Effect of Nucleos(t)ide Analogue Therapy on Risk of Intrahepatic Cholangiocarcinoma in Patients With Chronic Hepatitis B.

PubMed

Lee, Teng-Yu; Hsu, Yao-Chun; Yu, Shi-Hang; Lin, Jaw-Town; Wu, Ming-Shiang; Wu, Chun-Ying

2018-06-01

Chronic infection with hepatitis B virus (HBV) increases risk of intrahepatic cholangiocarcinoma (ICC), but it is not clear whether antiviral therapy reduces risk. We investigated the association between nucleos(t)ide analogue therapy and ICC risk. We performed a nationwide long-term cohort study using Taiwan's National Health Insurance Research Database to obtain data on 185,843 patients with chronic HBV infection from October 1, 2003 through December 31, 2012. We excluded patients with confounding disorders such as infection with hepatitis C virus, HIV, or other hepatitis-associated viruses; liver flukes; biliary stone diseases; cholangitis; congenital biliary anomalies; biliary tract surgeries; or cancer. We identified 10,062 patients who received nucleos(t)ide analogue therapy (the treated group), and used propensity scores to match them (1:1) with patients who received hepatoprotectants (the untreated group). Cumulative incidences of and hazard ratios (HRs) for ICC development were analyzed. The cumulative incidence of ICC was significantly lower in the treated group after 3 years of therapy (1.28%; 95% CI, 0.56-2.01) than in the untreated group (3.14%; 95% CI, 2.02-4.27) and after 5 years of therapy (1.53%; 95% CI, 0.73-2.33 vs 4.32% in untreated group; 95% CI, 2.96-5.6869). In multivariable regression analysis, nucleos(t)ide analogue therapy was independently associated with a reduced risk of ICC (HR, 0.44; 95% CI, 0.25-0.78; P = .005). Older age (HR 1.05 per year; 95% CI, 1.03-1.07) and cirrhosis (HR, 2.80; 95% CI, 1.52-5.1415) were independently associated with an increased risk of ICC. Sensitivity analyses verified the association between nucleos(t)ide analogue therapy and a reduced ICC risk. A nationwide long-term cohort study in Taiwan showed that nucleos(t)ide analogue therapy for chronic HBV infection is significantly associated with a reduced ICC risk. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Multiple allosteric sites are involved in the modulation of insulin-degrading-enzyme activity by somatostatin.

PubMed

Tundo, Grazia R; Di Muzio, Elena; Ciaccio, Chiara; Sbardella, Diego; Di Pierro, Donato; Polticelli, Fabio; Coletta, Massimo; Marini, Stefano

2016-10-01

Somatostatin is a cyclic peptide, released in the gastrointestinal system and the central nervous system, where it is involved in the regulation of cognitive and sensory functions, motor activity and sleep. It is a substrate of insulin-degrading enzyme (IDE), as well as a modulator of its activity and expression. In the present study, we have investigated the modulatory role of somatostatin on IDE activity at 37 °C and pH 7.3 for various substrates [i.e. insulin, β-amyloid (Aβ) 1-40 and bradykinin], aiming to quantitatively characterize the correlation between the specific features of the substrates and the regulatory mechanism. Functional data indicate that somatostatin, in addition to the catalytic site of IDE (being a substrate), is also able to bind to two additional exosites, which play different roles according to the size of the substrate and its binding mode to the IDE catalytic cleft. In particular, one exosite, which displays high affinity for somatostatin, regulates only the interaction of IDE with larger substrates (such as insulin and Aβ 1-40 ) in a differing fashion according to their various modes of binding to the enzyme. A second exosite, which is involved in the regulation of enzymatic processing by IDE of all substrates investigated (including a 10-25 amino acid long amyloid-like peptide, bradykinin and somatostatin itself, which had been studied previously), probably acts through the alteration of an 'open-closed' equilibrium. © 2016 Federation of European Biochemical Societies.

Characterization of Piezoresistive PEDOT:PSS Pressure Sensors with Inter-Digitated and Cross-Point Electrode Structures

PubMed Central

Wang, Jer-Chyi; Karmakar, Rajat Subhra; Lu, Yu-Jen; Huang, Chiung-Yin; Wei, Kuo-Chen

2015-01-01

The piezoresistive characteristics of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) pressure sensors with inter-digitated (IDE) and cross-point electrode (CPE) structures have been investigated. A small variation of the resistance of the pressure sensors with IDE without bottom indium-tin-oxide (b-ITO) film and with CPE structures was observed owing to the single carrier-conducting pathway. For the IDE pressure sensors with b-ITO, the piezoresistive characteristics at low and high pressure were similar to those of the pressure sensors with IDE without b-ITO and with CPE structures, respectively, leading to increased piezoresistive pressure sensitivity as the PEDOT:PSS film thickness decreased. A maximum sensitivity of more than 42 kΩ/Pa was achieved. When the normal pressure was applied, the increased number of conducting points or the reduced distance between the PEDOT oligomers within the PEDOT:PSS film resulted in a decrease of the resistance. The piezoresistive pressure sensors with a single carrier-conducting pathway, i.e., IDE without b-ITO and CPE structures, exhibited a small relaxation time and a superior reversible operation, which can be advantageous for fast piezoresistive response applications. PMID:25569756

Characterization of piezoresistive PEDOT:PSS pressure sensors with inter-digitated and cross-point electrode structures.

PubMed

Wang, Jer-Chyi; Karmakar, Rajat Subhra; Lu, Yu-Jen; Huang, Chiung-Yin; Wei, Kuo-Chen

2015-01-05

The piezoresistive characteristics of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) pressure sensors with inter-digitated (IDE) and cross-point electrode (CPE) structures have been investigated. A small variation of the resistance of the pressure sensors with IDE without bottom indium-tin-oxide (b-ITO) film and with CPE structures was observed owing to the single carrier-conducting pathway. For the IDE pressure sensors with b-ITO, the piezoresistive characteristics at low and high pressure were similar to those of the pressure sensors with IDE without b-ITO and with CPE structures, respectively, leading to increased piezoresistive pressure sensitivity as the PEDOT:PSS film thickness decreased. A maximum sensitivity of more than 42 kΩ/Pa was achieved. When the normal pressure was applied, the increased number of conducting points or the reduced distance between the PEDOT oligomers within the PEDOT:PSS film resulted in a decrease of the resistance. The piezoresistive pressure sensors with a single carrier-conducting pathway, i.e., IDE without b-ITO and CPE structures, exhibited a small relaxation time and a superior reversible operation, which can be advantageous for fast piezoresistive response applications.

Nigella sativa Oil and Chromium Picolinate Ameliorate Fructose-Induced Hyperinsulinemia by Enhancing Insulin Signaling and Suppressing Insulin-Degrading Enzyme in Male Rats.

PubMed

Elseweidy, Mohamed Mahmoud; Amin, Rawia Sarhan; Atteia, Hebatallah Husseini; Aly, Maha Abdo

2017-10-04

In vivo and in vitro studies suggested that chromium enhances insulin sensitivity by promoting insulin receptor signaling. However, its effect on insulin clearance has not been yet identified. Nigella sativa, a widely used spice, possesses an antidiabetic activity. We, therefore, hypothesized that chromium picolinate may alter insulin clearance by modulating insulin-degrading enzyme (IDE) in insulin-resistant rats. We evaluated also the effect of Nigella sativa oil on insulin signaling and degradation with respect to chromium picolinate. To assess these hypotheses, insulin resistance was induced in 30 male Wistar albino rats through daily oral administration of high-fructose water (HFW, 20% w/v) for 45 days. These rats were then divided into three groups (n = 10/group). They were given either no treatment (control group) or Nigella sativa oil (500 mg/kg bw/day) or chromium picoloinate (200 μg/kg bw/day) orally along with HFW (20% w/v) for 45 days. Nigella sativa oil or chromium picolinate concurrent administration with HFW significantly decreased body weight, serum lipids, glucagon, insulin resistance, and hepatic IDE level but increased its mRNA expression and insulin receptor phosphorlyation as well as high-density lipoprotein cholesterol (HDL-C) level as compared to control group values, suggesting their potential as modulators for insulin signaling and clearance. However, Nigella sativa oil exerted better improvement in feeding efficacy ratio as well as the levels of glucagon, insulin, insulin resistance, hepatic IDE level and insulin receptor phosphorylation than chromium picolinate, suggesting its greater insulin sensitizing capacity. Our data, for the first time, prove that Nigella sativa oil and chromium picolinate monotherapy can reduce fructose-induced insulin resistance by reduction of hepatic IDE protein and activation of insulin receptor signaling.

Fabrication and energy harvesting characteristics of unimorph piezoelectric cantilever generators with interdigitated electrode lead zirconate titanate laminates

NASA Astrophysics Data System (ADS)

Lee, Min-seon; Yun, Ji-sun; Park, Woon-ik; Hong, Youn-woo; Cho, Jeong-ho; Paik, Jong-hoo; Park, Yong Ho; Son, Chun-myung; Jeong, Young Hun

2017-12-01

Interdigitated electrode (IDE) unimorph piezoelectric cantilever generators (UPCGs) were fabricated and their energy harvesting characteristics were investigated. A hard lead zirconate titanate (PZT) material with a high mechanical quality factor (Q m) of 1280 was used for the active piezoelectric film of the IDE UPCGs. Two different laminated IDE UPCGs were prepared; one has Ag/Pd interdigitated electrode (IDE) formed only on the top and bottom PZT sheets (D-IDE), while the other has Ag/Pd IDE on all of the PZT sheets (M-IDE). Cofiring was conducted at 1050 °C for 2 h for PZT laminates with IDEs. The fabricated IDE UPCGs exhibited power densities of 50.4 µW/cm3 for the D-IDE and 820 µW/cm3 for the M-IDE. The UPCG with the M-IDE exhibited a higher performance than that with the D-IDE. Specifically, a significantly enhanced normalized power factor of 670 µW/(g2·cm3) was found at 118 Hz across 100 kΩ.

Abeta-degrading enzymes in Alzheimer's disease.

PubMed

Miners, James Scott; Baig, Shabnam; Palmer, Jennifer; Palmer, Laura E; Kehoe, Patrick G; Love, Seth

2008-04-01

In Alzheimer's disease (AD) Abeta accumulates because of imbalance between the production of Abeta and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Abeta is partly, if not in some cases solely, because of defects in its removal--mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Abeta. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Abeta-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Abetain vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEepsilon4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to Abeta plaque load. Up-regulation of some Abeta-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Abeta-clearance pathways, reductions in the activity of particular Abeta-degrading enzymes may become critical, leading to the development of AD and CAA.

Customizing the management of chronic hepatitis B virus infection.

PubMed

Gish, Robert G; Perrillo, Robert P; Jacobson, Ira M

2007-08-01

As of October 2006, 6 medications are approved in the United States for the management of chronic hepatitis B virus (HBV) infection: 2 formulations of interferon and 4 oral nucleos(t)ide analogues. For the treating practitioner, tailoring the pharmaceutical regimen according to patient features and clinical circumstances can be a challenge. First-line therapeutic regimens for the management of HBV infection include monotherapy with a U.S. Food and Drug Administration-approved agent that has potent on-treatment viral response and low rates of resistance; in the future, these regimens may include a combination of more than one nucleos(t)ide analogue or a combination of a nucleos(t)ide analogue and pegylated interferon. The oral nucleos(t)ide analogues are generally better tolerated than interferon; however, they can be expensive when administered for lengthy periods and can also lead to medication resistance. Lamivudine, the first approved nucleoside analogue for the treatment of HBV infection, has a very high resistance profile; in fact, lamivudine exposure increases viral resistance to other commercially available nucleos(t)ide analogues: entecavir, telbivudine, and adefovir. For these reasons, the 2007 American Association for the Study of Liver Diseases (AASLD) guidelines no longer recommend lamivudine as first-line therapy for the management of HBV infection. A satellite symposium conducted during the 57th Annual Meeting of the AASLD in Boston, Massachusetts, presented approaches to customizing the management of chronic HBV infection. The presentation highlighted recent findings suggesting that early, profound, and sustained viral suppression improves the probability of sustained virologic response and reduces the likelihood of nucleos(t)ide resistance.

Identification and Characterization of IgdE, a Novel IgG-degrading Protease of Streptococcus suis with Unique Specificity for Porcine IgG*

PubMed Central

Spoerry, Christian; Seele, Jana; Valentin-Weigand, Peter; Baums, Christoph G.; von Pawel-Rammingen, Ulrich

2016-01-01

Streptococcus suis is a major endemic pathogen of pigs causing meningitis, arthritis, and other diseases. Zoonotic S. suis infections are emerging in humans causing similar pathologies as well as severe conditions such as toxic shock-like syndrome. Recently, we discovered an IdeS family protease of S. suis that exclusively cleaves porcine IgM and represents the first virulence factor described, linking S. suis to pigs as their natural host. Here we report the identification and characterization of a novel, unrelated protease of S. suis that exclusively targets porcine IgG. This enzyme, designated IgdE for immunoglobulin G-degrading enzyme of S. suis, is a cysteine protease distinct from previous characterized streptococcal immunoglobulin degrading proteases of the IdeS family and mediates efficient cleavage of the hinge region of porcine IgG with a high degree of specificity. The findings that all S. suis strains investigated possess the IgG proteolytic activity and that piglet serum samples contain specific antibodies against IgdE strongly indicate that the protease is expressed in vivo during infection and represents a novel and putative important bacterial virulence/colonization determinant, and a thus potential therapeutic target. PMID:26861873

Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications.

PubMed

Jha, Niraj Kumar; Jha, Saurabh Kumar; Kumar, Dhiraj; Kejriwal, Noopur; Sharma, Renu; Ambasta, Rashmi K; Kumar, Pravir

2015-01-01

Alzheimer's disease (AD) is a neurodegenerative process primarily characterized by amyloid-β (Aβ) agglomeration, neuroinflammation, and cognitive dysfunction. The prominent cause for dementia is the deposition of Aβ plaques and tau-neurofibrillary tangles that hamper the neuronal organization and function. Aβ pathology further affects numerous signaling cascades that disturb the neuronal homeostasis. For instance, Aβ deposition is responsible for altered expression of insulin encoding genes that lead to insulin resistance, and thereby affecting insulin signaling pathway and glucose metabolism in the brain. As a result, the common pathology of insulin resistance between Type-2 diabetes mellitus and AD has led AD to be proposed as a form of diabetes and termed 'Type-3 diabetes'. Since accumulation of Aβ is the prominent cause of neuronal toxicity in AD, its clearance is the prime requisite for therapeutic prospects. This purpose is expertly fulfilled by the potential role of Aβ degrading enzymes such as insulin degrading enzyme (IDE) and Neprilysin (NEP). Therefore, their molecular study is important to uncover the proteolytic and regulatory mechanism of Aβ degradation. Herein, (i) In silico sequential and structural analysis of IDE and NEP has been performed to identify the molecular entities for proteolytic degradation of Aβ in the AD brain, (ii) to analyze their catalytic site to demonstrate the enzymatic action played by IDE and NEP, (iii) to identify their structural homologues that could behave as putative partners of IDE and NEP with similar catalytic action and (iv) to illustrate various IDE- and NEP-mediated therapeutic approaches and factors for clearing Aβ in AD.

Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors

PubMed Central

Kiss, Joseph E.; Steele, Whitney R.; Wright, David J.; Mast, Alan E.; Carey, Patricia M.; Murphy, Edward L.; Gottschall, Jerry L.; Simon, Toby L.; Cable, Ritchard G.

2014-01-01

BACKGROUND Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. STUDY DESIGN AND METHODS A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/ RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 µ.g/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. RESULTS HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 u.g/L was a good surrogate for assessing IDE. CONCLUSION RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency. PMID:23617531

Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors.

PubMed

Kiss, Joseph E; Steele, Whitney R; Wright, David J; Mast, Alan E; Carey, Patricia M; Murphy, Edward L; Gottschall, Jerry L; Simon, Toby L; Cable, Ritchard G

2013-11-01

Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 μg/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 μg/L was a good surrogate for assessing IDE. RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency. © 2013 American Association of Blood Banks.

Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer disease.

PubMed

Ertekin-Taner, Nilüfer; Allen, Mariet; Fadale, Daniel; Scanlin, Leah; Younkin, Linda; Petersen, Ronald C; Graff-Radford, Neill; Younkin, Steven G

2004-04-01

Risk for late onset Alzheimer disease (LOAD) and plasma amyloid beta levels (Abeta42; encoded by APP), an intermediate phenotype for LOAD, show linkage to chromosome 10q. Several strong candidate genes (VR22, PLAU, IDE) lie within the 1-lod support interval for linkage. Others have independently identified haplotypes in the chromosome 10q region harboring IDE that show highly significant association with intermediate AD phenotypes and with risk for AD. To pursue these associations, we analyzed the same haplotypes for association with plasma Abeta42 in 24 extended LOAD families and for association with LOAD in two independent case-control series. One series (MCR, 188 age-matched case-control pairs) did not show association (p=0.64) with the six haplotypes in the 276-kb region spanning three genes (IDE, KNSL1, and HHEX) previously shown to associate with LOAD. The other series (MCJ, 109 age-matched case-control pairs) showed significant (p=0.003) association with these haplotypes. In the MCJ series, the H4 (odds ratio [OR]=5.1, p=0.003) and H2(H7) haplotypes (OR=0.60, p=0.04) had the same effects previously reported. In this series, the H8 haplotype (OR=2.7, p=0.098) also had an effect similar as in one previous case control series but not in others. In the extended families, the H8 haplotype was associated with significantly elevated plasma Abeta42 (p=0.02). In addition, the H5(H10) haplotype, which is associated with reduced risk for AD in the other study is associated with reduced plasma Abeta42 (p=0.007) in our family series. These results provide strong evidence for pathogenic variant(s) in the 276-kb region harboring IDE that influence intermediate AD phenotypes and risk for AD. Copyright 2004 Wiley-Liss, Inc.

Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.

PubMed

Tang, Wei-Jen

2016-01-01

Insulin-degrading enzyme (IDE) selectively degrades peptides, such as insulin, amylin, and amyloid β (Aβ) that form toxic aggregates, to maintain proteostasis. IDE defects are linked to the development of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Structural and biochemical analyses revealed the molecular basis for IDE-mediated destruction of amyloidogenic peptides and this information has been exploited to develop promising inhibitors of IDE to improve glucose homeostasis. However, the inhibition of IDE can also lead to glucose intolerance. In this review, I focus on recent advances regarding our understanding of the structure and function of IDE and the discovery of IDE inhibitors, as well as challenges in developing IDE-based therapy for human diseases, particularly T2DM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conformational states and recognition of amyloidogenic peptides of human insulin-degrading enzyme.

PubMed

McCord, Lauren A; Liang, Wenguang G; Dowdell, Evan; Kalas, Vasilios; Hoey, Robert J; Koide, Akiko; Koide, Shohei; Tang, Wei-Jen

2013-08-20

Insulin-degrading enzyme (IDE) selectively degrades the monomer of amyloidogenic peptides and contributes to clearance of amyloid β (Aβ). Thus, IDE retards the progression of Alzheimer's disease. IDE possesses an enclosed catalytic chamber that engulfs and degrades its peptide substrates; however, the molecular mechanism of IDE function, including substrate access to the chamber and recognition, remains elusive. Here, we captured a unique IDE conformation by using a synthetic antibody fragment as a crystallization chaperone. An unexpected displacement of a door subdomain creates an ~18-Å opening to the chamber. This swinging-door mechanism permits the entry of short peptides into the catalytic chamber and disrupts the catalytic site within IDE door subdomain. Given the propensity of amyloidogenic peptides to convert into β-strands for their polymerization into amyloid fibrils, they also use such β-strands to stabilize the disrupted catalytic site resided at IDE door subdomain for their degradation by IDE. Thus, action of the swinging door allows IDE to recognize amyloidogenicity by substrate-induced stabilization of the IDE catalytic cleft. Small angle X-ray scattering (SAXS) analysis revealed that IDE exists as a mixture of closed and open states. These open states, which are distinct from the swinging door state, permit entry of larger substrates (e.g., Aβ, insulin) to the chamber and are preferred in solution. Mutational studies confirmed the critical roles of the door subdomain and hinge loop joining the N- and C-terminal halves of IDE for catalysis. Together, our data provide insights into the conformational changes of IDE that govern the selective destruction of amyloidogenic peptides.

Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in vitro evaluation.

PubMed

Montenegro, Lucia; Sinico, Chiara; Castangia, Ines; Carbone, Claudia; Puglisi, Giovanni

2012-09-15

Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant activity that could be beneficial in the treatment of skin oxidative damages. In this work, the feasibility of targeting IDE into the upper layers of the skin by topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated. SLN loading different amounts of IDE were prepared by the phase inversion temperature method using cetyl palmitate as solid lipid and three different non-ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN showed a mean particle size in the range of 30-49 nm and a single peak in size distribution. In vitro permeation/penetration experiments were performed on pig skin using Franz-type diffusion cells. IDE penetration into the different skin layers depended on the type of SLN used while no IDE permeation occurred from all the SLN under investigation. The highest IDE content was found in the epidermis when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution into the upper skin layers depended on the amount of IDE loaded when oleth-20 was used as surfactant. These results suggest that the SLN tested could be an interesting carrier for IDE targeting to the upper skin layers. Copyright © 2012 Elsevier B.V. All rights reserved.

Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice

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

Deprez-Poulain, Rebecca; Hennuyer, Nathalie; Bosc, Damien

Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer’s disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisinglymore » impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.« less

Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme

PubMed Central

Bailey, Lucas J; Tan, Yong Zi; Wei, Hui; Wang, Andrew; Farcasanu, Mara; Woods, Virgil A; McCord, Lauren A; Lee, David; Shang, Weifeng; Deprez-Poulain, Rebecca; Deprez, Benoit; Liu, David R; Koide, Akiko; Koide, Shohei; Kossiakoff, Anthony A

2018-01-01

Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies. PMID:29596046

Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG.

PubMed

Wenig, Katja; Chatwell, Lorenz; von Pawel-Rammingen, Ulrich; Björck, Lars; Huber, Robert; Sondermann, Peter

2004-12-14

Pathogenic bacteria have developed complex and diverse virulence mechanisms that weaken or disable the host immune defense system. IdeS (IgG-degrading enzyme of Streptococcus pyogenes) is a secreted cysteine endopeptidase from the human pathogen S. pyogenes with an extraordinarily high degree of substrate specificity, catalyzing a single proteolytic cleavage at the lower hinge of human IgG. This proteolytic degradation promotes inhibition of opsonophagocytosis and interferes with the killing of group A Streptococcus. We have determined the crystal structure of the catalytically inactive mutant IdeS-C94S by x-ray crystallography at 1.9-A resolution. Despite negligible sequence homology to known proteinases, the core of the structure resembles the canonical papain fold although with major insertions and a distinct substrate-binding site. Therefore IdeS belongs to a unique family within the CA clan of cysteine proteinases. Based on analogy with inhibitor complexes of papain-like proteinases, we propose a model for substrate binding by IdeS.

Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice

DOE PAGES

Deprez-Poulain, Rebecca; Hennuyer, Nathalie; Bosc, Damien; ...

2015-09-23

Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer’s disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisinglymore » impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.« less

Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study.

PubMed

Cable, Ritchard G; Glynn, Simone A; Kiss, Joseph E; Mast, Alan E; Steele, Whitney R; Murphy, Edward L; Wright, David J; Sacher, Ronald A; Gottschall, Jerry L; Tobler, Leslie H; Simon, Toby L

2012-04-01

Blood donors are at risk of iron deficiency. We evaluated the effects of blood donation intensity on iron and hemoglobin (Hb) in a prospective study. Four cohorts of frequent and first-time or reactivated (FT/RA) blood donors (no donation in 2 years), female and male, totaling 2425, were characterized and followed as they donated blood frequently. At enrollment and the final visit, ferritin, soluble transferrin receptor (sTfR), and Hb were determined. Models to predict iron deficiency and Hb deferral were developed. Iron depletion was defined at two levels: iron deficiency erythropoiesis (IDE) [log(sTfR/ferritin) ≥ 2.07] and absent iron stores (AIS; ferritin < 12 ng/mL). Among returning female FT and RA donors, 20 and 51% had AIS and IDE at their final visit, respectively; corresponding proportions for males were 8 and 20%. Among female frequent donors who returned, 27 and 62% had AIS and IDE, respectively, while corresponding proportions for males were 18 and 47%. Predictors of IDE and/or AIS included a higher frequency of blood donation in the past 2 years, a shorter interdonation interval, and being female and young; conversely, taking iron supplements reduced the risk of iron depletion. Predictors of Hb deferral included female sex, black race, and a shorter interdonation interval. There is a high prevalence of iron depletion in frequent blood donors. Increasing the interdonation interval would reduce the prevalence of iron depletion and Hb deferral. Alternatively, replacement with iron supplements may allow frequent donation without the adverse outcome of iron depletion. © 2011 American Association of Blood Banks.

Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus.

PubMed

Hamilton, Kelly A; Wang, Yue; Raefsky, Sophia M; Berkowitz, Sean; Spangler, Ryan; Suire, Caitlin N; Camandola, Simonetta; Lipsky, Robert H; Mattson, Mark P

2018-01-01

Bhlhe40 is a transcription factor that is highly expressed in the hippocampus; however, its role in neuronal function is not well understood. Here, we used Bhlhe40 null mice on a congenic C57Bl6/J background (Bhlhe40 KO) to investigate the impact of Bhlhe40 on neuronal excitability and synaptic plasticity in the hippocampus. Bhlhe40 KO CA1 neurons had increased miniature excitatory post-synaptic current amplitude and decreased inhibitory post-synaptic current amplitude, indicating CA1 neuronal hyperexcitability. Increased CA1 neuronal excitability was not associated with increased seizure severity as Bhlhe40 KO relative to +/+ (WT) control mice injected with the convulsant kainic acid. However, significant reductions in long term potentiation and long term depression at CA1 synapses were observed in Bhlhe40 KO mice, indicating impaired hippocampal synaptic plasticity. Behavioral testing for spatial learning and memory on the Morris Water Maze (MWM) revealed that while Bhlhe40 KO mice performed similarly to WT controls initially, when the hidden platform was moved to the opposite quadrant Bhlhe40 KO mice showed impairments in relearning, consistent with decreased hippocampal synaptic plasticity. To investigate possible mechanisms for increased neuronal excitability and decreased synaptic plasticity, a whole genome mRNA expression profile of Bhlhe40 KO hippocampus was performed followed by a chromatin immunoprecipitation sequencing (ChIP-Seq) screen of the validated candidate genes for Bhlhe40 protein-DNA interactions consistent with transcriptional regulation. Of the validated genes identified from mRNA expression analysis, insulin degrading enzyme (Ide) had the most significantly altered expression in hippocampus and was significantly downregulated on the RNA and protein levels; although Bhlhe40 did not occupy the Ide gene by ChIP-Seq. Together, these findings support a role for Bhlhe40 in regulating neuronal excitability and synaptic plasticity in the hippocampus and that indirect regulation of Ide transcription may be involved in these phenotypes.

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

Manolopoulou, Marika; Guo, Qing; Malito, Enrico

Insulin is a hormone vital for glucose homeostasis, and insulin-degrading enzyme (IDE) plays a key role in its clearance. IDE exhibits a remarkable specificity to degrade insulin without breaking the disulfide bonds that hold the insulin A and B chains together. Using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to obtain high mass accuracy, and electron capture dissociation (ECD) to selectively break the disulfide bonds in gas phase fragmentation, we determined the cleavage sites and composition of human insulin fragments generated by human IDE. Our time-dependent analysis of IDE-digested insulin fragments reveals that IDE is highly processive in itsmore » initial cleavage at the middle of both the insulin A and B chains. This ensures that IDE effectively splits insulin into inactive N- and C-terminal halves without breaking the disulfide bonds. To understand the molecular basis of the recognition and unfolding of insulin by IDE, we determined a 2.6-A resolution insulin-bound IDE structure. Our structure reveals that IDE forms an enclosed catalytic chamber that completely engulfs and intimately interacts with a partially unfolded insulin molecule. This structure also highlights how the unique size, shape, charge distribution, and exosite of the IDE catalytic chamber contribute to its high affinity ( approximately 100 nm) for insulin. In addition, this structure shows how IDE utilizes the interaction of its exosite with the N terminus of the insulin A chain as well as other properties of the catalytic chamber to guide the unfolding of insulin and allowing for the processive cleavages.« less

Electrical immunosensor based on a submicron-gap interdigitated electrode and gold enhancement.

PubMed

Ahn, Junhyoung; Lee, Tae Han; Li, Taihua; Heo, Kwang; Hong, Seunghun; Ko, Jeongheon; Kim, Yongsam; Shin, Yong-Beom; Kim, Min-Gon

2011-08-15

We demonstrated that the detection of human interleukin 5 (IL5) with a higher sensitivity than the enzyme-linked immunosorbent assay (ELISA) was possible using mass-producible submicron-gap interdigitated electrodes (IDEs) combined with signal amplification by a gold nanoparticle (AuNP) and gold enhancement. IDEs, facing comb-shape electrodes, can act as simple and miniaturized devices for immunoassay. An IDE with a gap size of 400nm was fabricated by a stepper photolithography process and was applied for the immunoassay of human IL5. A biotinylated anti-human IL5 was immobilized on the streptavidin-modified IDE, and biotin-bovine serum albumin (BSA) and BSA were added sequentially to reduce non-specific binding between the streptavidin-immobilized IDE surface and other proteins. The immunoassay procedure included three main steps: the reaction of human IL5 to form antigen-antibody complexes, the binding of AuNP conjugation with an antibody against human IL5 for the sandwich immunoassay, and gold enhancement for electrical signal amplification. The measurement of electrical current at each step showed that the gold enhancement step was very critical in detection of the concentration of human IL5. Analysis by scanning electron microscope (SEM) showed that close to 1μm particles were formed from 10nm AuNP by the gold enhancement reaction using gold ions and hydroxylamine. Under optimized conditions, human IL5 could be analyzed at 1pgmL(-1) with a wide dynamic range (from 10(-3) to 100ngmL(-1) concentrations). Copyright © 2011 Elsevier B.V. All rights reserved.

Generating and Purifying Fab Fragments from Human and Mouse IgG Using the Bacterial Enzymes IdeS, SpeB and Kgp.

PubMed

Sjögren, Jonathan; Andersson, Linda; Mejàre, Malin; Olsson, Fredrik

2017-01-01

Fab fragments are valuable research tools in various areas of science including applications in imaging, binding studies, removal of Fc-mediated effector functions, mass spectrometry, infection biology, and many others. The enzymatic tools for the generation of Fab fragments have been discovered through basic research within the field of molecular bacterial pathogenesis. Today, these enzymes are widely applied as research tools and in this chapter, we describe methodologies based on bacterial enzymes to generate Fab fragments from both human and mouse IgG. For all human IgG subclasses, the IdeS enzyme from Streptococcus pyogenes has been applied to generate F(ab')2 fragments that subsequently can be reduced under mild conditions to generate a homogenous pool of Fab' fragments. The enzyme Kgp from Porphyromonas gingivalis has been applied to generate intact Fab fragments from human IgG1 and the Fab fragments can be purified using a CH1-specific affinity resin. The SpeB protease, also from S. pyogenes, is able to digest mouse IgGs and has been applied to digest antibodies and Fab fragments can be purified on light chain affinity resins. In this chapter, we describe methodologies that can be used to obtain Fab fragments from human and mouse IgG using bacterial proteases.

Alternating current electric fields of varying frequencies: effects on proliferation and differentiation of porcine neural progenitor cells.

