts and causes economically serious diseases, including Pierce's Disease (PD) of grapevines. X. fastidiosa biocontrol strain EB92-1 was isolated from elderberry and is infectious and persistent in grapevines but causes only very slight symptoms under ideal conditions. The draft genome of EB92-1 revealed that it appeared to be missing genes encoding 10 potential PD pathogenicity effectors found in Temecula1. Subsequent PCR and sequencing analyses confirmed that EB92-1 was missing the following predicted effectors found in Temecula1: two type II secreted enzymes, including a lipase (LipA; PD1703) and a serine protease (PD0956); two identical genes encoding proteins similar to Zonula occludens toxins (Zot; PD0915 and PD0928), and at least one relatively short, hemagglutinin-like protein (PD0986). Leaves of tobacco and citrus inoculated with cell-free, crude protein extracts of E. coli BL21(DE3) overexpressing PD1703 exhibited a hypersensitive response (HR) in less than 24 hours. When cloned into shuttle vector pBBR1MCS-5, PD1703 conferred strong secreted lipase activity to Xanthomonas citri, E. coli and X. fastidiosa EB92-1 in plate assays. EB92-1/PD1703 transformants also showed significantly increased disease symptoms on grapevines, characteristic of PD. Genes predicted to encode PD0928 (Zot) and a PD0986 (hemagglutinin) were also cloned into pBBR1MCS-5 and moved into EB92-1; both transformants also showed significantly increased symptoms on V. vinifera vines, characteristic of PD. Together, these results reveal that PD effectors include at least a lipase, two Zot-like toxins and a possibly redundant hemagglutinin, none of which are necessary for parasitic survival of X. fastidiosa populations in grapevines or elderberry.

Three New Pierce's Disease Pathogenicity Effectors Identified Using Xylella fastidiosa Biocontrol Strain EB92-1

PubMed Central

Zhang, Shujian; Chakrabarty, Pranjib K.; Fleites, Laura A.; Rayside, Patricia A.; Hopkins, Donald L.; Gabriel, Dean W.

2015-01-01

Xylella fastidiosa (X. fastidiosa) infects a wide range of plant hosts and causes economically serious diseases, including Pierce's Disease (PD) of grapevines. X. fastidiosa biocontrol strain EB92-1 was isolated from elderberry and is infectious and persistent in grapevines but causes only very slight symptoms under ideal conditions. The draft genome of EB92-1 revealed that it appeared to be missing genes encoding 10 potential PD pathogenicity effectors found in Temecula1. Subsequent PCR and sequencing analyses confirmed that EB92-1 was missing the following predicted effectors found in Temecula1: two type II secreted enzymes, including a lipase (LipA; PD1703) and a serine protease (PD0956); two identical genes encoding proteins similar to Zonula occludens toxins (Zot; PD0915 and PD0928), and at least one relatively short, hemagglutinin-like protein (PD0986). Leaves of tobacco and citrus inoculated with cell-free, crude protein extracts of E. coli BL21(DE3) overexpressing PD1703 exhibited a hypersensitive response (HR) in less than 24 hours. When cloned into shuttle vector pBBR1MCS-5, PD1703 conferred strong secreted lipase activity to Xanthomonas citri, E. coli and X. fastidiosa EB92-1 in plate assays. EB92-1/PD1703 transformants also showed significantly increased disease symptoms on grapevines, characteristic of PD. Genes predicted to encode PD0928 (Zot) and a PD0986 (hemagglutinin) were also cloned into pBBR1MCS-5 and moved into EB92-1; both transformants also showed significantly increased symptoms on V. vinifera vines, characteristic of PD. Together, these results reveal that PD effectors include at least a lipase, two Zot-like toxins and a possibly redundant hemagglutinin, none of which are necessary for parasitic survival of X. fastidiosa populations in grapevines or elderberry. PMID:26218423

Inhibition of Cardiomyocytes Differentiation of Mouse Embryonic Stem Cells by CD38/cADPR/Ca2+ Signaling Pathway*

PubMed Central

Wei, Wen-Jie; Sun, Hai-Ying; Ting, Kai Yiu; Zhang, Li-He; Lee, Hon-Cheung; Li, Gui-Rong; Yue, Jianbo

2012-01-01

Cyclic adenosine diphosphoribose (cADPR) is an endogenous Ca2+ mobilizing messenger that is formed by ADP-ribosyl cyclases from nicotinamide adenine dinucleotide (NAD). The main ADP-ribosyl cyclase in mammals is CD38, a multi-functional enzyme and a type II membrane protein. Here we explored the role of CD38-cADPR-Ca2+ in the cardiomyogenesis of mouse embryonic stem (ES) cells. We found that the mouse ES cells are responsive to cADPR and possess the key components of the cADPR signaling pathway. In vitro cardiomyocyte (CM) differentiation of mouse ES cells was initiated by embryoid body (EB) formation. Interestingly, beating cells appeared earlier and were more abundant in CD38 knockdown EBs than in control EBs. Real-time RT-PCR and Western blot analyses further showed that the expression of several cardiac markers, including GATA4, MEF2C, NKX2.5, and α-MLC, were increased markedly in CD38 knockdown EBs than those in control EBs. Similarly, FACS analysis showed that more cardiac Troponin T-positive CMs existed in CD38 knockdown or 8-Br-cADPR, a cADPR antagonist, treated EBs compared with that in control EBs. On the other hand, overexpression of CD38 in mouse ES cells significantly inhibited CM differentiation. Moreover, CD38 knockdown ES cell-derived CMs possess the functional properties characteristic of normal ES cell-derived CMs. Last, we showed that the CD38-cADPR pathway negatively modulated the FGF4-Erks1/2 cascade during CM differentiation of ES cells, and transiently inhibition of Erk1/2 blocked the enhanced effects of CD38 knockdown on the differentiation of CM from ES cells. Taken together, our data indicate that the CD38-cADPR-Ca2+ signaling pathway antagonizes the CM differentiation of mouse ES cells. PMID:22908234

Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment.

PubMed

Fréal, Amélie; Fassier, Coralie; Le Bras, Barbara; Bullier, Erika; De Gois, Stéphanie; Hazan, Jamilé; Hoogenraad, Casper C; Couraud, François

2016-04-20

The axon initial segment (AIS) is required for generating action potentials and maintaining neuronal polarity. Significant progress has been made in deciphering the basic building blocks composing the AIS, but the underlying mechanisms required for AIS formation remains unclear. The scaffolding protein ankyrin-G is the master-organizer of the AIS. Microtubules and their interactors, particularly end-binding proteins (EBs), have emerged as potential key players in AIS formation. Here, we show that the longest isoform of ankyrin-G (480AnkG) selectively associates with EBs via its specific tail domain and that this interaction is crucial for AIS formation and neuronal polarity in cultured rodent hippocampal neurons. EBs are essential for 480AnkG localization and stabilization at the AIS, whereas 480AnkG is required for the specific accumulation of EBs in the proximal axon. Our findings thus provide a conceptual framework for understanding how the cooperative relationship between 480AnkG and EBs induces the assembly of microtubule-AIS structures in the proximal axon. Neuronal polarity is crucial for the proper function of neurons. The assembly of the axon initial segment (AIS), which is the hallmark of early neuronal polarization, relies on the longest 480 kDa ankyrin-G isoform. The microtubule cytoskeleton and its interacting proteins were suggested to be early key players in the process of AIS formation. In this study, we show that the crosstalk between 480 kDa ankyrin-G and the microtubule plus-end tracking proteins, EBs, at the proximal axon is decisive for AIS assembly and neuronal polarity. Our work thus provides insight into the functional mechanisms used by 480 kDa ankyrin-G to drive the AIS formation and thereby to establish neuronal polarity. Copyright © 2016 the authors 0270-6474/16/364421-13$15.00/0.

Modeling of Coupled Thermo-Hydro-Mechanical-Chemical Processes for Bentonite in a Clay-rock Repository for Heat-generating Nuclear Waste

NASA Astrophysics Data System (ADS)

Xu, H.; Rutqvist, J.; Zheng, L.; Birkholzer, J. T.

2016-12-01

Engineered Barrier Systems (EBS) that include a bentonite-based buffer are designed to isolate the high-level radioactive waste emplaced in tunnels in deep geological formations. The heat emanated from the waste can drive the moisture flow transport and induce strongly coupled Thermal (T), Hydrological (H), Mechanical (M) and Chemical (C) processes within the bentonite buffer and may also impact the evolution of the excavation disturbed zone and the sealing between the buffer and walls of an emplacement tunnel The flow and contaminant transport potential along the disturbed zone can be minimized by backfilling the tunnels with bentonite, if it provides enough swelling stress when hydrated by the host rock. The swelling capability of clay minerals within the bentonite is important for sealing gaps between bentonite block, and between the EBS and the surrounding host rock. However, a high temperature could result in chemical alteration of bentonite-based buffer and backfill materials through illitization, which may compromise the function of these EBS components by reducing their plasticity and capability to swell under wetting. Therefore, an adequate THMC coupling scheme is required to understand and to predict the changes of bentonite for identifying whether EBS bentonite can sustain higher temperatures. More comprehensive links between chemistry and mechanics, taking advantage of the framework provided by a dual-structure model, named Barcelona Expansive Model (BExM), was implemented in TOUGHREACT-FLAC3D and is used to simulate the response of EBS bentonite in in clay formation for a generic case. The current work is to evaluate the chemical changes in EBS bentonite and the effects on the bentonite swelling stress under high temperature. This work sheds light on the interaction between THMC processes, evaluates the potential deterioration of EBS bentonite and supports the decision making in the design of a nuclear waste repository in light of the maximum allowance temperature.

Fertility following CIDR based synchronization regimens in anoestrous Nili-Ravi buffaloes.

PubMed

Naseer, Z; Ahmad, E; Singh, J; Ahmad, N

2011-10-01

The objective of this study was to compare oestrus expression and fertility rate in used and new controlled internal drug releasing (CIDR) device treated anoestrous buffaloes. Furthermore, to determine the timing of ovulation, and fertility rate in estradiol benzoate (EB) and GnRH-administered CIDR-treated anoestrous Nili-Ravi buffaloes. In experiment 1, buffaloes received either a used CIDR (UCIDR, n = 35) or a new CIDR (NCIDR, n = 36) for 7 day and PGF2α on day 6. Oestrous expression was similar (p > 0.05) between UCIDR (88.5%) and NCIDR (96.6%) buffaloes. The pregnancy rate did not differ (p > 0.05) because of treatment (37.1% in UCIDR vs 36.6% in NCIDR). In experiment 2, buffaloes (n = 55) received CIDR device for 7 days and PGF2α, on day 6 and randomly assigned into three treatment groups: (i) CIDR-EB (n = 17) received EB on day 8, (ii) CIDR-GnRH (n = 18) received GnRH on day 9 and (iii) control (n = 20) received no further treatment. Mean interval from CIDR removal to ovulation in CIDR-EB, CIDR-GnRH and CIDR group were 61.3 ± 0.8, 64.9 ± 1.8 and 65.1 ± 16.7 h, respectively. However, the buffaloes in the CIDR-EB and CIDR-GnRH group had lesser variability in the timing of ovulation compared to control. The pregnancy rate of both CIDR-EB group (58%) and CIDR-GnRH group (61%) were tended to be higher (p < 0.1) than control (30%). In conclusion, compared to NCIDR devices, previously UCIDR devices are equally effective to induce oestrus in anoestrous buffaloes resulting optimal pregnancy rate. Administration of EB and GnRH after CIDR removal results in tighter synchrony (less variability) and improved fertility in anoestrous buffaloes. CIDR based synchronization regimens have great potential in fertility improvement in anoestrous buffaloes. © 2011 Blackwell Verlag GmbH.

The expression and crucial roles of BMP signaling in development of smooth muscle progenitor cells in the mouse embryonic gut.