PubMed

Lim, Ji-Hey; McCullen, Seth D; Piedrahita, Jorge A; Loboa, Elizabeth G; Olby, Natasha J

2013-10-01

Application of sinusoidal electric fields (EFs) has been observed to affect cellular processes, including alignment, proliferation, and differentiation. In the present study, we applied low-frequency alternating current (AC) EFs to porcine neural progenitor cells (pNPCs) and investigated the effects on cell patterning, proliferation, and differentiation. pNPCs were grown directly on interdigitated electrodes (IDEs) localizing the EFs to a region accessible visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1 V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control cultures. Immunocytochemistry was performed to evaluate the expression of neural markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no change in cell numbers when compared with controls. Nestin expression was shown in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was significantly higher in the cultures exposed to 10- and 50-Hz EFs than the controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and proliferation of pNPCs, but higher frequency stimulation appeared to delay differentiation into mature astrocytes.

Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated With Clinical Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy.

PubMed

Chi, Heng; Li, Zhandong; Hansen, Bettina E; Yu, Tao; Zhang, Xiaoyong; Sun, Jian; Hou, Jinlin; Janssen, Harry L A; Peng, Jie

2018-06-11

Levels of antibodies against the hepatitis B virus (HBV) core protein (anti-HBc) have been associated with response to nucleos(t)ide analogue and (peg)interferon therapy in patients with chronic HBV infection. We performed a prospective study to determine whether the total serum level of anti-HBc level (immunoglobulins M and G) is associated with clinical relapse after discontinuation of nucleos(t)ide analogue-based therapy. We collected data from patients with chronic HBV infection who discontinued nucleos(t)ide analogue therapy according to pre-specified stopping criteria, recruited from November 2012 through July 2016 at an academic hospital in Guangzhou, China. Patients were followed through February 2017. We performed comprehensive biochemical and virologic tests at every visit, and anti-HBc was quantified for 2 years after treatment cessation (at baseline and weeks 4, 8, 12, 24, 48, and 96). The primary endpoint was clinical relapse, defined as level of HBV DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal-these were also the criteria for retreatment. We followed 100 patients (71% positive for HB e antigen [HBeAg] at the start of nucleos(t)ide analogue therapy, 43% treated with entecavir or tenofovir) for a median of 2.5 years after stopping therapy. Clinical relapse occurred in 39 patients (in 46% of patients at year 4 after discontinuation). High level of anti-HBc at the end of treatment (hazard ratio [HR], 0.31 per log IU/mL; P=.002) and low level of HB surface antigen (HBsAg) at the end of treatment (HR, 1.71 per log IU/mL; P=.032) were associated with a reduced risk of clinical relapse after adjusting for age, start of nucleos(t)ide analogue therapy HBeAg-status, and consolidation therapy duration. At year 4, 21% of patients with anti-HBc levels at the end of treatment ≥1000 IU/mL developed a clinical relapse compared to 85% of patients with levels <100 IU/mL (P<.001). An HBsAg level at the end of treatment ≤100 IU/mL was associated with a reduced risk of relapse (HR 0.30; P=.045). However, 82% of patients had levels of HBsAg above 100 IU/mL; for these patients, level of anti-HBc at the end of treatment could be used to determine the risk of relapse (HR 0.39 per log IU/mL; P=.005). In a median 2.5-year follow-up study of patients with chronic HBV infection who stopped nucleos(t)ide analogue therapy, total serum level of anti-HBc at the end of treatment was associated with risk of clinical relapse. Serum level of anti-HBc might be used to select patients suitable for discontinuing nucleos(t)ide analogue therapy. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Integration of Wireless Sensor Networks into a Commercial Off-the-Shelf (COTS) Multimedia Network

DTIC Science & Technology

2008-12-01

IDE) which supports JAVA ME or in a basic text editor. The simplest IDE to use is the Netbeans IDE, which is supported by Sun 34 Microsystems...discussion,” https://www.sunspotworld.com/forums, November 2008. [28] Netbeans.org, “ Netbeans IDE version 6.5 download,” http://www.netbeans.org

Impaired performance of female APP/PS1 mice in the Morris water maze is coupled with increased Aβ accumulation and microglial activation.

PubMed

Gallagher, J J; Minogue, A M; Lynch, M A

2013-01-01

Alzheimer's disease (AD) is characterized by progressive neuronal loss and cognitive decline. Epidemiological studies suggest that the risk of AD is higher in women even when data are adjusted for age. We set out to compare changes in 9-month-old male and female mice which overexpress amyloid precursor protein (APP) with presenilin (PS1; APP/PS1 mice) and to evaluate whether any changes were coupled with deficits in spatial learning. APP/PS1 mice were assessed for their ability to learn in the Morris water maze and Aβ burden assessed by Congo Red and Aβ triple ultrasensitive assay. Neuroinflammatory changes were examined in brain tissue along with expression of Aβ-generating and Aβ-degrading enzymes. A deficit in reversal phase learning in the Morris water maze was observed in female mice and was paralleled by evidence of increased accumulation of Aβ, microglial activation and expression of IL-1β. Accumulation of Aβ was coupled with an increase in expression of BACE-1 and a decrease in insulin-degrading enzyme (IDE). The results indicate that the observed impairment in spatial memory in female APP/PS1 mice correlated with increased Aβ burden and the changes in Aβ may have occurred as a result of enhanced BACE-1 and decreased IDE expression. Copyright © 2012 S. Karger AG, Basel.

Effective quadrature formula in solving linear integro-differential equations of order two

NASA Astrophysics Data System (ADS)

Eshkuvatov, Z. K.; Kammuji, M.; Long, N. M. A. Nik; Yunus, Arif A. M.

2017-08-01

In this note, we solve general form of Fredholm-Volterra integro-differential equations (IDEs) of order 2 with boundary condition approximately and show that proposed method is effective and reliable. Initially, IDEs is reduced into integral equation of the third kind by using standard integration techniques and identity between multiple and single integrals then truncated Legendre series are used to estimate the unknown function. For the kernel integrals, we have applied Gauss-Legendre quadrature formula and collocation points are chosen as the roots of the Legendre polynomials. Finally, reduce the integral equations of the third kind into the system of algebraic equations and Gaussian elimination method is applied to get approximate solutions. Numerical examples and comparisons with other methods reveal that the proposed method is very effective and dominated others in many cases. General theory of existence of the solution is also discussed.

Dual Exosite-binding Inhibitors of Insulin-degrading Enzyme Challenge Its Role as the Primary Mediator of Insulin Clearance in Vivo*

PubMed Central

Durham, Timothy B.; Toth, James L.; Klimkowski, Valentine J.; Cao, Julia X. C.; Siesky, Angela M.; Alexander-Chacko, Jesline; Wu, Ginger Y.; Dixon, Jeffrey T.; McGee, James E.; Wang, Yong; Guo, Sherry Y.; Cavitt, Rachel Nicole; Schindler, John; Thibodeaux, Stefan J.; Calvert, Nathan A.; Coghlan, Michael J.; Sindelar, Dana K.; Christe, Michael; Kiselyov, Vladislav V.; Michael, M. Dodson; Sloop, Kyle W.

2015-01-01

Insulin-degrading enzyme (IDE, insulysin) is the best characterized catabolic enzyme implicated in proteolysis of insulin. Recently, a peptide inhibitor of IDE has been shown to affect levels of insulin, amylin, and glucagon in vivo. However, IDE−/− mice display variable phenotypes relating to fasting plasma insulin levels, glucose tolerance, and insulin sensitivity depending on the cohort and age of animals. Here, we interrogated the importance of IDE-mediated catabolism on insulin clearance in vivo. Using a structure-based design, we linked two newly identified ligands binding at unique IDE exosites together to construct a potent series of novel inhibitors. These compounds do not interact with the catalytic zinc of the protease. Because one of these inhibitors (NTE-1) was determined to have pharmacokinetic properties sufficient to sustain plasma levels >50 times its IDE IC50 value, studies in rodents were conducted. In oral glucose tolerance tests with diet-induced obese mice, NTE-1 treatment improved the glucose excursion. Yet in insulin tolerance tests and euglycemic clamp experiments, NTE-1 did not enhance insulin action or increase plasma insulin levels. Importantly, IDE inhibition with NTE-1 did result in elevated plasma amylin levels, suggesting the in vivo role of IDE action on amylin may be more significant than an effect on insulin. Furthermore, using the inhibitors described in this report, we demonstrate that in HEK cells IDE has little impact on insulin clearance. In total, evidence from our studies supports a minimal role for IDE in insulin metabolism in vivo and suggests IDE may be more important in helping regulate amylin clearance. PMID:26085101

Association and haplotype analysis of the insulin-degrading enzyme (IDE) gene, a strong positional and biological candidate for type 2 diabetes susceptibility.

PubMed

Groves, Christopher J; Wiltshire, Steven; Smedley, Damian; Owen, Katherine R; Frayling, Timothy M; Walker, Mark; Hitman, Graham A; Levy, Jonathan C; O'Rahilly, Stephen; Menzel, Stephan; Hattersley, Andrew T; McCarthy, Mark I

2003-05-01

The gene for insulin-degrading enzyme (IDE) represents a strong positional and biological candidate for type 2 diabetes susceptibility. IDE maps to chromosome 10q23.3, a region linked to diabetes in several populations; the rat homolog has been directly implicated in diabetes susceptibility; and known functions of IDE support an important role in glucose homeostasis. We sought evidence for association between IDE variation and diabetes by mutation screening, defining local haplotype structure, and genotyping variants delineating common haplotypic diversity. An initial case-control analysis (628 diabetic probands from multiplex sibships and 604 control subjects) found no haplotypic associations, although one variant (IDE2, -179T-->C) showed modest association with diabetes (odds ratio [OR]1.25, P = 0.03). Linkage partitioning analyses failed to support this association, but provided borderline evidence for a different variant (IDE10, IVS20-405A-->G) (P = 0.06). Neither variant was associated with diabetes when replication was sought in 377 early onset diabetic subjects and 825 control subjects, though combined analysis of all typed cohorts indicated a nominally significant effect at IDE2 (OR 1.21 [1.04-1.40], P = 0.013). In the absence of convincing support for this association from linkage partitioning or analyses of continuous measures of glycemia, we conclude that analysis of over 2,400 samples provides no compelling evidence that variation in IDE contributes to diabetes susceptibility in humans.

Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones

PubMed Central

Maianti, Juan Pablo; McFedries, Amanda; Foda, Zachariah H.; Kleiner, Ralph E.; Du, Xiu Quan; Leissring, Malcolm A.; Tang, Wei-Jen; Charron, Maureen J.; Seeliger, Markus A.; Saghatelian, Alan; Liu, David R.

2014-01-01

Despite decades of speculation that inhibiting endogenous insulin degradation might treat type-2 diabetes1, 2, and the identification of IDE (insulin-degrading enzyme) as a diabetes susceptibility gene3, 4, the relationship between the activity of the zinc metalloprotein IDE and glucose homeostasis remains unclear. Although Ide−/− mice have elevated insulin levels, they exhibit impaired, rather than improved, glucose tolerance that may arise from compensatory insulin signalling dysfunction5, 6. IDE inhibitors that are active in vivo are therefore needed to elucidate IDE’s physiological roles and to determine its potential to serve as a target for the treatment of diabetes. Here we report the discovery of a physiologically active IDE inhibitor identified from a DNA-templated macrocycle library. An X-ray structure of the macrocycle bound to IDE reveals that it engages a binding pocket away from the catalytic site, which explains its remarkable selectivity. Treatment of lean and obese mice with this inhibitor shows that IDE regulates the abundance and signalling of glucagon and amylin, in addition to that of insulin. Under physiological conditions that augment insulin and amylin levels, such as oral glucose administration, acute IDE inhibition leads to substantially improved glucose tolerance and slower gastric emptying. These findings demonstrate the feasibility of modulating IDE activity as a new therapeutic strategy to treat type-2 diabetes and expand our understanding of the roles of IDE in glucose and hormone regulation. PMID:24847884

Streptococcus pyogenes Infection and the Human Proteome with a Special Focus on the Immunoglobulin G-cleaving Enzyme IdeS.

PubMed

Karlsson, Christofer A Q; Järnum, Sofia; Winstedt, Lena; Kjellman, Christian; Björck, Lars; Linder, Adam; Malmström, Johan A

2018-06-01

Infectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a combined mass spectrometry-based proteomics strategy to investigate how the human proteome is transiently modified by the pathogen Streptococcus pyogenes , with a particular focus on bacterial cleavage of IgG in vivo In invasive diseases, S. pyogenes evokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG. S. pyogenes produces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments. The results show that IdeS contributes to the adaptation of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures.

PubMed

Mueller, Jakob C; Riemenschneider, Matthias; Schoepfer-Wendels, Andreas; Gohlke, Henning; Konta, Lidija; Friedrich, Patricia; Illig, Thomas; Laws, Simon M; Förstl, Hans; Kurz, Alexander

2007-05-01

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.

Faster bridge construction using precast substructures : brief.

DOT National Transportation Integrated Search

2011-07-01

Bridge replacement often requires road closures and detours that frustrate road users. It remains a key goal of Wisconsin DOT to reduce construction-related road use interruptions. This will be a challenge with bridges: Bridge inspections in 2007 ide...

Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer's Disease.

PubMed

Pan, Yongming; Xu, Jianqin; Chen, Cheng; Chen, Fangming; Jin, Ping; Zhu, Keyan; Hu, Chenyue W; You, Mengmeng; Chen, Minli; Hu, Fuliang

2018-01-01

Alzheimer's disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of β-site APP cleaving enzyme-1 (BACE1) and receptor for advanced glycation end products (RAGE), and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1) and insulin degrading enzyme (IDE). In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA) and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD.

Surface morphology of titanium dioxide (TiO{sub 2}) nanoparticles on aluminum interdigitated device electrodes (IDEs)

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

Azizah, N., E-mail: norazizahparmin84@gmail.com; Gopinath, Subash C. B.; Nadzirah, Sh.

2016-07-06

Titanium dioxide (TiO{sub 2}) nanoparticles based Interdigitated Device Electrodes (IDEs) Nanobiosensor device was developed for intracellular biochemical detection. Fabrication and characterization of Scanning Electron Microscopy (SEM) using IDE nanocoated with TiO{sub 2} was studied in this paper. SEM analysis was carried out at 10 kV acceleration volatege and a 9.8 mA emission current to compare IDE with and without TiO{sub 2} on the surface area. The simple fabrication process, high sensitivity, and fast response of the TiO{sub 2} based IDEs facilitate their applications in a wide range of areas. The small size of semiconductor TiO{sub 2} based IDE for sensitive,more » label-free, real time detection of a wide range of biological species could be explored in vivo diagnostics and array-based screening.« less

Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular geometry

PubMed Central

Li, Liwen; Tang, Qinghuang; Nakamura, Takashi; Suh, Jun-Gyo; Ohshima, Hayato; Jung, Han-Sung

2016-01-01

The anatomic and functional combinations of cusps and lophs (ridges) define the tooth shape of rodent molars, which distinguishes species. The species-specific cusp patterns result from the spatiotemporal induction of enamel knots (EKs), which require precisely controlled cellular behavior to control the epithelial invagination. Despite the well-defined roles of EK in cusp patterning, the determinants of the ultimate cuspal shapes and involvement of epithelial cellular geometry are unknown. Using two typical tooth patterns, the lophodont in gerbils and the bunodont in mice, we showed that the cuspal shape is determined by the dental epithelium at the cap stage, whereas the cellular geometry in the inner dental epithelium (IDE) is correlated with the cuspal shape. Intriguingly, fine tuning Rac1 and RhoA interconvert cuspal shapes between two species by remolding the cellular geometry. Either inhibition of Rac1 or ectopic expression of RhoA could region-distinctively change the columnar shape of IDE cells in gerbils to drive invagination to produce cusps. Conversely, RhoA reduction in mice inhibited invagination and developed lophs. Furthermore, we found that Rac1 and RhoA modulate the choices of cuspal shape by coordinating adhesion junctions, actin distribution, and fibronectin localization to drive IDE invagination. PMID:27892530

Efficacy of Nucleot(s)ide Analogs Therapy in Patients with Unresectable HBV-Related Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

PubMed

He, Lingling; Liu, Xiaoli; Zhao, Yalin; Zhang, Shuan; Jiang, Yuyong; Wang, Xianbo; Yang, Zhiyun

2017-01-01

Aim . To determine whether nucleot(s)ide analogs therapy has survival benefit for patients with HBV-related HCC after unresectable treatment. Method . A systematic search was conducted through seven electronic databases including PubMed, OVID, EMBASE, Cochrane Databases, Elsevier, Wiley Online Library, and BMJ Best Practice. All studies comparing NA combined with unresectable treatment versus unresectable treatment alone were considered for inclusion. The primary outcome was the overall survival (OS) after unresectable treatment for patients with HBV-related HCC. The secondary outcome was the progression-free survival (PFS). Results were expressed as hazard ratio (HR) for survival with 95% confidence intervals. Results . We included six studies with 994 patients: 409 patients in nucleot(s)ide analogs therapy group and 585 patients without antiviral therapy in control group. There were significant improvements for the overall survival (HR = 0.57; 95% CI = 0.47-0.70; p < 0.001) and progression-free survival (HR = 0.84; 95% CI = 0.71-0.99; p = 0.034) in the NA-treated group compared with the control group. Funnel plot showed that there was no significant publication bias in these studies. When it comes to antiviral drugs and operation method, it also showed benefit in NA-treated group. At the same time, overall mortality as well as mortality secondary to liver failure in NA-treated group was obviously lesser. Sensitivity analyses confirmed the robustness of the results. Conclusions . Nucleot(s)ide analogs therapy after unresectable treatment has potential beneficial effects in terms of overall survival and progression-free survival. NA therapy should be considered in clinical practice.

Harvard Catalyst | The Clinical Translational Science Center IND/IDE Consult Service: providing an IND/IDE consult service in a decentralized network of academic healthcare centers.

PubMed

Kim, Min J; Winkler, Sabune J; Bierer, Barbara E; Wolf, Delia

2014-04-01

The Food and Drug Administration (FDA) regulations require sponsors of clinical investigations involving an investigational drug or device to submit an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application. Strict adherence to applicable regulations is vital to the success of clinical research. Unlike most major pharmaceutical sponsors, investigator sponsors often do not fully appreciate their regulatory obligations nor have resources to ensure compliance. As a result they can place themselves and their institutions at risk. Nevertheless, investigator-initiated clinical trials are vital to the further development of innovative drugs, biologics, and medical devices. The IND/IDE Subcommittee under the Regulatory Knowledge and Support Program at Harvard Catalyst, The Harvard Clinical and Translational Science Center worked in collaboration with Harvard and Harvard affiliated institutions to create and launch an IND/IDE Consult Service in a decentralized network of collaborating Academic Healthcare Centers (AHC). The IND/IDE Consult Service offers expertise, resources, and shared experiences to assist sponsor-investigators and IRBs in meeting regulatory requirements for conducting and reviewing investigator-initiated IND/IDE studies. The scope of the services provided by the Harvard Catalyst IND/IDE Consult Service are described, including the specifics of the service, lessons learned, and challenges faced, in a scalable model that builds inter-institutional capacity. © 2014 Wiley Periodicals, Inc.

Identification of a Novel Host-Specific IgM Protease in Streptococcus suis

PubMed Central

Seele, Jana; Singpiel, Alena; Spoerry, Christian; von Pawel-Rammingen, Ulrich; Valentin-Weigand, Peter

2013-01-01

Streptococcus suis serotype 2 is a highly invasive, extracellular pathogen in pigs with the capacity to cause severe infections in humans. This study was initiated by the finding that IgM degradation products are released after opsonization of S. suis. The objective of this work was to identify the bacterial factor responsible for IgM degradation. The results of this study showed that a member of the IdeS family, designated IdeSsuis (Immunoglobulin M-degrading enzyme of S. suis), is responsible and sufficient for IgM cleavage. Recombinant IdeSsuis was found to degrade only IgM but neither IgG nor IgA. Interestingly, Western blot analysis revealed that IdeSsuis is host specific, as it exclusively cleaves porcine IgM but not IgM from six other species, including a closely related member of the Suidae family. As demonstrated by flow cytometry and immunofluorescence microscopy, IdeSsuis modulates binding of IgM to the bacterial surface. IdeSsuis is the first prokaryotic IgM-specific protease described, indicating that this enzyme is involved in a so-far-unknown mechanism of host-pathogen interaction at an early stage of the host immune response. Furthermore, cleavage of porcine IgM by IdeSsuis is the first identified phenotype reflecting functional adaptation of S. suis to pigs as the main host. PMID:23243300

Harvard Catalyst | The Clinical Translational Science Center IND/IDE Consult Service: Providing an IND/IDE Consult Service in a Decentralized Network of Academic Healthcare Centers

PubMed Central

Winkler, Sabune J.; Bierer, Barbara E.; Wolf, Delia

2014-01-01

Abstract The Food and Drug Administration (FDA) regulations require sponsors of clinical investigations involving an investigational drug or device to submit an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application. Strict adherence to applicable regulations is vital to the success of clinical research. Unlike most major pharmaceutical sponsors, investigator sponsors often do not fully appreciate their regulatory obligations nor have resources to ensure compliance. As a result they can place themselves and their institutions at risk. Nevertheless, investigator‐initiated clinical trials are vital to the further development of innovative drugs, biologics, and medical devices. The IND/IDE Subcommittee under the Regulatory Knowledge and Support Program at Harvard Catalyst, The Harvard Clinical and Translational Science Center worked in collaboration with Harvard and Harvard affiliated institutions to create and launch an IND/IDE Consult Service in a decentralized network of collaborating Academic Healthcare Centers (AHC). The IND/IDE Consult Service offers expertise, resources, and shared experiences to assist sponsor‐investigators and IRBs in meeting regulatory requirements for conducting and reviewing investigator‐initiated IND/IDE studies. The scope of the services provided by the Harvard Catalyst IND/IDE Consult Service are described, including the specifics of the service, lessons learned, and challenges faced, in a scalable model that builds inter‐institutional capacity. PMID:24455986

Measurement of effective piezoelectric coefficients of PZT thin films for energy harvesting application with interdigitated electrodes.

PubMed

Chidambaram, Nachiappan; Mazzalai, Andrea; Muralt, Paul

2012-08-01

Interdigitated electrode (IDE) systems with lead zirconate titanate (PZT) thin films play an increasingly important role for two reasons: first, such a configuration generates higher voltages than parallel plate capacitor-type electrode (PPE) structures, and second, the application of an electric field leads to a compressive stress component in addition to the overall stress state, unlike a PPE structure, which results in tensile stress component. Because ceramics tend to crack at relatively moderate tensile stresses, this means that IDEs have a lower risk of cracking than PPEs. For these reasons, IDE systems are ideal for energy harvesting of vibration energy, and for actuators. Systematic investigations of PZT films with IDE systems have not yet been undertaken. In this work, we present results on the evaluation of the in-plane piezoelectric coefficients with IDE systems. Additionally, we also propose a simple and measurable figure of merit (FOM) to analyze and evaluate the relevant piezoelectric parameter for harvesting efficiency without the need to fabricate the energy harvesting device. Idealized effective coefficients e(IDE) and h(IDE) are derived, showing its composite nature with about one-third contribution of the transverse effect, and about two-thirds contribution of the longitudinal effect in the case of a PZT film deposited on a (100)-oriented silicon wafer with the in-plane electric field along one of the <011> Si directions. Randomly oriented 1-μm-thick PZT 53/47 film deposited by a sol-gel technique, was evaluated and yielded an effective coefficient e(IDE) of 15 C·m(-2). Our FOM is the product between effective e and h coefficient representing twice the electrical energy density stored in the piezoelectric film per unit strain deformation (both for IDE and PPE systems). Assuming homogeneous fields between the fingers, and neglecting the contribution from below the electrode fingers, the FOM for IDE structures with larger electrode gap is derived to be twice as large as for PPE structures, for PZT-5H properties. The experiments yielded an FOM of the IDE structures of 1.25 × 10(10) J/m(3) and 14 mV/μ strain.

Lessons learned from IDeAl - 33 recommendations from the IDeAl-net about design and analysis of small population clinical trials.

PubMed

Hilgers, Ralf-Dieter; Bogdan, Malgorzata; Burman, Carl-Fredrik; Dette, Holger; Karlsson, Mats; König, Franz; Male, Christoph; Mentré, France; Molenberghs, Geert; Senn, Stephen

2018-05-11

IDeAl (Integrated designs and analysis of small population clinical trials) is an EU funded project developing new statistical design and analysis methodologies for clinical trials in small population groups. Here we provide an overview of IDeAl findings and give recommendations to applied researchers. The description of the findings is broken down by the nine scientific IDeAl work packages and summarizes results from the project's more than 60 publications to date in peer reviewed journals. In addition, we applied text mining to evaluate the publications and the IDeAl work packages' output in relation to the design and analysis terms derived from in the IRDiRC task force report on small population clinical trials. The results are summarized, describing the developments from an applied viewpoint. The main result presented here are 33 practical recommendations drawn from the work, giving researchers a comprehensive guidance to the improved methodology. In particular, the findings will help design and analyse efficient clinical trials in rare diseases with limited number of patients available. We developed a network representation relating the hot topics developed by the IRDiRC task force on small population clinical trials to IDeAl's work as well as relating important methodologies by IDeAl's definition necessary to consider in design and analysis of small-population clinical trials. These network representation establish a new perspective on design and analysis of small-population clinical trials. IDeAl has provided a huge number of options to refine the statistical methodology for small-population clinical trials from various perspectives. A total of 33 recommendations developed and related to the work packages help the researcher to design small population clinical trial. The route to improvements is displayed in IDeAl-network representing important statistical methodological skills necessary to design and analysis of small-population clinical trials. The methods are ready for use.

Elucidation of interactions of Alzheimer amyloid beta peptides (Abeta40 and Abeta42) with insulin degrading enzyme: a molecular dynamics study.

PubMed

Bora, Ram Prasad; Prabhakar, Rajeev

2010-05-11

In this study, interactions of the two full-length Alzheimer amyloid beta peptides (Abeta40 and Abeta42) with the fully active form of insulin degrading enzyme (IDE) through unrestrained, all-atom MD simulations have been investigated. This enzyme is a Zn-containing metallopeptidase that catalyzes the degradation of the monomeric forms of these peptides, and this process is critical for preventing the progression of Alzheimer's disease (AD). The available X-ray structures of the free and small fragment-bound (Asp1-Glu3 and Lys16-Asp23 of Abeta40 and Asp1-Glu3 and Lys16-Glu22 of Abeta42) mutated forms of IDE and NMR structures of the full-length Abeta40 and Abeta42 have been used to build the starting structures for these simulations. The most representative structures derived from the Abeta40-IDE and Abeta42-IDE simulations accurately reproduced the locations of the active site Zn(2+) metal and small fragments of the substrates and their interactions with the enzyme from the X-ray structures. The remaining fragments of both the substrates were found to interact with IDE through several hydrogen bonding, pi-pi, CH-pi, and NH-pi interactions. In comparison to Abeta40, Abeta42 is more flexible and interacts through a smaller number (17-22) of hydrogen bonds in the catalytic chamber of IDE. Both the substrates adopted more beta-sheet character in the IDE environment, an observation that is in line with experiments. Their structural characteristics inside IDE are significantly different than the ones observed in aqueous solution. The atomistic level details provided by these simulations can help in the elucidation of binding and degrading mechanisms of the Abeta peptides by IDE.

Somatostatin: a novel substrate and a modulator of insulin-degrading enzyme activity.

PubMed

Ciaccio, Chiara; Tundo, Grazia R; Grasso, Giuseppe; Spoto, Giuseppe; Marasco, Daniela; Ruvo, Menotti; Gioia, Magda; Rizzarelli, Enrico; Coletta, Massimo

2009-02-06

Insulin-degrading enzyme (IDE) is an interesting pharmacological target for Alzheimer's disease (AD), since it hydrolyzes beta-amyloid, producing non-neurotoxic fragments. It has also been shown that the somatostatin level reduction is a pathological feature of AD and that it regulates the neprilysin activity toward beta-amyloid. In this work, we report for the first time that IDE is able to hydrolyze somatostatin [k(cat) (s(-1))=0.38 (+/-0.05); K(m) (M)=7.5 (+/-0.9) x 10(-6)] at the Phe6-Phe7 amino acid bond. On the other hand, somatostatin modulates IDE activity, enhancing the enzymatic cleavage of a novel fluorogenic beta-amyloid through a decrease of the K(m) toward this substrate, which corresponds to the 10-25 amino acid sequence of the Abeta(1-40). Circular dichroism spectroscopy and surface plasmon resonance imaging experiments show that somatostatin binding to IDE brings about a concentration-dependent structural change of the secondary and tertiary structure(s) of the enzyme, revealing two possible binding sites. The higher affinity binding site disappears upon inactivation of IDE by ethylenediaminetetraacetic acid, which chelates the catalytic Zn(2+) ion. As a whole, these features suggest that the modulatory effect is due to an allosteric mechanism: somatostatin binding to the active site of one IDE subunit (where somatostatin is cleaved) induces an enhancement of IDE proteolytic activity toward fluorogenic beta-amyloid by another subunit. Therefore, this investigation on IDE-somatostatin interaction contributes to a more exhaustive knowledge about the functional and structural aspects of IDE and its pathophysiological implications in the amyloid deposition and somatostatin homeostasis in the brain.

Study of surface functionalization on IDE by using 3-aminopropyl triethoxysilane (APTES) for cervical cancer detection

NASA Astrophysics Data System (ADS)

Raqeema, S.; Hashim, U.; Azizah, N.

2016-07-01

This paper presented the study of surface functionalization on IDE by using 3-Aminopropyl triethoxysilane (APTES). The DNA nanochip based interdigitated (IDE) has been proposed to optimized the sensitivity of the device due to the cervical cancer detection. The DNA nanochip will be more efficient using surface modification of TiO2 nanoparticles with 3-Aminopropyl triethoxysilane (APTES). Furthermore, APTES gain the better functionalization of the adsorption mechanism on IDE. The combination of the DNA probe and the HPV target will produce more sensitivity and speed of the DNA nanochip due to their properties. The IDE has been characterized using current-voltage (IV) measurement. This functionalization of the surface would be applicable, sensitive, selective and low cost for cervical cancer detection.

A globally distributed mobile genetic element inhibits natural transformation of Vibrio cholerae

PubMed Central

Dalia, Ankur B.; Seed, Kimberley D.; Calderwood, Stephen B.; Camilli, Andrew

2015-01-01

Natural transformation is one mechanism of horizontal gene transfer (HGT) in Vibrio cholerae, the causative agent of cholera. Recently, it was found that V. cholerae isolates from the Haiti outbreak were poorly transformed by this mechanism. Here, we show that an integrating conjugative element (ICE)-encoded DNase, which we name IdeA, is necessary and sufficient for inhibiting natural transformation of Haiti outbreak strains. We demonstrate that IdeA inhibits this mechanism of HGT in cis via DNA endonuclease activity that is localized to the periplasm. Furthermore, we show that natural transformation between cholera strains in a relevant environmental context is inhibited by IdeA. The ICE encoding IdeA is globally distributed. Therefore, we analyzed the prevalence and role for this ICE in limiting natural transformation of isolates from Bangladesh collected between 2001 and 2011. We found that IdeA+ ICEs were nearly ubiquitous in isolates from 2001 to 2005; however, their prevalence decreased to ∼40% from 2006 to 2011. Thus, IdeA+ ICEs may have limited the role of natural transformation in V. cholerae. However, the rise in prevalence of strains lacking IdeA may now increase the role of this conserved mechanism of HGT in the evolution of this pathogen. PMID:26240317

Mycoplasmas and cancer: focus on nucleoside metabolism

PubMed Central

Vande Voorde, Johan; Balzarini, Jan; Liekens, Sandra

2014-01-01

The standard of care for patients suffering cancer often includes treatment with nucleoside analogues (NAs). NAs are internalized by cell-specific nucleobase/nucleoside transporters and, after enzymatic activation (often one or more phosphorylation steps), interfere with cellular nucleo(s)(t)ide metabolism and DNA/RNA synthesis. Therefore, their efficacy is highly dependent on the expression and activity of nucleo(s)(t)ide-metabolizing enzymes, and alterations thereof (e.g. by down/upregulated expression or mutations) may change the susceptibility to NA-based therapy and/or confer drug resistance. Apart from host cell factors, several other variables including microbial presence may determine the metabolome (i.e. metabolite concentrations) of human tissues. Studying the diversity of microorganisms that are associated with the human body has already provided new insights in several diseases (e.g. diabetes and inflammatory bowel disease) and the metabolic exchange between tissues and their specific microbiota was found to affect the bioavailability and toxicity of certain anticancer drugs, including NAs. Several studies report a preferential colonization of tumor tissues with some mycoplasma species (mostly Mycoplasma hyorhinis). These prokaryotes are also a common source of cell culture contamination and alter the cytostatic activity of some NAs in vitro due to the expression of nucleoside-catabolizing enzymes. Mycoplasma infection may therefore bias experimental work with NAs, and their presence in the tumor microenvironment could be of significance when optimizing nucleoside-based cancer treatment. PMID:26417262

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme.

PubMed

Affholter, J A; Cascieri, M A; Bayne, M L; Brange, J; Casaretto, M; Roth, R A

1990-08-21

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, we have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor I (25 nM and approximately 16,000 nM, respectively), the first set of analogues studied were hybrid molecules of insulin and IGF I. IGF I mutants [insB1-17,17-70]IGF I, [Tyr55,Gln56]IGF I, and [Phe23,Phe24,Tyr25]IGF I have been synthesized and share the property of having insulin-like amino acids at positions corresponding to primary sites of cleavage of insulin by IDE. Whereas the first two exhibit affinities for IDE similar to that of wild type IGF I, the [Phe23,Phe24,Tyr25]IGF I analogue has a 32-fold greater affinity for the immobilized enzyme. Replacement of Phe-23 by Ser eliminates this increase. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25-Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental characterization of PZT fibers using IDE electrodes

NASA Astrophysics Data System (ADS)

Wyckoff, Nicholas; Ben Atitallah, Hassene; Ounaies, Zoubeida

2016-04-01

Lead zirconate titanate (PZT) fibers are mainly used in active fiber composites (AFC) where they are embedded in a polymer matrix. Interdigitated electrodes (IDE) along the direction of the fibers are used to achieve planar actuation, hereby exploiting the d33 coefficient of PZT. When embedded in the AFC, the PZT fibers are subjected to mechanical loading as well as non-uniform electric field as a result of the IDEs. Therefore, it is important to characterize the electrical and electromechanical behavior of these fibers ex-situ using the IDE electrodes to assess the impact of nonuniform electric field on the properties of the fibers. For that reason, this work aims at quantifying the impact of IDE electrodes on the electrical and electromechanical behavior of PZT fibers, which is necessary for their successful implementation in devices like AFC. The tested fibers were purchased from Advanced Cerametrics and they have an average diameter of 250 micrometers. The IDE electrodes were screen printed on an acrylic substrate. The PZT fibers were subjected to frequency sweeps at low voltages to determine permittivity for parallel and interdigitated electrodes. The piezoelectric e33 constant is determined from electromechanical testing of PZT fibers in parallel electrodes to compare the electromechanical behavior for PZT in bulk and fiber form. The dielectric constant and e33 were found to be lower for the IDE and parallel electrodes compared to bulk but comparable to results published in literature.

Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels.

PubMed

Khodadadi, Davar; Gharakhanlou, Reza; Naghdi, Naser; Salimi, Mona; Azimi, Mohammad; Shahed, Atabak; Heysieattalab, Soomaayeh

2018-06-11

Aggregated amyloid beta (Aβ) peptides are believed to play a decisive role in the pathology of Alzheimer's disease (AD). Previous evidence suggested that exercise contributes to the improvement of cognitive decline and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise on spatial memory via central and peripheral Aβ clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aβ 1-42 injection in male Wistar rats. We found Aβ 1-42 -treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aβ 1-42 (sAβ 1-42 ), decreased mRNA and protein expression of neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein receptor-related protein-1 (LRP-1) in the hippocampus. Aβ 1-42 -treated animals also exhibited a higher level of sAβ 1-42 and a lower level of soluble LRP-1 (sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein content in the liver. However, exercise training improved the spatial learning and memory deficits, reduced both plaque load and sAβ 1-42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aβ 1-42 -treated animals. Aβ 1-42 -treated animals subjected to treadmill exercise also revealed decreased levels of sAβ 1-42 and increased levels of sLRP-1 in plasma, as well as increased levels of LRP-1 mRNA and protein in the liver. In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aβ clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD. Future studies need to determine their relative contribution.

Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.

PubMed

Bourlière, Marc; Rabiega, Pascaline; Ganne-Carrie, Nathalie; Serfaty, Lawrence; Marcellin, Patrick; Barthe, Yoann; Thabut, Dominique; Guyader, Dominique; Hezode, Christophe; Picon, Magali; Causse, Xavier; Leroy, Vincent; Bronowicki, Jean Pierre; Carrieri, Patrizia; Riachi, Ghassan; Rosa, Isabelle; Attali, Pierre; Molina, Jean Michel; Bacq, Yannick; Tran, Albert; Grangé, Jean Didier; Zoulim, Fabien; Fontaine, Hélène; Alric, Laurent; Bertucci, Inga; Bouvier-Alias, Magali; Carrat, Fabrice

2017-03-01

Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (< or ≥2·25 log 10 IU/mL) to allocate patients (1:1) to receive a 48 week course of subcutaneous injections of 180 μg per week of pegylated interferon alfa-2a in addition to the nucleos(t)ide analogue regimen or to continue to receive nucleos(t)ide analogues only. The primary endpoint was HBsAg loss at week 96 by intention-to-treat analysis. This trial is closed and registered with ClinicalTrials.gov, number NCT01172392. Between Jan 20, 2011, and July 18, 2012, we randomly allocated 185 patients (92 [50%] to pegylated interferon and nucleos(t)ide analogues and 93 [50%] to nucleos(t)ide analogues alone). We excluded two patients from the pegylated interferon plus nucleos(t)ide analogues group from analyses because of withdrawal of consent (one patient) or violation of inclusion criteria (one patient). At week 96, loss of HBsAg was reported in seven (7·8%) of 90 patients in the pegylated interferon plus nucleos(t)ide analogues group versus three (3·2%) of 93 in the nucleos(t)ide analogues-alone group (difference 4·6% [95% CI -2·6 to 12·5]; p=0·15). 85 (94%) of 90 patients started pegylated interferon, three (4%) of whom had a dose reduction and 17 (20%) had an early discontinuation of pegylated interferon (seven [41%] for serious adverse events). Grade 3 and 4 adverse events were more frequent in the pegylated interferon plus nucleos(t)ide analogues group (26 [29%] grade 3 adverse events; 19 [21%] grade 4 adverse events) than in the nucleos(t)ide analogues-alone group (three [3%] grade 3; six [6%] grade 4). Addition of a 48 week course of pegylated interferon to nucleos(t)ide analogue therapy in patients with HBeAg-negative chronic hepatitis B with undetectable HBV DNA for a least 1 year was poorly tolerated and did not result in a significant increase of HBsAg clearance. Institut national de la santé et de la recherche médicale-Agence nationale de recherches sur le sida et les hépatites virales (France Recherche Nord&sud Sida-vih Hepatites). Copyright © 2017 Elsevier Ltd. All rights reserved.

Genomic population structure of freshwater-resident and anadromous ide (Leuciscus idus) in north-western Europe.

PubMed

Skovrind, Mikkel; Olsen, Morten Tange; Vieira, Filipe Garrett; Pacheco, George; Carl, Henrik; Gilbert, M Thomas P; Møller, Peter Rask

2016-02-01

Climate change experts largely agree that future climate change and associated rises in oceanic water levels over the upcoming decades, will affect marine salinity levels. The subsequent effects on fish communities in estuarine ecosystems however, are less clear. One species that is likely to become increasingly affected by changes in salinity is the ide (Leuciscus idus). The ide is a stenohaline freshwater fish that primarily inhabits rivers, with frequent anadromous behavior when sea salinity does not exceed 15%. Unlike most other anadromous Baltic Sea fish species, the ide has yet to be subjected to large-scale stocking programs, and thus provides an excellent opportunity for studying the natural population structure across the current salinity gradient in the Danish Belts. To explore this, we used Genotyping-by-Sequencing to determine genomic population structure of both freshwater resident and anadromous ide populations in the western Baltic Sea region, and relate the results to the current salinity gradient and the demographic history of ide in the region. The sample sites separate into four clusters, with all anadromous populations in one cluster and the freshwater resident populations in the remaining three. Results demonstrate high level of differentiation between sites hosting freshwater resident populations, but little differentiation among anadromous populations. Thus ide exhibit the genomic population structure of both a typical freshwater species, and a typical anadromous species. In addition to providing a first insight into the population structure of north-western European ide, our data also (1) provide indications of a single illegal introduction by man; (2) suggest limited genetic effects of heavy pollution in the past; and (3) indicate possible historical anadromous behavior in a now isolated freshwater population.

Increasing Diversity in the Earth Sciences - Impact of the IDES Program in Oregon

NASA Astrophysics Data System (ADS)

de Silva, S. L.; Guerrero, E. F.; Duncan, R. A.; de Silva, L. L.; Eriksson, S. C.

2014-12-01

The NSF-OEDG funded Increasing Diversity in the Earth Sciences (IDES) program hosted at Oregon State University targets undergraduate students from diverse backgrounds and diverse ethnicity to engage in research. Partnering with local community colleges, non-traditional students are the hallmark of this program. The IDES program has several components to support the students in the transition from community college to the four-year universities of Oregon State University and Portland State University. Over the four years, the program has adapted while adhering to its primary goals: (1) to increase the number of students from underrepresented groups who prepare for and pursue careers in Earth Science research and education, and (2) to strengthen the understanding of Earth Sciences and their relevance to society among broad and diverse segments of the population. Now in its final year under an extension, 53 participants have participated in the program. An ongoing external evaluation of the program reveals that the various stakeholders consider IDES very successful. Participant surveys and interviews document several impacts: expanded opportunities, making professional contacts, building self-confidence, enhanced ability to be employable, and personal acknowledgement. Research mentors and administrators from partner institutions see positive impacts on the students and on their organizations. Challenges include better communication between the IDES program, mentors, and students. IDES is poised to move forward with its current experiences and successes as a foundation for further funding. IDES-like activities can be funded from private sources and it is a good fit for funding from Research Experiences for Undergraduates at NSF. The new emphasis on education and research at community colleges is an exciting opportunity and Oregon State University has already used aspects of the IDES program in current grant proposals to obtain funds for more undergraduate research.

Liberation of Desmosine and Isodesmosine as Amino Acids from Insoluble Elastin by Elastolytic Proteases

PubMed Central

Umeda, Hideyuki; Aikawa, Masanori; Libby, Peter

2011-01-01

The development of atherosclerotic lesions and abdominal aortic aneurysms involves degradation and loss of extracellular matrix components, such as collagen and elastin. Releases of the elastin cross-links desmosine (DES) and isodesmosine (IDE) may reflect elastin degradation in cardiovascular diseases. This study investigated the production of soluble elastin cross-linking structures by proteinases implicated in arterial diseases. Recombinant MMP-12 and neutrophil elastase liberated DES and IDE as amino acids from insoluble elastin. DES and IDE were also released from insoluble elastin exposed to monocyte/macrophage cell lines or human primary macrophages derived from peripheral blood monocytes. Elastin oxidized by reactive oxygen species (ROS) liberated more unconjugated DES and IDE than did non-oxidized elastin when incubated with MMP-12 or neutrophil elastase. These results support the exploration of free DES and IDE as biomarkers of elastin degradation. PMID:21726534

Identification of Compounds from Etonia Rosemary (Conradina etonia)

DTIC Science & Technology

2007-05-15

to reduce the dis- ase risk to humans and animals from these insects. Some f these are the use of spatial repellents, pesticides , larvi- ides...from the mint family, Lamiaceae, are widely uti- ized by human culture. Culinary herbs such as basil , thyme, pearmint, oregano, sage, and rosemary belong

Integrated titanium dioxide (TiO2) nanoparticles on interdigitated device electrodes (IDEs) for pH analysis

NASA Astrophysics Data System (ADS)

Azizah, N.; Hashim, U.; Arshad, M. K. Md.; Gopinath, Subash C. B.; Nadzirah, Sh.; Farehanim, M. A.; Fatin, M. F.; Ruslinda, A. R.; Ayub, R. M.

2016-07-01

Titanium dioxide (TiO2) nanoparticles based Interdigitated Device Electrodes (IDEs) Nanobiosensor device was developed for intracellular biochemical detection. Fabrication and characterization of pH sensors using IDE nanocoated with TiO2 was studied in this paper. In this paper, a preliminary assessment of this intracellular sensor with electrical measurement under different pH levels. 3-aminopropyltriethoxysilane (APTES) was used to enhance the sensitivity of titanium dioxide layer as well as able to provide surface modification by undergoing protonation and deprotonation process. Different types of pH solution provide different resistivity and conductivity towards the surface. Base solution has the higher current compared to an acid solution. Amine and oxide functionalized TiO2 based IDE exhibit pH-dependent could be understood in terms of the change in surface charge during protonation and deprotonation. The simple fabrication process, high sensitivity, and fast response of the TiO2 based IDEs facilitate their applications in a wide range of areas. The small size of semiconductor TiO2 based IDE for sensitive, label-free, real time detection of a wide range of biological species could be explored in vivo diagnostics and array-based screening.

Analysis of high-order SNP barcodes in mitochondrial D-loop for chronic dialysis susceptibility.

PubMed

Yang, Cheng-Hong; Lin, Yu-Da; Chuang, Li-Yeh; Chang, Hsueh-Wei

2016-10-01

Positively identifying disease-associated single nucleotide polymorphism (SNP) markers in genome-wide studies entails the complex association analysis of a huge number of SNPs. Such large numbers of SNP barcode (SNP/genotype combinations) continue to pose serious computational challenges, especially for high-dimensional data. We propose a novel exploiting SNP barcode method based on differential evolution, termed IDE (improved differential evolution). IDE uses a "top combination strategy" to improve the ability of differential evolution to explore high-order SNP barcodes in high-dimensional data. We simulate disease data and use real chronic dialysis data to test four global optimization algorithms. In 48 simulated disease models, we show that IDE outperforms existing global optimization algorithms in terms of exploring ability and power to detect the specific SNP/genotype combinations with a maximum difference between cases and controls. In real data, we show that IDE can be used to evaluate the relative effects of each individual SNP on disease susceptibility. IDE generated significant SNP barcode with less computational complexity than the other algorithms, making IDE ideally suited for analysis of high-order SNP barcodes. Copyright © 2016 Elsevier Inc. All rights reserved.

Femtosecond laser ablation of gold interdigitated electrodes for electronic tongues

NASA Astrophysics Data System (ADS)

Manzoli, Alexandra; de Almeida, Gustavo F. B.; Filho, José A.; Mattoso, Luiz H. C.; Riul, Antonio; Mendonca, Cleber R.; Correa, Daniel S.

2015-06-01

Electronic tongue (e-tongue) sensors based on impedance spectroscopy have emerged as a potential technology to evaluate the quality and chemical composition of food, beverages, and pharmaceuticals. E-tongues usually employ transducers based on metal interdigitated electrodes (IDEs) coated with a thin layer of an active material, which is capable of interacting chemically with several types of analytes. IDEs are usually produced by photolithographic methods, which are time-consuming and costly, therefore, new fabrication technologies are required to make it more affordable. Here, we employed femtosecond laser ablation with pulse duration of 50 fs to microfabricate gold IDEs having finger width from 2.3 μm up to 3.2 μm. The parameters used in the laser ablation technique, such as light intensity, scan speed and beam spot size have been optimized to achieve uniform IDEs, which were characterized by optical and scanning electron microscopy. The electrical properties of gold IDEs fabricated by laser ablation were evaluated by impedance spectroscopy, and compared to those produced by conventional photolithography. The results show that femtosecond laser ablation is a promising alternative to conventional photolithography for fabricating metal IDEs for e-tongue systems.

Development of a Sensitive Electrochemical Enzymatic Reaction-Based Cholesterol Biosensor Using Nano-Sized Carbon Interdigitated Electrodes Decorated with Gold Nanoparticles

PubMed Central

Sharma, Deepti; Lee, Jongmin; Seo, Junyoung; Shin, Heungjoo

2017-01-01

We developed a versatile and highly sensitive biosensor platform. The platform is based on electrochemical-enzymatic redox cycling induced by selective enzyme immobilization on nano-sized carbon interdigitated electrodes (IDEs) decorated with gold nanoparticles (AuNPs). Without resorting to sophisticated nanofabrication technologies, we used batch wafer-level carbon microelectromechanical systems (C-MEMS) processes to fabricate 3D carbon IDEs reproducibly, simply, and cost effectively. In addition, AuNPs were selectively electrodeposited on specific carbon nanoelectrodes; the high surface-to-volume ratio and fast electron transfer ability of AuNPs enhanced the electrochemical signal across these carbon IDEs. Gold nanoparticle characteristics such as size and morphology were reproducibly controlled by modulating the step-potential and time period in the electrodeposition processes. To detect cholesterol selectively using AuNP/carbon IDEs, cholesterol oxidase (ChOx) was selectively immobilized via the electrochemical reduction of the diazonium cation. The sensitivity of the AuNP/carbon IDE-based biosensor was ensured by efficient amplification of the redox mediators, ferricyanide and ferrocyanide, between selectively immobilized enzyme sites and both of the combs of AuNP/carbon IDEs. The presented AuNP/carbon IDE-based cholesterol biosensor exhibited a wide sensing range (0.005–10 mM) and high sensitivity (~993.91 µA mM−1 cm−2; limit of detection (LOD) ~1.28 µM). In addition, the proposed cholesterol biosensor was found to be highly selective for the cholesterol detection. PMID:28914766

Zn(II) stimulation of Fe(II)-activated repression in the iron-dependent repressor from Mycobacterium tuberculosis.

PubMed

Stapleton, Brian; Walker, Lawrence R; Logan, Timothy M

2013-03-19

Thermodynamic measurements of Fe(II) binding and activation of repressor function in the iron-dependent repressor from Mycobacterium tuberculosis (IdeR) are reported. IdeR, a member of the diphtheria toxin repressor family of proteins, regulates iron homeostasis and contributes to the virulence response in M. tuberculosis. Although iron is the physiological ligand, this is the first detailed analysis of iron binding and activation in this protein. The results showed that IdeR binds 2 equiv of Fe(II) with dissociation constants that differ by a factor of 25. The high- and low-affinity iron binding sites were assigned to physical binding sites I and II, respectively, using metal binding site mutants. IdeR was also found to contain a high-affinity Zn(II) binding site that was assigned to physical metal binding site II through the use of binding site mutants and metal competition assays. Fe(II) binding was modestly weaker in the presence of Zn(II), but the coupled metal binding-DNA binding affinity was significantly stronger, requiring 30-fold less Fe(II) to activate DNA binding compared to Fe(II) alone. Together, these results suggest that IdeR is a mixed-metal repressor, where Zn(II) acts as a structural metal and Fe(II) acts to trigger the physiologically relevant promoter binding. This new model for IdeR activation provides a better understanding of IdeR and the biology of iron homeostasis in M. tuberculosis.

Liver X receptor-β improves autism symptoms via downregulation of β-amyloid expression in cortical neurons.

PubMed

Zhang, Ji-Xiang; Zhang, Jun; Li, Ye

2016-05-06

We study the effect of liver X receptor β (LXRβ) on β-amyloid (Aβ) peptide generation and autism behaviors by conducting an animal experiment. In autistic mice treated with LXRβ agonist T0901317, enzyme linked immunosorbent assay was used to measure Aβ in brain tissue homogenates. Western blot was used to detect Aβ precursors, Aβ degradation and secretase enzymes, and expression of autophagy-related proteins and Ras/Raf/Erkl/2 signaling pathway proteins in brain tissue. Changes in autism spectrum disorder syndromes of the BTBR mice were compared before and after T0901317 treatment. Compared with the control group, autistic mice treated with LXRβ agonist T0901317 showed significantly lower Aβ level in brain tissue (P < 0.05), significantly higher Aβ degradation enzyme (NEP, IDE proteins) levels (all P < 0.05), significantly lower Aβ secretase enzyme BACE1 protein level (P < 0.05), and significantly lower Ras, P-C-Raf, C-Raf, P-Mekl/2, P-Erkl/2 protein levels (all P < 0.05). BTBR mice treated with T0901317 showed improvements in repetitive stereotyped behavior, inactivity, wall-facing standing time, self-combing time and center stay time, stayed longer in platform quadrant, and crossed the platform more frequently (all P < 0.05). LXRβ could potentially reduce brain Aβ generation by inhibiting Aβ production and promoting Aβ degradation, thereby increasing the expression of autophagy-related proteins, reducing Ras/Raf/Erkl/2 signaling pathway proteins, and improving autism behaviors.

Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer’s Disease

PubMed Central

Pan, Yongming; Xu, Jianqin; Chen, Cheng; Chen, Fangming; Jin, Ping; Zhu, Keyan; Hu, Chenyue W.; You, Mengmeng; Chen, Minli; Hu, Fuliang

2018-01-01

Alzheimer’s disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of β-site APP cleaving enzyme-1 (BACE1) and receptor for advanced glycation end products (RAGE), and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1) and insulin degrading enzyme (IDE). In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA) and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD. PMID:29556189

Fabrication and characterization of spiral interdigitated electrodes based biosensor for salivary glucose detection

NASA Astrophysics Data System (ADS)

Adelyn, P. Y. P.; Hashim, U.; Arshad, M. K. Md; Voon, C. H.; Liu, Wei-Wen; Kahar, S. M.; Huda, A. R. N.; Lee, H. Cheun

2017-03-01

This work introduces the non-invasive glucose monitoring technique by using the Complementary Metal Oxide Semiconductor (CMOS) technologically fabricated spiral Interdigitated Electrodes (IDE) based biosensor. Scanning Electron Microscopy (SEM) image explores the morphology of spiral IDE while Energy Dispersive X-Ray (EDX) determines the elements induced in spiral IDE. Oral saliva of two patients are collected and tested on the spiral IDE sensor with electrical characterization as glucose detection results. However, both patients exhibit their glucose level characteristics inconsistently. Therefore, this work could be extended and enhanced by adding Glutaraldehyde in between 3-Aminoproply)triethoxysilane (APTES) modified and glucose oxidase (GOD) enzyme immobilized layer with FTIR validation for bonding attachment.

Human ApoE Isoforms Differentially Modulate Glucose and Amyloid Metabolic Pathways in Female Brain: Evidence of the Mechanism of Neuroprotection by ApoE2 and Implications for Alzheimer's Disease Prevention and Early Intervention.

PubMed

Keeney, Jeriel Thomas-Richard; Ibrahimi, Shaher; Zhao, Liqin

2015-01-01

Three major genetic isoforms of apolipoprotein E (ApoE), ApoE2, ApoE3, and ApoE4, exist in humans and lead to differences in susceptibility to Alzheimer's disease (AD). This study investigated the impact of human ApoE isoforms on brain metabolic pathways involved in glucose utilization and amyloid-β (Aβ) degradation, two major areas that are significantly perturbed in preclinical AD. Hippocampal RNA samples from middle-aged female mice with targeted human ApoE2, ApoE3, and ApoE4 gene replacement were comparatively analyzed with a qRT-PCR custom array for the expression of 85 genes involved in insulin/insulin-like growth factor (Igf) signaling. Consistent with its protective role against AD, ApoE2 brain exhibited the most metabolically robust profile among the three ApoE genotypes. When compared to ApoE2 brain, both ApoE3 and ApoE4 brains exhibited markedly reduced levels of Igf1, insulin receptor substrates (Irs), and facilitated glucose transporter 4 (Glut4), indicating reduced glucose uptake. Additionally, ApoE4 brain exhibited significantly decreased Pparg and insulin-degrading enzyme (Ide), indicating further compromised glucose metabolism and Aβ dysregulation associated with ApoE4. Protein analysis showed significantly decreased Igf1, Irs, and Glut4 in ApoE3 brain, and Igf1, Irs, Glut4, Pparg, and Ide in ApoE4 brain compared to ApoE2 brain. These data provide the first documented evidence that human ApoE isoforms differentially affect brain insulin/Igf signaling and downstream glucose and amyloid metabolic pathways, illustrating a potential mechanism for their differential risk in AD. A therapeutic strategy that enhances brain insulin/Igf1 signaling activity to a more robust ApoE2-like phenotype favoring both energy production and amyloid homeostasis holds promise for AD prevention and early intervention.

Characterization of the terminal stages of chlorophyll (ide) synthesis in etioplast membrane preparations.

PubMed Central

Griffiths, W T

1975-01-01

1. Chlorophyll (ide) formation from protochlorophyll (ide) that is normally inactive was demonstrated in etioplast membranes isolated from maize and barlley plants, the process being dependent on intermittent illumination and the addition of NADPH. 2. The addition of NADPH to the membranes was shown to result in the conversion of inactive protochlorophyll (ide) absorbing at about 630 nm into a form(s) with light-absorption maxima at about 640 and 652 nm, both of which disappear when chlorophyll (ide) is formed on illumination. 3. The temperature-dependence of the activation process and its response to a variety of reagents were examined. From these, the conclusion is drawn that -SH groups are involved in the activation but in the active complex these are unavailable for reaction with -SH reagents. 4. Evidence is presented for the occurrence of glucose 6-phosphate dehydrogenase activity within etioplasts and the suggestion is made that the oxidative pentose phosphate pathway can provide the NADPH required for chlorophyll biosynthesis during the early stages of greening. PMID:5998

Peptidomics approach to elucidate the proteolytic regulation of bioactive peptides

PubMed Central

Kim, Yun-Gon; Lone, Anna Mari; Nolte, Whitney M.; Saghatelian, Alan

2012-01-01

Peptide hormones and neuropeptides have important roles in physiology and therefore the regulation of these bioactive peptides is of great interest. In some cases proteolysis controls the concentrations and signaling of bioactive peptides, and the peptidases that mediate this biochemistry have proven to be extremely successful drug targets. Due to the lack of any general method to identify these peptidases, however, the role of proteolysis in the regulation of most neuropeptides and peptide hormones is unknown. This limitation prompted us to develop an advanced peptidomics-based strategy to identify the peptidases responsible for the proteolysis of significant bioactive peptides. The application of this approach to calcitonin gene-related peptide (CGRP), a neuropeptide associated with blood pressure and migraine, revealed the endogenous CGRP cleavage sites. This information was then used to biochemically purify the peptidase capable of proteolysis of CGRP at those cleavage sites, which led to the identification of insulin-degrading enzyme (IDE) as a candidate CGRP-degrading enzyme. CGRP had not been identified as an IDE substrate before and we tested the physiological relevance of this interaction by quantitative measurements of CGRP using IDE null (IDE−/−) mice. In the absence of IDE, full-length CGRP levels are elevated in vivo, confirming IDE as an endogenous CGRP-degrading enzyme. By linking CGRP and IDE, this strategy uncovers a previously unknown pathway for CGRP regulation and characterizes an additional role for IDE. More generally, this work suggests that this may be an effective general strategy for characterizing these pathways and peptidases moving forward. PMID:22586115

Electrical DNA biosensor using aluminium interdigitated electrode for E.Coli O157:H7 detection

NASA Astrophysics Data System (ADS)

Natasha, N. Z.; Rajapaksha, R. D. A. A.; Uda, M. N. A.; Hashim, U.

2017-09-01

Escherichia Coli (E.Coli) O157:H7 is the one of the most dangerous foodborne pathogens based diseases that presence in our daily life that causes illness and death increase every year. Aluminum Interdigitated Electrode (Al IDE) biosensor was introduced to detect E.Coli O157:H7 in earlier stage. In this paper we investigated ssDNA of E.Coli O157:H7 bacteria detection through electrical behavior of Al IDE sensor. The physical properties of Al IDE biosensor has been characterized using Low Power Microscope (LPM), High Power Microscope (HPM), Scanning Electron Microscope (SEM) and 3D Nano Profiler. The bare Al IDE was electrical characterized by using I-V measurement. The surface modification was accomplished by salinization using APTES and immobilization using Carboxylic Probe E.Coli which was the first step in preparing Al IDE biosensor. Geared up prepared biosensor was hybridized with complementary, non-complementary and single based mismatch ssDNA to confirmed specificity detection of E Coli O157:H7 ssDNA target. The Current - Voltage was performed for each step such as bare Al IDE, surface modification, immobilization and hybridization. Sensitivity measurement was accomplished using different concentration of complementary ssDNA target from 1 fM - 10 µM. Selectivity measurements was achieved using same concentration which was 10 µM concentration for complement, non-complement and mismatch E.Coli O157:H7 ssDNA target. It's totally proved that the Al IDE able to detect specific and small current down to Femtomolar concentration.

Efficient attenuation of Friedreich's ataxia (FRDA) cardiomyopathy by modulation of iron homeostasis-human induced pluripotent stem cell (hiPSC) as a drug screening platform for FRDA.

PubMed

Lee, Yee-Ki; Lau, Yee-Man; Ng, Kwong-Man; Lai, Wing-Hon; Ho, Shu-Leong; Tse, Hung-Fat; Siu, Chung-Wah; Ho, Philip Wing-Lok

2016-01-15

Friedreich's ataxia (FRDA), a recessive neurodegenerative disorder commonly associated with hypertrophic cardiomyopathy, is caused by silencing of the frataxin (FXN) gene encoding the mitochondrial protein involved in iron-sulfur cluster biosynthesis. Application of our previously established FRDA human induced pluripotent stem cell (hiPSC) derived cardiomyocytes model as a platform to assess the efficacy of treatment with either the antioxidant coenzyme Q10 analog, idebenone (IDE) or the iron chelator, deferiprone (DFP), which are both under clinical trial. DFP was able to more significantly suppress synthesis of reactive oxygen species (ROS) than IDE at the dosages of 25 μM and 10nM respectively which agreed with the reduced rate of intracellular accumulation of iron by DFP treatment from 25 to 50 μM. With regard to cardiac electrical-contraction (EC) coupling function, decay velocity of calcium handling kinetics in FRDA-hiPSC-cardiomyocytes was significantly improved by DFP treatment but not by IDE. Further mechanistic studies revealed that DFP also modulated iron induced mitochondrial stress as reflected by mitochondria network disorganization and decline level of respiratory chain protein, succinate dehydrogenase (CxII) and cytochrome c oxidase (COXIV). In addition, iron-response protein (IRP-1) regulatory loop was overridden by DFP as reflected by resumed level of ferritin (FTH) back to basal level and the attenuated transferrin receptor (TSFR) mRNA level suppression thereby reducing further iron uptake. DFP modulated iron homeostasis in FRDA-hiPSC-cardiomyocytes and effectively relieved stress-stimulation related to cardiomyopathy. The resuming of redox condition led to the significantly improved cardiac prime events, cardiac electrical-coupling during contraction. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Inhibitory Effect of Memantine on Streptozotocin-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Neurotrophic Factor Decline in Astrocytes.