PubMed

Torihashi, Shigeko; Hattori, Takako; Hasegawa, Hirotaka; Kurahashi, Masaaki; Ogaeri, Takunori; Fujimoto, Toyoshi

2009-03-01

Bone morphogenetic protein (BMP) signaling is essential for normal development of the gastrointestinal (GI) tract. BMPs also play multiple roles in vascular smooth muscle cells; however, the BMP signaling in the development of the GI musculature remains to be clarified. We investigated the expression of BMPs and their receptors in mouse embryonic GI tracts by immunohistochemistry and in situ hybridization. We demonstrated that BMP2, BMP receptor Ib and BMP receptor II were expressed in the smooth muscle progenitors from E12 to E13 for the first time. BMP signaling on smooth muscle differentiation was examined by implantation of agarose beads soaked with BMPs in the in vitro developmental model that is gut-like structures from mouse embryonic stem (ES) cells. BMP2 rather than BMP4 beads enhanced smooth muscle differentiation, and increased gut-like structures showing spontaneous contractions and expressing intensive alpha-smooth muscle actin immunoreactivity. This increase was confirmed by up-regulation of SM22 mRNA shown by real-time PCR. By addition of noggin beads or noggin to the medium at BMP2 bead implantation, the ratio of contractive gut-like structures decreased. Implantation of BMP2 beads at EB7 (EB--embryoid bodies) (corresponding to E12 or E13 of mouse embryo) showed the highest effects and up-regulation of transcription factors msx-1 after 24h. This increase was blocked by noggin, and msx-1 decreased to almost the control level after 60 h. BMP2 beads at EB7 increased platelet-derived growth factor-A (PDGF-A) in the differentiating smooth muscle cells. We have recently reported that PDGF-A is expressed in the developing inner circular smooth muscle and is crucial for the longitudinal smooth muscle differentiation. Taken together, BMP signaling was expressed for a short window in the smooth muscle progenitors and the signal, especially BMP2, plays an essential role in smooth muscle differentiation in cooperation with PDGF signaling.

Electric bus systems.

DOT National Transportation Integrated Search

2017-04-01

Pure electric buses (EBs) offer an alternative fuel for the nations transit bus systems. To : evaluate EBs in a transit setting, this project investigated the five electric bus fleet of the : StarMetro transit system of the city of Tallahassee, FL...

Higher-order gravitational lensing reconstruction using Feynman diagrams

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

Jenkins, Elizabeth E.; Manohar, Aneesh V.; Yadav, Amit P.S.

2014-09-01

We develop a method for calculating the correlation structure of the Cosmic Microwave Background (CMB) using Feynman diagrams, when the CMB has been modified by gravitational lensing, Faraday rotation, patchy reionization, or other distorting effects. This method is used to calculate the bias of the Hu-Okamoto quadratic estimator in reconstructing the lensing power spectrum up to  O (φ{sup 4}) in the lensing potential φ. We consider both the diagonal noise TT TT, EB EB, etc. and, for the first time, the off-diagonal noise TT TE, TB EB, etc. The previously noted large  O (φ{sup 4}) term in the second order noise ismore » identified to come from a particular class of diagrams. It can be significantly reduced by a reorganization of the φ expansion. These improved estimators have almost no bias for the off-diagonal case involving only one B component of the CMB, such as EE EB.« less

Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening

NASA Astrophysics Data System (ADS)

Kim, Young L.; Liu, Yang; Turzhitsky, Vladimir M.; Roy, Hemant K.; Wali, Ramesh K.; Subramanian, Hariharan; Pradhan, Prabhakar; Backman, Vadim

2006-07-01

The phenomenon of enhanced backscattering (EBS) of light, also known as coherent backscattering (CBS) of light, has been the object of intensive investigation in nonbiological media over the last two decades. However, there have been only a few attempts to explore EBS for tissue characterization and diagnosis. We have recently made progress in the EBS measurements in tissue by taking advantage of low spatial coherence illumination, which has led us to the development of low-coherence enhanced backscattering (LEBS) spectroscopy. In this work, we review the current state of research on LEBS. After a brief discussion of the basic principle of EBS and LEBS, we present an overview of the unique features of LEBS for tissue characterization, and show that LEBS enables depth-selective spectroscopic assessment of mucosal tissue. Then, we demonstrate the potential of LEBS spectroscopy for predicting the risk of colon carcinogenesis and colonoscopy-free screening for colorectal cancer (CRC).

A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation.

PubMed

Wu, Huei-Wen; Hsiao, Yi-Hsing; Chen, Chih-Chen; Yet, Shaw-Fang; Hsu, Chia-Hsien

2016-07-06

The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip.

Analysis of Intrinsic Stability Criteria for Isotropic Third-Order Green Elastic and Compressible Neo-Hookean Solids

DTIC Science & Technology

2014-03-01

components with increasing pressure. At high pressures, this tendency may lead to the onset of instability and subsequent amor - phization (Chen et al...C0IJKLMNEIJEKLEMN ¼ 1 2 C0abEaEb þ 1 6 C0abvEaEbEv: ð2:28Þ Stress S and tangent modulus C are Sa ¼ C0abEb þ 1 2 C0abvEbEv; Cab ¼ C 0 ab þ C 0 abvEv: ð2:29Þ Second...123Þ: ð2:33Þ Second-order compliance components M0ab ¼ ½C 0 ab 1 are M011 ¼ C011 þ C 0 12 ðC011 C 0 12ÞðC 0 11 þ 2C 0 12Þ ; M012 ¼ C012 ðC011 C 0

Dental management of patients with epidermolysis bullosa.

PubMed

Dağ, Canan; Bezgin, Tuğba; Özalp, Nurhan

2014-09-01

Epidermolysis Bullosa (EB) is a group of rare, genetic skin disorders characterized by fragility and blistering to minimal trauma. All oral surfaces may be involved, including the tongue, buccal mucosa, palate, floor of the mouth and gingiva. Common oral findings of the disease include microstomia, intraoral ulcerations and bullae formation, ankyloglossia, tongue atrophy, elimination of buccal and vestibular sulci, lingual depapillation and atrophy of the palatal folds. In these case reports; systemic findings, oral manifestations and preventive measures are described for 3 patients with EB, all of whom required extensive oral management. Early dental management and preventive care to minimize caries development and improve oral health is very important for patients with EB. Pediatric dentists play an especially important role in early intervention. In describing the dental management of three EB cases, this article stresses the importance of an aggressive dental preventive programme with strict oral hygiene instructions for patients and parents along with frequent professional cleaning and fluoride therapy.

Observation of giant exchange bias in bulk Mn50Ni42Sn8 Heusler alloy

NASA Astrophysics Data System (ADS)

Sharma, Jyoti; Suresh, K. G.

2015-02-01

We report a giant exchange bias (EB) field of 3520 Oe in bulk Mn50Ni42Sn8 Heusler alloy. The low temperature magnetic state of the martensite phase has been studied by DC magnetization and AC susceptibility measurements. Frequency dependence of spin freezing temperature (Tf) on critical slowing down relation and observation of memory effect in zero field cooling mode confirms the super spin glass (SSG) phase at low temperatures. Large EB is attributed to the strong exchange coupling between the SSG clusters formed by small regions of ferromagnetic order embedded in an antiferromagnetic (AFM) matrix. The temperature and cooling field dependence of EB have been studied and related to the change in unidirectional anisotropy at SSG/AFM interface. The training effect also corroborates with the presence of frozen (SSG) moments at the interface and their role in EB.

Enthalpy By Energy Balance for Aerodynamic Heating Facility at NASA Ames Research Center Arc Jet Complex

NASA Technical Reports Server (NTRS)

Hightower, T. Mark; MacDonald, Christine L.; Martinez, Edward R.; Balboni, John A.; Anderson, Karl F.; Arnold, Jim O. (Technical Monitor)

2002-01-01

The NASA Ames Research Center (ARC) Arc Jet Facilities' Aerodynamic Heating Facility (AHF) has been instrumented for the Enthalpy By Energy Balance (EB2) method. Diagnostic EB2 data is routinely taken for all AHF runs. This paper provides an overview of the EB2 method implemented in the AHF. The chief advantage of the AHF implementation over earlier versions is the non-intrusiveness of the instruments used. For example, to measure the change in cooling water temperature, thin film 1000 ohm Resistance Temperature Detectors (RTDs) are used with an Anderson Current Loop (ACL) as the signal conditioner. The ACL with 1000 ohm RTDs allows for very sensitive measurement of the increase in temperature (Delta T) of the cooling water to the arc heater, which is a critical element of the EB2 method. Cooling water flow rates are measured with non-intrusive ultrasonic flow meters.

Spectraplakins promote microtubule-mediated axonal growth by functioning as structural microtubule-associated proteins and EB1-dependent +TIPs (tip interacting proteins).

PubMed

Alves-Silva, Juliana; Sánchez-Soriano, Natalia; Beaven, Robin; Klein, Melanie; Parkin, Jill; Millard, Thomas H; Bellen, Hugo J; Venken, Koen J T; Ballestrem, Christoph; Kammerer, Richard A; Prokop, Andreas

2012-07-04

The correct outgrowth of axons is essential for the development and regeneration of nervous systems. Axon growth is primarily driven by microtubules. Key regulators of microtubules in this context are the spectraplakins, a family of evolutionarily conserved actin-microtubule linkers. Loss of function of the mouse spectraplakin ACF7 or of its close Drosophila homolog Short stop/Shot similarly cause severe axon shortening and microtubule disorganization. How spectraplakins perform these functions is not known. Here we show that axonal growth-promoting roles of Shot require interaction with EB1 (End binding protein) at polymerizing plus ends of microtubules. We show that binding of Shot to EB1 requires SxIP motifs in Shot's C-terminal tail (Ctail), mutations of these motifs abolish Shot functions in axonal growth, loss of EB1 function phenocopies Shot loss, and genetic interaction studies reveal strong functional links between Shot and EB1 in axonal growth and microtubule organization. In addition, we report that Shot localizes along microtubule shafts and stabilizes them against pharmacologically induced depolymerization. This function is EB1-independent but requires net positive charges within Ctail which essentially contribute to the microtubule shaft association of Shot. Therefore, spectraplakins are true members of two important classes of neuronal microtubule regulating proteins: +TIPs (tip interacting proteins; plus end regulators) and structural MAPs (microtubule-associated proteins). From our data we deduce a model that relates the different features of the spectraplakin C terminus to the two functions of Shot during axonal growth.

Low-coherence enhanced backscattering of light: characteristics and applications for colon cancer screening

NASA Astrophysics Data System (ADS)

Kim, Young L.; Pradhan, Prabhakar; Turzhitsky, Vladimir M.; Subramanian, Hariharan; Liu, Yang; Wali, Ramesh K.; Roy, Hemant K.; Backman, Vadim

2007-02-01

The phenomenon of enhanced backscattering (EBS) of light, also known as coherent backscattering (CBS) of light, is a spectacular manifestation of self-interference effects in elastic light scattering, which gives rise to an enhanced scattered intensity in the backward direction. Although EBS has been the object of intensive investigation in non-biological media over the last two decades, there have been only a few attempts to explore EBS for tissue characterization and diagnosis. We have recently made progress in the EBS measurements of biological tissue by taking advantage of lowcoherence (or partially coherent) illumination, which is referred to as low-coherence EBS (LEBS) of light. LEBS possess novel and intriguing properties such as speckle reduction, self-averaging effect, broadening of the EBS width, depth-selectivity, double scattering, and circular polarization memory effect. After we review the current state of research on LEBS, we discuss how these characteristics apply for early cancer detection, especially in colorectal cancer (CRC), which is the second leading cause of cancer mortality in the United States. Although colonoscopy remains the gold standard for CRC screening, resource constraints and potential complications make it impractical to perform colonoscopy on the entire population at risk (age > 50). Thus, identifying patients who are most likely to benefit from colonoscopy is of paramount importance. We demonstrate that LEBS measurements in easily accessible colonoscopically normal mucosa (e.g., in the rectum of the colon) can be used for predicting the risk of CRC, and thus LEBS has the potential to serve as accurate markers of the risk of neoplasia elsewhere in the colon.

Analysis of microtubule growth dynamics arising from altered actin network structure and contractility in breast tumor cells

NASA Astrophysics Data System (ADS)

Ory, Eleanor C.; Bhandary, Lekhana; E Boggs, Amanda; Chakrabarti, Kristi R.; Parker, Joshua; Losert, Wolfgang; Martin, Stuart S.