PubMed

Rajasekar, N; Nath, Chandishwar; Hanif, Kashif; Shukla, Rakesh

2016-12-01

Our earlier studies showed that insulin receptor (IR) dysfunction along with neuroinflammation and amyloidogenesis played a major role in streptozotocin (STZ)-induced toxicity in astrocytes. N-methyl-D-aspartate (NMDA) receptor antagonist-memantine shows beneficial effects in Alzheimer's disease (AD) pathology. However, the protective molecular and cellular mechanism of memantine in astrocytes is not properly understood. Therefore, the present study was undertaken to investigate the effect of memantine on insulin receptors, neurotrophic factors, neuroinflammation, and amyloidogenesis in STZ-treated astrocytes. STZ (100 μM) treatment for 24 h in astrocytes resulted significant decrease in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and insulin-degrading enzyme (IDE) expression in astrocytes. Treatment with memantine (1-10 μM) improved STZ-induced neurotrophic factor decline (BDNF, GDNF) along with IR dysfunction as evidenced by a significant increase in IR protein expression, phosphorylation of IRS-1, Akt, and GSK-3 α/β in astrocytes. Further, memantine attenuated STZ-induced amyloid precursor protein (APP), β-site APP-cleaving enzyme-1 and amyloid-β 1-42 expression and restored IDE expression in astrocytes. In addition, memantine also displays protective effects against STZ-induced astrocyte activation showed by reduction of inflammatory markers, nuclear factor kappa-B translocation, glial fibrillary acidic protein, cyclooxygenase-2, tumor necrosis factor-α level, and oxidative-nitrostative stress. The results suggest that besides the NMDA receptor antagonisic activity, effect on astroglial IR and neurotrophic factor may also be an important factor in the beneficial effect of memantine in AD pathology. Graphical Abstract Novel neuroprotective mechanisms of memenatine in streptozotocin-induced toxicity in astrocytes.

IDeF-X ECLAIRs: A CMOS ASIC for the Readout of CdTe and CdZnTe Detectors for High Resolution Spectroscopy

NASA Astrophysics Data System (ADS)

Gevin, Olivier; Baron, Pascal; Coppolani, Xavier; Daly, FranÇois; Delagnes, Eric; Limousin, Olivier; Lugiez, Francis; Meuris, Aline; Pinsard, FrÉdÉric; Renaud, Diana

2009-08-01

The very last member of the IDeF-X ASIC family is presented: IDeF-X ECLAIRs is a 32-channel front end ASIC designed for the readout of Cadmium Telluride (CdTe) and Cadmium Zinc Telluride (CdZnTe) Detectors. Thanks to its noise performance (Equivalent Noise Charge floor of 33 e- rms) and to its radiation hardened design (Single Event Latchup Linear Energy Transfer threshold of 56 MeV.cm2.mg-1), the chip is well suited for soft X-rays energy discrimination and high energy resolution, ldquospace proof,rdquo hard X-ray spectroscopy. We measured an energy low threshold of less than 4 keV with a 10 pF input capacitor and a minimal reachable sensitivity of the Equivalent Noise Charge (ENC) to input capacitance of less than 7 e-/pF obtained with a 6 mus peak time. IDeF-X ECLAIRs will be used for the readout of 6400 CdTe Schottky monopixel detectors of the 2D coded mask imaging telescope ECLAIRs aboard the SVOM satellite. IDeF-X ECLAIRs (or IDeF-X V2) has also been designed for the readout of a pixelated CdTe detector in the miniature spectro-imager prototype Caliste 256 that is currently foreseen for the high energy detector module of the Simbol-X mission.

New technique for fertilizing eggs of burbot, asp and ide under hatchery conditions.

PubMed

Kucharczyk, Dariusz; Nowosad, Joanna; Łuczyński, Marek J; Targońska, Katarzyna

2016-09-01

The development of a new protocol for egg fertilization may increase embryo survival and benefit the aquaculture process. In the present study, a new technique of partially adding sperm to activated eggs in the artificial fertilization of burbot (Lota lota), ide (Leuciscus idus) and asp (Aspius aspius) eggs was evaluated. If the same volume of sperm was divided into two or three parts and added to eggs in 30-60s intervals, it significantly improved embryo survival at the eyed-egg-stage of development. In the present study, the periodic addition of spermatozoa to eggs affected fertilization (ide and asp) and embryo survival rates (ide, asp and burbot) and might be successfully applied under hatchery conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Interdigitated electrode (IDE) for porcine detection based on titanium dioxide (TiO2) thin films

NASA Astrophysics Data System (ADS)

Nordin, N.; Hashim, U.; Azizah, N.

2016-07-01

Interdigited Electrode (IDE) porcine detection can be accomplished to authenticate the halal issue that has been a concern to Muslim not only in Malaysia but all around the world. The method used is photolithography that used the p-type photoresist on the spin coater with 2500 rpm. Bare IDEs device is deposited with Titanium Dioxide (TiO2) to improve the performance of the device. The result indicates that current-voltage (I-V) measurement of porcine probe line slightly above porcine target due to negative charges repelled each other. The IDE device can detect the porcine presence in food as lowest as 1.0 µM. Better performance of the device can be achieved with the replacement of gold deposited to trigger more sensitivity of the device.

Governance in Open Source Software Development Projects: Towards a Model for Network-Centric Edge Organizations

DTIC Science & Technology

2008-06-01

project is not an isolated OSSD project. Instead, the NetBeans IDE which is the focus of development activities in the NetBeans.org project community...facilitate or constrain the intended usage of the NetBeans IDE. Figure 1 provides a rendering of some of the more visible OSSD projects that...as BioBeans and RefactorIT communities build tools on top of or extending the NetBeans platform or IDE. How do these organizations interact with

A Software Agent Toolkit for Effective Information Processing in the Battle Command Domain

DTIC Science & Technology

2006-11-01

the ADE will be based on a popular Integrated Development Environment (IDE) such as NetBeans or Eclipse. We further specified that the IDE is to be...JBuilder, NetBeans , and Eclipse. We quickly eliminated Visual Studio and JBuilder because they did not meet our basic requirements of being Java...based and freely obtainable. This left us with NetBeans and Eclipse. Each is a solid IDE with features that permit extensions well suited to our

Long Duration Exposure Facility (LDEF) attitude measurements of the interplanetary dust experiment

NASA Technical Reports Server (NTRS)

Kassel, Philip C., Jr.; Singer, S. Fred; Mulholland, J. Derral; Oliver, John P.; Weinberg, Jerry L.; Cooke, William J.; Wortman, Jim J.; Motley, William R., III

1992-01-01

The Long Duration Exposure Facility (LDEF) Interplanetary Dust Experiment (IDE) was unique in providing a time history of impacts of micron-sized particles on six orthogonal faces of LDEF during the first year in orbit. The value of this time resolved data depended on and was enhanced by the proper operation of some basic LDEF systems. Thus, the value of the data is greatly enhanced when the location and orientation of LDEF is known for each time of impact. The location and velocity of LDEF as a function of time can be calculated from the 'two-line elements' published by GSFC during the first year of the LDEF mission. The attitude of LDEF was passively stabilized in a gravity-gradient mode and a magnetically anchored viscous damper was used to dissipate roll, pitch, and yaw motions. Finally, the IDE used a standard LDEF Experiment Power and Data System (EPDS) to collect and store data and also to provide a crystal derived clock pulse (1 count every 13.1072 seconds) for all IDE time measurements. All that remained for the IDE was to provide a system to calibrate the clock, eliminating accumulative errors, and also verify the attitude of LDEF. The IDE used solar cells on six orthogonal faces to observe the LDEF sunrise and provide data about the LDEF attitude. The data was recorded by the EPDS about 10 times per day for the first 345 days of the LDEF mission. This data consist of the number of IDE counts since the last LDEF sunrise and the status of the six solar cells (light or dark) at the time of the last IDE count. The EPDS determined the time that data was recorded and includes, with each record, the master EPDS clock counter (1 count every 1.6384 seconds) that provided the range and resolution for time measurements. The IDE solar cells provided data for an excellent clock calibration, meeting their primary purpose, and the time resolved LDEF attitude measurements that can be gleaned from this data are presented.

Interdigitated electrode (IDE) for porcine detection based on titanium dioxide (TiO{sub 2}) thin films

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

Nordin, N.; Azizah, N.; Hashim, U., E-mail: uda@unimap.edu.my

2016-07-06

Interdigited Electrode (IDE) porcine detection can be accomplished to authenticate the halal issue that has been a concern to Muslim not only in Malaysia but all around the world. The method used is photolithography that used the p-type photoresist on the spin coater with 2500 rpm. Bare IDEs device is deposited with Titanium Dioxide (TiO{sub 2}) to improve the performance of the device. The result indicates that current-voltage (I-V) measurement of porcine probe line slightly above porcine target due to negative charges repelled each other. The IDE device can detect the porcine presence in food as lowest as 1.0 µM.more » Better performance of the device can be achieved with the replacement of gold deposited to trigger more sensitivity of the device.« less

Patient and Staff Perceptions of Intradialytic Exercise before and after Implementation: A Qualitative Study

PubMed Central

Young, Hannah M. L.; Hudson, Nicky; Clarke, Amy L.; Dungey, Maurice; Feehally, John; Burton, James O.; Smith, Alice C.

2015-01-01

Introduction Despite guidance and evidence for the beneficial effects of intradialytic exercise (IDE), such programmes are rarely adopted within practice and little is known about how they may best be sustained. The Theoretical Domains Framework (TDF) was used to guide the understanding of the barriers and facilitators to initial and ongoing IDE participation and to understand how these are influential at each stage. Materials and Methods Focus groups explored patient (n=24) and staff (n=9) perceptions of IDE prior to the introduction of a programme and, six months later, face to face semi-structured interviews captured exercising patients (n=11) and staffs’ (n=8) actual experiences. Data were collected at private and NHS haemodialysis units within the UK. All data were audio-recorded, translated where necessary, transcribed verbatim and subject to framework analysis. Results IDE initiation can be facilitated by addressing the pre-existing beliefs about IDE through the influence of peers (for patients) and training (for staff). Participation was sustained through the observation of positive outcomes and through social influences such as teamwork and collaboration. Despite this, environment and resource limitations remained the greatest barrier perceived by both groups. Conclusions Novel methods of staff training and patient education should enhance engagement. Programmes that clearly highlight the benefits of IDE should be more successful in the longer term. The barrier of staff workload needs to be addressed through specific guidance that includes recommendations on staffing levels, roles, training and skill mix. PMID:26068875

Long-term microparticle flux variability indicated by comparison of Interplanetary Dust Experiment (IDE) timed impacts for LDEF's first year in orbit with impact data for the entire 5.77-year orbital lifetime

NASA Technical Reports Server (NTRS)

Simon, Charles G.; Mulholland, J. Derral; Oliver, John P.; Cooke, William J.; Kassel, Philip C., Jr.

1993-01-01

The electronic sensors of the Interplanetary Dust Experiment (IDE) recorded precise impact times and approximate directions for submicron to approximately 100 micron size particles on all six primary sides of the spacecraft for the first 346 days of the LDEF orbital mission. Previously-reported analyses of the timed impact data have established their spatio-temporal features, including the demonstration that a preponderance of the particles in this regime are orbital debris and that a large fraction of the debris particles are encountered in megameter-size clouds. Short-term fluxes within such clouds can rise several orders of magnitude above the long-term average. These unexpectedly large short-term variations in debris flux raise the question of how representative an indication of the multi-year average flux is given by the nearly one year of timed data. One of the goals of the IDE was to conduct an optical survey of impact sites on detectors that remained active during the entire LDEF mission, to obtain full-mission fluxes. We present here the comparisons and contrasts among the new IDE optical survey impact data, the IDE first-year timed impact data, and impact data from other LDEF micrometeoroid and debris experiments. The following observations are reported: (1) the 5.77 year long-term integrated microparticle impact fluxes recorded by IDE detectors matched the integrated impact fluxes measured by other LDEF investigators for the same period; (2) IDE integrated microparticle impact fluxes varied by factors from 0.5 to 8.3 for LDEF days 1-346, 347-2106 and 1-2106 (5.77 years) on rows 3 (trailing edge, or West), 6 (South side), 12 (North side), and the Earth and Space ends; and (3) IDE integrated microparticle impact fluxes varied less than 3 percent for LDEF days 1-346, 347-2106 and 1-2106 (5.77 years) on row 9 (leading edge, or East). These results give further evidence of the accuracy and internal consistency of the recorded IDE impact data. This leads to the further conclusion that the utility of long-term ratios for impacts on various sides of a stabilized satellite in low Earth orbit (LEO) is extremely limited. These observations and their consequences highlight the need for continuous, real time monitoring of the dynamic microparticle environment in LEO.

Structure–activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme

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

Charton, Julie; Gauriot, Marion; Totobenazara, Jane

Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-â and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer's disease, amyloid-â clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along withmore » improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE's role.« less

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

Azizah, N., E-mail: norazizahparmin84@gmail.com; Gopinath, Subash C. B.; Nadzirah, Sh.

Titanium dioxide (TiO{sub 2}) nanoparticles based Interdigitated Device Electrodes (IDEs) Nanobiosensor device was developed for intracellular biochemical detection. Fabrication and characterization of pH sensors using IDE nanocoated with TiO{sub 2} was studied in this paper. In this paper, a preliminary assessment of this intracellular sensor with electrical measurement under different pH levels. 3-aminopropyltriethoxysilane (APTES) was used to enhance the sensitivity of titanium dioxide layer as well as able to provide surface modification by undergoing protonation and deprotonation process. Different types of pH solution provide different resistivity and conductivity towards the surface. Base solution has the higher current compared to anmore » acid solution. Amine and oxide functionalized TiO{sub 2} based IDE exhibit pH-dependent could be understood in terms of the change in surface charge during protonation and deprotonation. The simple fabrication process, high sensitivity, and fast response of the TiO{sub 2} based IDEs facilitate their applications in a wide range of areas. The small size of semiconductor TiO{sub 2} based IDE for sensitive, label-free, real time detection of a wide range of biological species could be explored in vivo diagnostics and array-based screening.« less

Analysis of Interplanetary Dust Experiment Detectors and Other Witness Plates

NASA Technical Reports Server (NTRS)

Griffis, D. P.; Wortman, J. J.

1992-01-01

The development of analytical procedures for identifying the chemical composition of residue from impacts that occurred on the Interplanetary Dust Experiment (IDE) detectors during the flight of Long Duration Exposure Facility (LDEF) and the carrying out of actual analysis on IDE detectors and other witness plates are discussed. Two papers on the following topics are presented: (1) experimental analysis of hypervelocity microparticle impact sites on IDE sensor surfaces; and (2) contaminant interfaces with secondary Ion Mass Spectrometer (SIMS) analysis of microparticle impactor residues on LDEF surfaces.

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

PubMed

Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

2016-05-01

The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

Cost effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B from a Canadian public payer perspective.

PubMed

Dakin, Helen; Sherman, Morris; Fung, Scott; Fidler, Carrie; Bentley, Anthony

2011-12-01

Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe. Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers. A Markov model was used to calculate the costs and benefits of nucleos(t)ide therapy in three groups of patients with hepatitis B e antigen (HBeAg)-positive and -negative CHB: nucleos(t)ide-naive patients without cirrhosis; nucleos(t)ide-naive patients with compensated cirrhosis; and lamivudine-resistant patients. Disease progression was modelled as annual transitions between 18 disease states. Transition probabilities, quality of life and costs were based on published studies. Health benefits were measured in QALYs. The reference year for costs was 2007 and costs and outcomes were discounted at 5% per annum. First-line tenofovir DF was the most effective nucleos(t)ide strategy for managing CHB, generating 6.85-9.39 QALYs per patient. First-line tenofovir DF was also the most cost-effective strategy in all patient subgroups investigated, costing between $Can43,758 and $Can48,015 per QALY gained compared with lamivudine then tenofovir. First-line tenofovir DF strongly dominated first-line entecavir. Giving tenofovir DF monotherapy immediately after lamivudine resistance developed was less costly and more effective than any other active treatment strategy investigated for lamivudine-resistant CHB, including second-line use of adefovir or adefovir + lamivudine. Probabilistic sensitivity analysis demonstrated 50% confidence that first-line tenofovir DF is the most cost-effective nucleos(t)ide strategy for treatment-naive patients with CHB, at a $Can50,000 per QALY threshold, and confirmed that first-line tenofovir DF has the highest expected net benefits. First-line tenofovir DF appears to be the most cost-effective nucleos(t)ide treatment for both cirrhotic and non-cirrhotic CHB patients in Canada, providing that society is willing to pay at least $Can48,015 per QALY gained, although sensitivity analyses highlighted uncertainty around the results.

Retrospective epidemiological study of canine epilepsy in Japan using the International Veterinary Epilepsy Task Force classification 2015 (2003-2013): etiological distribution, risk factors, survival time, and lifespan.

PubMed

Hamamoto, Yuji; Hasegawa, Daisuke; Mizoguchi, Shunta; Yu, Yoshihiko; Wada, Masae; Kuwabara, Takayuki; Fujiwara-Igarashi, Aki; Fujita, Michio

2016-11-09

Epilepsy is the most common neurological disease in veterinary practice. However, contrary to human medicine, epilepsy classification in veterinary medicine had not been clearly defined until recently. A number of reports on canine epilepsy have been published, reflecting in part updated proposals from the human epilepsy organization, the International League Against Epilepsy. In 2015, the International Veterinary Epilepsy Task Force (IVETF) published a consensus report on the classification and definition of canine epilepsy. The purpose of this retrospective study was to investigate the etiological distribution, survival time of dogs with idiopathic epilepsy (IdE) and structural epilepsy (StE), and risk factors for survival time, according to the recently published IVETF classification. We investigated canine cases with epilepsy that were referred to our teaching hospital in Japan during the past 10 years, and which encompassed a different breed population from Western countries. A total of 358 dogs with epilepsy satisfied our etiological study criteria. Of these, 172 dogs (48 %) were classified as IdE and 76 dogs (21 %) as StE. Of these dogs, 100 dogs (consisting of 65 with IdE and 35 with StE) were included in our survival study. Median survival time from the initial epileptic seizure in dogs with IdE and StE was 10.4 and 4.5 years, respectively. Median lifespan of dogs with IdE and StE was 13.5 and 10.9 years, respectively. Multivariable analysis demonstrated that risk factors for survival time in IdE were high seizure frequency (≥0.3 seizures/month) and focal epileptic seizures. Focal epileptic seizures were identified as a risk factor for survival time in IdE. Clinicians should carefully differentiate seizure type as it is difficult to identify focal epileptic seizures. With good seizure control, dogs with IdE can survive for nearly the same lifespan as the general dog population. Our results using the IVETF classification are similar to previous studies, although some features were noted in our Japanese canine population (which was composed of mainly small-breed dogs), including a longer lifespan in dogs with epilepsy and a larger percentage of meningoencephalomyelitis of unknown origin in dogs with StE.

Association between polymorphisms of the insulin-degrading enzyme gene and late-onset Alzheimer disease.

PubMed

Wang, Shitao; He, Feiyan; Wang, Ying

2015-06-01

The insulin-degrading enzyme (IDE) gene is a strong positional and biological candidate for late-onset Alzheimer disease (LOAD) susceptibility, with recent studies independently demonstrating an association between IDE gene variants and LOAD. However, previous data have been controversial. To investigate the relationship between IDE gene polymorphisms and LOAD risk, a case-control association study of 406 Han Chinese participants in Xinjiang, China, was undertaken. The LOAD and control groups consisted of 202 and 204 participants, respectively. The single-nucleotide polymorphisms rs1887922 and rs1999764 of the IDE gene were linked to LOAD incidence. The presence of the CT+CC genotype of rs1999764 had a protective effect compared to the TT genotype (adjusted P=.0001; odds ratio [OR]=0.226; 95% confidence interval [CI]=0.116-0.441), while the CT+CC genotype of rs1887922 was associated with increased LOAD risk (adjusted P=.0001; OR=3.640; 95% CI=1.889-7.016). Moreover, the effects of rs1887922 and rs1999764 were associated with LOAD risk independent of the apolipoprotein E ∊4 polymorphism and were more significant in men and women, respectively. These results demonstrate that the polymorphisms rs1887922 and rs1999764 of the IDE gene are associated with LOAD susceptibility in the Xinjiang Han population. © The Author(s) 2014.

Induction of group A Streptococcus virulence by a human antimicrobial peptide.

PubMed

Gryllos, Ioannis; Tran-Winkler, Hien J; Cheng, Ming-Fang; Chung, Hachung; Bolcome, Robert; Lu, Wuyuan; Lehrer, Robert I; Wessels, Michael R

2008-10-28

Group A streptococci (Streptococcus pyogenes or GAS) freshly isolated from individuals with streptococcal sore throat or invasive ("flesh-eating") infection often grow as mucoid colonies on primary culture but lose this colony appearance after laboratory passage. The mucoid phenotype is due to abundant production of the hyaluronic acid capsular polysaccharide, a key virulence determinant associated with severe GAS infections. These observations suggest that signal(s) from the human host trigger increased production of capsule and perhaps other virulence factors during infection. Here we show that subinhibitory concentrations of the human antimicrobial cathelicidin peptide LL-37 stimulate expression of the GAS capsule synthesis operon (hasABC). Up-regulation is mediated by the CsrRS 2-component regulatory system: it requires a functional CsrS sensor protein and can be antagonized by increased extracellular Mg(2+), the other identified environmental signal for CsrS. Up-regulation was also evident for other CsrRS-regulated virulence genes, including the IL-8 protease PrtS/ScpC and the integrin-like/IgG protease Mac/IdeS, findings that suggest a coordinated GAS virulence response elicited by this antimicrobial immune effector peptide. LL-37 signaling through CsrRS led to a marked increase in GAS resistance to opsonophagocytic killing by human leukocytes, an in vitro measure of enhanced GAS virulence, consistent with increased expression of the antiphagocytic capsular polysaccharide and Mac/IdeS. We propose that the human cathelicidin LL-37 has the paradoxical effect of stimulating CsrRS-regulated virulence gene expression, thereby enhancing GAS pathogenicity during infection. The ability of GAS to sense and respond to LL-37 may explain, at least in part, the unique susceptibility of the human species to streptococcal infection.

MollDE: a homology modeling framework you can click with.

PubMed

Canutescu, Adrian A; Dunbrack, Roland L

2005-06-15

Molecular Integrated Development Environment (MolIDE) is an integrated application designed to provide homology modeling tools and protocols under a uniform, user-friendly graphical interface. Its main purpose is to combine the most frequent modeling steps in a semi-automatic, interactive way, guiding the user from the target protein sequence to the final three-dimensional protein structure. The typical basic homology modeling process is composed of building sequence profiles of the target sequence family, secondary structure prediction, sequence alignment with PDB structures, assisted alignment editing, side-chain prediction and loop building. All of these steps are available through a graphical user interface. MolIDE's user-friendly and streamlined interactive modeling protocol allows the user to focus on the important modeling questions, hiding from the user the raw data generation and conversion steps. MolIDE was designed from the ground up as an open-source, cross-platform, extensible framework. This allows developers to integrate additional third-party programs to MolIDE. http://dunbrack.fccc.edu/molide/molide.php rl_dunbrack@fccc.edu.

Sensitivity enhancement of capacitive tumor necrosis factor-α detection by deposition of nanoparticles on interdigitated electrode

NASA Astrophysics Data System (ADS)

Yagati, Ajay Kumar; Park, Jinsoo; Kim, Jungsuk; Ju, Heongkyu; Chang, Keun-A.; Cho, Sungbo

2016-06-01

An interdigitated electrodes (IDE) modified with gold nanoparticles (AuNPs) was fabricated to enhance the capacitive detection of tumor necrosis factor-α (TNF-α) and compared with a bare IDE. A TNF-α immunosensor was developed by covalently conjugating TNF-α antibodies with 3-mercaptopropionic acid by a carbodiimide/N-hydroxysuccinimide reaction on the AuNP/IDE. After the application of human serum samples containing various concentrations of TNF-α to the sensing electrode, changes in both the impedance spectrum and the electrode interfacial capacitance were measured. The capacitance changes were dependent on the TNF-α concentration in the range of 1 pg ml-1 to 10 ng ml-1, and the device had the calculated detection limit of 0.83 pg ml-1. The developed AuNP/IDE-based immunosensor was successfully used for the capacitive detection of the binding of TNF-α to its antibody, and was found to be feasible for the analysis of TNF-α in human blood serum.

Validation of reference genes for normalization of qPCR gene expression data from Coffea spp. hypocotyls inoculated with Colletotrichum kahawae

PubMed Central

2013-01-01

Background Coffee production in Africa represents a significant share of the total export revenues and influences the lives of millions of people, yet severe socio-economic repercussions are annually felt in result of the overall losses caused by the coffee berry disease (CBD). This quarantine disease is caused by the fungus Colletotrichum kahawae Waller and Bridge, which remains one of the most devastating threats to Coffea arabica production in Africa at high altitude, and its dispersal to Latin America and Asia represents a serious concern. Understanding the molecular genetic basis of coffee resistance to this disease is of high priority to support breeding strategies. Selection and validation of suitable reference genes presenting stable expression in the system studied is the first step to engage studies of gene expression profiling. Results In this study, a set of ten genes (S24, 14-3-3, RPL7, GAPDH, UBQ9, VATP16, SAND, UQCC, IDE and β-Tub9) was evaluated to identify reference genes during the first hours of interaction (12, 48 and 72 hpi) between resistant and susceptible coffee genotypes and C. kahawae. Three analyses were done for the selection of these genes considering the entire dataset and the two genotypes (resistant and susceptible), separately. The three statistical methods applied GeNorm, NormFinder, and BestKeeper, allowed identifying IDE as one of the most stable genes for all datasets analysed, and in contrast GADPH and UBQ9 as the least stable ones. In addition, the expression of two defense-related transcripts, encoding for a receptor like kinase and a pathogenesis related protein 10, were used to validate the reference genes selected. Conclusion Taken together, our results provide guidelines for reference gene(s) selection towards a more accurate and widespread use of qPCR to study the interaction between Coffea spp. and C. kahawae. PMID:24073624

Hollow Threats: Why Coercive Diplomacy Fails

DTIC Science & Technology

2015-06-01

IDE from the Curso del Estado Mayor de las Fuerzas Armadas in Madrid, Spain. Maj Schore has a bachelor’s degree in Economics from the University...this element presupposes that the nature of a liberal democracy not only reduces its credibility to administer a severe level of hurt, but damages...of resistance increased Aidid’s ability to portray his forces as national liberators and augmented his support among the Somali people.40 This

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

Wakui, Yuta; Inoue, Jun; Ueno, Yoshiyuki, E-mail: yueno@mail.tains.tohoku.ac.jp

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-{alpha}, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPAR{alpha} ligand, bezafibrate, and a PPAR{gamma} ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced themore » amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPAR{gamma}, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-{alpha}-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.« less

77 FR 13343 - Pilot Program for Early Feasibility Study Investigational Device Exemption Applications...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

...] Pilot Program for Early Feasibility Study Investigational Device Exemption Applications; Termination of... acceptance of nominations for the Early Feasibility Study Investigational Device Exemption (IDE) Applications... technologies to participate in a pilot program for early feasibility study IDE applications. FDA is also...

Development of a Spanish version of the "Backache Index".

PubMed

Cuesta-Vargas, Antonio; Gonzaleaz-Sanchez, Manuel; Farasyn, Andre

2010-01-01

In routine clinical practice a physical examination should include an assessment of ability/function. The use of a scale or index in low back pain (LBP) is mainly used to categorize patients and to measure syndrome severity. For this reason we developed an easy and quick to perform standardised measuring procedure of impairment in patients with LBP without using inclinometers. The new "Backache Index" (BAI) is applied in order to help therapists, doctors, and surgeons perform physical examinations easily. The factor of presence or absence of pain with respect to different lumbar movements is elaborated for the patient with LBP, standing in an erect position. This resulted in outcome scores (0-3) for five impairment examinations of the trunk from which the sum of the scores gives the BAI (max. 15 points). The purpose of this study was to develop the linguistic adaptation and to explore the reliability of this new Backache Index translated in a Spanish version called "indice de Dolor de Espalda" or IDE, which can fulfil the existing need for a reliable routine examination in the clinical environment for Spanish speaking clinicians and patients. Two independent translations were made by two separate professional translators to Spanish. Both versions were compared and consensus resulted in a single translation. In a pain center patients were asked to participate in this project as volunteers. The exclusion criteria have been used in patients with LBP suffering of severe spinal pathology or having deseases. In total 46 patients (67% females, age = 52 ± 13 years) underwent the physical examination at the first session (IDE-1) and were retested without any treatment after 3 days (IDE-2). The two translations submitted by respective experts were identical and the final IDE was used in futher clinical examinations. The test-retest after 3 days of the same group revailed that the reliability for the 5 outcome scores was good (ICC ⩾ 0.73). No significant difference was found between IDE-1 (4.65 ± 4.15 ) and IDE-2 (4.72 ± 4.20) and the absolute reliability was perfect with an ICC=0.97. The IDE form facilitates a better diffusion under the Spanish speaking population, allowing it to maintain the degree of homogenenity and acceptance that the "Indice de Dolor de Espalda" or IDE has in clinical practice, helping to spread among the Hispanic world one of the objectives that the creator of this index raised when it was developed.

The diacylglycerol acyltransferase Rv3371 of Mycobacterium tuberculosis is required for growth arrest and involved in stress-induced cell wall alterations.

PubMed

Rastogi, Shivangi; Singh, Amit Kumar; Chandra, Gyan; Kushwaha, Pragati; Pant, Garima; Singh, Kavita; Mitra, Kalyan; Sashidhara, Koneni V; Krishnan, Manju Y

2017-05-01

Triacylglycerol (TAG) is important to mycobacteria both as cell envelope component and energy reservoir. Mycobacterium tuberculosis (Mtb) genome encodes at least 15 putative TAG synthase (tgs)s. We report that one of these genes, Rv3371, specific to pathogenic mycobacteria, when expressed in M. smegmatis leads to modifications in colony morphotype, bacterial architecture, cell surface properties and elevated TAG levels. Rv3371 was found to largely localize in the cell membrane. The Rv3371 promoter is minimally active during exponential growth in vitro, however, is up-regulated under stationary phase, hypoxia, nutrient starvation, nitrosative stress, low iron, in IFN-γ activated macrophages and infected mice. The low iron-induced expression of Rv3371 is likely due to the de-repression by Rv1404, which is probably activated by ideR. An Rv3371 deletion mutant of Mtb showed impaired non-replicating persistence in vitro and altered sensitivity to anti-mycobacterial drugs. In low iron medium, the Rv3371 deletion mutant showed reduced formation of TAG containing extracellular vesicles. Therefore Rv3371 is likely involved in Mtb growth arrest and cell wall alterations during persistence. Copyright © 2017 Elsevier Ltd. All rights reserved.

21 CFR 812.19 - Address for IDE correspondence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and Drug... Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705-1266. (b... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Address for IDE correspondence. 812.19 Section 812...

78 FR 41908 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-12

... issued by the CSB to the U.S. Occupational Safety and Health Administration: (1) 2001-05-I-DE-1 (revision... INFORMATION: Recommendation to the U.S. Occupational Safety and Health Administration 2001-05-I-DE-1.... Occupational Safety and Health Review Commission. The decision, exempts from PSM coverage, ``flammable liquids...

The Scenario Analysis Tool Suite: A User’s Guide

DTIC Science & Technology

2009-01-01

be exported at any stage and continued manually. The free, open-source integrated development environment (IDE) NetBeans [14] was used in the creation...and Technology Organisation, Australia. 14. Sun Microsystems & CollabNet (2008) NetBeans IDE 6.0, http://wwwnetbeans.org. 15. Tri, N., Boswell, S

Insulin‐degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population

PubMed Central

Vepsäläinen, Saila; Parkinson, Michele; Helisalmi, Seppo; Mannermaa, Arto; Soininen, Hilkka; Tanzi, Rudolph E; Bertram, Lars; Hiltunen, Mikko

2007-01-01

The gene for insulin‐degrading enzyme (IDE), which is located at chromosome 10q24, has been previously proposed as a candidate gene for late‐onset Alzheimer's disease (AD) based on its ability to degrade amyloid β‐protein. Genotyping of single nucleotide polymorphisms (SNPs) in the IDE gene in Finnish patients with AD and controls revealed SNPs rs4646953 and rs4646955 to be associated with AD, conferring an approximately two‐fold increased risk. Single locus findings were corroborated by the results obtained from haplotype analyses. This suggests that genetic alterations in or near the IDE gene may increase the risk for developing AD. PMID:17496198

Terabyte IDE RAID-5 Disk Arrays

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

David A. Sanders et al.

2003-09-30

High energy physics experiments are currently recording large amounts of data and in a few years will be recording prodigious quantities of data. New methods must be developed to handle this data and make analysis at universities possible. We examine some techniques that exploit recent developments in commodity hardware. We report on tests of redundant arrays of integrated drive electronics (IDE) disk drives for use in offline high energy physics data analysis. IDE redundant array of inexpensive disks (RAID) prices now are less than the cost per terabyte of million-dollar tape robots! The arrays can be scaled to sizes affordablemore » to institutions without robots and used when fast random access at low cost is important.« less

Large-Scale Dynamic Observation Planning for Unmanned Surface Vessels

DTIC Science & Technology

2007-06-01

programming language. In addition, the useful development software NetBeans IDE is free and makes the use of Java very user-friendly. 92...3. We implemented the greedy and 3PAA algorithms in Java using the NetBeans IDE version 5.5. 4. The test datasets were generated in MATLAB. 5

Fingerprinting Desmosine-Containing Elastin Peptides

NASA Astrophysics Data System (ADS)

Schräder, Christoph U.; Heinz, Andrea; Majovsky, Petra; Schmelzer, Christian E. H.

2015-05-01

Elastin is a vital protein of the extracellular matrix of jawed vertebrates and provides elasticity to numerous tissues. It is secreted in the form of its soluble precursor tropoelastin, which is subsequently cross-linked in the course of the elastic fiber assembly. The process involves the formation of the two tetrafunctional amino acids desmosine (DES) and isodesmosine (IDES), which are unique to elastin. The resulting high degree of cross-linking confers remarkable properties, including mechanical integrity, insolubility, and long-term stability to the protein. These characteristics hinder the structural elucidation of mature elastin. However, MS2 data of linear and cross-linked peptides released by proteolysis can provide indirect insights into the structure of elastin. In this study, we performed energy-resolved collision-induced dissociation experiments of DES, IDES, their derivatives, and DES-/IDES-containing peptides to determine characteristic product ions. It was found that all investigated compounds yielded the same product ion clusters at elevated collision energies. Elemental composition determination using the exact masses of these ions revealed molecular formulas of the type CxHyN, suggesting that the pyridinium core of DES/IDES remains intact even at relatively high collision energies. The finding of these specific product ions enabled the development of a similarity-based scoring algorithm that was successfully applied on LC-MS/MS data of bovine elastin digests for the identification of DES-/IDES-cross-linked peptides. This approach facilitates the straightforward investigation of native cross-links in elastin.

Fingerprinting desmosine-containing elastin peptides.

PubMed

Schräder, Christoph U; Heinz, Andrea; Majovsky, Petra; Schmelzer, Christian E H

2015-05-01

Elastin is a vital protein of the extracellular matrix of jawed vertebrates and provides elasticity to numerous tissues. It is secreted in the form of its soluble precursor tropoelastin, which is subsequently cross-linked in the course of the elastic fiber assembly. The process involves the formation of the two tetrafunctional amino acids desmosine (DES) and isodesmosine (IDES), which are unique to elastin. The resulting high degree of cross-linking confers remarkable properties, including mechanical integrity, insolubility, and long-term stability to the protein. These characteristics hinder the structural elucidation of mature elastin. However, MS(2) data of linear and cross-linked peptides released by proteolysis can provide indirect insights into the structure of elastin. In this study, we performed energy-resolved collision-induced dissociation experiments of DES, IDES, their derivatives, and DES-/IDES-containing peptides to determine characteristic product ions. It was found that all investigated compounds yielded the same product ion clusters at elevated collision energies. Elemental composition determination using the exact masses of these ions revealed molecular formulas of the type CxHyN, suggesting that the pyridinium core of DES/IDES remains intact even at relatively high collision energies. The finding of these specific product ions enabled the development of a similarity-based scoring algorithm that was successfully applied on LC-MS/MS data of bovine elastin digests for the identification of DES-/IDES-cross-linked peptides. This approach facilitates the straightforward investigation of native cross-links in elastin.

Synthesis and Characterization of Stimuli-Responsive Star-Like Polypept(o)ides: Introducing Biodegradable PeptoStars.

PubMed

Holm, Regina; Weber, Benjamin; Heller, Philipp; Klinker, Kristina; Westmeier, Dana; Docter, Dominic; Stauber, Roland H; Barz, Matthias

2017-06-01

Star-like polymers are one of the smallest systems in the class of core crosslinked polymeric nanoparticles. This article reports on a versatile, straightforward synthesis of three-arm star-like polypept(o)ide (polysarcosine-block-polylysine) polymers, which are designed to be either stable or degradable at elevated levels of glutathione. Polypept(o)ides are a recently introduced class of polymers combining the stealth-like properties of the polypeptoid polysarcosine with the functionality of polypeptides, thus enabling the synthesis of materials completely based on endogenous amino acids. The star-like homo and block copolymers are synthesized by living nucleophilic ring opening polymerization of the corresponding N-carboxyanhydrides (NCAs) yielding polymeric stars with precise control over the degree of polymerization (X n = 25, 50, 100), Poisson-like molecular weight distributions, and low dispersities (Đ = 1.06-1.15). Star-like polypept(o)ides display a hydrodynamic radius of 5 nm (μ 2 < 0.05) as determined by dynamic light scattering (DLS). While star-like polysarcosines and polypept(o)ides based on disulfide containing initiators are stable in solution, degradation occurs at 100 × 10 -3 m glutathione concentration. The disulfide cleavage yields the respective polymeric arms, which possess Poisson-like molecular weight distributions and low dispersities (Đ = 1.05-1.12). Initial cellular uptake and toxicity studies reveal that PeptoStars are well tolerated by HeLa, HEK 293, and DC 2.4 cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Global Earth Observation System of Systems (GEOSS): Initial Actions to Enhance Data Sharing to Meet Societal Needs

NASA Astrophysics Data System (ADS)

Adang, T.

2006-05-01

Over 60 nations and 50 participating organizations are working to make the Global Earth Observation System of Systems (GEOSS) a reality. The U.S. contribution to GEOSS is the Integrated Earth Observation System (IEOS), with a vision of enabling a healthy public, economy and planet through an integrated, comprehensive, and sustained Earth observation system. The international Group on Earth Observations (GEO) and the U.S. Group on Earth Observations have developed strategic plans for both GEOSS and IEOS, respectively, and are now working the first phases of implementation. Many of these initial actions are data architecture related and are being addressed by architecture and data working groups from both organizations - the GEO Architecture and Data Committee and the USGEO Architecture and Data Management Working Group. NOAA has actively participated in both architecture groups and has taken internal action to better support GEOSS and IEOS implementation by establishing the Global Earth Observation Integrated Data Environment (GEO IDE). GEO IDE provides a "system of systems" framework for effective and efficient integration of NOAA's many quasi-independent systems, which individually address diverse mandates in such areas resource management, weather forecasting, safe navigation, disaster response, and coastal mapping among others. GEO IDE will have a services oriented architecture, allowing NOAA Line Offices to retain a high level of independence in many of their data management decisions, and encouraging innovation in pursuit of their missions. Through GEO IDE, NOAA partners (both internal and external) will participate in a well-ordered, standards-based data and information infrastructure that will allow users to easily locate, acquire, integrate and utilize NOAA data and information. This paper describes the initial progress being made by GEO and USGEO architecture and data working groups, a status report on GEO IDE development within NOAA, and an assessment of how GEO IDE can facilitate greater progress in GEOSS and IEOS development.

Sci-Thur AM: YIS – 03: Combining sagittally-reconstructed 3D and live-2D ultrasound for high-dose-rate prostate brachytherapy needle segmentation

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

Hrinivich, Thomas; Hoover, Douglas; Surry, Kathlee

Ultrasound-guided high-dose-rate prostate brachytherapy (HDR-BT) needle segmentation is performed clinically using live-2D sagittal images. Organ segmentation is then performed using axial images, introducing a source of geometric uncertainty. Sagittally-reconstructed 3D (SR3D) ultrasound enables both needle and organ segmentation, but suffers from shadow artifacts. We present a needle segmentation technique augmenting SR3D with live-2D sagittal images using mechanical probe tracking to mitigate image artifacts and compare it to the clinical standard. Seven prostate cancer patients underwent TRUS-guided HDR-BT during which the clinical and proposed segmentation techniques were completed in parallel using dual ultrasound video outputs. Calibrated needle end-length measurements were usedmore » to calculate insertion depth errors (IDEs), and the dosimetric impact of IDEs was evaluated by perturbing clinical treatment plan source positions. The proposed technique provided smaller IDEs than the clinical approach, with mean±SD of −0.3±2.2 mm and −0.5±3.7mm respectively. The proposed and clinical techniques resulted in 84% and 43% of needles with IDEs within ±3mm, and IDE ranges across all needles of [−7.7mm, 5.9mm] and [−9.3mm, 7.7mm] respectively. The proposed and clinical IDEs lead to mean±SD changes in the volume of the prostate receiving the prescription dose of −0.6±0.9% and −2.0±5.3% respectively. The proposed technique provides improved HDR-BT needle segmentation accuracy over the clinical technique leading to decreased dosimetric uncertainty by eliminating the axial-to-sagittal registration, and mitigates the effect of shadow artifacts by incorporating mechanically registered live-2D sagittal images.« less

The effect of transmitted HIV-1 drug resistance on pre-therapy viral load.

PubMed

Harrison, Linda; Castro, Hannah; Cane, Patricia; Pillay, Deenan; Booth, Clare; Phillips, Andrew; Geretti, Anna Maria; Dunn, David

2010-07-31

Reduced replication capacity of viruses expressing drug resistant mutations implies that patients with transmitted drug resistance (TDR) could have lower HIV RNA viral load than those infected with wild-type virus. We performed analysis using data from the UK HIV Drug Resistance Database and the UK CHIC study. Eligible patients had a resistance test performed between 1997 and 2007 while naive to antiretroviral therapy, were 16 years or older, and had a viral load and CD4 cell count measurement within 6 months of this test. Models were adjusted for CD4 cell count, viral subtype, ethnicity, risk group, sex, age, calendar year, clinical centre, and viral load assay. Of a total of 7994 patients included, 709 (9%) had TDR: 604 (85%) had resistance to one drug class only [350 nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 164 non-nucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 90 protease inhibitors (PIs)], 77 (11%) to two classes (42 NRTIs/NNRTIs, 31 NRTIs/PIs, 4 NNRTIs/PIs), and 28 (4%) had resistance to all three classes. The overall mean (SD) viral load at the time of resistance testing was 4.60 (0.82) log(10) copies/ml, and did not differ by class of TDR. However, patients harbouring M184V/I (n = 61) had a significantly lower viral load [adjusted mean difference -0.33 log10 copies/ml (95% CI -0.54 to -0.11), 53% lower (95% CI 22 to 71%), P = 0.002] compared to wild-type virus. Our study provides clear evidence of an in-vivo fitness cost associated with the M184V/I mutation independent of drug effects which select for this mutation. This was not observed for any other mutation, but true effects may have been obscured by reversion of initially resistant viruses to wild-type.

Evaluation of Learning Environments for Object-Oriented Programming: Measuring Cognitive Load with a Novel Measurement Technique

ERIC Educational Resources Information Center

Uysal, Murat Pasa

2016-01-01

Various methods and tools have been proposed to overcome the learning obstacles for Object-Oriented Programming (OOP). However, it remains difficult especially for novice learners. The problem may be not only adopting an instructional method, but also an Integrated Development Environment (IDE). Learners employ IDEs as a means to solve programming…

Support Vector Machines: Relevance Feedback and Information Retrieval.

ERIC Educational Resources Information Center

Drucker, Harris; Shahrary, Behzad; Gibbon, David C.

2002-01-01

Compares support vector machines (SVMs) to Rocchio, Ide regular and Ide dec-hi algorithms in information retrieval (IR) of text documents using relevancy feedback. If the preliminary search is so poor that one has to search through many documents to find at least one relevant document, then SVM is preferred. Includes nine tables. (Contains 24…

Project Scheduling Tool for Maintaining Capability Interdependencies and Defence Program Investment: A User’s Guide

DTIC Science & Technology

2014-09-01

The free, open-source Integrated Development Environment (IDE) NetBeans [11] was used in the creation of the Graphical User Interface (GUI) for the tool...Oracle Corporation (2013) NetBeans IDE 7.4, http://www.netbeans.org. 12. O’Shea, K., Pong, P. & Bulluss, G. (2012) Fit-for-Purpose Visualisation of

Categorizing the Educational Affordances of 3-Dimensional Immersive Digital Environments

ERIC Educational Resources Information Center

Rueda, Christian Jonathan Angel; Godínes, Juan Carlos Valdés; Rudman, Paul Douglas

2018-01-01

Aim/Purpose: This paper provides a general-purpose categorization scheme for assessing the utility of new and emerging three-dimensional interactive digital environments (3D-IDEs), along with specific pedagogic approaches that are known to work. It argues for the use of 3D-IDEs on the basis of their ludic appeal and ability to provide intrinsic…

Understanding United States Investigational Device Exemption Studies-Clinical Relevance and Importance for Healthcare Economics.

PubMed

Ament, Jared D; Mollan, Scott; Greenan, Krista; Binyamin, Tamar; Kim, Kee D

2017-06-01

The US Food and Drug Administration allows a previously unapproved device to be used clinically to collect safety and effectiveness data under their Investigational Device Exemption (IDE) category. The process usually falls under 3 different trial categories: noninferiority, equivalency, and superiority. To confidently inform our patients, understanding the basic concepts of these trials is paramount. The purpose of this manuscript was to provide a comprehensive review of these topics using recently published IDE trials and economic analyses of cervical total disc replacement as illustrative examples. In 2006, an IDE was initiated to study the safety and effectiveness of total disc replacement controlled against the standard of care, anterior cervical discectomy, and fusion. Under the IDE, randomized controlled trials comparing both 1 and 2 level cervical disease were completed. The sponsor designed the initial trial as noninferiority; however, using adaptive methodology, superiority could be claimed in the 2-level investigation. Healthcare economics are critical in medical decision making and reimbursement practices. Once both cost- and quality-adjusted life-year (QALY) are known for each patient, the incremental cost-effectiveness ratio is calculated. Willingness-to-pay is controversial, but a commonly cited guideline considers interventions costing below 20 000 $/QALY strongly cost effective and more than 100 000 $/QALY as not cost effective. While large Food and Drug Administration IDE studies are often besieged by complex statistical considerations and calculations, it is fundamentally important that clinicians understand at least the terminology and basic concepts on a practical level. Copyright © 2017 by the Congress of Neurological Surgeons

Long-term bilayer encapsulation performance of atomic layer deposited Al₂O₃ and Parylene C for biomedical implantable devices.

PubMed

Xie, Xianzong; Rieth, Loren; Caldwell, Ryan; Diwekar, Mohit; Tathireddy, Prashant; Sharma, Rohit; Solzbacher, Florian

2013-10-01

We present an encapsulation scheme that combines atomic layer deposited (ALD) Al₂O₃ and Parylene C for the encapsulation of implantable devices. The encapsulation performances of combining alumina and Parylene C was compared to individual layers of Parylene C or alumina and the bilayer coating had superior encapsulation properties. The alumina-Parylene coated interdigitated electrodes (IDEs) soaked in PBS for up to nine months at temperatures from 37 to 80 °C for accelerated lifetime testing. For 52-nm alumina and 6-μm Parylene C, leakage current was ∼20 pA at 5 VDC, and the impedance was about 3.5 MΩ at 1 kHz with a phase near -87° from electrochemical impedance spectroscopy for samples soaked at 67 °C for equivalent lifetime of 72 months at 37 °C. The change of impedance during the whole soaking period (up to 70 months of equivalent soaking time at 37 °C) over 1 to 10⁶ Hz was within 5%. The stability of impedance indicated almost no degradation of the encapsulation. Bias voltage effect was studied by continuously applying 5 VDC, and it reduced the lifetime of Parylene coating by ∼75% while it showed no measurable effect on the bilayer coating. Lifetime of encapsulation of IDEs with topography generated by attaching a coil and surface mount device (SMD) capacitor was about half of that of planer IDEs. The stable long-term insulation impedance, low leakage current, and better lifetime under bias voltage and topography made this double-layer encapsulation very promising for chronic implantable devices.

Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

PubMed Central

Chin-Chan, Miguel; Navarro-Yepes, Juliana; Quintanilla-Vega, Betzabet

2015-01-01

Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action. PMID:25914621

Technology Readiness Assessment (TRA) Deskbook

DTIC Science & Technology

2009-07-01

Document CDER Center for Drug Evaluation and Research CDR Critical Design Review CDRH Center for Devices and Radiologic Health CFD computational fluid...gational Device Exemption (IDE) meeting is held with Center for Devices and Radiological Health ( CDRH ) for proposed Class III devices, and the IDE...is prepared and submitted to CDRH . For a 510(k), determine substantially equivalent devices and their classification, validate func- tioning model

Interdigitated electrodes (IDE) using elastomer functionalized multi-walled carbon nanotube (MWNT) nanocomposites for the detection of oil spills

NASA Astrophysics Data System (ADS)

Kim, Tae-Yong; Lee, Hyunseung; Park, Boyeong; Kim, Yangsoo

2018-03-01

IDE using elastomer functionalized MWNT nanocomposites was fabricated and applied for the oil sensor. Two types of nanocomposites (i.e., MWNT-grafting-polyisoprene and Si-MWNT/natural rubber) having elastomer content of ~70 wt% were used as a sensing material of oil sensor and the relative electrical resistance response of the sensor to three different kinds of oils (i.e., gasoline, engine oil and pump oil) was investigated. Among three kinds of oils, the response of MWNT-grafting-polyisoprene nanocomposites IDE sensor to gasoline was the most significant. It showed the maximum relative electrical resistance of 18 within 20 min of dropping of 200 μL gasoline at room temperature for the MWNT-grafting-polyisoprene nanocomposites, which is far superior in sensitivity to the experimental results reported by Ponnamma et al in 2016 [1]. On the other hand, the response of Si-MWNT/natural rubber nanocomposites IDE sensor to gasoline was not appreciable. The elastomer functionalized MWNT nanocomposites prepared by “grafting-from” method, which is MWNT-grafting-polyisoprene in this study, is an excellent candidate material for the detection of oil spills.

Structure-activity relationships of Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human Insulin-Degrading Enzyme

PubMed Central

Charton, Julie; Gauriot, Marion; Totobenazara, Jane; Hennuyer, Nathalie; Dumont, Julie; Bosc, Damien; Marechal, Xavier; Elbakali, Jamal; Herledan, Adrien; Wen, Xiaoan; Ronco, Cyril; Gras-Masse, Helene; Heninot, Antoine; Pottiez, Virginie; Landry, Valerie; Staels, Bart; Liang, Wenguang G.; Leroux, Florence; Tang, Wei-Jen; Deprez, Benoit; Deprez-Poulain, Rebecca

2015-01-01

Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-β and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer’s disease, amyloid-β clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along with improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE’s role. PMID:25489670

Tool Integration Framework for Bio-Informatics

DTIC Science & Technology

2007-04-01

Java NetBeans [11] based Integrated Development Environment (IDE) for developing modules and packaging computational tools. The framework is extremely...integrate an Eclipse front-end for Desktop Integration. Eclipse was chosen over Netbeans owing to a higher acceptance, better infrastructure...5.0. This version of Dashboard ran with NetBeans IDE 3.6 requiring Java Runtime 1.4 on a machine with Windows XP. The toolchain is executed by

Recommendations from the Investigational New Drug/Investigational Device Exemption Task Force of the clInical and Translational Science Award Consortium: developing and implementing a sponsor-investigators training program.

PubMed

Holbein, M E Blair; Berglund, Jelena Petrovic; O'Reilly, Erin K; Hartman, Karen; Speicher, Lisa A; Adamo, Joan E; O'Riordan, Gerri; Brown, Jennifer Swanton; Schuff, Kathryn G

2014-06-01

The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers. A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role. The participants who developed the recommendations were representatives of institutions with IND/IDE support programs. Through an informal survey, the task force determined that a variety and mix of models are used to provide support for IND/IDE holders within CTSA institutions. In addition, a CTSA consortium-wide resources survey was used. The participants worked from the models and survey results to develop consensus recommendations to address institutional support, training content, and implementation. The CTSA IND/IDE Task Force recommendations are as follows: (1) Institutions should assess the scope of Food and Drug Administration-regulated research, perform a needs analysis, and provide resources to implement a suitable training program; (2) The model of training program should be tailored to each institution; (3) The training should specifically address the unique role of sponsor-investigators, and the effectiveness of training should be evaluated regularly by methods that fit the model adopted by the institution; and (4) Institutional leadership should mandate sponsor-investigator training and effectively communicate the necessity and availability of training.

Transient Response of Superconducting Microbridges to Supercritical Currents.

DTIC Science & Technology

1983-06-01

KEY WMORS (Conitnue an revers. ide It necee.ary and Ide.ntfy by block umi. ) Time-resolved measurements voltage waveforms phase slip center...nonequilibrium superconductivity theory 10. ABSTRACT (Coninue a Faoed *#do it nocassety and identify by block ewher) We have made time-resolved measurements ... measurements were made on indium microbridges and represent an important extension of the work of Pals and Wolter (1979) to a higher critical temperature

Learning Management Platform for CyberCIEGE

DTIC Science & Technology

2011-12-01

developments were done using the NetBeans Integrated Development Environment (IDE) 7.0, which is a free and open source IDE. Some of these...developments could be implemented using the GUI design features of NetBeans . However, it was not done so because the existing Campaign Analyzer code base...directory through a dialog window. Also, the existing directory structures are not consistent with NetBeans project management assumptions and thus

Unraveling Alzheimer's: Making Sense of the Relationship between Diabetes and Alzheimer's Disease1.

PubMed

Schilling, Melissa A

2016-01-01

Numerous studies have documented a strong association between diabetes and Alzheimer's disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intranasal insulin or the inhibition of IDE would exacerbate the disease. Such antithetical conclusions pose a serious obstacle to making progress on treatments. However, careful integration of multiple strands of research, with attention to the methods used in different studies, makes it possible to disentangle the research on AD. This integration suggests that there is an important relationship between insulin, IDE, and AD that yields multiple pathways to AD depending on the where deficiency or excess in the cycle occurs. I review evidence for each of these pathways here. The results suggest that avoiding excess insulin, and supporting robust IDE levels, could be important ways of preventing and lessening the impact of AD. I also describe what further tests need to be conducted to verify the arguments made in the paper, and their implications for treating AD.

Identification and Characterization of IgdE, a Novel IgG-degrading Protease of Streptococcus suis with Unique Specificity for Porcine IgG.

PubMed

Spoerry, Christian; Seele, Jana; Valentin-Weigand, Peter; Baums, Christoph G; von Pawel-Rammingen, Ulrich

2016-04-08

Streptococcus suisis a major endemic pathogen of pigs causing meningitis, arthritis, and other diseases. ZoonoticS. suisinfections are emerging in humans causing similar pathologies as well as severe conditions such as toxic shock-like syndrome. Recently, we discovered an IdeS family protease ofS. suisthat exclusively cleaves porcine IgM and represents the first virulence factor described, linkingS. suisto pigs as their natural host. Here we report the identification and characterization of a novel, unrelated protease ofS. suisthat exclusively targets porcine IgG. This enzyme, designated IgdE forimmunoglobulinG-degradingenzyme ofS. suis, is a cysteine protease distinct from previous characterized streptococcal immunoglobulin degrading proteases of the IdeS family and mediates efficient cleavage of the hinge region of porcine IgG with a high degree of specificity. The findings that allS. suisstrains investigated possess the IgG proteolytic activity and that piglet serum samples contain specific antibodies against IgdE strongly indicate that the protease is expressedin vivoduring infection and represents a novel and putative important bacterial virulence/colonization determinant, and a thus potential therapeutic target. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Distributed Electrical Energy Systems: Needs, Concepts, Approaches and Vision (in Chinese)

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

Zhang, Yingchen; Zhang, Jun; Gao, Wenzhong

Intelligent distributed electrical energy systems (IDEES) are featured by vast system components, diversifled component types, and difficulties in operation and management, which results in that the traditional centralized power system management approach no longer flts the operation. Thus, it is believed that the blockchain technology is one of the important feasible technical paths for building future large-scale distributed electrical energy systems. An IDEES is inherently with both social and technical characteristics, as a result, a distributed electrical energy system needs to be divided into multiple layers, and at each layer, a blockchain is utilized to model and manage its logicmore » and physical functionalities. The blockchains at difierent layers coordinate with each other and achieve successful operation of the IDEES. Speciflcally, the multi-layer blockchains, named 'blockchain group', consist of distributed data access and service blockchain, intelligent property management blockchain, power system analysis blockchain, intelligent contract operation blockchain, and intelligent electricity trading blockchain. It is expected that the blockchain group can be self-organized into a complex, autonomous and distributed IDEES. In this complex system, frequent and in-depth interactions and computing will derive intelligence, and it is expected that such intelligence can bring stable, reliable and efficient electrical energy production, transmission and consumption.« less

Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

PubMed Central

2011-01-01

Background To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in subjects with mild to moderate Alzheimer's disease (AD). Methods Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4) were examined. Results Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group. Conclusions Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD. Trial registration This trial was registered with ClinicalTrials.gov, registry number NCT00142805. PMID:21992747

An Intervention to Maximize Medication Management by Caregivers of Persons with Memory Loss: Intervention Overview and Two-Month Outcomes

PubMed Central

Lingler, Jennifer H.; Arida, Janet; Houze, Martin; Kaufman, Robert; Knox, Melissa; Sereika, Susan M.; Tamres, Lisa; Erlen, Judith; Amspaugh, Carolyn; Tang, Fengyan; Happ, Mary Beth

2016-01-01

Overseeing medication-taking is a critical aspect of dementia caregiving. This randomized controlled trial examined the efficacy of a tailored, problem-solving intervention designed to maximize medication management practices among caregivers of persons with memory loss. Eighty-three community-dwelling dyads (patient + informal caregiver) with a baseline average of 3 medication deficiencies participated. Home- and telephone-based sessions were delivered by nurse or social worker interventionists and addressed basic aspects of managing medications, plus tailored problem solving for specific challenges. The outcome of medication management practices was assessed using the Medication Management Instrument for Deficiencies in the Elderly (MedMaIDE) and an investigator-developed Medication Deficiency Checklist (MDC). Linear mixed modeling showed both the intervention and usual care groups had decreases in medication management problems as measured by the MedMaIDE (F=6.91, p<.01) and MDC (F=9.72, p<.01) at 2 months post-intervention. The phenomenon of reduced medication deficiencies in both groups suggests that when nurses or social workers merely raise awareness of the importance of medication adherence, there may be benefit. PMID:26804450

Altered tooth morphogenesis after silencing the planar cell polarity core component, Vangl2.

PubMed

Wu, Zhaoming; Epasinghe, Don Jeevanie; He, Jinquan; Li, Liwen; Green, David W; Lee, Min-Jung; Jung, Han-Sung

2016-12-01

Vangl2, one of the core components of the planar cell polarity (PCP) pathway, has an important role in the regulation of morphogenesis in several tissues. Although the expression of Vangl2 has been detected in the developing tooth, its role in tooth morphogenesis is not known. In this study, we show that Vangl2 is expressed in the inner dental epithelium (IDE) and in the secondary enamel knots (SEKs) of bell stage tooth germs. Inhibition of Vangl2 expression by siRNA treatment in in vitro-cultured tooth germs resulted in retarded tooth germ growth with deregulated cell proliferation and apoptosis. After kidney transplantation of Vangl2 siRNA-treated tooth germs, teeth were observed to be small and malformed. We also show that Vangl2 is required to maintain the proper pattern of cell alignment in SEKs, which maybe important for the function of SEKs as signaling centers. These results suggest that Vangl2 plays an important role in the morphogenesis of teeth.

The Importance of Artificial Intelligence for Naval Intelligence Training Simulations

DTIC Science & Technology

2006-09-01

experimental investigation described later. B. SYSTEM ARCHITECTURE The game-based simulator was created using NetBeans , which is an open source integrated...development environment (IDE) written entirely in Java using the NetBeans Platform. NetBeans is based upon the Java language which contains the...involved within the simulation are conducted in a GUI built within the NetBeans IDE. The opening display allows the user to setup the simulation

Color separation in forensic image processing using interactive differential evolution.

PubMed

Mushtaq, Harris; Rahnamayan, Shahryar; Siddiqi, Areeb

2015-01-01

Color separation is an image processing technique that has often been used in forensic applications to differentiate among variant colors and to remove unwanted image interference. This process can reveal important information such as covered text or fingerprints in forensic investigation procedures. However, several limitations prevent users from selecting the appropriate parameters pertaining to the desired and undesired colors. This study proposes the hybridization of an interactive differential evolution (IDE) and a color separation technique that no longer requires users to guess required control parameters. The IDE algorithm optimizes these parameters in an interactive manner by utilizing human visual judgment to uncover desired objects. A comprehensive experimental verification has been conducted on various sample test images, including heavily obscured texts, texts with subtle color variations, and fingerprint smudges. The advantage of IDE is apparent as it effectively optimizes the color separation parameters at a level indiscernible to the naked eyes. © 2014 American Academy of Forensic Sciences.

IDE spatio-temporal impact fluxes and high time-resolution studies of multi-impact events and long-lived debris clouds

NASA Technical Reports Server (NTRS)

Mulholland, J. Derral; Singer, S. Fred; Oliver, John P.; Weinberg, Jerry L.; Cooke, William J.; Montague, Nancy L.; Wortman, Jim J.; Kassel, Phillip C.; Kinard, William H.

1992-01-01

The purpose of the Interplanetary Dust Experiment (IDE) on the Long Duration Exposure Facility (LDEF) was to sample the cosmic dust environment and to use the spatio-temporal aspect of the experiment to distinguish between the various components of the environment: zodiacal cloud, beta meteoroids, meteor streams, interstellar dust, and orbital debris. It was found that the introduction of precise time and even rudimentary directionality as co-lateral observables in sampling the particulate environment in near-Earth space produces an enormous qualitative improvement in the information content of the impact data. The orbital debris population is extremely clumpy, being dominated by persistent clouds in which the fluxes may rise orders of magnitude above the background. The IDE data suggest a strategy to minimize the damage to sensitive spacecraft components, using the observed characteristics of cloud encounters.