2017-04-01

The periphery of epithelial cells is shaped by opposing cytoskeletal physical forces generated predominately by two dynamic force generating systems—growing microtubule ends push against the boundary from the cell center, and the actin cortex contracts the attached plasma membrane. Here we investigate how changes to the structure and dynamics of the actin cortex alter the dynamics of microtubules. Current drugs target actin polymerization and contraction to reduce cell division and invasiveness; however, the impacts on microtubule dynamics remain incompletely understood. Using human MCF-7 breast tumor cells expressing GFP-tagged microtubule end-binding-protein-1 (EB1) and coexpression of cytoplasmic fluorescent protein mCherry, we map the trajectories of growing microtubule ends and cytoplasmic boundary respectively. Based on EB1 tracks and cytoplasmic boundary outlines, we calculate the speed, distance from cytoplasmic boundary, and straightness of microtubule growth. Actin depolymerization with Latrunculin-A reduces EB1 growth speed as well as allows the trajectories to extend beyond the cytoplasmic boundary. Blebbistatin, a direct myosin-II inhibitor, reduced EB1 speed and yielded less straight EB1 trajectories. Inhibiting signaling upstream of myosin-II contractility via the Rho-kinase inhibitor, Y-27632, altered EB1 dynamics differently from Blebbistatin. These results indicate that reduced actin cortex integrity can induce distinct alterations in microtubule dynamics. Given recent findings that tumor stem cell characteristics are increased by drugs which reduce actin contractility or stabilize microtubules, it remains important to clearly define how cytoskeletal drugs alter the interactions between these two filament systems in tumor cells.

Potential effects of fat mass and fat-free mass on energy intake in different states of energy balance.

PubMed

Stubbs, R James; Hopkins, M; Finlayson, G S; Duarte, C; Gibbons, C; Blundell, J E

2018-05-01

Recently models have attempted to integrate the functional relationships of fat mass (FM) and fat-free mass (FFM) with the control of human energy intake (EI). Cross-sectional evidence suggests that at or close to EB, FFM is positively related to hunger and EI, whereas FM either shows a weak negative or no association with ad libitum EI. Further analysis suggests that the effects of FFM and FM on EI may be mediated by resting metabolic rate (RMR). These studies suggest that energy turnover is associated with EI and the largest determinant of energy requirements in most humans is FFM. During chronic positive EBs both FM and FFM expand (but disproportionately so), increasing energy demands. There is little evidence that an expanding FM exerts strong negative feedback on longer term EI. However, during chronic negative EBs FM, FFM and RMR all decrease but appetite increases. Some studies suggest that proportionate loss of FFM during weight loss predicts subsequent weight regain. Taken together these lines of evidence suggest that changes in the size and functional integrity of FFM may influence appetite and EI. Increases in FFM associated with either weight gain or high levels of exercise may 'pull' EI upwards but energy deficits that decrease FFM may exert a distinct drive on appetite. The current paper discusses how FM and FFM relationships influence appetite regulation, and how size, structure and functional integrity of FFM may drive EI in humans (i) at EB (ii) during positive EB and (iii) during negative EB.

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

PubMed

Miller, Douglas L; Li, Peng; Dou, Chunyan; Gordon, David; Edwards, Chris A; Armstrong, William F

2005-10-01

To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P < .02) and 2.0 MPa (P < .005) relative to the cell counts at sham myocardial contrast echocardiography. Premature heartbeats had a similar exposure-response relationship; however, number of premature heartbeats and EB-stained cell count did not appear to be directly related (coefficient of determination r2 = 0.03). The EB-stained cell counts at end-diastolic triggering were not significantly different from those at end-systolic triggering (P > .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure. RSNA, 2005

Effects of dry period length and dietary energy source on milk yield, energy balance, and metabolic status of dairy cows over 2 consecutive years: Effects in the second year.

PubMed

Chen, J; Remmelink, G J; Gross, J J; Bruckmaier, R M; Kemp, B; van Knegsel, A T M

2016-06-01

The objective of the current study was to evaluate the effect of dry period (DP) length on milk yield, energy balance (EB), and metabolic status in cows fed a lipogenic or glucogenic diet in the second year after implementation of DP and dietary treatments. Holstein-Friesian dairy cows (n=167) were assigned randomly to 1 of 3 DP lengths (0, 30, or 60d) and 1 of 2 early lactation diets (glucogenic or lipogenic) for 2 consecutive years. Results of the first year were reported previously. In the second year, 19 cows in the 0-d DP group were attributed to a new group (0→67d DP) because these cows had a milk yield of <4kg/d at least 30d before expected calving date and were dried off. Milk yield was recorded and EB was calculated from wk -8 to 9 relative to calving. Blood samples were taken weekly from wk -3 to 8 relative to calving. Liver samples were taken in wk -2, 2, and 4 relative to calving. At the onset of lactation, cows with a 0-d or 0→67-d DP had greater body condition score (BCS) than cows with a 60-d DP. During the first 9wk, cows with a 0- or 30-d DP produced 5.0 and 4.3kg less milk per day, respectively, but had similar EB compared with cows with a 60-d DP. Cows with a 0- or 30-d DP produced additional milk precalving, which could compensate milk yield losses in the first 9wk postcalving. Cows with a 0-d DP did not have milk yield losses or improve EB in the second year as much as in the first year. Cows with a 0-d DP had greater plasma insulin and insulin-like growth factor-I (IGF-I) and lower liver triacylglycerol concentrations than cows with other DP lengths. Cows with a 0→67-d DP had lower EB, and greater plasma free fatty acids (FFA) and β-hydroxybutyrate (BHB) concentrations than cows with other DP lengths. Feeding a glucogenic diet increased plasma glucose, IGF-I, and insulin concentrations, and decreased plasma FFA, BHB, and urea concentrations compared with a lipogenic diet, independent of DP length. In conclusion, omitting the DP or feeding a glucogenic diet improved metabolic status in early lactation of the second year after implementation of DP length and dietary treatments, although effects of omitting the DP were less pronounced in the second year than in the first year. The less pronounced improvement of EB in the second year was related to the high BCS at the onset of lactation and reduced milk yield losses in cows with a 0-d DP. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

FLCN: The causative gene for Birt-Hogg-Dubé syndrome.

PubMed

Schmidt, Laura S; Linehan, W Marston

2018-01-15

Germline mutations in the novel tumor suppressor gene FLCN are responsible for the autosomal dominant inherited disorder Birt-Hogg-Dubé (BHD) syndrome that predisposes to fibrofolliculomas, lung cysts and spontaneous pneumothorax, and an increased risk for developing kidney tumors. Although the encoded protein, folliculin (FLCN), has no sequence homology to known functional domains, x-ray crystallographic studies have shown that the C-terminus of FLCN has structural similarity to DENN (differentially expressed in normal cells and neoplasia) domain proteins that act as guanine nucleotide exchange factors (GEFs) for small Rab GTPases. FLCN forms a complex with folliculin interacting proteins 1 and 2 (FNIP1, FNIP2) and with 5' AMP-activated protein kinase (AMPK). This review summarizes FLCN functional studies which support a role for FLCN in diverse metabolic pathways and cellular processes that include modulation of the mTOR pathway, regulation of PGC1α and mitochondrial biogenesis, cell-cell adhesion and RhoA signaling, control of TFE3/TFEB transcriptional activity, amino acid-dependent activation of mTORC1 on lysosomes through Rag GTPases, and regulation of autophagy. Ongoing research efforts are focused on clarifying the primary FLCN-associated pathway(s) that drives the development of fibrofolliculomas, lung cysts and kidney tumors in BHD patients carrying germline FLCN mutations. Copyright © 2017 Elsevier B.V. All rights reserved.

gene2drug: a computational tool for pathway-based rational drug repositioning.

PubMed

Napolitano, Francesco; Carrella, Diego; Mandriani, Barbara; Pisonero-Vaquero, Sandra; Sirci, Francesco; Medina, Diego L; Brunetti-Pierri, Nicola; di Bernardo, Diego

2018-05-01

Drug repositioning has been proposed as an effective shortcut to drug discovery. The availability of large collections of transcriptional responses to drugs enables computational approaches to drug repositioning directly based on measured molecular effects. We introduce a novel computational methodology for rational drug repositioning, which exploits the transcriptional responses following treatment with small molecule. Specifically, given a therapeutic target gene, a prioritization of potential effective drugs is obtained by assessing their impact on the transcription of genes in the pathway(s) including the target. We performed in silico validation and comparison with a state-of-art technique based on similar principles. We next performed experimental validation in two different real-case drug repositioning scenarios: (i) upregulation of the glutamate-pyruvate transaminase (GPT), which has been shown to induce reduction of oxalate levels in a mouse model of primary hyperoxaluria, and (ii) activation of the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy, whose modulation may be beneficial in neurodegenerative disorders. A web tool for Gene2drug is freely available at http://gene2drug.tigem.it. An R package is under development and can be obtained from https://github.com/franapoli/gep2pep. dibernardo@tigem.it. Supplementary data are available at Bioinformatics online.

Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression

PubMed Central

Blessing, Alicia M.; Rajapakshe, Kimal; Reddy Bollu, Lakshmi; Shi, Yan; White, Mark A.; Pham, Alexander H.; Lin, Chenchu; Jonsson, Philip; Cortes, Constanza J.; Cheung, Edwin; La Spada, Albert R.; Bast, Robert C.; Merchant, Fatima A.; Coarfa, Cristian; Frigo, Daniel E.

2017-01-01

ABSTRACT AR (androgen receptor) signaling is crucial for the development and maintenance of the prostate as well as the initiation and progression of prostate cancer. Despite the AR's central role in prostate cancer progression, it is still unclear which AR-mediated processes drive the disease. Here, we identified 4 core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of AR in prostate cancer. These findings were significant in light of our recent observation that androgens promoted prostate cancer cell growth in part through the induction of autophagy. Expression of these 5 genes was essential for maximal androgen-mediated autophagy and cell proliferation. In addition, expression of each of these 5 genes alone or in combination was sufficient to increase prostate cancer cell growth independent of AR activity. Further, bioinformatic analysis demonstrated that the expression of these genes correlated with disease progression in 3 separate clinical cohorts. Collectively, these findings demonstrate a functional role for increased autophagy in prostate cancer progression, provide a mechanism for how autophagy is augmented, and highlight the potential of targeting this process for the treatment of advanced prostate cancer. PMID:27977328

Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression.

PubMed

Blessing, Alicia M; Rajapakshe, Kimal; Reddy Bollu, Lakshmi; Shi, Yan; White, Mark A; Pham, Alexander H; Lin, Chenchu; Jonsson, Philip; Cortes, Constanza J; Cheung, Edwin; La Spada, Albert R; Bast, Robert C; Merchant, Fatima A; Coarfa, Cristian; Frigo, Daniel E

2017-03-04

AR (androgen receptor) signaling is crucial for the development and maintenance of the prostate as well as the initiation and progression of prostate cancer. Despite the AR's central role in prostate cancer progression, it is still unclear which AR-mediated processes drive the disease. Here, we identified 4 core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of AR in prostate cancer. These findings were significant in light of our recent observation that androgens promoted prostate cancer cell growth in part through the induction of autophagy. Expression of these 5 genes was essential for maximal androgen-mediated autophagy and cell proliferation. In addition, expression of each of these 5 genes alone or in combination was sufficient to increase prostate cancer cell growth independent of AR activity. Further, bioinformatic analysis demonstrated that the expression of these genes correlated with disease progression in 3 separate clinical cohorts. Collectively, these findings demonstrate a functional role for increased autophagy in prostate cancer progression, provide a mechanism for how autophagy is augmented, and highlight the potential of targeting this process for the treatment of advanced prostate cancer.

E.B. White: Aspects of Style.

ERIC Educational Resources Information Center

Neumeyer, Peter F.

1987-01-01

Assesses the writing style of a famous author of children's books, concluding that E.B. White's informal tone uses anaphora, simple sentences, doubling and redundancy, and mixes colloquial with standard English. Provides examples of his style, from 10 years old to maturity. (NKA)

[Emotional burnout syndrome and pedagogical styles in teachers of a medical high school].