Energy value of poultry byproduct meal and animal-vegetable oil blend for broiler chickens by the regression method.

PubMed

Cao, M H; Adeola, O

2016-02-01

The energy values of poultry byproduct meal (PBM) and animal-vegetable oil blend (A-V blend) were determined in 2 experiments with 288 broiler chickens from d 19 to 25 post hatching. The birds were fed a starter diet from d 0 to 19 post hatching. In each experiment, 144 birds were grouped by weight into 8 replicates of cages with 6 birds per cage. There were 3 diets in each experiment consisting of one reference diet (RD) and 2 test diets (TD). The TD contained 2 levels of PBM (Exp. 1) or A-V blend (Exp. 2) that replaced the energy sources in the RD at 50 or 100 g/kg (Exp. 1) or 40 or 80 g/kg (Exp. 2) in such a way that the same ratio were maintained for energy ingredients across experimental diets. The ileal digestible energy (IDE), ME, and MEn of PBM and A-V blend were determined by the regression method. Dry matter of PBM and A-V blend were 984 and 999 g/kg; the gross energies were 5,284 and 9,604 kcal/kg of DM, respectively. Addition of PBM to the RD in Exp. 1 linearly decreased (P < 0.05) DM, ileal and total tract of DM, energy and nitrogen digestibilities and utilization. In Exp. 2, addition of A-V blend to the RD linearly increased (P < 0.001) ileal digestibilities and total tract utilization of DM, energy and nitrogen as well as IDE, ME, and MEn. Regressions of PBM-associated IDE, ME, or MEn intake in kcal against PBM intake were: IDE = 3,537x + 4.953, r(2) = 0.97; ME = 3,805x + 1.279, r(2) = 0.97; MEn = 3,278x + 0.164, r(2) = 0.90; and A-V blend as follows: IDE = 10,616x + 7.350, r(2) = 0.96; ME = 10,121x + 0.447, r(2) = 0.99; MEn = 10,124x + 2.425, r(2) = 0.99. These data indicate the respective IDE, ME, MEn values (kcal/kg of DM) of PBM evaluated to be 3,537, 3,805, and 3,278, and A-V blend evaluated to be 10,616, 10,121, and 10,124. © 2015 Poultry Science Association Inc.

The Impact of Sino-Indian Energy Security Ambitions on Burma’s Domestic and Foreign Politics

DTIC Science & Technology

2011-12-01

and India. 142 As summarized in: Koji Kubo, “Natural Gas Export Revenue, Fiscal Balance and Inflation in Myanmar,” IDE Discussion Paper, no.225 (March...The Arab State, 87. 162 Luciani, ed., The Arab State, 89. 163 As summarized in: Koji Kubo, “Natural Gas Export Revenue, Fiscal Balance and...Inflation in Myanmar,” IDE Discussion Paper, no.225 (March 2011): 3. 164 As summarized in: Koji Kubo, “Natural Gas Export Revenue, Fiscal Balance and

Implementation and Analysis of a Threat Model for IPv6 Host Autoconfiguration

DTIC Science & Technology

2006-09-01

Collision Generator”, two Denial of Service attacks. The software was developed in NetBeans IDE 5.0, and the comments were converted to Javadoc with the...appropriate NetBeans function. A. ICMPV6 SUPPORT FOR JPCAP As the attack uses ICMPv6 messages, a means must be provided to generate these messages...ICMP packet. * * Developed in NetBeans IDE 5.0 * Makes use of Jpcap 0.5.1 library * (http://netresearch.ics.uci.edu/kfujii/jpcap/doc

The Italian Diabetes and Exercise Study 2 (IDES-2): a long-term behavioral intervention for adoption and maintenance of a physically active lifestyle.

PubMed

Balducci, Stefano; Sacchetti, Massimo; Haxhi, Jonida; Orlando, Giorgio; Zanuso, Silvano; Cardelli, Patrizia; Cavallo, Stefano; D'Errico, Valeria; Ribaudo, Maria Cristina; Di Biase, Nicolina; Salvi, Laura; Vitale, Martina; Bollanti, Lucilla; Conti, Francesco G; Nicolucci, Antonio; Pugliese, Giuseppe

2015-12-11

Physical activity (PA)/exercise have become an integral part of the management of type 2 diabetes mellitus (T2DM). However, current guidelines are difficult to put into action in this population due to a number of barriers, especially the lack of acceptable, feasible, and validated behavioral intervention strategies. The present manuscript reports the rationale, study design and methods, and design considerations of the Italian Diabetes and Exercise Study (IDES)-2, a randomized controlled trial testing the efficacy of a behavior change strategy in increasing total daily PA and reducing sedentary time (SED-time) in patients with T2DM. Starting 7 January 2014, the IDES_2 began enrolling 300 patients with known T2DM of at least 1-year duration in three tertiary referral outpatient Diabetes Clinics in Rome. Additional requirements are age 40 to 80 years, body mass index 27 to 40 kg/m(2), sedentary lifestyle, and physically inactive for at least 6 months, ability to walk 1.6 km without assistance, and eligibility after cardiovascular evaluation. Patients are randomized by center and within each center, by age and type of diabetes treatment to either the intervention or the control group. Patients in the intervention (INT) group (n = 150) receive theoretical and practical exercise counseling consisting of aggregated behavior change techniques (one individual theoretical counseling session plus eight twice-a-week individual theoretical and practical exercise counseling sessions) once a year for 3 years. Patients in the control (CON) group (n = 150), receive standard care, including general physician recommendations for daily PA. The primary outcomes are total daily PA and SED-time, as measured objectively by the use of an accelerometer. Secondary outcomes include physical fitness, modifiable cardiovascular risk factors, musculoskeletal disturbances, well-being/depression, and health-related quality of life. The behavioral intervention strategy tested in the IDES_2 is based on solid theoretical grounds and uses several behavioral change techniques, two factors which were found to improve effectiveness of behavioral intervention. In addition, physicians and exercise specialists have been specifically trained for counselling/prescribing and supervising PA/exercise, respectively, in subjects suffering from metabolic disorders. Finally, the large sample size, the long study duration, and the objective measurement of PA allow statistically significant and scientifically robust conclusions to be drawn on the feasibility and efficacy of this intervention in T2DM patients. ClinicalTrials.gov; NCT01600937 ; 10 October 2012.

[Interdisciplinary aspects of and new drugs for chronic hepatitis B].

PubMed

Horváth, Gábor

2013-07-21

Hepatitis B virus infection is a significant health problem worldwide. The prevalence of HBsAg positivity is about 0.5-0.7% in Hungary. Liver cirrhosis and/or hepatocellular carcinoma develops in 15-40% of chronic hepatitis B virus infected patients without treatment. The ultimate goal of treatment would be to clear the virus from the infected subject; however, in practice, we can usually achieve long term suppression of viral replicaton with consequent prevention of the progression of liver disease, and reduction of the risk of the development of liver cirrhosis and hepatocellular carcinoma. Currently, there are two different treatment strategies for patients with chronic hepatitis B virus infection: therapy of finite duration with interferon or long-term treatment with nucleot(s)ide analogues. Entecavir and tenofovir are the two most effective nucleot(s)ide analogues with high barrier to resistance, thus, they can be confidently used as first-line treatments. Lamivudine engenders very high rates of resistance; adefovir is less efficacious than entecavir or tenofovir, and also engendering higher rates of resistance, thus none of them are recommended for initiation of a new treatment. Tenofovir is the treatment option in cases with lamivudine resistance, because entecavir has an unfavourable resistance-profile in this group of patients. Interferon is contraindicated during pregnancy. Should treatment of chronic hepatitis B virus infection be necessary during pregnancy, tenofovir, listed by the FDA as pregnancy category B drug, is to be preferred. Nucleot(s)ide analogues may be used to reduce the risk of intra-uterine and perinatal transmission of hepatitis B virus, which may occur in a proportion of newborns from highly viremic mothers, despite active and passive immunization. Similarly, tenofovir is recommended in the last trimester of pregnancy for women with high viremia. The risk of reactivation of chronic hepatitis B virus infection is high in HBsAg positive patients, and in patients with occult hepatitis B virus infection during and after chemotherapy or immunosuppressive treatment, including biological response modifiers (particularly related to rituximab therapy). Therefore, all candidates for these treatments should be screened for HBsAg and anti-HBc. Pre-emptive nucleot(s)ide analogues therapy should be initiated in patients with HBsAg positivity, and patients with occult hepatitis B virus infection. The role of general practitioners and occupational health physicians in the identification and the prevention of hepatitis B virus infection is stressed. Issues of high risk population groups, candidacy for vaccination, and methodology of active and passive immunisation are also reviewed in this paper.

The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes

PubMed Central

Tavis, John E.; Totten, Michael; Cao, Feng; Michailidis, Eleftherios; Aurora, Rajeev; Meyers, Marvin J.; Jacobsen, E. Jon; Parniak, Michael A.; Sarafianos, Stefan G.

2013-01-01

Nucleos(t)ide analog therapy blocks DNA synthesis by the hepatitis B virus (HBV) reverse transcriptase and can control the infection, but treatment is life-long and has high costs and unpredictable long-term side effects. The profound suppression of HBV by the nucleos(t)ide analogs and their ability to cure some patients indicates that they can push HBV to the brink of extinction. Consequently, more patients could be cured by suppressing HBV replication further using a new drug in combination with the nucleos(t)ide analogs. The HBV ribonuclease H (RNAseH) is a logical drug target because it is the second of only two viral enzymes that are essential for viral replication, but it has not been exploited, primarily because it is very difficult to produce active enzyme. To address this difficulty, we expressed HBV genotype D and H RNAseHs in E. coli and enriched the enzymes by nickel-affinity chromatography. HBV RNAseH activity in the enriched lysates was characterized in preparation for drug screening. Twenty-one candidate HBV RNAseH inhibitors were identified using chemical structure-activity analyses based on inhibitors of the HIV RNAseH and integrase. Twelve anti-RNAseH and anti-integrase compounds inhibited the HBV RNAseH at 10 µM, the best compounds had low micromolar IC50 values against the RNAseH, and one compound inhibited HBV replication in tissue culture at 10 µM. Recombinant HBV genotype D RNAseH was more sensitive to inhibition than genotype H. This study demonstrates that recombinant HBV RNAseH suitable for low-throughput antiviral drug screening has been produced. The high percentage of compounds developed against the HIV RNAseH and integrase that were active against the HBV RNAseH indicates that the extensive drug design efforts against these HIV enzymes can guide anti-HBV RNAseH drug discovery. Finally, differential inhibition of HBV genotype D and H RNAseHs indicates that viral genetic variability will be a factor during drug development. PMID:23349632

Ultrasensitive interdigitated capacitance immunosensor using gold nanoparticles.

PubMed

Alizadeh Zeinabad, Hojjat; Ghourchian, Hedayatollah; Falahati, Mojtaba; Fathipour, Morteza; Azizi, Marzieh; Boutorabi, Seyed Mehdi

2018-06-29

Immunosensors based on interdigitated electrodes (IDEs), have recently demonstrated significant improvements in the sensitivity of capacitance detection. Herein, a novel type of highly sensitive, compact and portable immunosensor based on a gold interdigital capacitor has been designed and developed for the rapid detection of hepatitis B surface antigen (HBsAg). To improve the efficiency of antibody immobilization and time-saving, a self-assembled monolayer (SAM) of 2-mercaptoethylamine film was coated on IDEs. Afterwards, carboxyl groups on primary antibodies were activated through 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and were immobilized on amino-terminated SAM for better control of the oriented immobilization of antibodies on gold IDEs. In addition, gold nanoparticles conjugated with a secondary antibody were used to enhance the sensitivity. Under optimal conditions, the immunosensor exhibited the sensitivity of 0.22 nF.pg ml -1 , the linear range from 5 pg ml -1 to 1 ng ml -1 and the detection limit of 1.34 pg ml -1 , at a signal-to-noise ratio of 3.

Simulations of Interdigitated Electrode Interactions with Gold Nanoparticles for Impedance-Based Biosensing Applications

PubMed Central

MacKay, Scott; Hermansen, Peter; Wishart, David; Chen, Jie

2015-01-01

In this paper, we describe a point-of-care biosensor design. The uniqueness of our design is in its capability for detecting a wide variety of target biomolecules and the simplicity of nanoparticle enhanced electrical detection. The electrical properties of interdigitated electrodes (IDEs) and the mechanism for gold nanoparticle-enhanced impedance-based biosensor systems based on these electrodes are simulated using COMSOL Multiphysics software. Understanding these properties and how they can be affected is vital in designing effective biosensor devices. Simulations were used to show electrical screening develop over time for IDEs in a salt solution, as well as the electric field between individual digits of electrodes. Using these simulations, it was observed that gold nanoparticles bound closely to IDEs can lower the electric field magnitude between the digits of the electrode. The simulations are also shown to be a useful design tool in optimizing sensor function. Various different conditions, such as electrode dimensions and background ion concentrations, are shown to have a significant impact on the simulations. PMID:26364638

A sensitive electrochemical immunosensor for label-free detection of Zika-virus protein.

PubMed

Kaushik, Ajeet; Yndart, Adriana; Kumar, Sanjeev; Jayant, Rahul Dev; Vashist, Arti; Brown, Ashley N; Li, Chen-Zhong; Nair, Madhavan

2018-06-26

This work, as a proof of principle, presents a sensitive and selective electrochemical immunosensor for Zika-virus (ZIKV)-protein detection using a functionalized interdigitated micro-electrode of gold (IDE-Au) array. A miniaturized IDE-Au immunosensing chip was prepared via immobilization of ZIKV specific envelop protein antibody (Zev-Abs) onto dithiobis(succinimidyl propionate) i.e., (DTSP) functionalized IDE-Au (electrode gap/width of 10 µm). Electrochemical impedance spectroscopy (EIS) was performed to measure the electrical response of developed sensing chip as a function of ZIKV-protein concentrations. The results of EIS studies confirmed that sensing chip detected ZIKV-protein selectively and exhibited a detection range from 10 pM to 1 nM and a detection limit of 10 pM along with a high sensitivity of 12 kΩM -1 . Such developed ZIKV immune-sensing chip can be integrated with a miniaturized potentiostat (MP)-interfaced with a smartphone for rapid ZIKV-infection detection required for early stage diagnostics at point-of-care application.

HPV DNA target hybridization concentrations studies using interdigitated electrodes (IDE) for early detection of cervical cancer

NASA Astrophysics Data System (ADS)

Noriani, C.; Hashim, U.; Azizah, N.; Nadzirah, Sh.; Arshad, M. K. Md; Ruslinda, A. R.; Gopinath, Subash C. B.

2017-03-01

Human Papillomaviruses (HPV) is the major cause of cervical cancer. HPV 16 and HPV 18 are the two types of HPV are the most HPV-associated cancers and responsible as a high-risk HPV. Cervical cancer took about 70 percent of all cases due to HPV infections. Cervical cancer mostly growth on a woman's cervix and its was developed slowly as cancer. TiO2 particles give better performance and low cost of the biosensor. The used of 3-aminopropyl triethoxysilane (APTES) will be more efficient for DNA nanochip. APTES used as absorption reaction to immobilize organic biomolecules on the inorganic surface. Furthermore, APTES provide better functionalization of the adsorption mechanism on IDE. The surface functionalized for immobilizing the DNA, which is the combination of the DNA probe and the HPV target produces high sensitivity and speed detection of the IDE. The Current-Voltage (IV) characteristic proved the sensitivity of the DNA nanochip increase as the concentration varied from 0% concentration to 24% of APTES concentration.

Ultrasensitive interdigitated capacitance immunosensor using gold nanoparticles

NASA Astrophysics Data System (ADS)

Alizadeh Zeinabad, Hojjat; Ghourchian, Hedayatollah; Falahati, Mojtaba; Fathipour, Morteza; Azizi, Marzieh; Boutorabi, Seyed Mehdi

2018-06-01

Immunosensors based on interdigitated electrodes (IDEs), have recently demonstrated significant improvements in the sensitivity of capacitance detection. Herein, a novel type of highly sensitive, compact and portable immunosensor based on a gold interdigital capacitor has been designed and developed for the rapid detection of hepatitis B surface antigen (HBsAg). To improve the efficiency of antibody immobilization and time-saving, a self-assembled monolayer (SAM) of 2-mercaptoethylamine film was coated on IDEs. Afterwards, carboxyl groups on primary antibodies were activated through 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and were immobilized on amino-terminated SAM for better control of the oriented immobilization of antibodies on gold IDEs. In addition, gold nanoparticles conjugated with a secondary antibody were used to enhance the sensitivity. Under optimal conditions, the immunosensor exhibited the sensitivity of 0.22 nF.pg ml–1, the linear range from 5 pg ml‑1 to 1 ng ml–1 and the detection limit of 1.34 pg ml‑1, at a signal-to-noise ratio of 3.

Subunit mass analysis for monitoring antibody oxidation.

PubMed

Sokolowska, Izabela; Mo, Jingjie; Dong, Jia; Lewis, Michael J; Hu, Ping

2017-04-01

Methionine oxidation is a common posttranslational modification (PTM) of monoclonal antibodies (mAbs). Oxidation can reduce the in-vivo half-life, efficacy and stability of the product. Peptide mapping is commonly used to monitor the levels of oxidation, but this is a relatively time-consuming method. A high-throughput, automated subunit mass analysis method was developed to monitor antibody methionine oxidation. In this method, samples were treated with IdeS, EndoS and dithiothreitol to generate three individual IgG subunits (light chain, Fd' and single chain Fc). These subunits were analyzed by reversed phase-ultra performance liquid chromatography coupled with an online quadrupole time-of-flight mass spectrometer and the levels of oxidation on each subunit were quantitated based on the deconvoluted mass spectra using the UNIFI software. The oxidation results obtained by subunit mass analysis correlated well with the results obtained by peptide mapping. Method qualification demonstrated that this subunit method had excellent repeatability and intermediate precision. In addition, UNIFI software used in this application allows automated data acquisition and processing, which makes this method suitable for high-throughput process monitoring and product characterization. Finally, subunit mass analysis revealed the different patterns of Fc methionine oxidation induced by chemical and photo stress, which makes it attractive for investigating the root cause of oxidation.

Substrate effects in high gain, low operating voltage SnSe2 photoconductor

NASA Astrophysics Data System (ADS)

Krishna, Murali; Kallatt, Sangeeth; Majumdar, Kausik

2018-01-01

High gain photoconductive devices find wide spread applications in low intensity light detection. Ultra-thin layered materials have recently drawn a lot of attention from researchers in this regard. However, in general, a large operating voltage is required to obtain large responsivity in these devices. In addition, the characteristics are often confounded by substrate induced trap effects. Here we report multi-layer SnSe2 based photoconductive devices using two different structures: (1) SiO2 substrate supported inter-digitated electrode (IDE), and (2) suspended channel. The IDE device exhibits a responsivity of ≈ {10}3 A W-1 and ≈ 8.66× {10}4 A W-1 at operating voltages of 1 mV and 100 mV, respectively—a superior low voltage performance over existing literature on planar 2D structures. However, the responsivity reduces by more than two orders of magnitude, while the transient response improves for the suspended device—providing insights into the critical role played by the channel-substrate interface in the gain mechanism. The results, on one hand, are promising for highly sensitive photoconductive applications consuming ultra-low power, and on the other hand, show a generic methodology that could be applied to other layered material based photoconductive devices as well for extracting the intrinsic behavior.

The study of concentration effects of target hybridization on cervical cancer detection using interdigitated electrodes (IDE)

NASA Astrophysics Data System (ADS)

Noriani, C.; Hashim, U.; Azizah, N.

2016-07-01

Human Papilloma Virus (HPV) is a virus from the Papilloma virus family that affects human skin and the moist membranes that line the body, such as the throat, mouth, feet, fingers, nails, anus and cervix [1]. There are over 100 types, of which 40 can affect the genital area. Most known HPV types cause no symptoms to humans. Some, however, can cause verrucae (warts), while a small number can increase the risk of developing several cancers, such as that of the cervix, penis, vagina, anus and oropharynx (oral part of the pharynx - throat cancer). HPV strand 16 and 18 are well known for causing the advanced of Cervical Cancer (CC). Currently, integrated electrodes (IDEs) are implemented in various sensing devices including surface acoustic wave (SAW) sensors, chemical sensors as well as current MEMS biosensors. IDEs have been optimized for a variety of sensing applications including biosensors sensors, acoustic sensors, and chemical sensors. However, optimization for cancer cell detection has yet to be reported. The output signal strength of IDEs is controlled through careful design of the active area, width, and spacing of the electrode fingers the efficiency of DNA nanochip depends mainly on the sequence of the capture probes and the way they are attached to the support [2]. This strategy presented a simple, rapid and sensitive platform for HPV detection and would become a powerful tool for pathogenic microorganisms screening in clinical diagnosis. The coupling procedure must be quick, covalent, and reproducible.

Fabrication of interdigitated high-performance zinc oxide nanowire modified electrodes for glucose sensing.

PubMed

Haarindraprasad, R; Hashim, Uda; Gopinath, Subash C B; Perumal, Veeradasan; Liu, Wei-Wen; Balakrishnan, S R

2016-06-21

Diabetes is a metabolic disease with a prolonged elevated level of glucose in the blood leads to long-term complications and increases the chances for cardiovascular diseases. The present study describes the fabrication of a ZnO nanowire (NW)-modified interdigitated electrode (IDE) to monitor the level of blood glucose. A silver IDE was generated by wet etching-assisted conventional lithography, with a gap between adjacent electrodes of 98.80 μm. The ZnO-based thin films and NWs were amended by sol-gel and hydrothermal routes. High-quality crystalline and c-axis orientated ZnO thin films were observed by XRD analyses. The ZnO thin film was annealed for 1, 3 and 5 h, yielding a good-quality crystallite with sizes of 50, 100 and 110 nm, and the band gaps were measured as 3.26, 3.20 and 3.17 eV, respectively. Furthermore, a flower-modeled NW was obtained with the lowest diameter of 21 nm. Our designed ZnO NW-modified IDE was shown to have a detection limit as low as 0.03 mg/dL (correlation coefficient = 0.98952) of glucose with a low response time of 3 s, perform better than commercial glucose meter, suitable to instantly monitor the glucose level of diabetes patients. This study demonstrated the high performance of NW-mediated IDEs for glucose sensing as alternative to current glucose sensors. Copyright © 2016 Elsevier B.V. All rights reserved.

Wind Turbine Power Generation Emulation Via Doubly Fed Induction Generator Control

DTIC Science & Technology

2009-12-01

vde thetas vqs_pu vds_pu synchronous...to stationary 0 ide_ref 200 Vdc_ref I_ref I_meas vqe PI iq I_ref I_meas vde PI id v_ref v_meas iqs PI Vdc 4 theta_s 3 ide 2 iqe 1 Vdc 21 between...1-1 x(-1)- a b a + b+ Sy stem Generator Variac P/S 60V 60HzVariac P/S 60V 60Hz 70 Vabc_s THETA CALCULATION 5 vde 4 vqe 3 Vas 2 Vdc_out 1

Gene expression changes leading extreme alkaline tolerance in Amur ide (Leuciscus waleckii) inhabiting soda lake

PubMed Central

2013-01-01

Background Amur ide (Leuciscus waleckii) is an economically and ecologically important cyprinid species in Northern Asia. The Dali Nor population living in the soda lake Dali Nor can adapt the extremely high alkalinity, providing us a valuable material to understand the adaptation mechanism against extreme environmental stress in teleost. Results In this study, we generated high-throughput RNA-Seq data from three tissues gill, liver and kidney of L. waleckii living in the soda lake Dali Nor and the fresh water lake Ganggeng Nor, then performed parallel comparisons of three tissues. Our results showed that out of assembled 64,603 transcript contigs, 28,391 contigs had been assigned with a known function, corresponding to 20,371 unique protein accessions. We found 477, 2,761 and 3,376 differentially expressed genes (DEGs) in the gill, kidney, and liver, respectively, of Dali Nor population compared to Ganggeng Nor population with FDR ≤ 0.01and fold-change ≥ 2. Further analysis revealed that well-known functional categories of genes and signaling pathway, which are associated with stress response and extreme environment adaptation, have been significantly enriched, including the functional categories of “response to stimulus”, “transferase activity”, “transporter activity” and “oxidoreductase activity”, and signaling pathways of “mTOR signaling”, “EIF2 signaling”, “superpathway of cholesterol biosynthesis”. We also identified significantly DEGs encoding important modulators on stress adaptation and tolerance, including carbonic anhydrases, heat shock proteins, superoxide dismutase, glutathione S-transferases, aminopeptidase N, and aminotransferases. Conclusions Overall, this study demonstrated that transcriptome changes in L. waleckii played a role in adaptation to complicated environmental stress in the highly alkalized Dali Nor lake. The results set a foundation for further analyses on alkaline-responsive candidate genes, which help us understand teleost adaptation under extreme environmental stress and ultimately benefit future breeding for alkaline-tolerant fish strains. PMID:24094069

Investigating the application of AOP methodology in development of Financial Accounting Software using Eclipse-AJDT Environment

NASA Astrophysics Data System (ADS)

Sharma, Amita; Sarangdevot, S. S.

2010-11-01

Aspect-Oriented Programming (AOP) methodology has been investigated in development of real world business application software—Financial Accounting Software. Eclipse-AJDT environment has been used as open source enhanced IDE support for programming in AOP language—Aspect J. Crosscutting concerns have been identified and modularized as aspects. This reduces the complexity of the design considerably due to elimination of code scattering and tangling. Improvement in modularity, quality and performance is achieved. The study concludes that AOP methodology in Eclipse-AJDT environment offers powerful support for modular design and implementation of real world quality business software.

Characterization of Insulin Degrading Enzyme and other Aβ Degrading Proteases in Human Serum: a Role in Alzheimer’s disease?

PubMed Central

Liu, Zhiheng; Zhu, Haihao; Fang, Guang Guang; Walsh, Kathryn; Mwamburi, Maya; Wolozin, Benjamin; Abdul-Hay, Same O.; Ikezu, Tsuneya; Lessring, Malcolm A.; Qiu, Wei Qiao

2013-01-01

Sporadic Alzheimer’s disease (AD) patients have low amyloid-β peptide (Aβ) clearance in the central nervous system (CNS). The peripheral Aβ clearance may also be important but its role in AD remains unclear. We aimed to study the Aβ degrading proteases including insulin degrading enzyme (IDE), angiotensin converting enzyme (ACE) and others in blood. Using the fluorogenic substrate V—a substrate of IDE and other metalloproteases, we showed that human serum degraded the substrate V, and the activity was inhibited by adding increasing dose of Aβ. The existence of IDE activity was demonstrated by the inhibition of insulin, amylin or EDTA, and further confirmed by immunocapture of IDE using monoclonal antibodies. The involvement of ACE was indicated by the ability of the ACE inhibitor, lisinopril, to inhibit the substrate V degradation. To test the variations of substrate V degradation in humans, we used serum samples from a homebound elderly population with cognitive diagnoses. Compared with the elderly who had normal cognition, those with probable AD and amnestic mild cognitive impairment (amnestic MCI) had lower peptidase activities. Probable AD or amnestic MCI as an outcome remained negatively associated with serum substrate V degradation activity after adjusting for the confounders. The elderly with probable AD had lower serum substrate V degradation activity compared with those who had vascular dementia. The blood proteases mediating Aβ degradation may be important for the AD pathogenesis. More studies are needed to specify each Aβ degrading protease in blood as a useful biomarker and a possible treatment target for AD. PMID:22232014

Structure guided inhibitor designing of CDK2 and discovery of potential leads against cancer.

PubMed

Kumar, Arun V A; Mohan, Keshav; Riyaz, Syed

2013-09-01

On the basis of stereo specific information obtained from crystal structures of CDK2, indole and chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked with target protein for calculating binding affinities. The binding affinities are represented in glide score. (5E)-5-[(1-methyl-1H-indol-3-yl)methylidene]-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I1), (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were selected for synthesis and biological testing based on vital interactions. (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide(I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were proved to be active against MCF-7 and HeLa cell lines.

Actuation of Piezoelectric Layered Beams With and Coupling.

PubMed

Nguyen, Cuong H; Hanke, Ulrik; Halvorsen, Einar

2018-05-01

In this paper, we derive and compare the linear static bending of piezoelectric actuators with transversal ( ) and longitudinal ( ) coupling. The transducers are, respectively, structures utilizing top and bottom electrodes (TBEs) and interdigitated electrodes (IDEs). While the theory is well developed for the TBE beam, governing equations for the bending of the piezoelectric beams with IDEs are far less developed. We improve on this by deriving the governing equation for the IDE beam with an arbitrary number of layers and with coupling consistently included. In addition, we introduce a phenomenological quadratic form for the nonuniform field that lets us derive a deflection formula with nontrivial effects of the field accounted for. The theory is applied to derive deflection formulas for both cantilever and clamped-clamped beams. All analytic results are validated with numerical simulations. From the analytic models, two different figures of merit (FOMs) are derived. We show that these FOMs are the same for cantilevers and doubly clamped beams. The analysis indicates the optimal transducer length for clamped-clamped beams and gives a criterion that can be used to determine which design concept ( or ) gives the largest deflection.

Study of different 3-aminopropyl triethoxysilane (APTES) concentration on TiO2 particles based IDE for cervical cancer detection

NASA Astrophysics Data System (ADS)

Raqeema, S.; Hashim, U.; Azizah, N.; Nadzirah, Sh.; Arshad, M. K. Md; Ruslinda, A. R.; Gopinath, Subash C. B.

2017-03-01

HPV that also called Human Papillomaviruses is the major cause of the cervical cancer. HPV 16 and HPV 18 are the two types of HPV are the most HPV-associated cancers and responsible as a high-risk HPV. Cervical cancer taken about 70 percent of all cases due HPV infections. Cervical malignancy for the most part development on a lady's cervix and its was developed slowly as cancer disease. TiO2 particles give better performance and low cost of the biosensor. The used of 3-aminopropyl triethoxysilane (APTES) will be more efficient for DNA nanochip. APTES used as absorption reaction to immobilize organic biomolecules on the inorganic surface. Besides, APTES give better functionalization of the adsorption mechanism on IDE. The surface functionalized for immobilizing the DNA, which is the combination of the DNA probe and the HPV target produce high sensitivity andfast detection of the IDE. The Current-Voltage (IV) characteristic proved the sensitivity of the DNA nanochip increase as the concentration varied from 0% concentration to 24% of APTES concentration.

Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study

PubMed Central

Chamberlain, Samuel R.; Odlaug, Brian L.; Potenza, Marc N.; Kim, Suck Won

2012-01-01

Rationale Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl d-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. Objective This study sought to examine the safety and efficacy of Memantine in PG. Methods Twenty-nine subjects (18 females) with DSM-IV PG were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra-dimensional (ID/ED) set shift task (assessing cognitive flexibility). Results Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8±4.3 at baseline to 8.9±7.1 at study endpoint (p<0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p<0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p=0.037) at study endpoint. The mean effective dose of memantine was 23.4±8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. Conclusions These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design. PMID:20721537

Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study.

PubMed

Grant, Jon E; Chamberlain, Samuel R; Odlaug, Brian L; Potenza, Marc N; Kim, Suck Won

2010-12-01

Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. This study sought to examine the safety and efficacy of Memantine in PG. Twenty-nine subjects (18 females) with DSM-IV PG were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra-dimensional (ID/ED) set shift task (assessing cognitive flexibility). Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8 ± 4.3 at baseline to 8.9 ± 7.1 at study endpoint (p < 0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p < 0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p = 0.037) at study endpoint. The mean effective dose of memantine was 23.4 ± 8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

An Introduction to a Reliability Shorthand.

DTIC Science & Technology

1981-03-01

II 00r.nt m 0 e@et IS. SUPPLEMENTARy NOTES It. KEY WORDS (CeMMle soewe" ad s it meomE, d aienf Iyp M mumbw) reliability system survival survival...function systems reliability shorthand redundant systems 20. ASISTRAGT (C411M en .MVm ideS if m I O 1411011010 IV N au11 l) -The determination of a system’s...OF TWOS IS 1 (Uim Urn. lincrl nqqi fi Pd "MTV C P06 L&a TIO 0 To oe 0S S e s O" M ef. Item 20, continued: Simple examples show the convenience of this

Evaluation of factor IX deficiency by interdigitated electrode (IDE)

NASA Astrophysics Data System (ADS)

Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

2017-03-01

Factor IX deficiency is the main cause of hemophilia A and B. This a severe excessive bleeding disorder that can even kill the patient if not treated with the right prescription of Factor IX hormone to stop the bleeding. The bleeding can be caused by an injury or even a sudden bleeding in some very rare cases. To find the Factor IX effectiveness and to understand the deficiency more carefully for the future of medicine, experiments are conducted to test the Factor IX using the Interdigitated Electrode (IDE) and gold Nanoparticle with the help of Nanoelectrical technology.

Multi-scale heterogeneity of the 2011 Great Tohoku-oki Earthquake from dynamic simulations

NASA Astrophysics Data System (ADS)

Aochi, H.; Ide, S.

2011-12-01

In order to explain the scaling issues of earthquakes of different sizes, multi-scale heterogeneity conception is necessary to characterize earthquake faulting property (Ide and Aochi, JGR, 2005; Aochi and Ide, JGR, 2009).The 2011 Great Tohoku-oki earthquake (M9) is characterized by a slow initial phase of about M7, a M8 class deep rupture, and a M9 main rupture with quite large slip near the trench (e.g. Ide et al., Science, 2011) as well as the presence of foreshocks. We dynamically model these features based on the multi-scale conception. We suppose a significantly large fracture energy (corresponding to slip-weakening distance of 3.2 m) in most of the fault dimension to represent the M9 rupture. However we give local heterogeneity with relatively small circular patches of smaller fracture energy, by assuming the linear scaling relation between the radius and fracture energy. The calculation is carried out using 3D Boundary Integral Equation Method. We first begin only with the mainshock (Aochi and Ide, EPS, 2011), but later we find it important to take into account of a series of foreshocks since the 9th March (M7.4). The smaller patches including the foreshock area are necessary to launch the M9 rupture area of large fracture energy. We then simulate the ground motion in low frequencies using Finite Difference Method. Qualitatively, the observed tendency is consistent with our simulations, in the meaning of the transition from the central part to the southern part in low frequencies (10 - 20 sec). At higher frequencies (1-10 sec), further small asperities are inferred in the observed signals, and this feature matches well with our multi-scale conception.

Going Beyond the Millennium Ecosystem Assessment: An Index System of Human Dependence on Ecosystem Services

PubMed Central

Yang, Wu; Dietz, Thomas; Liu, Wei; Luo, Junyan; Liu, Jianguo

2013-01-01

The Millennium Ecosystem Assessment (MA) estimated that two thirds of ecosystem services on the earth have degraded or are in decline due to the unprecedented scale of human activities during recent decades. These changes will have tremendous consequences for human well-being, and offer both risks and opportunities for a wide range of stakeholders. Yet these risks and opportunities have not been well managed due in part to the lack of quantitative understanding of human dependence on ecosystem services. Here, we propose an index of dependence on ecosystem services (IDES) system to quantify human dependence on ecosystem services. We demonstrate the construction of the IDES system using household survey data. We show that the overall index and sub-indices can reflect the general pattern of households' dependences on ecosystem services, and their variations across time, space, and different forms of capital (i.e., natural, human, financial, manufactured, and social capitals). We support the proposition that the poor are more dependent on ecosystem services and further generalize this proposition by arguing that those disadvantaged groups who possess low levels of any form of capital except for natural capital are more dependent on ecosystem services than those with greater control of capital. The higher value of the overall IDES or sub-index represents the higher dependence on the corresponding ecosystem services, and thus the higher vulnerability to the degradation or decline of corresponding ecosystem services. The IDES system improves our understanding of human dependence on ecosystem services. It also provides insights into strategies for alleviating poverty, for targeting priority groups of conservation programs, and for managing risks and opportunities due to changes of ecosystem services at multiple scales. PMID:23717634

Going beyond the Millennium Ecosystem Assessment: an index system of human dependence on ecosystem services.

PubMed

Yang, Wu; Dietz, Thomas; Liu, Wei; Luo, Junyan; Liu, Jianguo

2013-01-01

The Millennium Ecosystem Assessment (MA) estimated that two thirds of ecosystem services on the earth have degraded or are in decline due to the unprecedented scale of human activities during recent decades. These changes will have tremendous consequences for human well-being, and offer both risks and opportunities for a wide range of stakeholders. Yet these risks and opportunities have not been well managed due in part to the lack of quantitative understanding of human dependence on ecosystem services. Here, we propose an index of dependence on ecosystem services (IDES) system to quantify human dependence on ecosystem services. We demonstrate the construction of the IDES system using household survey data. We show that the overall index and sub-indices can reflect the general pattern of households' dependences on ecosystem services, and their variations across time, space, and different forms of capital (i.e., natural, human, financial, manufactured, and social capitals). We support the proposition that the poor are more dependent on ecosystem services and further generalize this proposition by arguing that those disadvantaged groups who possess low levels of any form of capital except for natural capital are more dependent on ecosystem services than those with greater control of capital. The higher value of the overall IDES or sub-index represents the higher dependence on the corresponding ecosystem services, and thus the higher vulnerability to the degradation or decline of corresponding ecosystem services. The IDES system improves our understanding of human dependence on ecosystem services. It also provides insights into strategies for alleviating poverty, for targeting priority groups of conservation programs, and for managing risks and opportunities due to changes of ecosystem services at multiple scales.

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution.

PubMed

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler's formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly "adaptable" and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time.

Surgical Treatment for Discogenic Low-Back Pain: Lumbar Arthroplasty Results in Superior Pain Reduction and Disability Level Improvement Compared With Lumbar Fusion

PubMed Central

2007-01-01

Background The US Food and Drug Administration approved the Charité artificial disc on October 26, 2004. This approval was based on an extensive analysis and review process; 20 years of disc usage worldwide; and the results of a prospective, randomized, controlled clinical trial that compared lumbar artificial disc replacement to fusion. The results of the investigational device exemption (IDE) study led to a conclusion that clinical outcomes following lumbar arthroplasty were at least as good as outcomes from fusion. Methods The author performed a new analysis of the Visual Analog Scale pain scores and the Oswestry Disability Index scores from the Charité artificial disc IDE study and used a nonparametric statistical test, because observed data distributions were not normal. The analysis included all of the enrolled subjects in both the nonrandomized and randomized phases of the study. Results Subjects from both the treatment and control groups improved from the baseline situation (P < .001) at all follow-up times (6 weeks to 24 months). Additionally, these pain and disability levels with artificial disc replacement were superior (P < .05) to the fusion treatment at all follow-up times including 2 years. Conclusions The a priori statistical plan for an IDE study may not adequately address the final distribution of the data. Therefore, statistical analyses more appropriate to the distribution may be necessary to develop meaningful statistical conclusions from the study. A nonparametric statistical analysis of the Charité artificial disc IDE outcomes scores demonstrates superiority for lumbar arthroplasty versus fusion at all follow-up time points to 24 months. PMID:25802574

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution

PubMed Central

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler’s formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly “adaptable” and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time. PMID:29123436

Hepatitis B Virus Capsid Assembly Modulators, but Not Nucleoside Analogs, Inhibit the Production of Extracellular Pregenomic RNA and Spliced RNA Variants

PubMed Central

Ren, Suping; Espiritu, Christine; Kelly, Mollie; Lau, Vincent; Zheng, Lingjie; Hartman, George D.; Flores, Osvaldo A.; Klumpp, Klaus

2017-01-01

ABSTRACT The hepatitis B virus (HBV) core protein serves multiple essential functions in the viral life cycle, and antiviral agents that target the core protein are being developed. Capsid assembly modulators (CAMs) are compounds that target core and misdirect capsid assembly, resulting in the suppression of HBV replication and virion production. Besides HBV DNA, circulating HBV RNA has been detected in patient serum and can be associated with the treatment response. Here we studied the effect of HBV CAMs on the production of extracellular HBV RNA using infected HepaRG cells and primary human hepatocytes. Representative compounds from the sulfonamide carboxamide and heteroaryldihydropyrimidine series of CAMs were evaluated and compared to nucleos(t)ide analogs as inhibitors of the viral polymerase. The results showed that CAMs blocked extracellular HBV RNA with efficiencies similar to those with which they blocked pregenomic RNA (pgRNA) encapsidation, HBV DNA replication, and Dane particle production. Nucleos(t)ide analogs inhibited viral replication and virion production but not encapsidation or production of extracellular HBV RNA. Profiling of HBV RNA from both culture supernatants and patient serum showed that extracellular viral RNA consisted of pgRNA and spliced pgRNA variants with an internal deletion(s) but still retained the sequences at both the 5′ and 3′ ends. Similar variants were detected in the supernatants of infected cells with and without nucleos(t)ide analog treatment. Overall, our data demonstrate that HBV CAMs represent direct antiviral agents with a profile differentiated from that of nucleos(t)ide analogs, including the inhibition of extracellular pgRNA and spliced pgRNA. PMID:28559265

Dynamical insurance models with investment: Constrained singular problems for integrodifferential equations

NASA Astrophysics Data System (ADS)

Belkina, T. A.; Konyukhova, N. B.; Kurochkin, S. V.

2016-01-01

Previous and new results are used to compare two mathematical insurance models with identical insurance company strategies in a financial market, namely, when the entire current surplus or its constant fraction is invested in risky assets (stocks), while the rest of the surplus is invested in a risk-free asset (bank account). Model I is the classical Cramér-Lundberg risk model with an exponential claim size distribution. Model II is a modification of the classical risk model (risk process with stochastic premiums) with exponential distributions of claim and premium sizes. For the survival probability of an insurance company over infinite time (as a function of its initial surplus), there arise singular problems for second-order linear integrodifferential equations (IDEs) defined on a semiinfinite interval and having nonintegrable singularities at zero: model I leads to a singular constrained initial value problem for an IDE with a Volterra integral operator, while II model leads to a more complicated nonlocal constrained problem for an IDE with a non-Volterra integral operator. A brief overview of previous results for these two problems depending on several positive parameters is given, and new results are presented. Additional results are concerned with the formulation, analysis, and numerical study of "degenerate" problems for both models, i.e., problems in which some of the IDE parameters vanish; moreover, passages to the limit with respect to the parameters through which we proceed from the original problems to the degenerate ones are singular for small and/or large argument values. Such problems are of mathematical and practical interest in themselves. Along with insurance models without investment, they describe the case of surplus completely invested in risk-free assets, as well as some noninsurance models of surplus dynamics, for example, charity-type models.

Comparison of originator and biosimilar therapeutic monoclonal antibodies using comprehensive two-dimensional liquid chromatography coupled with time-of-flight mass spectrometry.

PubMed

Sorensen, Matthew; Harmes, David C; Stoll, Dwight R; Staples, Gregory O; Fekete, Szabolcs; Guillarme, Davy; Beck, Alain

2016-10-01

As research, development, and manufacturing of biosimilar protein therapeutics proliferates, there is great interest in the continued development of a portfolio of complementary analytical methods that can be used to efficiently and effectively characterize biosimilar candidate materials relative to the respective reference (i.e., originator) molecule. Liquid phase separation techniques such as liquid chromatography and capillary electrophoresis are powerful tools that can provide both qualitative and quantitative information about similarities and differences between reference and biosimilar materials, especially when coupled with mass spectrometry. However, the inherent complexity of these protein materials challenges even the most modern one-dimensional (1D) separation methods. Two-dimensional (2D) separations present a number of potential advantages over 1D methods, including increased peak capacity, 2D peak patterns that can facilitate unknown identification, and improvement in the compatibility of some separation methods with mass spectrometry. In this study, we demonstrate the use of comprehensive 2D-LC separations involving cation-exchange (CEX) and reversed-phase (RP) separations in the first and second dimensions to compare 3 reference/biosimilar pairs of monoclonal antibodies (cetuximab, trastuzumab and infliximab) that cover a range of similarity/disimilarity in a middle-up approach. The second dimension RP separations are coupled to time-of-flight mass spectrometry, which enables direct identification of features in the chromatograms obtained from mAbs digested with the IdeS enzyme, or digestion with IdeS followed by reduction with dithiothreitol. As many as 23 chemically unique mAb fragments were detected in a single sample. Our results demonstrate that these rich datasets enable facile assesment of the degree of similarity between reference and biosimilar materials.

TARANIS XGRE and IDEE detection capability of terrestrial gamma-ray flashes and associated electron beams

NASA Astrophysics Data System (ADS)

Sarria, David; Lebrun, Francois; Blelly, Pierre-Louis; Chipaux, Remi; Laurent, Philippe; Sauvaud, Jean-Andre; Prech, Lubomir; Devoto, Pierre; Pailot, Damien; Baronick, Jean-Pierre; Lindsey-Clark, Miles

2017-07-01

With a launch expected in 2018, the TARANIS microsatellite is dedicated to the study of transient phenomena observed in association with thunderstorms. On board the spacecraft, XGRE and IDEE are two instruments dedicated to studying terrestrial gamma-ray flashes (TGFs) and associated terrestrial electron beams (TEBs). XGRE can detect electrons (energy range: 1 to 10 MeV) and X- and gamma-rays (energy range: 20 keV to 10 MeV) with a very high counting capability (about 10 million counts per second) and the ability to discriminate one type of particle from another. The IDEE instrument is focused on electrons in the 80 keV to 4 MeV energy range, with the ability to estimate their pitch angles. Monte Carlo simulations of the TARANIS instruments, using a preliminary model of the spacecraft, allow sensitive area estimates for both instruments. This leads to an averaged effective area of 425 cm2 for XGRE, used to detect X- and gamma-rays from TGFs, and the combination of XGRE and IDEE gives an average effective area of 255 cm2 which can be used to detect electrons/positrons from TEBs. We then compare these performances to RHESSI, AGILE and Fermi GBM, using data extracted from literature for the TGF case and with the help of Monte Carlo simulations of their mass models for the TEB case. Combining this data with the help of the MC-PEPTITA Monte Carlo simulations of TGF propagation in the atmosphere, we build a self-consistent model of the TGF and TEB detection rates of RHESSI, AGILE and Fermi. It can then be used to estimate that TARANIS should detect about 200 TGFs yr-1 and 25 TEBs yr-1.

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

Zheng, Xiaogang; Biesiada, Marek; Cao, Shuo

A new compilation of 012 angular-size/redshift data for compact radio quasars from very-long-baseline interferometry (VLBI) surveys motivates us to revisit the interaction between dark energy and dark matter with these probes reaching high redshifts z ∼ 3.0. In this paper, we investigate observational constraints on different phenomenological interacting dark energy (IDE) models with the intermediate-luminosity radio quasars acting as individual standard rulers, combined with the newest BAO and CMB observation from Planck results acting as statistical rulers. The results obtained from the MCMC method and other statistical methods including figure of Merit and Information Criteria show that: (1) Compared withmore » the current standard candle data and standard clock data, the intermediate-luminosity radio quasar standard rulers , probing much higher redshifts, could provide comparable constraints on different IDE scenarios. (2) The strong degeneracies between the interaction term and Hubble constant may contribute to alleviate the tension of H {sub 0} between the recent Planck and HST measurements. (3) Concerning the ranking of competing dark energy models, IDE with more free parameters are substantially penalized by the BIC criterion, which agrees very well with the previous results derived from other cosmological probes.« less

Sulfamoylbenzamide Derivatives Inhibit the Assembly of Hepatitis B Virus Nucleocapsids

PubMed Central

Campagna, Matthew R.; Liu, Fei; Mao, Richeng; Mills, Courtney; Cai, Dawei; Guo, Fang; Zhao, Xuesen; Ye, Hong; Cuconati, Andrea; Guo, Haitao; Chang, Jinhong; Xu, Xiaodong; Block, Timothy M.

2013-01-01

Chronic hepatitis B virus (HBV) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegIFN-α) or one of the five nucleos(t)ide analogue viral DNA polymerase inhibitors. However, neither pegIFN-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. In order to develop novel antiviral drugs against HBV, we established a cell-based screening assay by using an immortalized mouse hepatocyte-derived stable cell line supporting a high level of HBV replication in a tetracycline-inducible manner. Screening of a library consisting of 26,900 small molecules led to the discovery of a series of sulfamoylbenzamide (SBA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA. Structure-activity relationship studies have thus far identified a group of fluorine-substituted SBAs with submicromolar antiviral activity against HBV in human hepatoma cells. Mechanistic analyses reveal that the compounds dose dependently inhibit the formation of pregenomic RNA (pgRNA)-containing nucleocapsids of HBV but not other animal hepadnaviruses, such as woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Moreover, heterologous genetic complementation studies of capsid protein, DNA polymerase, and pgRNA between HBV and WHV suggest that HBV capsid protein confers sensitivity to the SBAs. In summary, SBAs represent a novel chemical entity with superior activity and a unique antiviral mechanism and are thus warranted for further development as novel antiviral therapeutics for the treatment of chronic hepatitis B. PMID:23576513

Existence and stability of periodic solutions of an impulsive differential equation and application to CD8 T-cell differentiation.

PubMed

Girel, Simon; Crauste, Fabien

2018-06-01

Unequal partitioning of the molecular content at cell division has been shown to be a source of heterogeneity in a cell population. We propose to model this phenomenon with the help of a scalar, nonlinear impulsive differential equation (IDE). To study the effect of molecular partitioning at cell division on the effector/memory cell-fate decision in a CD8 T-cell lineage, we study an IDE describing the concentration of the protein Tbet in a CD8 T-cell, where impulses are associated to cell division. We discuss how the degree of asymmetry of molecular partitioning can affect the process of cell differentiation and the phenotypical heterogeneity of a cell population. We show that a moderate degree of asymmetry is necessary and sufficient to observe irreversible differentiation. We consider, in a second part, a general autonomous IDE with fixed times of impulse and a specific form of impulse function. We establish properties of the solutions of that equation, most of them obtained under the hypothesis that impulses occur periodically. In particular, we show how to investigate the existence of periodic solutions and their stability by studying the flow of an autonomous differential equation. Then we apply those properties to prove the results presented in the first part.

Oxygen Generation from Carbon Dioxide for Advanced Life Support

NASA Technical Reports Server (NTRS)

Bishop, Sean; Duncan, Keith; Hagelin-Weaver, Helena; Neal, Luke; Sanchez, Jose; Paul, Heather L.; Wachsman, Eric

2007-01-01

The partial electrochemical reduction of carbon dioxide (CO2) using ceramic oxygen generators (COGs) is well known and widely studied. However, complete reduction of metabolically produced CO2 (into carbon and oxygen) has the potential of reducing oxygen storage weight for life support if the oxygen can be recovered. Recently, the University of Florida devel- oped novel ceramic oxygen generators employing a bilayer elec- trolyte of gadolinia-doped ceria and erbia-stabilized bismuth ox- ide (ESB) for NASA's future exploration of Mars. The results showed that oxygen could be reliably produced from CO2 at temperatures as low as 400 C. The strategy discussed here for advanced life support systems employs a catalytic layer com- bined with a COG cell so that CO2 is reduced all the way to solid carbon and oxygen without carbon buildup on the COG cell and subsequent deactivation.

Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications.

PubMed

Yun, Joho; Kim, Jinhwan; Lee, Jong-Hyun

2017-11-28

We have introduced a fabrication method for electrical impedance spectroscopy (EIS)-on-a-needle (EoN: EIS-on-a-needle) to locate target tissues in the body by measuring and analyzing differences in the electrical impedance between dissimilar biotissues. This paper describes the fabrication method of fine interdigitated electrodes (IDEs) at the tip of a hypodermic needle using a photoresist spray coating and flexible film photomask in the photolithography process. A polyethylene terephthalate (PET) heat shrink tube (HST) with a wall thickness of 25 µm is employed as the insulation and passivation layer. The PET HST shows a higher mechanical durability compared with poly(p-xylylene) polymers, which have been widely used as a dielectric coating material. Furthermore, the HST shows good chemical resistance to most acids and bases, which is advantageous for limiting chemical damage to the EoN. The use of the EoN is especially preferred for the characterization of chemicals/biomaterials or fabrication using acidic/basic chemicals. The fabricated gap and width of the IDEs are as small as 20 µm, and the overall width and length of the IDEs are 400 µm and 860 µm, respectively. The fabrication margin from the tip (distance between the tip of hypodermic needle and starting point of the IDEs) of the hypodermic needle is as small as 680 µm, which indicates that unnecessarily excessive invasion into biotissues can be avoided during the electrical impedance measurement. The EoN has a high potential for clinical use, such as for thyroid biopsies and anesthesia drug delivery in a spinal space. Further, even in surgery that involves the partial resection of tumors, the EoN can be employed to preserve as much normal tissue as possible by detecting the surgical margin (normal tissue that is removed with the surgical excision of a tumor) between the normal and lesion tissues.

Long-term particle flux variability indicated by comparison of Interplanetary Dust Experiment (IDE) timed impacts for LDEF's first year in orbit with impact data for the entire 5.75-year orbital lifetime

NASA Technical Reports Server (NTRS)

Mulholland, J. Derral; Simon, Charles G.; Cooke, William J.; Oliver, John P.; Misra, V.

1992-01-01

The electronic sensors of the Interplanetary Dust Experiment (IDE) recorded precise impact times and approximate directions for submicron to approximately 100-micron size particles on all six primary sides of the spacecraft for the first 346 days of the Long Duration Exposure Facility (LDEF) orbital mission. Previously-reported analyses of the timed impact data have established their spatio-temporal features, including the demonstration that a preponderance of the particles in this regime are orbital debris and that a large fraction of the debris particles are encountered as megameter-size clouds, some of which persist for long times. Short-term fluxes within such clouds can rise several orders of magnitude above the long-term average. These finding are consistent with the results of the first catastrophic hypervelocity laboratory impacts on a real satellite, recently reported in the press. Analysis continues on the geometric and evolutionary characteristics of these clouds, as well as on the isolation and characterization of the natural micrometeoroid component in the IDE data, but the unexpectedly large short-term variations in debris flux raises the question of how representative an indication of the multi-year average flux is given by the nearly one year of timed data. It has, therefore, always been one of the goals of IDE to conduct an optical survey of the craters on the IDE detectors, to obtain full-mission fluxes for comparisons with the timed data. This work is underway, and the results presently in hand are significant. Optical scanning of the ram and wake (East and West) panels is complete, and it is clear that the first year was in some respects not representative of the subsequent years. The 5.75-year average flux on East panel was 90 percent of the value predicted by the average flux recorded during the first year, while it was only 34 percent on West panel. This suggests that western hemisphere spacecraft launches are a major contributor to the long-term flux and that their contribution is primarily in the smaller end of the size distribution. This conclusion follows from the fact that a closely-spaced series of launch failures (Titan, Delta, Ariane, and Challenger) caused a virtual hiatus in launch activity during a large part of the later years of the LDEF mission. We hope to provide a quantification of the particle size distribution function in this case.

Metabolism of Cryptic Peptides Derived from Neuropeptide FF Precursors: The Involvement of Insulin-Degrading Enzyme

PubMed Central

Grasso, Giuseppe; Mielczarek, Przemyslaw; Niedziolka, Magdalena; Silberring, Jerzy

2014-01-01

The term “cryptome” refers to the subset of cryptic peptides with bioactivities that are often unpredictable and very different from the parent protein. These cryptic peptides are generated by proteolytic cleavage of proteases, whose identification in vivo can be very challenging. In this work, we show that insulin-degrading enzyme (IDE) is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor), generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate. The reported experimental findings support the increasingly accredited hypothesis, according to which, due to its wide substrate selectivity, IDE is involved in a wide variety of physiopathological processes. PMID:25247577

Lessons Learned From The Investigational Device Exemption (IDE) Review of Children's Oncology Group Trial AAML1031

PubMed Central

Meshinchi, Soheil; Hunger, Stephen P.; Aplenc, Richard; Adamson, Peter C.; Jessup, J. Milburn

2012-01-01

The FDA is now exerting its regulatory authority over molecular diagnostics and their assays used for medical-decision making in clinical trials by performing pre-Investigational Device Exemption (IDE) reviews in all phases of clinical trials. This review assesses the analytical performance of the assay for the diagnostic and considers how that performance affects the diagnostic and the patient and their risks and benefits from treatment. This manuscript reviews the process of the first review that was performed on a new Children's Oncology Group (COG) Phase III trial in Acute Myelogenous Leukemia. The lessons learned and recommendations for how to prepare for and incorporate this new level of regulatory review into the protocol development process are presented. PMID:22422407

Interdigitated electrodes as impedance and capacitance biosensors: A review

NASA Astrophysics Data System (ADS)

Mazlan, N. S.; Ramli, M. M.; Abdullah, M. M. A. B.; Halin, D. S. C.; Isa, S. S. M.; Talip, L. F. A.; Danial, N. S.; Murad, S. A. Z.

2017-09-01

Interdigitated electrodes (IDEs) are made of two individually addressable interdigitated comb-like electrode structures. IDEs are one of the most favored transducers, widely utilized in technological applications especially in the field of biological and chemical sensors due to their inexpensive, ease of fabrication process and high sensitivity. In order to detect and analyze a biochemical molecule or analyte, the impedance and capacitance signal need to be obtained. This paper investigates the working principle and influencer of the impedance and capacitance biosensors. The impedance biosensor depends on the resistance and capacitance while the capacitance biosensor influenced by the dielectric permittivity. However, the geometry and structures of the interdigitated electrodes affect both impedance and capacitance biosensor. The details have been discussed in this paper.

The lateral line receptor array of cyprinids from different habitats.

PubMed

Schmitz, Anke; Bleckmann, Horst; Mogdans, Joachim

2014-04-01

The lateral line system of teleost fishes consists of an array of superficial and canal neuromasts (CN). Number and distribution of neuromasts and the morphology of the lateral line canals vary across species. We investigated the morphology of the lateral line system in four diurnal European cyprinids, the limnophilic bitterling (Rhodeus sericeus), the indifferent gudgeon (Gobio gobio), and ide (Leuciscus idus), and the rheophilic minnow (Phoxinus phoxinus). All fish had lateral line canals on head and trunk. The total number of both, CN and superficial neuromasts (SN), was comparable in minnow and ide but was greater than in gudgeon and bitterling. The ratio of SNs to CNs for the head was comparable in minnow and bitterling but was greater in gudgeon and ide. The SN-to-CN ratio for the trunk was greatest in bitterling. Polarization of hair cells in CNs was in the direction of the canal. Polarization of hair cells in SNs depended on body area. In cephalic SNs, hair cell polarization was dorso-ventral or rostro-caudal. In trunk SNs, it was rostro-caudal on lateral line scales and dorso-ventral on other trunk scales. On the caudal fin, hair cell polarization was rostro-caudal. The data show that, in the four species studied here, number, distribution, and orientation of CNs and SNs cannot be unequivocally related to habitat. Copyright © 2013 Wiley Periodicals, Inc.

Summer School in Deep Ecology.

ERIC Educational Resources Information Center

Macmillan, Catherine Hume

1995-01-01

Describes one teacher's experiences at the Institute for Deep Ecology Education (IDEE) Summer School in Applied Deep Ecology. Reviews the program offered and the focus on interactive, experiential activities. (LZ)

Physical and chemical limnology of Ides Cove near Rochester, New York, 1970-1982

USGS Publications Warehouse

Bubeck, R.C.; Staubitz, W.W.; Weidemann, A.D.; Spittal, L.P.

1995-01-01

Ides Cove is a small embayment on the western shore of Irondequoit Bay near Rochester, N.Y. In 1982, alum was applied to the cove to seal the bottom sediments and thereby decrease nutrient fluxes in an effort to assess the applicability of this technique to Irondequoit Bay. Published data were used to develop a baseline analysis of the chemical and physical limnology of Ides Cove prior to the alum treatment and to provide a basis for comparison and evaluation of post-treatment data. The baseline analysis also enables evaluation of trends in the nutrient status and mixing patterns in Ides Cove since the decrease of sewage inflows and use of road salt in the Irondequoit Bay and Ides Cove drainage basins during 1970-82. Data from 1970-72 and 1979-82 were used to construct partial and full-year depth profiles of several physical properties and chemical constituents of water in the cove; comparison of these profiles indicates a significant improvement in water quality between 1970 and 1982. The diversion of sewage out of the Irondequoit Creek drainage basin in the late 1970's resulted in an 80-percent decrease in total phosphate concentration and a 50- to 60-percent decrease in nitrogen (nitrate and ammonia) concentration in the cove. Indications of decreased primary productivity are associated with these lowered nutrient concentrations. Summer Secchi-disk transparency increased from 0.6 m (meters) in 1970-72 to 1.2 m in 1980-82; peak epilimnetic dissolved oxygen levels decreased from a range of 22 to 28 mg/L (milligrams per liter) to a range of 16 to 20 mg/L; and peak epilimnetic pH decreased from greater than 9.4 to between 8.8 and 9.0. The decrease in the use of road salt in the Irondequoit basin beginning in 1974 resulted in a decrease in chloride concentration and gradient (difference between the surface and bottom con- centration). The maximum annual chloride concentration in the epilimnion decreased from the 210-to-225-mg/L range in the spring of 1971-72 to the 140-to-l50-mg/L range in the spring of 1980-82, and the gradient between the hypolimnion and epilimnion during the spring decreased from the 80- to 160-mg/L range in 1971-72 to the O- to 90-mg/L range in 1980-82. Specific conductance values decreased similarly and indicate a comparable decrease in the density gradient from 1970-72 to 1980-82. The decrease in the density gradient resulted in an increase in the depth and duration of mixing in both the spring and fall of 1980-82, as illustrated by the profiles of physical properties, including temperature and specific conductance, and of chemical properties and constituents, including pH, alkalinity, dissolved oxygen, chloride, silica, and several species of nitrogen, phosphorus, and sulfur. These data indicate that Ides Cove, which was described as marginally meromictic in the early 1970's, had evolved by the early 1980's into a spring meromictic water body that underwent complete mixing in the fall and was approaching a consistent dimictic condition with spring and fall mixing. Thus, water quality and mixing patterns of the cove improved with the removal of sewage and the decrease in the use of road salt.

Transportation of hazardous materials

DOT National Transportation Integrated Search

1986-07-01

This report discusses transportation of all hazardous materials (commodities, : radioactive materials including spent nuclear fuel, and hazardous wastes) that : travel by truck, rail, water, or air. The Office of Technology Assessment (OTA) : has ide...

Impact of a multicarbohydrase containing α-galactosidase and xylanase on ileal digestible energy, crude protein digestibility, and ileal amino acid digestibility in broiler chickens.