PubMed

Ivanova, E I; Ivanov, I V; Serdakova, K G

2011-01-01

The study involved 20 teachers of medical institutions who gave consent to be examined for emotional burnout syndrome (EBS). Diagnosis of moderate EBS was confirmed by relevant clinical tests and analysis of pedagogical communication style in 30% of the participants. The pedagogical style of teachers exhibiting no signs of burnout is characterized by personality-oriented model of communication with differential attitudes toward students and active interaction with them. Teachers presenting with EBS relied on the disciplinary model of communication prevailed by authoritarian and dictatorial behaviour lacking communicability and flexibility; these persons showed pronounced hyperreflexia.

Kindler syndrome.

PubMed

Lai-Cheong, Joey E; McGrath, John A

2010-01-01

Kindler syndrome (MIM173650) is an autosomal recessive genodermatosis characterized by poikiloderma, trauma-induced skin blistering, mucosal inflammation, and photosensitivity. Loss-of-function mutations in the FERMT1 gene are the cause of Kindler syndrome. Kindler syndrome is categorized as a subtype of epidermolysis bullosa (EB). During infancy and childhood, there is clinical overlap between Kindler syndrome and dystrophic EB. Unlike other forms of EB, Kindler syndrome is characterized by impaired actin cytoskeleton-extracellular matrix interactions and a variable plane of blister formation at or close to the dermal-epidermal junction. This article reviews clinicopathologic and molecular features of Kindler syndrome and discusses patient management.

Electron beam curing — taking good ideas to the manufacturing floor

NASA Astrophysics Data System (ADS)

Saunders, C.; Lopata, V.; Barnard, J.; Stepanik, T.

2000-03-01

Acsion is exploiting several emerging electron beam EB applications ranging from composite curing and repair to viscose manufacturing. EB curing of composite structures offers several advantages: significantly reduced curing times; improvements in part quality and performance; reduced environmental and health concerns; improvements in material handling; and reduced overall manufacturing costs compared to thermal curing. The aerospace industry is developing EB technology in all of their market sectors, including military aviation and space products. Some specific products include cryogenic fuel tanks, improved canopy frames for jet aircraft, and the all-composite military aircraft. This paper discusses each of these opportunities.

On the involvement of progesterone in sexually rewarded choice behavior of the female rat.

PubMed

de Jonge, F H; van de Poll, N E

1986-01-01

The present experiment was designed to investigate the role of Progesterone in the regulation of two aspects of the female's appetitive sexual behavior. Ovariectomized females were tested for partner preference using either a test in which sexual interaction was not possible ("sexual orientation") or a test which included the possibility of sexual interaction ("sexually rewarded choice behavior"). The females were either primed with OIL, Estradiol benzoate (EB) or with Testosterone propionate (TP). Additional groups of females which were primed with EB or TP were treated with Progesterone (P) four hours prior to testing. The results indicate that females which are either treated with EB or with TP, show a male-directed orientation, while OIL-treated females do not. Sexually rewarded choice behavior however, was not affected by hormonal treatment with EB or TP. Additional treatment with P did not further increase the female's male-directed sexual orientation. Sexually rewarded choices for males, in contrast, were drastically increased. EB + P- or TP + P-treated females also showed a significant increase in heterosexual interactions with males in the goal box. The present results support the hypothesis that P plays a role in the female's appetitive sexual behavior, only when the possibility for interaction with a male is present.

Reduction of Interhemispheric Functional Brain Connectivity in Early Blindness: A Resting-State fMRI Study

PubMed Central

2017-01-01

Objective The purpose of this study was to investigate the resting-state interhemispheric functional connectivity in early blindness by using voxel-mirrored homotopic connectivity (VMHC). Materials and Methods Sixteen early blind patients (EB group) and sixteen age- and gender-matched sighted control volunteers (SC group) were recruited in this study. We used VMHC to identify brain areas with significant differences in functional connectivity between different groups and used voxel-based morphometry (VBM) to calculate the individual gray matter volume (GMV). Results VMHC analysis showed a significantly lower connectivity in primary visual cortex, visual association cortex, and somatosensory association cortex in EB group compared to sighted controls. Additionally, VBM analysis revealed that GMV was reduced in the left lateral calcarine cortices in EB group compared to sighted controls, while it was increased in the left lateral middle occipital gyri. Statistical analysis showed the duration of blindness negatively correlated with VMHC in the bilateral middle frontal gyri, middle temporal gyri, and inferior temporal gyri. Conclusions Our findings help elucidate the pathophysiological mechanisms of EB. The interhemispheric functional connectivity was impaired in EB patients. Additionally, the middle frontal gyri, middle temporal gyri, and inferior temporal gyri may be potential target regions for rehabilitation. PMID:28656145

A newly discovered bacterium associated with parthenogenesis and a change in host selection behavior in parasitoid wasps.

PubMed

Zchori-Fein, E; Gottlieb, Y; Kelly, S E; Brown, J K; Wilson, J M; Karr, T L; Hunter, M S

2001-10-23

The symbiotic bacterium Wolbachia pipientis has been considered unique in its ability to cause multiple reproductive anomalies in its arthropod hosts. Here we report that an undescribed bacterium is vertically transmitted and associated with thelytokous parthenogenetic reproduction in Encarsia, a genus of parasitoid wasps. Although Wolbachia was found in only one of seven parthenogenetic Encarsia populations examined, the "Encarsia bacterium" (EB) was found in the other six. Among seven sexually reproducing populations screened, EB was present in one, and none harbored Wolbachia. Antibiotic treatment did not induce male production in Encarsia pergandiella but changed the oviposition behavior of females. Cured females accepted one host type at the same rate as control females but parasitized significantly fewer of the other host type. Phylogenetic analysis based on the 16S rDNA gene sequence places the EB in a unique clade within the Cytophaga-Flexibacter-Bacteroid group and shows EB is unrelated to the Proteobacteria, where Wolbachia and most other insect symbionts are found. These results imply evolution of the induction of parthenogenesis in a lineage other than Wolbachia. Importantly, these results also suggest that EB may modify the behavior of its wasp carrier in a way that enhances its transmission.

Obstructive sleep apnea and energy balance regulation: A systematic review.

PubMed

Shechter, Ari

2017-08-01

Obesity and obstructive sleep apnea (OSA) have a reciprocal relationship. Sleep disruptions characteristic of OSA may promote behavioral, metabolic, and/or hormonal changes favoring weight gain and/or difficulty losing weight. The regulation of energy balance (EB), i.e., the relationship between energy intake (EI) and energy expenditure (EE), is complex and multi-factorial, involving food intake, hormonal regulation of hunger/satiety/appetite, and EE via metabolism and physical activity (PA). The current systematic review describes the literature on how OSA affects EB-related parameters. OSA is associated with a hormonal profile characterized by abnormally high leptin and ghrelin levels, which may encourage excess EI. Data on actual measures of food intake are lacking, and not sufficient to make conclusions. Resting metabolic rate appears elevated in OSA vs. Findings on PA are inconsistent, but may indicate a negative relationship with OSA severity that is modulated by daytime sleepiness and body weight. A speculative explanation for the positive EB in OSA is that the increased EE via metabolism induces an overcompensation in the drive for hunger/food intake, which is larger in magnitude than the rise in EI required to re-establish EB. Understanding how OSA affects EB-related parameters can help improve weight loss efforts in these patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electron-beam lithography with character projection technique for high-throughput exposure with line-edge quality control

NASA Astrophysics Data System (ADS)

Ikeno, Rimon; Maruyama, Satoshi; Mita, Yoshio; Ikeda, Makoto; Asada, Kunihiro

2016-07-01

The high throughput of character projection (CP) electron-beam (EB) lithography makes it a promising technique for low-to-medium volume device fabrication with regularly arranged layouts, such as for standard-cell logics and memory arrays. However, non-VLSI applications such as MEMS and MOEMS may not be able to fully utilize the benefits of the CP method due to the wide variety of layout figures including curved and oblique edges. In addition, the stepwise shapes that appear because of the EB exposure process often result in intolerable edge roughness, which degrades device performances. In this study, we propose a general EB lithography methodology for such applications utilizing a combination of the CP and variable-shaped beam methods. In the process of layout data conversion with CP character instantiation, several control parameters were optimized to minimize the shot count, improve the edge quality, and enhance the overall device performance. We have demonstrated EB shot reduction and edge-quality improvement with our methodology by using a leading-edge EB exposure tool, ADVANTEST F7000S-VD02, and a high-resolution hydrogen silsesquioxane resist. Atomic force microscope observations were used to analyze the resist edge profiles' quality to determine the influence of the control parameters used in the data conversion process.

Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem.

PubMed

Martins-Júnior, J L; Bernardi, M M; Bondan, E F

2016-03-01

Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test. Copyright © 2016 Elsevier Inc. All rights reserved.

Housing accessibility for senior citizens in Sweden: Estimation of the effects of targeted elimination of environmental barriers.

PubMed

Pettersson, Cecilia; Slaug, Björn; Granbom, Marianne; Kylberg, Marianne; Iwarsson, Susanne

2017-01-24

To estimate the effects of targeted elimination of environmental barriers (EB) in the ordinary housing stock in Sweden, and to explore the estimated effects on accessibility at a population level in relation to (a) residents with different functional profiles, (b) different housing types and (c) building periods. Data on dwellings from existing Swedish research databases were utilized. EB and accessibility were assessed by means of the Housing Enabler instrument. In simulations of EB removal, five items that correspond to the most common housing adaptations were selected. The simulations were applied to four functional profiles of different complexity. EB known to be commonly removed by housing adaptations exist in large proportions of the existing ordinary housing stock. Estimated targeted elimination of selected barriers would have the largest accessibility effects for the more complex functional profiles. The effects would be consistently larger for one-family houses, and for all types of dwellings built before 1960. The elimination of the EB most commonly addressed by housing adaptations could result in a reduction of the housing accessibility problems that community-living older people are facing. For society to solve the housing situation for the ageing population well-informed and efficient upgrading of ordinary housing is imperative.

Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a countermeasure to the nitrogen mustard mechlorethamine.

PubMed

Lulla, Anju; Reznik, Sandra; Trombetta, Louis; Billack, Blase

2014-12-01

Previous studies in this and other laboratories have demonstrated that ebselen (EB-1), an organoselenium compound, spares cells from mechlorethamine (HN2) toxicity in vitro. In the present study, the hypothesis that EB-1 will reduce dermal toxicity of HN2 in vivo is put forward and found to have merit. Using the mouse ear vesicant model (MEVM), HN2, applied topically, showed a dose-dependent effect upon ear swelling and thickness 24 h after treatment; whereas tissue injury consistent with vesication was observed at the higher test doses of HN2 (≥ 0.250 µmol per ear). To examine HN2 countermeasure activity using the MEVM, either hydrocortisone (HC), as a positive control, or EB-1, the test countermeasure, was administered as three topical treatments 15 min, 4 and 8 h after HN2 exposure. Using this approach, both HC and EB-1 were found to reduce tissue swelling associated with HN2 toxicity 24 h after exposure to the vesicant. Taken together, these data demonstrate for the first time the effectiveness of EB-1 as a vesicant countermeasure in a relevant in vivo model. Copyright © 2013 John Wiley & Sons, Ltd.

Development and preventative effect against pine wilt disease of a novel liquid formulation of emamectin benzoate.

PubMed

Takai, Kazuya; Suzuki, Toshio; Kawazu, Kazuyoshi

2003-03-01

Injection of the poorly water-soluble emamectin benzoate (EB) into pine trunks required the development of an efficient liquid formulation. For injection into big trees in forests a good rate of injection and a high active content were required. Tests on the viscosity and EB-solubilizing ability of 14 various solubilizers in diethylene glycol monobutyl ether (DGMBE) led to the selection of Sorpol SM-100PM as the solubilizer of the formulation. Relationships between the solubilizing ability and amounts of Sorpol SM-100PM and DGMBE relative to that of EB, and between the concentration of the latter and the viscosity or the injection rate of the formulation led to a novel 40 g litre(-1) emamectin benzoate formulation (Shot Wan Liquid Formulation), which was composed of EB (40), Sorpol SM-100PM (120), DGMBE (160) and distilled water (50 g litre(-1)) in methanol. Injection of this formulation at a dose of 10 g EB per unit volume of pine tree prevented over 90% of the trees from wilting caused by pine wood nematode, and this preventative effect continued for 3 years. Neither discolouration of the leaves nor injury around the injection hole on the trees was observed after injection of the formulation.

EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.

PubMed

Gemoll, Timo; Kollbeck, Sophie L; Karstens, Karl F; Hò, Gia G; Hartwig, Sonja; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Oberländer, Martina; Kalies, Kathrin; Lehr, Stefan; Habermann, Jens K

2017-08-15

While carcinogenesis in Sporadic Colorectal Cancer (SCC) has been thoroughly studied, less is known about Ulcerative Colitis associated Colorectal Cancer (UCC). This study aimed to identify and validate differentially expressed proteins between clinical samples of SCC and UCC to elucidate new insights of UCC/SCC carcinogenesis and progression. Multiplex-fluorescence two-dimensional gel electrophoresis (2-D DIGE) and mass spectrometry identified 67 proteoforms representing 43 distinct proteins. After analysis by Ingenuity Pathway Analysis ® (IPA), subsequent Western blot validation proofed the differential expression of Heat shock 27 kDA protein 1 (HSPB1) and Microtubule-associated protein R/EB family, member 1 (EB1) while the latter one showed also expression differences by immunohistochemistry. Fresh frozen tissue of UCC ( n = 10) matched with SCC ( n = 10) was investigated. Proteins of cancerous intestinal mucosal cells were obtained by Laser Capture Microdissection (LCM) and compared by 2-D DIGE. Significant spots were identified by mass spectrometry. After IPA, three proteins [EB1, HSPB1, and Annexin 5 (ANXA5)] were chosen for further validation by Western blotting and tissue microarray-based immunohistochemistry. This study identified significant differences in protein expression of colorectal carcinoma cells from UCC patients compared to patients with SCC. Particularly, EB1 was validated in an independent clinical cohort.

Evidence-based Practices Addressed in Community-based Children’s Mental Health Clinical Supervision

PubMed Central

Accurso, Erin C.; Taylor, Robin M.; Garland, Ann F.

2013-01-01

Context Clinical supervision is the principal method of training for psychotherapeutic practice, however there is virtually no research on supervision practice in community settings. Of particular interest is the role supervision might play in facilitating implementation of evidence-based (EB) care in routine care settings. Objective This study examines the format and functions of clinical supervision sessions in routine care, as well as the extent to which supervision addresses psychotherapeutic practice elements common to EB care for children with disruptive behavior problems, who represent the majority of patients served in publicly-funded routine care settings. Methods Supervisors (n=7) and supervisees (n=12) from four publicly-funded community-based child mental health clinics reported on 130 supervision sessions. Results Supervision sessions were primarily individual in-person meetings lasting one hour. The most common functions included case conceptualization and therapy interventions. Coverage of practice elements common to EB treatments was brief. Discussion Despite the fact that most children presenting to public mental health services are referred for disruptive behavior problems, supervision sessions are infrequently focused on practice elements consistent with EB treatments for this population. Supervision is a promising avenue through which training in EB practices could be supported to improve the quality of care for children in community-based “usual care” clinics. PMID:24761163

Characterization of the Microstructures and the Cryogenic Mechanical Properties of Electron Beam Welded Inconel 718

NASA Astrophysics Data System (ADS)

Kwon, Soon Il; Bae, Sang Hyun; Do, Jeong Hyeon; Jo, Chang Yong; Hong, Hyun Uk

2016-02-01

The microstructures and the cryogenic mechanical properties of electron beam (EB) welds between cast and forged Inconel 718 superalloys with a thickness of 10 mm were investigated in comparison with gas tungsten arc (GTA) welds. EB welding with a heat input lower than 250 J/mm caused the formation of liquation microfissuring in the cast-side heat-affected-zone (HAZ) of the EB welds. HAZ liquation microfissuring appeared to be associated with the constitutional liquation of primary NbC carbides at the grain boundaries. Compared with the GTA welding process, the EB welding produced welds with superior microstructure, exhibiting fine dendritic structure associated with the reduction in size and fraction of the Laves phase due to the rapid cooling rate. This result was responsible for the superior mechanical properties of the EB welds at 77 K (-196 °C). Laves particles in both welds were found to provide the preferential site for the crack initiation and propagation, leading to a significant decrease in the Charpy impact toughness at 77 K (-196 °C). Crack initiation and propagation induced by Charpy impact testing were discussed in terms of the dendrite arm spacing, the Laves size and the dislocation structure ahead of the crack arisen from the fractured Laves phase in the two welds.

Implementation of a multi-professional standardized care plan in electronic health records for the care of stroke patients.

PubMed

Pöder, Ulrika; Fogelberg-Dahm, Marie; Wadensten, Barbro

2011-09-01

To compare staff opinions about standardized care plans and self-reported habits with regard to documentation, and their perceived knowledge about the evidence-based guidelines in stroke care before and after implementation of an evidence-based-standardized care plan (EB-SCP) and quality standard for stroke care. The aim was also to describe staff opinions about, and their use of, the implemented EB-SCP. To facilitate evidence-based practice (EBP), a multi-professional EB-SCP and quality standard for stroke care was implemented in the electronic health record (EHR). Quantitative, descriptive and comparative, based on questionnaires completed before and after implementation. Perceived knowledge about evidence-based guidelines in stroke care increased after implementation of the EB-SCP. The majority agreed that the EB-SCP is useful and facilitates their work. There was no change between before and after implementation with regard to opinions about standardized care plans, self-reported documentation habits or time spent on documentation. An evidence-based SCP seems to be useful in patient care and improves perceived knowledge about evidence-based guidelines in stroke care. For nursing managers, introduction of evidence-based SCP in the EHR may improve the prerequisites for promoting high-quality EBP in multi-professional care. 2011 Blackwell Publishing Ltd.

High dietary calcium intake does not counteract disuse-induced bone loss

NASA Astrophysics Data System (ADS)

Baecker, N.; Boese, A.; Smith, S. M.; Heer, M.

Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation, increases osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization and space flight are common causes of disuse osteoporosis. There are sufficient data supporting the use of calcium in combination with vitamin D in the prevention and treatment of postmenopausal osteoporosis. In our study we examined the potential of high dietary calcium intake as a nutrition therapy for disuse-induced bone loss during head-down bed rest in healthy young men. In 2 identical metabolic ward, head-down bed rest (HDBR) experiments (crossover design), we studied the effect of high dietary calcium intake (2000 mg/d) in comparison to the recommended calcium intake of 1000 mg/d on markers of bone turnover. Experiment A (EA) was a 6-day randomized, controlled HDBR study. Experiment B (EB) was a 14-day randomized, controlled HDBR study. In both experiments, the test subjects stayed under well-controlled environmental conditions in our metabolic ward. Subjects' diets in the relevant study phases (HDBR versus Ambulatory Control) of EA and EB were identical except for the calcium intake. The subjects obtained 2000 mg/d Calcium in EA and 2000 mg/d in EB. Blood was drawn at baseline, before entering the relevant intervention period, on day 5 in study EA, and on days 6, 11 and 14 in study EB. Serum calcium, bone formation markers - Procollagen-I-C-Propeptide (PICP) and bone alkaline phosphatase (bAP) were analyzed in serum. 24h-urine was collected throughout the studies for determination of the excretion of calcium (UCaV) and a bone resorption marker, C-terminal telopeptide of collagen type I (UCTX). In both studies, serum calcium levels were unchanged. PICP tended to decrease in EA (p=0.08). In EB PICP decreased significantly over time (p=0.003) in both the control and HDBR periods, and tended to further decrease in the HDBR period (p=0.06). While HDBR did not affect bAP in both EA and EB, bAP decreased significantly over time in both groups of EB (p<0.001). UCaV significantly increased during HDBR in EA (p=0.002) and EB (p=0.004) compared to the ambulatory controls. UCTX significantly increased on the second day of HDBR by 18% (p<0.001) in EA and by 27% (p=0.03) in EB. We conclude from these results that doubling dietary calcium intake from the recommended level of 1000 mg/d to 2000 mg/d does not prevent the decrease in bone formation activity and the increase of bone resorption activity in disuse-induced bone loss.

Time course for the modulation of hepatic cytochrome P450 after administration of ethylbenzene and its correlation with toluene metabolism.

PubMed

Yuan, W; Sequeira, D J; Cawley, G F; Eyer, C S; Backes, W L

1997-03-01

The goal of the present study was to examine the time course for changes in P450 expression and hydrocarbon metabolism after acute treatment with the simple aromatic hydrocarbon ethylbenzene (EB) and to correlate these alterations with the changes observed in alkylbenzene metabolism. Male Holtzman rats were treated with a single intraperitoneal injection of EB, and the effects on specific P450-dependent activities, immunoreactive P450 isozyme levels, and RNA levels were measured at various times after injection. Toluene was used as the test alkylbenzene for examination of the EB-mediated changes on in vitro hydrocarbon metabolism. In untreated rats, toluene was metabolized almost entirely by aliphatic hydroxylation (to benzyl alcohol); however, in EB-treated rats, significant quantities of benzyl alcohol, o-cresol, and p-cresol were produced. Interestingly, 5-10 h after EB treatment, there was a 40% decrease in benzyl alcohol production. By 24 h, rates of benzyl alcohol formation returned to control levels, whereas there was a 7-fold increase in o-cresol and a greater that 50-fold increase in p-cresol production. The changes in the disposition of toluene were then correlated with changes in particular P450 isozymes. Several P450 isozymes were induced after EB administration. P450 2B1/2-dependent testosterone 16 beta-hydroxylation and P450 2B1/2-immunoreactive protein were elevated 30-fold after EB administration, reaching maxima by 24 h and remaining elevated 48 h after exposure. Changes in P450 2B1 and 2B2 RNA preceded those of the proteins. Similar results were observed with P450 1A1. P450 2E1 RNA levels were elevated after a single EB injection. However, the elevation in P450 2E1-dependent activities and immunoreactive protein levels preceded the changes in RNA, suggesting that multiple steps are affected by EB exposure. In contrast to the increases in some isozymes, P450 2C11 protein was rapidly suppressed (within the first 2-10 h) after hydrocarbon exposure, suggestive of a destabilization of the protein. When comparing the changes in P450 isozymes to alterations in toluene metabolism, the immediate suppression in aliphatic hydroxylation of toluene (in the first 5-10 h) was consistent with the decrease in P450 2C11. Subsequent to this effect, P450 2B1/2 and 2E1 were induced, which elevated production of this metabolite to control levels. The increase in the aromatic hydroxylation of toluene to both o, and p-cresol was consistent with the induction of P450s 2B1/2, 2E1, and 1A1.

47 CFR 27.1237 - Pro rata allocation of transition costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

....1237 Section 27.1237 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband... commercial EBS licensees in the BTA where the center point of the EBS licensee's GSA is located. In addition...

47 CFR 27.1200 - Change to BRS and EBS.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1200 Change to BRS and EBS... Multichannel Multipoint Distribution Service (MMDS) shall be reassigned to the Broadband Radio Service (BRS...

47 CFR 27.1200 - Change to BRS and EBS.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1200 Change to BRS and EBS... Multichannel Multipoint Distribution Service (MMDS) shall be reassigned to the Broadband Radio Service (BRS...

47 CFR 27.1200 - Change to BRS and EBS.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1200 Change to BRS and EBS... Multichannel Multipoint Distribution Service (MMDS) shall be reassigned to the Broadband Radio Service (BRS...

47 CFR 27.1216 - Grandfathered E and F group EBS licenses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Grandfathered E and F group EBS licenses. 27.1216 Section 27.1216 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband...

47 CFR 27.1216 - Grandfathered E and F group EBS licenses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Grandfathered E and F group EBS licenses. 27.1216 Section 27.1216 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband...

47 CFR 27.1200 - Change to BRS and EBS.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1200 Change to BRS and EBS... Multichannel Multipoint Distribution Service (MMDS) shall be reassigned to the Broadband Radio Service (BRS...

47 CFR 27.1200 - Change to BRS and EBS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1200 Change to BRS and EBS... Multichannel Multipoint Distribution Service (MMDS) shall be reassigned to the Broadband Radio Service (BRS...

New Pleiades Eclipsing Binaries and a Hyades Transiting System Identified by K2

NASA Astrophysics Data System (ADS)

David, Trevor J.; Conroy, Kyle E.; Hillenbrand, Lynne A.; Stassun, Keivan G.; Stauffer, John; Rebull, Luisa M.; Cody, Ann Marie; Isaacson, Howard; Howard, Andrew W.; Aigrain, Suzanne

2016-05-01

We present the discovery in Kepler’s K2 mission observations and our follow-up radial velocity (RV) observations from Keck/HIRES for four eclipsing binary (EB) star systems in the young benchmark Pleiades and Hyades clusters. Based on our modeling results, we announce two new low mass ({M}{tot}\\lt 0.6 {M}⊙ ) EBs among Pleiades members (HCG 76 and MHO 9) and we report on two previously known Pleiades binaries that are also found to be EB systems (HII 2407 and HD 23642). We measured the masses of the binary HCG 76 to ≲2.5% precision, and the radii to ≲4.5% precision, which together with the precise effective temperatures yield an independent Pleiades distance of 132 ± 5 pc. We discuss another EB toward the Pleiades that is a possible but unlikely Pleiades cluster member (AK II 465). The two new confirmed Pleiades systems extend the mass range of Pleiades EB components to 0.2-2 {M}⊙ . Our initial measurements of the fundamental stellar parameters for the Pleiades EBs are discussed in the context of the current stellar models and the nominal cluster isochrone, finding good agreement with the stellar models of Baraffe et al. at the nominal Pleiades age of 120 Myr. Finally, in the Hyades, we report a new low mass eclipsing system (vA 50) that was concurrently discovered and studied by Mann et al. We confirm that the eclipse is likely caused by a Neptune-sized transiting planet, and with the additional RV constraints presented here we improve the constraint on the maximum mass of the planet to be ≲1.2 MJup.

Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women.

PubMed

Farshchi, Hamid R; Taylor, Moira A; Macdonald, Ian A

2005-02-01

Breakfast consumption is recommended, despite inconclusive evidence of health benefits. The study's aim was to ascertain whether eating breakfast (EB) or omitting breakfast (OB) affects energy intake, energy expenditure, and circulating insulin, glucose, and lipid concentrations in healthy women. In a randomized crossover trial, 10 women [x+/-SD body mass index (BMI; in kg/m2): 23.2+/-1.4] underwent two 14-d EB or OB interventions separated by a 2-wk interval. In the EB period, subjects consumed breakfast cereal with 2%-fat milk before 0800 and a chocolate-covered cookie between 1030 and 1100. In the OB period, subjects consumed the cookie between 1030 and 1100 and the cereal and milk between 1200 and 1330. Subjects then consumed 4 additional meals with content similar to usual at predetermined times later in the day and recorded food intake on 3 d during each period. Fasting and posttest meal glucose, lipid, and insulin concentrations and resting energy expenditure were measured before and after each period. Reported energy intake was significantly lower in the EB period (P=0.001), and resting energy expenditure did not differ significantly between the 2 periods. OB was associated with significantly higher fasting total and LDL cholesterol than was EB (3.14 and 3.43 mmol/L and 1.55 and 1.82 mmol/L, respectively; P=0.001). The area under the curve of insulin response to the test meal was significantly lower after EB than after OB (P<0.01). OB impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained.

[Association between food behavior and hypercholesterolemia-LDL in university students].

PubMed

Salazar Ruiz, Erika Nohemi; Márquez Sandoval, Yolanda Fabiola; Vizmanos Lamotte, Bárbara; Altamirano Martínez, Martha Betzaida; Salgado Bernabé, Aralia Berenice; Salgado Goytia, Lorenzo; Muñoz Valle, José Francisco; Parra Rojas, Isela

2015-06-01

Hypercholesterolemia-LDL (H-LDL) is associated with increased risk of cardiovascular disease. The association between H-LDL and feeding has focused on nutritional aspects. The study of the association between eating behavior (EB) and H-LDL in university students, could provide nutritional elements for correction and/or prevention in this population. To assess the association between EB and H-LDL in university students. A cross-sectional study was carried out in a sample of 167 students from the Autonomous University of Guerrero, Mexico. LDL cholesterol in serum was measured and a concentration ≥100 mg/dL was considered hypercholesterolemia. The EB was assessed using a previously validated questionnaire. The association between EB and H-LDL was determined with a bivariate logistic regression, adjusting for sex, age, socioeconomic status, smoking, energy intake, physical activity, presence or absence of obesity and family history. Eating lunch (morning snack) was related with 63% lower risk of H-LDL (OR 0.37; 95% CI 0.15, 0.90). Take food away from home once or twice a week was associated with a fourfold increased risk of H-LDL (R 5.14; 95% CI 1.12, 23.62). Subjects who reported consuming excess food (1 or 2, and 3 or more times/week) had higher risk of H-LDL (OR 3.26; 95% CI 1.10, 9.64 and OR 10.52; 95% CI 2.66, 41.60 respectively). Some usual EB of the university students (Guerrero, Mexico) involve greater risk of H-LDL. To encourage actions corrective and/or preventive focused on these EB, could improve the health of this population. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Full Bayesian evaluation of the safety effects of reducing the posted speed limit in urban residential area.

PubMed

Islam, Md Tazul; El-Basyouny, Karim

2015-07-01

Full Bayesian (FB) before-after evaluation is a newer approach than the empirical Bayesian (EB) evaluation in traffic safety research. While a number of earlier studies have conducted univariate and multivariate FB before-after safety evaluations and compared the results with the EB method, often contradictory conclusions have been drawn. To this end, the objectives of the current study were to (i) perform a before-after safety evaluation using both the univariate and multivariate FB methods in order to enhance our understanding of these methodologies, (ii) perform the EB evaluation and compare the results with those of the FB methods and (iii) apply the FB and EB methods to evaluate the safety effects of reducing the urban residential posted speed limit (PSL) for policy recommendation. In addition to three years of crash data for both the before and after periods, traffic volume, road geometry and other relevant data for both the treated and reference sites were collected and used. According to the model goodness-of-fit criteria, the current study found that the multivariate FB model for crash severities outperformed the univariate FB models. Moreover, in terms of statistical significance of the safety effects, the EB and FB methods led to opposite conclusions when the safety effects were relatively small with high standard deviation. Therefore, caution should be taken in drawing conclusions from the EB method. Based on the FB method, the PSL reduction was found effective in reducing crashes of all severities and thus is recommended for improving safety on urban residential collector roads. Copyright © 2015 Elsevier Ltd. All rights reserved.

IR and NMR spectroscopic correlation of enterobactin by DFT

NASA Astrophysics Data System (ADS)

Moreno, M.; Zacarias, A.; Porzel, A.; Velasquez, L.; Gonzalez, G.; Alegría-Arcos, M.; Gonzalez-Nilo, F.; Gross, E. K. U.

2018-06-01

Emerging and re-emerging epidemic diseases pose an ongoing threat to global health. Currently, Enterobactin and Enterobactin derivatives have gained interest, owing to their potential application in the pharmaceutical field. As it is known [J. Am. Chem. Soc (1979) 101, 20, 6097-6104], Enterobactin (H6EB) is an efficient iron carrier synthesized and secreted by many microbial species. In order to facilitate the elucidation of enterobactin and its analogues, here we propose the creation of a H6EB standard set using Density Functional Theory Infrared (IR) and NMR spectra. We used two exchange-correlation (xc) functionals (PBE including long-range corrections sbnd LC-PBEsbnd and mPW1), 2 basis sets (QZVP and 6-31G(d)) and 2 grids (fine and ultrafine) for most of the H6EB structures dependent of dihedral angles. The results show a significant difference between the Osbnd H and Nsbnd H bands, while the Cdbnd O amide and Osbnd (Cdbnd O)sbnd IR bands are often found on top of each other. The NMR DFT calculations show a strong dependence on the xc functional, basis set, and grid used for the H6EB structure. Calculated 1H and 13C NMR spectra enable the effect of the solvent to be understood in the context of the experimental measurements. The good agreement between the experimental and the calculated spectra using LC-PBE/QZVP and ultrafine grid suggest the possibility of the systems reported here to be considered as a standard set. The dependence of electrostatic potential and frontier orbitals with the catecholamide dihedral angles of H6EB is described. The matrix-assisted laser desorption/ionization time of the flight mass spectrometry (MALDI-TOF MS) of H6EB is also reported of manner to enrich the knowledge about its reactivity.

The endocannabinoid system expression in the female reproductive tract is modulated by estrogen.

PubMed

Maia, J; Almada, M; Silva, A; Correia-da-Silva, G; Teixeira, N; Sá, S I; Fonseca, B M

2017-11-01

The endocannabinoid system (ECS) is involved in several physiological events that resulted in a growing interest in its modulation. Moreover, the uterine levels of anandamide (AEA), the major endocannabinoid, must be tightly regulated to create proper embryo implantation conditions. However, there are no evidences about the regulation of AEA in uterus by estrogen. Thus, the aim of this study is to elucidate whether estradiol benzoate (EB) and tamoxifen (TAM) administration to ovariectomized (OVX) rats can induce changes in the expression of cannabinoid receptors and AEA-metabolic enzymes in uterus by evaluating gene transcription and protein levels by qPCR, Western blot and immunohistochemistry. Moreover, the plasmatic and uterine levels of AEA and of prostaglandin E 2 (PGE 2 ) and prostaglandin F 2 α (PGF 2α ), the major cyclooxygenase-2 (COX-2) products, were determined by UPLC-MS/MS. The immunohistochemistry showed that cannabinoid receptors, as well as AEA-metabolic enzymes are mainly located in the epithelial cells of both lumen and glands and, to a lesser extent, in the muscle cells. Moreover, EB administration to OVX rats significantly increased CB1, CB2, NAPE-PLD, FAAH and COX-2 expression and transcription. These effects were absent in TAM and TAM+EB treatments showing that this response is estrogen receptor dependent. Additionally, although uterine levels of AEA remained unchanged in EB or TAM treated animals, they showed a rise with EB treatment in plasma. The latter also produced a decrease in uterine PGE 2 levels. In summary, these data collectively indicate that the expression of ECS components, as well as, the AEA and PGE 2 levels in rat uterus is modulated by EB. Thus, estradiol may have a direct regulatory role in the modulation of ECS in female reproductive tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

OGLE II Eclipsing Binaries In The LMC: Analysis With Class

NASA Astrophysics Data System (ADS)

Devinney, Edward J.; Prsa, A.; Guinan, E. F.; DeGeorge, M.

2011-01-01

The Eclipsing Binaries (EBs) via Artificial Intelligence (EBAI) Project is applying machine learning techniques to elucidate the nature of EBs. Previously, Prsa, et al. applied artificial neural networks (ANNs) trained on physically-realistic Wilson-Devinney models to solve the light curves of the 1882 detached EBs in the LMC discovered by the OGLE II Project (Wyrzykowski, et al.) fully automatically, bypassing the need for manually-derived starting solutions. A curious result is the non-monotonic distribution of the temperature ratio parameter T2/T1, featuring a subsidiary peak noted previously by Mazeh, et al. in an independent analysis using the EBOP EB solution code (Tamuz, et al.). To explore this and to gain a fuller understanding of the multivariate EBAI LMC observational plus solutions data, we have employed automatic clustering and advanced visualization (CAV) techniques. Clustering the OGLE II data aggregates objects that are similar with respect to many parameter dimensions. Measures of similarity for example, could include the multidimensional Euclidean Distance between data objects, although other measures may be appropriate. Applying clustering, we find good evidence that the T2/T1 subsidiary peak is due to evolved binaries, in support of Mazeh et al.'s speculation. Further, clustering suggests that the LMC detached EBs occupying the main sequence region belong to two distinct classes. Also identified as a separate cluster in the multivariate data are stars having a Period-I band relation. Derekas et al. had previously found a Period-K band relation for LMC EBs discovered by the MACHO Project (Alcock, et al.). We suggest such CAV techniques will prove increasingly useful for understanding the large, multivariate datasets increasingly being produced in astronomy. We are grateful for the support of this research from NSF/RUI Grant AST-05-75042 f.

An Evaluation of Treatments for Pruritus in Epidermolysis Bullosa

PubMed Central

Danial, Christina; Adeduntan, Rasidat; Gorell, Emily S.; Lucky, Anne W.; Paller, Amy S.; Bruckner, Anna L.; Pope, Elena; Morel, Kimberly D.; Levy, Moise L.; Li, Shufeng; Gilmore, Elaine S.; Lane, Alfred T

2016-01-01

Background Pruritus is a common complication in patients with epidermolysis bullosa (EB) and can be problematic. Objective data about the treatments used by EB patients for pruritus have not been reported and recommendations are limited. Objective To quantitatively determine which treatments have been used by EB patients for pruritus and to evaluate the perceived effectiveness of these treatments in pruritus relief. Methods A questionnaire was developed to evaluate which treatments and therapies have been used for pruritus in patients of all ages and types of EB. Questions about bathing products, moisturizers, topical products, oral medications, dressings, and alternative therapies were included. A 5-point Likert scale (-2=relieves itch a lot, -1=relieves itch a little, 0=no change, 1=increases itch a little, 2=increases itch a lot) was used to evaluate the perceived effectiveness of different treatments on pruritus relief. Patients from seven North American EB centers were invited to participate. Results Greasy ointments (53.4%), lotions (45.2%), creams (40.4%), and oral hydroxyzine (39.0%) were the most frequently used treatments for pruritus. Treatments that were used frequently and perceived to be the most effective included creams (mean=-1.1), topical prescription corticosteroids (mean=-1.0), oils (mean=-0.9), oral hydroxyzine (mean=-0.9), topical diphenhydramine (mean=-0.9), and vaporizing rub (menthol/camphor/eucalyptus) (mean=-0.9). Patients that used creams (p=0.05) or lotions (p=0.04) more often experienced significantly less pruritus. Systemic opioids (mean=0.3), adherent bandages (mean=0.3), and bleach baths (mean=0.2) slightly increased pruritus. Conclusions Randomized-controlled trials of therapies will be necessary to develop evidence-based recommendations for control of pruritus in EB patients. PMID:25557557

Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine.

PubMed

Guven, Sinan; Lindsey, Jennifer S; Poudel, Ishwari; Chinthala, Sireesha; Nickerson, Michael D; Gerami-Naini, Behzad; Gurkan, Umut A; Anchan, Raymond M; Demirci, Utkan

2015-03-01

Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin β-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine. ©AlphaMed Press.

Use of technology to facilitate physical activity in children with autism spectrum disorders: A pilot study.

PubMed

Bittner, Melissa D; Rigby, B Rhett; Silliman-French, Lisa; Nichols, David L; Dillon, Suzanna R

2017-08-01

Deficits in social behavior and communication skills are correlated with reduced gross motor skills in children with autism spectrum disorders (ASD). The ExerciseBuddy application (EB app) was designed to communicate these motor skills to those with ASD and integrates evidence-based practices such as visual support and video modeling supported by The National Professional Development Center on Autism Spectrum Disorders. The purpose of this study was to determine the effectiveness of the EB app in facilitating increased physiologic responses to physical activity via a continuous measurement of energy expenditure and heart rate versus practice-style teaching methods in children with ASD. Six children, ages 5 to 10years, diagnosed with ASD were recruited. Each participant performed a variety of locomotor or object control skills as defined by the Test of Gross Motor Development-2 once per week for 4weeks. Motor skills were communicated and demonstrated using either practice-style teaching methods or the instructional section of the EB app. Energy expenditure and heart rate were measured continuously during each 12-minute session. A Wilcoxon signed-rank test was performed to assess any differences between the use of the app and practice-style teaching methods. The use of the EB app elicited greater values for peak energy expenditure (p=0.043) and peak heart rate response (p=0.028) while performing locomotor skills but no differences were observed while performing object control skills. Similarities were observed with average physiologic responses between the use of the EB app and practice-style teaching methods. The use of the EB app may allow for a greater peak physiologic response during more dynamic movements and a similar average cardiovascular and metabolic response when compared to practice-style teaching methods in children with ASD. Published by Elsevier Inc.

A comparison of entropy balance and probability weighting methods to generalize observational cohorts to a population: a simulation and empirical example.

PubMed

Harvey, Raymond A; Hayden, Jennifer D; Kamble, Pravin S; Bouchard, Jonathan R; Huang, Joanna C

2017-04-01

We compared methods to control bias and confounding in observational studies including inverse probability weighting (IPW) and stabilized IPW (sIPW). These methods often require iteration and post-calibration to achieve covariate balance. In comparison, entropy balance (EB) optimizes covariate balance a priori by calibrating weights using the target's moments as constraints. We measured covariate balance empirically and by simulation by using absolute standardized mean difference (ASMD), absolute bias (AB), and root mean square error (RMSE), investigating two scenarios: the size of the observed (exposed) cohort exceeds the target (unexposed) cohort and vice versa. The empirical application weighted a commercial health plan cohort to a nationally representative National Health and Nutrition Examination Survey target on the same covariates and compared average total health care cost estimates across methods. Entropy balance alone achieved balance (ASMD ≤ 0.10) on all covariates in simulation and empirically. In simulation scenario I, EB achieved the lowest AB and RMSE (13.64, 31.19) compared with IPW (263.05, 263.99) and sIPW (319.91, 320.71). In scenario II, EB outperformed IPW and sIPW with smaller AB and RMSE. In scenarios I and II, EB achieved the lowest mean estimate difference from the simulated population outcome ($490.05, $487.62) compared with IPW and sIPW, respectively. Empirically, only EB differed from the unweighted mean cost indicating IPW, and sIPW weighting was ineffective. Entropy balance demonstrated the bias-variance tradeoff achieving higher estimate accuracy, yet lower estimate precision, compared with IPW methods. EB weighting required no post-processing and effectively mitigated observed bias and confounding. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Genetic diagnosis of epidermolysis bullosa: recommendations from an expert Spanish research group.

PubMed

Sánchez-Jimeno, C; Escámez, M J; Ayuso, C; Trujillo-Tiebas, M J; Del Río, M

2018-03-01

Epidermolysis bullosa (EB) is a rare genetic disease that causes mucocutaneous fragility. It comprises a clinically and genetically heterogeneous group of disorder characterized by spontaneous or contact/friction-induced blistering. EB is classified into 4 types-simplex, junctional, dystrophic, and Kindler syndrome-and 30 subtypes. The disease is caused by defects in proteins implicated in dermal-epidermal adhesion. At least 19 genes have been characterized and more than 1000 mutations identified, thus rendering diagnosis complex. Molecular diagnosis of EB is the last stage of a laborious process that starts with a detailed clinical history compilation and careful procurement of a skin fresh biopsy that includes an area where the epidermis detaches from the dermis. The detachment area makes it possible to establish the cleavage plane by antigen mapping and, in the best scenario, to identify a single candidate gene to search for pathogenic mutations. The results of the molecular diagnosis enable the physician to provide appropriate genetic counseling (inheritance pattern, risk of recurrence, and options for prenatal and preimplantation diagnosis) and implement subsequent preventive programs, as well as to establish a reasonable clinical prognosis facilitating access to specific therapy and rehabilitation. Lastly, molecular diagnosis is essential for the participation of patients in clinical trials, a critical issue given the current incurable status of EB. The present guidelines aim to disseminate the procedure for diagnosing EB in our laboratory and thus avoid suboptimal or incomplete clinical diagnoses. The recommendations we provide are the result of more than 10 years' experience in the molecular diagnosis of EB in Spain. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

The adoption of physical activity and eating behaviors among persons with obesity and in the general population: the role of implicit attitudes within the Theory of Planned Behavior.

PubMed

Chevance, Guillaume; Caudroit, Johan; Romain, Ahmed J; Boiché, Julie

2017-03-01

Obesity can be prevented by the combined adoption of a regular physical activity (PA) and healthy eating behaviors (EB). Researchers mainly focused on socio-cognitive models, such as the Theory of Planned Behavior (TPB), to identify the psychological antecedents of these behaviors. However, few studies were interested in testing the potential contribution of automatic processes in the prediction of PA and EB. Thus, the main objective of this study was to explore the specific role of implicit attitudes in the pattern of prediction of self-reported PA and EB in the TPB framework, among persons with obesity and in adults from the general population. One hundred and fifty-three adults participated to this cross-sectional study among which 59 obese persons (74% women, age: 50.6 ± 12.3 years, BMI: 36.8 ± 4.03 kg m - ²) and 94 people from the general population (51% women; age: 34.7 ± 8.9 years). Implicit attitudes toward PA and EB were estimated through two Implicit Association Tests. TPB variables, PA and EB were assessed by questionnaire. Regarding to the prediction of PA, a significant contribution of implicit attitudes emerged in obese people, β = .25; 95%[CI: .01, .50]; P = .044, beyond the TPB variables, contrary to participants from the general population. The present study suggests that implicit attitudes play a specific role among persons with obesity regarding PA. Other studies are needed to examine which kind of psychological processes are specifically associated with PA and EB among obese people.

Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia.

PubMed

Krysl, D; Deykun, K; Lambert, L; Pokorny, J; Mares, J

2012-04-01

We assessed blood-brain barrier (BBB) disruption in early stage of photothrombotic focal cerebral ischemia in the rat. We specifically looked for contralateral changes in BBB permeability and tested the influence of two anesthetics on the results. Adult Wistar rats were randomly anesthetized with pentobarbital (PB) or ketamine-xylazine (KX). Rats received intravenously (i.v.) Rose Bengal followed by Evans Blue (EB). Stereotactically defined spots on denuded skull were irradiated by laser (532 nm) for 18 min. Twenty four hours later, rats were killed, brains perfused, fixated, sectioned and slices analyzed by fluorescence microscopy. Volume of necrosis and volume of EB-albumin extravasation were calculated. Evidence of BBB breakdown in remote brain areas was sought and compared to sham handled controls. BBB disruption was consistently present, frequently with EB-albumin accumulating cells. Total lesion volume did not significantly differ among groups (TLVPB=9.4±1.3 mm³ vs. TLVKX=8.3±2.1 mm³); same was true for the volume of necrosis (NVPB=5.1±0.7 mm³ vs. NVKX=6.3±1.9 mm³). However, volume of EB-albumin extravasation area was significantly smaller in KX group (EBEVPB=4.3±0.8 mm³ vs. EBEVKX=2.0±0.5 mm³; p=0.0293). Median background EB-fluorescence signal density was higher in PB group (p<0.0001). Furthermore, regional increase in EB-fluorescence was found in two animals in PB group. Our study shows that anesthesia with NMDA-antagonist ketamine and α2-adrenergic agonist xylazine may reduce BBB breakdown in photothrombosis. Pentobarbital anesthesia lead to increased BBB permeability in the contralateral hemisphere.

17β-estradiol rapidly facilitates lordosis through G protein-coupled estrogen receptor 1 (GPER) via deactivation of medial preoptic nucleus μ-opioid receptors in estradiol primed female rats.

PubMed

Long, Nathan; Serey, Chhorvann; Sinchak, Kevin

2014-09-01

In female rats sexual receptivity (lordosis) can be induced with either a single large dose of estradiol benzoate (EB), or a priming dose of EB that does not induce sexual receptivity followed by 17β-estradiol (E2). Estradiol priming initially inhibits lordosis through a multi-synaptic circuit originating in the arcuate nucleus of the hypothalamus (ARH) that activates and internalizes μ-opioid receptors (MOR) in medial preoptic nucleus (MPN) neurons. Lordosis is facilitated when MPN MOR are deactivated after the initial estradiol-induced activation. We tested the hypothesis that E2 given 47.5 h post EB acts rapidly through G protein-coupled estrogen receptor 1 (GPER) in the ARH to deactivate MPN MOR and facilitate lordosis. Ovariectomized Long Evans rats implanted with a third ventricle cannula were primed with 2 μg EB. DMSO control, E2, or G1 (GPER selective agonist) was infused 47.5 h later, and rats were tested for sexual receptivity. E2 and G1 infusions significantly increased levels of sexual receptivity compared to DMSO controls and pretreatment with G15 (GPER antagonist) blocked the facilitation of sexual receptivity. Brains were processed for MPN MOR immunohistochemistry to measure MPN MOR activation levels. E2 and G1 both significantly reduced MPN MOR activation compared to DMSO controls, while pretreatment with G15 blocked MPN MOR deactivation. In another group of EB treated ovariectomized rats, GPER immunofluorescence positive staining was observed throughout the ARH. Together these data indicate that in the 2 μg EB primed rat, E2 rapidly signals through GPER in the ARH to deactivate MPN MOR and facilitate lordosis. Published by Elsevier Inc.

Pharmacovigilance of herbal medicines: the potential contributions of ethnobotanical and ethnopharmacological studies.

PubMed

Rodrigues, Eliana; Barnes, Joanne

2013-01-01

Typically, ethnobotanical/ethnopharmacological (EB/EP) surveys are used to describe uses, doses/dosages, sources and methods of preparation of traditional herbal medicines; their application to date in examining the adverse effects, contraindications and other safety aspects of these preparations is limited. From a pharmacovigilance perspective, numerous challenges exist in applying its existing methods to studying the safety profile of herbal medicines, particularly where used by indigenous cultures. This paper aims to contribute to the methodological aspects of EB/EP field work, and to extend the reach of pharmacovigilance, by proposing a tool comprising a list of questions that could be applied during interview and observational studies. The questions focus on the collection of information on the safety profile of traditional herbal medicines as it is embedded in traditional knowledge, as well as on identifying personal experiences (spontaneous reports) of adverse or undesirable effects associated with the use of traditional herbal medicines. Questions on the precise composition of traditional prescriptions or 'recipes', their preparation, storage, administration and dosing are also included. Strengths and limitations of the tool are discussed. From this interweaving of EB/EP and pharmacovigilance arises a concept of ethnopharmacovigilance for traditional herbal medicines: the scope of EB/EP is extended to include exploration of the potential harmful effects of medicinal plants, and the incorporation of pharmacovigilance questions into EB/EP studies provides a new opportunity for collection of 'general' traditional knowledge on the safety of traditional herbal medicines and, importantly, a conduit for collection of spontaneous reports of suspected adverse effects. Whether the proposed tool can yield data sufficiently rich and of an appropriate quality for application of EB/EP (e.g. data verification and quantitative analysis tools) and pharmacovigilance techniques (e.g. causality assessment and data mining) requires field testing.

Monetary Incentive Effects on Event-Based Prospective Memory Three Months after Traumatic Brain Injury in Children

PubMed Central

Pedroza, Claudia; Chapman, Sandra B.; Cook, Lori G.; Vásquez, Ana C.; Levin, Harvey S.

2011-01-01

Information regarding the remediation of event-based prospective memory (EB-PM) impairments following pediatric traumatic brain injury (TBI) is scarce. Addressing this, two levels of monetary incentives were used to improve EB-PM in children ages 7 to 16 years with orthopedic injuries (OI, n = 51), or moderate (n = 25), and severe (n = 39) TBI at approximately three months postinjury. The EB-PM task consisted of the child giving a specific verbal response to a verbal cue from the examiner while performing a battery of neuropsychological measures (ongoing task). Significant effects were found for Age-at-Test, Motivation Condition, Period, and Group. Within-group analyses indicated OI and moderate TBI groups performed significantly better under the high-versus low-incentive condition, but the severe TBI group demonstrated no significant improvement. These results indicate EB-PM can be significantly improved at three months postinjury in children with moderate, but not severe, TBI. PMID:21347945

Adsorption studies of methylene blue and gentian violet on sugarcane bagasse modified with EDTA dianhydride (EDTAD) in aqueous solutions: kinetic and equilibrium aspects.

PubMed

Gusmão, Karla Aparecida Guimarães; Gurgel, Leandro Vinícius Alves; Melo, Tânia Márcia Sacramento; Gil, Laurent Frédéric

2013-03-30

In this study the adsorption of cationic dyes by modified sugarcane bagasse with EDTA dianhydride (EB) was examined using methylene blue (MB) and gentian violet (GV) as model compounds in aqueous single solutions. The synthesized adsorbent (EB) was characterized by FTIR, elemental analysis, and BET. The capacity of EB to adsorb dyes was evaluated at different contact times, pH values, and initial dye concentrations. According to the obtained results, the adsorption processes could be described by a pseudo-second-order kinetic model. The adsorption isotherms were well fitted by the Langmuir model. Maximum adsorption capacities for MB and GV on EB were found to be 202.43 and 327.83 mg/g, respectively. The free energy change during adsorption of MB and GV was found to be -22.50 and -24.21 kJ/mol, respectively, suggesting that chemisorption is the main mechanism controlling the adsorption process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Short-Term Effects of the Anti-sea Lice Therapeutant Emamectin Benzoate on Clam Worms (Nereis virens).

PubMed

McBriarty, G J; Kidd, K A; Burridge, L E

2018-05-01

The polychaete Nereis virens occurs commonly in marine sediments, is widely distributed, and is a popular bait species, as well as a potential replacement for wild-caught fish in commercial fish feed preparations. It is being considered as a potential co-extractive species for culture in integrated multi-trophic aquaculture operations. However, it is not known whether pesticides or drugs used to treat sea lice on farmed salmon, such as emamectin benzoate (EB), would adversely affect cultured or wild worms, because these compounds may persist in the environment. To determine the potential effects of EB to N. virens, bioassays were performed wherein worms were exposed in sand for 30 days to a concentration of 400 µg/kg dw (nominal). While no treatment-related mortality occurred, significant decreases in worm mass and marked behavioral changes (lack of burrowing) were observed in EB-treated sand compared with controls. These lab-based observations suggest a potential hazard to worms at sites where EB treatments have occurred.

Observation of giant exchange bias in bulk Mn{sub 50}Ni{sub 42}Sn{sub 8} Heusler alloy

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

Sharma, Jyoti; Suresh, K. G., E-mail: suresh@iitb.ac.in

2015-02-16

We report a giant exchange bias (EB) field of 3520 Oe in bulk Mn{sub 50}Ni{sub 42}Sn{sub 8} Heusler alloy. The low temperature magnetic state of the martensite phase has been studied by DC magnetization and AC susceptibility measurements. Frequency dependence of spin freezing temperature (T{sub f}) on critical slowing down relation and observation of memory effect in zero field cooling mode confirms the super spin glass (SSG) phase at low temperatures. Large EB is attributed to the strong exchange coupling between the SSG clusters formed by small regions of ferromagnetic order embedded in an antiferromagnetic (AFM) matrix. The temperature and coolingmore » field dependence of EB have been studied and related to the change in unidirectional anisotropy at SSG/AFM interface. The training effect also corroborates with the presence of frozen (SSG) moments at the interface and their role in EB.« less

Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis: A comparison with ebselen.

PubMed

Petronilho, Fabricia; Michels, Monique; Danielski, Lucinéia G; Goldim, Mariana Pereira; Florentino, Drielly; Vieira, Andriele; Mendonça, Mariana G; Tournier, Moema; Piacentini, Bárbara; Giustina, Amanda Della; Leffa, Daniela D; Pereira, Gregório W; Pereira, Volnei D; Rocha, João Batista Teixeira Da

2016-09-01

The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations. Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model. The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB. Copyright © 2016 Elsevier GmbH. All rights reserved.

An Improved Quantum-Behaved Particle Swarm Optimization Algorithm with Elitist Breeding for Unconstrained Optimization.

PubMed

Yang, Zhen-Lun; Wu, Angus; Min, Hua-Qing

2015-01-01

An improved quantum-behaved particle swarm optimization with elitist breeding (EB-QPSO) for unconstrained optimization is presented and empirically studied in this paper. In EB-QPSO, the novel elitist breeding strategy acts on the elitists of the swarm to escape from the likely local optima and guide the swarm to perform more efficient search. During the iterative optimization process of EB-QPSO, when criteria met, the personal best of each particle and the global best of the swarm are used to generate new diverse individuals through the transposon operators. The new generated individuals with better fitness are selected to be the new personal best particles and global best particle to guide the swarm for further solution exploration. A comprehensive simulation study is conducted on a set of twelve benchmark functions. Compared with five state-of-the-art quantum-behaved particle swarm optimization algorithms, the proposed EB-QPSO performs more competitively in all of the benchmark functions in terms of better global search capability and faster convergence rate.

Estimation of resist sensitivity for extreme ultraviolet lithography using an electron beam

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

Oyama, Tomoko Gowa, E-mail: ohyama.tomoko@qst.go.jp; Oshima, Akihiro; Tagawa, Seiichi, E-mail: tagawa@sanken.osaka-u.ac.jp

2016-08-15

It is a challenge to obtain sufficient extreme ultraviolet (EUV) exposure time for fundamental research on developing a new class of high sensitivity resists for extreme ultraviolet lithography (EUVL) because there are few EUV exposure tools that are very expensive. In this paper, we introduce an easy method for predicting EUV resist sensitivity by using conventional electron beam (EB) sources. If the chemical reactions induced by two ionizing sources (EB and EUV) are the same, the required absorbed energies corresponding to each required exposure dose (sensitivity) for the EB and EUV would be almost equivalent. Based on this theory, wemore » calculated the resist sensitivities for the EUV/soft X-ray region. The estimated sensitivities were found to be comparable to the experimentally obtained sensitivities. It was concluded that EB is a very useful exposure tool that accelerates the development of new resists and sensitivity enhancement processes for 13.5 nm EUVL and 6.x nm beyond-EUVL (BEUVL).« less

[Role played by the adrenal cortex on the luteotrophic action of estrogens during the rat estrus cycle].

PubMed

Hassani, M

1978-01-01

Estrogen-induced changes in peripheral blood progesterone concentration have been studied in dexamethasone (DEX) and metopyrone (MET) treated 4-day cyclic female rats. Estradiol benzoate (EB) was injected at 10--11 h on diestrus I and peripheral blood was collected at 16--17 h on diestrus II for progesterone radioimmunoassay. The EB induced-increase in blood progesterone concentration was more pronounced, compared to non-injected females in intact DEX-treated females and in adrenalectomized females treated or not with DEX than in their intact counterparts. The adrenal cortex was then supposed to inhibit the luteotrophic action of EB. When injected for 10--12 days, MET caused an increase in blood progesterone concentration compared to uninjected control animals. No cumulative effects of EB and MET were observed. These results are discussed in the light of knowledge, on the feed-back mechanisms which are involved in the action of estrogen on the pituitary-ovarian-adrenocortical system.

Physicochemical and flavor characteristics of flavoring agent from mungbean protein hydrolyzed by bromelain.

PubMed

Sonklin, Chanikan; Laohakunjit, Natta; Kerdchoechuen, Orapin

2011-08-10

Enzymatic bromelain mungbean meal protein hydrolysate (eb-MPH) was produced from mungbean meal protein isolate (MPI). Enzymatic bromelain, with a known protease activity of 98,652 (unit/g), was used at concentrations of 0, 2, 6, 10, 14 and 18% (w/w) and with hydrolysis times of 0.5, 3, 6, 12, and 24 h. The pH and temperature were controlled at 6.0 and 50 °C, respectively. It was found that the best treatment combination for eb-MPH production by response surface methodology (RSM) was 18% bromelain and a hydrolysis time of 3 h, resulting in the greatest degree of hydrolysis (% DH) and percent yield, with values of 61.04 and 45.63%, respectively. Results also showed that the phenylalanine, tyrosine and leucine contents of the optimally produced eb-MPH were 20.88, 14.50 and 10.93%, respectively. Twelve volatile compounds were identified using gas chromatography mass spectrometry in eb-MPH; benzaldehyde, 2-pentylfuran and furfural were the predominant odorants.