PubMed

Jasek, A; Latham, R E; Mañón, A; Llamas-Moya, S; Adhikari, R; Poureslami, R; Lee, J T

2018-06-08

Exogenous enzymatic supplementation of poultry feeds, including α-galactosidase and xylanase, has been shown to increase metabolically available energy, although little information has been published on the impact on amino acid digestibility. An experiment was conducted to investigate a multicarbohydrase containing α-galactosidase and xylanase on amino acid digestibility, ileal digestible energy (IDE), and CP in male broiler chicks. The experiment was a 2 × 2 (diet × enzyme) factorial arrangement with 15 replicates of 8 male broilers per replicate raised for 21 d in a battery setting. The 2 dietary treatments included a positive control (PC) and a negative control (NC) diet formulated to contain 2.5% less calculated AME and digestible amino acids. Each of these diets was fed with and without enzyme. Broilers were fed a starter diet from 0-14 d (crumble) and a grower from 14-21 d (pellet). Birds were sampled on day 21 to determine ileal amino acid digestibility, IDE, and CP digestibility. Titanium dioxide (TiO2) was used as an indigestible marker for the determination of digestibility coefficients. Total ileal amino acid digestibility was increased (P = 0.008) by 3.80% with the inclusion of enzyme. Methionine and lysine digestibility was improved (P < 0.05) with the inclusion of enzyme by 3.37% and 2.61%, respectively. Enzyme inclusion increased (P = 0.001) cysteine digestibility by 9.3%. Diet-influenced ileal amino acid digestibility with tryptophan, threonine, isoleucine, and valine digestibility being increased (P < 0.05) in the PC when compared to the NC. IDE was decreased (P = 0.037) in broilers fed the NC diet by 100 kcal/kg feed when compared to broilers fed the PC diet. Enzyme inclusion increased (P = 0.047) IDE value by 90 kcal/kg. Crude protein digestibility was not influenced by diet; however, similar improvements in CP digestibility with enzyme inclusion were observed as with energy. These data support the benefits of a multicarbohydrase containing α-galactosidase and xylanase inclusion to improve nutrient and ileal amino acid digestibility across multiple dietary nutrient profiles.

Physical vapor deposited thin films of lignins extracted from sugar cane bagasse: morphology, electrical properties, and sensing applications.

PubMed

Volpati, Diogo; Machado, Aislan D; Olivati, Clarissa A; Alves, Neri; Curvelo, Antonio A S; Pasquini, Daniel; Constantino, Carlos J L

2011-09-12

The concern related to the environmental degradation and to the exhaustion of natural resources has induced the research on biodegradable materials obtained from renewable sources, which involves fundamental properties and general application. In this context, we have fabricated thin films of lignins, which were extracted from sugar cane bagasse via modified organosolv process using ethanol as organic solvent. The films were made using the vacuum thermal evaporation technique (PVD, physical vapor deposition) grown up to 120 nm. The main objective was to explore basic properties such as electrical and surface morphology and the sensing performance of these lignins as transducers. The PVD film growth was monitored via ultraviolet-visible (UV-vis) absorption spectroscopy and quartz crystal microbalance, revealing a linear relationship between absorbance and film thickness. The 120 nm lignin PVD film morphology presented small aggregates spread all over the film surface on the nanometer scale (atomic force microscopy, AFM) and homogeneous on the micrometer scale (optical microscopy). The PVD films were deposited onto Au interdigitated electrode (IDE) for both electrical characterization and sensing experiments. In the case of electrical characterization, current versus voltage (I vs V) dc measurements were carried out for the Au IDE coated with 120 nm lignin PVD film, leading to a conductivity of 3.6 × 10(-10) S/m. Using impedance spectroscopy, also for the Au IDE coated with the 120 nm lignin PVD film, dielectric constant of 8.0, tan δ of 3.9 × 10(-3), and conductivity of 1.75 × 10(-9) S/m were calculated at 1 kHz. As a proof-of-principle, the application of these lignins as transducers in sensing devices was monitored by both impedance spectroscopy (capacitance vs frequency) and I versus time dc measurements toward aniline vapor (saturated atmosphere). The electrical responses showed that the sensing units are sensible to aniline vapor with the process being reversible. AFM images conducted directly onto the sensing units (Au IDE coated with 120 nm lignin PVD film) before and after the sensing experiments showed a decrease in the PVD film roughness from 5.8 to 3.2 nm after exposing to aniline.

ID'ing innate and innate-like lymphoid cells.

PubMed

Verykokakis, Mihalis; Zook, Erin C; Kee, Barbara L

2014-09-01

The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The critical domain size of stochastic population models.

PubMed

Reimer, Jody R; Bonsall, Michael B; Maini, Philip K

2017-02-01

Identifying the critical domain size necessary for a population to persist is an important question in ecology. Both demographic and environmental stochasticity impact a population's ability to persist. Here we explore ways of including this variability. We study populations with distinct dispersal and sedentary stages, which have traditionally been modelled using a deterministic integrodifference equation (IDE) framework. Individual-based models (IBMs) are the most intuitive stochastic analogues to IDEs but yield few analytic insights. We explore two alternate approaches; one is a scaling up to the population level using the Central Limit Theorem, and the other a variation on both Galton-Watson branching processes and branching processes in random environments. These branching process models closely approximate the IBM and yield insight into the factors determining the critical domain size for a given population subject to stochasticity.

Compact Active Vibration Control System for a Flexible Panel

NASA Technical Reports Server (NTRS)

Schiller, Noah H. (Inventor); Cabell, Randolph H. (Inventor); Perey, Daniel F. (Inventor)

2014-01-01

A diamond-shaped actuator for a flexible panel has an inter-digitated electrode (IDE) and a piezoelectric wafer portion positioned therebetween. The IDE and/or the wafer portion are diamond-shaped. Point sensors are positioned with respect to the actuator and measure vibration. The actuator generates and transmits a cancelling force to the panel in response to an output signal from a controller, which is calculated using a signal describing the vibration. A method for controlling vibration in a flexible panel includes connecting a diamond-shaped actuator to the flexible panel, and then connecting a point sensor to each actuator. Vibration is measured via the point sensor. The controller calculates a proportional output voltage signal from the measured vibration, and transmits the output signal to the actuator to substantially cancel the vibration in proximity to each actuator.

LDEF Interplanetary Dust Experiment (IDE) results

NASA Technical Reports Server (NTRS)

Oliver, John P.; Singer, S. F.; Weinberg, J. L.; Simon, C. G.; Cooke, W. J.; Kassel, P. C.; Kinard, W. H.; Mulholland, J. D.; Wortman, J. J.

1995-01-01

The Interplanetary Dust Experiment (IDE) provided high time resolution detection of microparticle impacts on the Long Duration Exposure Facility satellite. Particles, in the diameter range from 0.2 microns to several hundred microns, were detected impacting on six orthogonal surfaces of the gravity-gradient stabilized LDEF spacecraft. The total sensitive surface area was about one square meter, distributed between LDEF rows 3 (Wake or West), 6 (South), 9 (Ram or East), 12 (North), as well as the Space and Earth ends of LDEF. The time of each impact is known to an accuracy that corresponds to better than one degree in orbital longitude. Because LDEF was gravity-gradient stabilized and magnetically damped, the direction of the normal to each detector panel is precisely known for each impact. The 11 1/2 month tape-recorded data set represents the most extensive record gathered of the number, orbital location, and incidence direction for microparticle impacts in low Earth orbit. Perhaps the most striking result from IDE was the discovery that microparticle impacts, especially on the Ram, South, and North surfaces, were highly episodic. Most such impacts occurred in localized regions of the orbit for dozens or even hundreds of orbits in what we have termed Multiple Orbit Event Sequences (MOES). In addition, more than a dozen intense and short-lived 'spikes' were seen in which impact fluxes exceeded the background by several orders of magnitude. These events were distributed in a highly non-uniform fashion in time and terrestrial longitude and latitude.

New species of cynipid inquilines of the genus Saphonecrus (Hymenoptera: Cynipidae: Synergini) from the Eastern Palaearctic, with a re-appraisal of known species world-wide.

PubMed

Schwéger, Szabina; Melika, George; Tang, Chang-Ti; Yang, Man-Miao; Stone, Graham N; Nicholls, James A; Sinclair, Frazer; Hearn, Jack; Bozsó, Miklós; Pénzes, Zsolt

2015-12-08

Fifteen new species of cynipid inquilines, Saphonecrus chinensis Tang & Schwéger, S. gilvus Melika & Schwéger, S. globosus Schwéger & Tang, S. leleyi Melika & Schwéger, S. lithocarpii Schwéger & Melika, S. longinuxi Schwéger & Melika, S. morii Schwéger & Tang, S. nantoui Tang, Schwéger & Melika, S. nichollsi Schwéger & Melika, S. pachylomai Schwéger, Tang & Melika, S. robustus Schwéger & Melika, S. saliciniai Melika, Tang & Schwéger, S. shanzhukui Melika & Tang, S. symbioticus Melika & Schwéger, and S. taitungi Schwéger, Tang & Melika, from the Eastern Palaearctic are described. Descriptions, diagnoses, biology, and host associations for the new species, and a key to Palaearctic Saphonecrus species are given. All new taxa form distinct units as demonstrated by the molecular phylogenetic analyses of Palaearctic Saphonecrus species. The status of some earlier described Saphonecrus species is discussed also. The Synergini genus Lithonecrus Nieves-Aldrey & Butterill, 2014 is synonymized with Lithosaphonecrus Tang, Melika & Bozsó, 2013. Three Saphonecrus species are transferred to Synergus: Synergus brevis (Weld) comb. nova, Synergus hupingshanensis (Liu, Yang & Zhu) comb. nova, and Synergus yukawai (Wachi, Ide & Abe) comb. nova. Synophrus vietnamensis Abe, Ide, Konishi & Ueno is transferred to Lithosaphonecrus: Lithosaphonecrus vietnamensis Abe, Ide, Konishi & Ueno), comb. nova. The current number of valid Saphonecrus species worldwide is 36.

Impact of FIB-4 index on hepatocellular carcinoma incidence during nucleos(t)ide analogue therapy in patients with chronic hepatitis B: An analysis using time-dependent receiver operating characteristic.

PubMed

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Tsuji, Kunihiko; Hiraoka, Atsushi; Tanaka, Junko

2017-02-01

Nucleos(t)ide analogue (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). However, even during NA therapy, development of HCC has been observed in patients with CHB. Therefore, we clarified the predictive power of clinical factors for HCC incidence using receiver operating characteristic (ROC) analysis that takes time dependence into account. A total of 539 patients with CHB treated with NAs were enrolled. Univariate, multivariate, and time-dependent ROC curves for clinical factors associated with the development of HCC were analyzed. Eighty-one patients developed HCC during the follow-up period (median duration, 5.9 years). α-fetoprotein (AFP) and FIB-4 index at 24 weeks from the initiation of treatment and sex were significantly associated with HCC incidence according to the log-rank test. Cox proportional hazards models including the covariates of sex, hepatitis B genotype, basal core promoter mutations, AFP at 24 weeks, and FIB-4 index at 24 weeks showed that FIB-4 index >2.65 (HR, 5.03; 95% CI, 3.06-8.26; P < 0.001) and male sex were independently associated with HCC incidence. In addition, time-dependent ROC analysis showed that compared with AFP at 24 weeks, FIB-4 index at 24 weeks had higher predictive power for HCC incidence throughout the follow-up period. Elevated FIB-4 index at 24 weeks in patients with CHB receiving NA therapy is a risk factor for developing HCC. The FIB-4 index is an excellent predictor of HCC development. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Discrimination Learning, Reversal, and Set-Shifting in First-Episode Schizophrenia: Stability Over Six Years and Specific Associations with Medication Type and Disorganization Syndrome

PubMed Central

Leeson, Verity C.; Robbins, Trevor W.; Matheson, Elizabeth; Hutton, Samuel B.; Ron, María A.; Barnes, Thomas R.E.; Joyce, Eileen M.

2009-01-01

Background The intradimensional/extradimensional (IDED) task assesses different forms of learning from feedback. Limited evidence suggests that attentional set-shifting deteriorates over time in schizophrenia. We tested this hypothesis and examined the specificity of learning impairments identified by this task. Method Two hundred sixty-two first-episode patients and 76 healthy control subjects, matched for age and premorbid IQ, were tested; 104 patients and 25 control subjects were reassessed 1 and 3 years later, and 31 patients were reassessed additionally 6 years later. Results Patients showed impaired set-shifting that correlated with current IQ and working memory, but there were no impairments when subgroups were matched on current IQ. In contrast, patients showed marked impairments in rule reversal learning that survived correction for IQ, were present in the context of intact rule abstraction, and correlated with disorganization symptoms. Patients prescribed second-generation antipsychotics were worse on set-shifting compared with first-generation, a finding not explained by demographic data, illness characteristics, or IQ. Patients and control subjects showed stable IDED performance over the first 6 years of illness, although set-shifting was inconsistent over the first year. Those with residual negative symptoms were more likely to fail the set-shifting stage at follow-up. Conclusions First-episode schizophrenia patients can learn and generalize rules but are inflexible when rules change, reflecting reduced responsiveness to negative feedback and difficulty in switching attention. Rule-reversal is a promising target for translational studies, because it is specific, clinically relevant, and might reflect orbitofrontal dysfunction. Set-shifting is related to poor function more generally but might be sensitive to medication effects and valuable for clinical trials. PMID:19576575

Nutritional characteristics of camelina meal for 3-week-old broiler chickens.

PubMed

Pekel, A Y; Kim, J I; Chapple, C; Adeola, O

2015-03-01

Limited information on nutritional characteristics on camelina meal for broiler chickens limits its use in diets of broiler chickens. The objectives of this study were to determine the ileal digestible energy (IDE), ME, and MEn contents of 2 different camelina meal (CM1 and CM2) samples for 3-wk-old broiler chickens using the regression method and to determine glucosinolate compounds in the camelina meal samples. The CM1 and CM2 were incorporated into a corn-soybean meal-based reference diet at 3 levels (0, 100, or 200 g/kg) by replacing the energy-yielding ingredients. These 5 diets (reference diet, and 100 and 200 g/kg camelina meal from each of CM1 and CM2) were fed to 320 male Ross 708 broilers from d 21 to 28 post hatching with 8 birds per cage and 8 replicates per treatment in a randomized complete block design. Excreta were collected twice daily from d 25 to 28, and jejunal digesta and ileal digesta from the Meckel's diverticulum to approximately 2 cm proximal to the ileocecal junction were collected on d 28. The total glucosinolate content for CM1 and CM2 were 24.2 and 22.7 nmol/mg, respectively. Jejunal digesta viscosity was linearly increased (P<0.001) from 2.2 to 4.1 cP with increasing dietary camelina meal levels. There were linear effects (P<0.001) of CM1 and CM2 substitution on final weight, weight gain, feed intake, and G:F. The inclusion of CM1 and CM2 linearly decreased (P<0.001) ileal digestibility of DM, energy, and IDE. The supplementation of CM1 and CM2 linearly decreased (P<0.001) the retention of DM, nitrogen, and energy; ME, and MEn. By regressing the CM1 and CM2-associated IDE intake in kilocalories against kilograms of CM1 and CM2 intake, the IDE regression equation was Y=-10+1,429×CM1+2,125×CM2, r2=0.55, which indicates that IDE values were 1,429 kcal/kg of DM for CM1 and 2,125 kcal/kg of DM for CM2. The ME regression was Y=5+882×CM1+925×CM2, r2=0.54, which implies ME values of 882 kcal/kg of DM for CM1 and 925 kcal/kg of DM for CM2. MEn regression was Y=2+795×CM1+844×CM2, r2=0.52, which implies MEn values of 795 kcal/kg of DM for CM1 and 844 kcal/kg of DM for CM2. Based on these results, utilization of energy and nitrogen in camelina meal by broiler chickens is low and the high viscosity observed in jejunal digesta as well as the total glucosinolate in camelina meal may have contributed to the poor energy and nitrogen utilization. © 2015 Poultry Science Association Inc.

An evaluation of emerging driver fatigue detection measures and technologies

DOT National Transportation Integrated Search

2009-06-01

Operator fatigue and sleep deprivation have been widely recognized as critical safety issues that cut across all modes in the transportation industry. FMCSA, the trucking industry, highway safety advocates, and transportation researchers have all ide...

75 FR 2869 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... life-threatening or serious conditions for which no comparable or satisfactory alternative therapy is... IDE, to assess the sponsor's due diligence in obtaining marketing clearance of the device and to...

Impedance Characterization of the Degradation of Insulating Layer Patterned on Interdigitated Microelectrode.

PubMed

Lee, Gihyun; Kim, Sohee; Cho, Sungbo

2015-10-01

Life-time and functionality of planar microelectrode-based devices are determined by not only the corrosion-resistance of the electrode, but also the durability of the insulation layer coated on the transmission lines. Degradation of the insulating layer exposed to a humid environment or solution may cause leakage current or signal loss, and a decrease in measurement sensitivity. In this study, degradation of SU-8, an epoxy-based negative photoresist and insulating material, patterned on Au interdigitated microelectrode (IDE) for long-term (>30 days) immersion in an electrolyte at 37 °C was investigated by electrical impedance spectroscopy and theoretical equivalent circuit modeling. From the experiment and simulation results, it was found that the degradation level of the insulating layer of the IDE electrode can be characterized by monitoring the resistance of the insulating layer among the circuit parameters of the designed equivalent circuit modeling.

AC electrokinetic drug delivery in dentistry using an interdigitated electrode assembly powered by inductive coupling.

PubMed

Ivanoff, Chris S; Wu, Jie Jayne; Mirzajani, Hadi; Cheng, Cheng; Yuan, Quan; Kevorkyan, Stepan; Gaydarova, Radostina; Tomlekova, Desislava

2016-10-01

AC electrokinetics (ACEK) has been shown to deliver certain drugs into human teeth more effectively than diffusion. However, using electrical wires to power intraoral ACEK devices poses risks to patients. The study demonstrates a novel interdigitated electrode arrays (IDE) assembly powered by inductive coupling to induce ACEK effects at appropriate frequencies to motivate drugs wirelessly. A signal generator produces the modulating signal, which multiplies with the carrier signal to produce the amplitude modulated (AM) signal. The AM signal goes through the inductive link to appear on the secondary coil, then rectified and filtered to dispose of its carrier signal, and the positive half of the modulating signal appears on the load. After characterizing the device, the device is validated under light microscopy by motivating carboxylate-modified microspheres, tetracycline, acetaminophen, benzocaine, lidocaine and carbamide peroxide particles with induced ACEK effects. The assembly is finally tested in a common dental bleaching application. After applying 35 % carbamide peroxide to human teeth topically or with the IDE at 1200 Hz, 5 Vpp for 20 min, spectrophotometric analysis showed that compared to diffusion, the IDE enhanced whitening in specular optic and specular optic excluded modes by 215 % and 194 % respectively. Carbamide peroxide absorbance by the ACEK group was two times greater than diffusion as measured by colorimetric oxidation-reduction and UV-Vis spectroscopy at 550 nm. The device motivates drugs of variable molecular weight and structure wirelessly. Wireless transport of drugs to intraoral targets under ACEK effects may potentially improve the efficacy and safety of drug delivery in dentistry.

Healthy Smile for Your Young Child: Tips to Keep Your Child Healthy

MedlinePlus

... teeth with a soft toothbrush and toothpaste with fluoride, twice a day, after breakfast and before bed. ... m Brush your child’s teeth with toothpaste with fluoride (floor-ide) twice a day, after breakfast and ...

Characteristics of broadband slow earthquakes explained by a Brownian model

NASA Astrophysics Data System (ADS)

Ide, S.; Takeo, A.

2017-12-01

Brownian slow earthquake (BSE) model (Ide, 2008; 2010) is a stochastic model for the temporal change of seismic moment release by slow earthquakes, which can be considered as a broadband phenomena including tectonic tremors, low frequency earthquakes, and very low frequency (VLF) earthquakes in the seismological frequency range, and slow slip events in geodetic range. Although the concept of broadband slow earthquake may not have been widely accepted, most of recent observations are consistent with this concept. Then, we review the characteristics of slow earthquakes and how they are explained by BSE model. In BSE model, the characteristic size of slow earthquake source is represented by a random variable, changed by a Gaussian fluctuation added at every time step. The model also includes a time constant, which divides the model behavior into short- and long-time regimes. In nature, the time constant corresponds to the spatial limit of tremor/SSE zone. In the long-time regime, the seismic moment rate is constant, which explains the moment-duration scaling law (Ide et al., 2007). For a shorter duration, the moment rate increases with size, as often observed for VLF earthquakes (Ide et al., 2008). The ratio between seismic energy and seismic moment is constant, as shown in Japan, Cascadia, and Mexico (Maury et al., 2017). The moment rate spectrum has a section of -1 slope, limited by two frequencies corresponding to the above time constant and the time increment of the stochastic process. Such broadband spectra have been observed for slow earthquakes near the trench axis (Kaneko et al., 2017). This spectrum also explains why we can obtain VLF signals by stacking broadband seismograms relative to tremor occurrence (e.g., Takeo et al., 2010; Ide and Yabe, 2014). The fluctuation in BSE model can be non-Gaussian, as far as the variance is finite, as supported by the central limit theorem. Recent observations suggest that tremors and LFEs are spatially characteristic, rather than random (Rubin and Armbruster, 2013; Bostock et al., 2015). Since even spatially characteristic source must be activated randomly in time, moment release from these sources are compatible to the fluctuation in BSE model. Therefore, BSE model contains the model of Gomberg et al. (2016), which suggests that the cluster of LFEs makes VLF signals, as a special case.

Mechanisms linking brain insulin resistance to Alzheimer's disease

PubMed Central

Matioli, Maria Niures P.S.; Nitrini, Ricardo

2015-01-01

Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

[Ilya Ilich Metchnikov and Paul Ehrlich: 1908 Nobel Prize winners for their research on immunity].

PubMed

Lokaj, J; John, C

2008-11-01

The Nobel Prize in Physiology or Medicine in 1908 was awarded to Ilya I. Mechnikov and Paul Ehrlich for recognition of their work on immunity. Mechnikov have discovered phagocytes and phagocytosis as the basis of natural cellular immunity. His ,,phagocytic theory" is the principle of immunological concept "self and not self" as the prerequisition of physiological inflammation, and selfmaintaining of organism. Ehrlich developed the methods for standardization of antibody activity in immune sera, described neutralizing and complement-depending effect of antibodies and enunciated the ,"ide-chain" theory of the formation of antibodies. Their concept of the key-stone of immunity was different, but they expressed the basic paradigma of immunology: immunity imply the protection of identity and guarantee the integrity of organism. Both are the founders of immunology as the scientific discipline. Discoveries and conceptions of I. Mechnikov and P. Ehrlich exceedingly influenced development of immunology and are also applicable, instructive and suggestive in contemporary immunology and microbiology.

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir

PubMed Central

Vivanti, Alexandre; Soheili, Tayebeh S.; Cuccuini, Wendy; Luce, Sonia; Mandelbrot, Laurent; Lechenadec, Jerome; Cordier, Anne-Gael; Azria, Elie; Soulier, Jean; Cavazzana, Marina; Blanche, Stéphane; André-Schmutz, Isabelle

2015-01-01

Objectives: Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero. Design: We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively). Methods: The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs. Results: Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups. Conclusion: Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes. PMID:25513819

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.

PubMed

Vivanti, Alexandre; Soheili, Tayebeh S; Cuccuini, Wendy; Luce, Sonia; Mandelbrot, Laurent; Lechenadec, Jerome; Cordier, Anne-Gael; Azria, Elie; Soulier, Jean; Cavazzana, Marina; Blanche, Stéphane; André-Schmutz, Isabelle

2015-07-17

Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero. We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively). The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs. Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups. Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes.

Warehouse location and freight attraction in the greater El Paso region.

DOT National Transportation Integrated Search

2013-12-01

This project analyzes the current and future warehouse and distribution center locations along the El Paso-Juarez regions in the U.S.-Mexico border. This research seeks has developed a comprehensive database to aid in decision support process for ide...

Hydraulic Capacitor Analogy

ERIC Educational Resources Information Center

Baser, Mustafa

2007-01-01

Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

An Analysis of the Crash Experience of Vehicles Equipped with Antilock Braking System

DOT National Transportation Integrated Search

1995-06-01

National Center for Statistics and Analysis has recently completed an initial : analysis of the crash experience of passenger cars (PCs) and light trucks and : vans (LTVs) equipped with antilock braking systems (ABS). Four types of crashes : were ide...

EVALUATING DISCONTINUITIES IN COMPLEX SYSTEMS: TOWARD QUANTITATIVE MEASURE OF RESILIENCE

EPA Science Inventory

The textural discontinuity hypothesis (TDH) is based on the observation that animal body mass distributions exhibit discontinuities that may reflect the texture of the landscape available for exploitation. This idea has been extended to other complex systems, hinting that the ide...

Web Services Integration on the Fly

DTIC Science & Technology

2008-12-01

NETBEANS 6.1 AND VERSION CONTROL............................................28 1. NetBeans Integrated Development Environment (IDE) ................28 2...Forward and Reverse Engineering...................................................28 3. Implementation using NetBeans ...29 4. Subversion (SVN) for Version Control in NetBeans ......................29 O. PROTÉGÉ AUTHORING TOOL FOR SEMANTIC WEB

U.S. EPA, Pesticide Product Label, CHLORINATING TABLETS, 02/18/1989

EPA Pesticide Factsheets

2011-04-21

... "sidu.1 un ~. uinhined • t ill Iiln ACCEPTED puu • Unf~n !! .. - r: ~''!I,!;!~ I!',~~i::"ide. Furl~;"i: _, . -:J!i ',,i " •• ii,h. Act. 01 Uu .. ~.; f~r tj.~ ;'tJ· .. &l.cide ...

Complications of Lumbar Artificial Disc Replacement Compared to Fusion: Results From the Prospective, Randomized, Multicenter US Food and Drug Administration Investigational Device Exemption Study of the Charité Artificial Disc

PubMed Central

Majd, Mohammed E.; Isaza, Jorge E.; Blumenthal, Scott L.; McAfee, Paul C.; Guyer, Richard D.; Hochschuler, Stephen H.; Geisler, Fred H.; Garcia, Rolando; Regan, John J.

2007-01-01

Background Previous reports of lumbar total disc replacement (TDR) have described significant complications. The US Food and Drug Administration (FDA) investigational device exemption (IDE) study of the Charité artificial disc represents the first level I data comparison of TDR to fusion. Methods In the prospective, randomized, multicenter IDE study, patients were randomized in a 2:1 ratio, with 205 patients in the Charité group and 99 patients in the control group (anterior lumbar interbody fusion [ALIF] with BAK cages). Inclusion criteria included confirmed single-level degenerative disc disease at L4-5 or L5-S1 and failure of nonoperative treatment for at least 6 months. Complications were reported throughout the study. Results The rate of approach-related complications was 9.8% in the investigational group and 10.1% in the control group. The rate of major neurological complications was similar between the 2 groups (investigational = 4.4%, control = 4.0%). There was a higher rate of superficial wound infection in the investigational group but no deep wound infections in either group. Pseudarthrosis occurred in 9.1% of control group patients. The rate of subsidence in the investigational group was 3.4%. The reoperation rate was 5.4% in the investigational group and 9.1% in the control group. Conclusions The incidence of perioperative and postoperative complications for lumbar TDR was similar to that of ALIF. Vigilance is necessary with respect to patient indications, training, and correct surgical technique to maintain TDR complications at the levels experienced in the IDE study. PMID:25802575

Selection of a new Mycobacterium tuberculosis H37Rv aptamer and its application in the construction of a SWCNT/aptamer/Au-IDE MSPQC H37Rv sensor.

PubMed

Zhang, XiaoQing; Feng, Ye; Yao, QiongQiong; He, Fengjiao

2017-12-15

A rapid and accurate detection method for Mycobacterium tuberculosis (M. tuberculosis) is essential for effectively treating tuberculosis. However, current detection methods cannot meet these clinical requirements because the methods are slow or of low specificity. Consequently, a new highly specific ssDNA aptamer against M. tuberculosis reference strain H37Rv was selected by using the whole-cell systematic evolution of ligands by exponential enrichment technique. The selected aptamer was used to construct a fast and highly specific H37Rv sensor. The probe was produced by immobilizing thiol-modified aptamer on an Au interdigital electrode (Au-IDE) of a multichannel series piezoelectric quartz crystal (MSPQC) through Au-S bonding, and then single-walled carbon nanotubes (SWCNTs) were bonded on the aptamer by π-π stacking. SWCNTs were used as a signal indicator because of their considerable difference in conductivity compared with H37Rv. When H37Rv is present, it replaces the SWCNTs because it binds to the aptamer much more strongly than SWCNTs do. The replacement of SWCNTs by H37Rv resulted in a large change in the electrical properties, and this change was detected by the MSPQC. The proposed sensor is highly selective and can distinguish H37Rv from Mycobacterium smegmatis (M. smegmatis) and Bacillus Calmette-Guerin vaccine (BCG). The detection time was 70min and the detection limit was 100cfu/mL. Compared with conventional methods, this new SWCNT/aptamer/Au-IDE MSPQC H37Rv sensor was specific, rapid, and sensitive, and it holds great potential for the early detection of H37Rv in clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Impedance biosensor for the rapid detection of Listeria spp. based on aptamer functionalized Pt-interdigitated microelectrodes array

NASA Astrophysics Data System (ADS)

Sidhu, R.; Rong, Y.; Vanegas, D. C.; Claussen, J.; McLamore, E. S.; Gomes, C.

2016-05-01

Listeria monocytogenes is one of the most common causes of food illness deaths worldwide, with multiple outbreaks in the United States alone. Current methods to detect foodborne pathogens are laborious and can take several hours to days to produce results. Thus, faster techniques are needed to detect bacteria within the same reliability level as traditional techniques. This study reports on a rapid, accurate, and sensitive aptamer biosensor device for Listeria spp. detection based on platinum interdigitated array microelectrodes (Pt-IDEs). Pt-IDEs with different geometric electrode gaps were fabricated by lithographic techniques and characterized by cyclic voltammetric (CV), electrochemical impedance spectroscopy (EIS), and potential amperometry (DCPA) measurements of reversible redox species. Based on these results, 50 μm Pt-IDE was chosen to further functionalize with a Listeria monocytogenes DNA aptamer selective to the cell surface protein internalin A, via metal-thiol self-assembly at the 5' end of the 47-mer's. EIS analysis was used to detect Listeria spp. without the need for label amplification and pre-concentration steps. The optimized aptamer concentration of 800 nM was selected to capture the bacteria through internalin A binding and the aptamer hairpin structure near the 3' end. The aptasensor was capable of detecting a wide range of bacteria concentration from 10 to 106 CFU/mL at lower detection limit of 5.39 +/- 0.21 CFU/mL with sensitivity of 268.1 +/- 25.40 (Ohms/log [CFU/mL]) in 17 min. The aptamer based biosensor offers a portable, rapid and sensitive alternative for food safety applications with one of the lowest detection limits reported to date.

Electronic Attack Platform Placement Optimization

DTIC Science & Technology

2014-09-01

Processing in VBA ...............................................................33 2. Client-Server Using Two Different Excel Application...6 Figure 3. Screenshot of the VBA IDE contained within all Microsoft Office products...application using MS Excel’s Applicatin.OnTime method. .....................................33 Figure 20. WINSOCK API Functions needed to use TCP via VBA

Illinois highway and street mileage statistics 2003

DOT National Transportation Integrated Search

2003-12-31

The tables represent all mileage in the State of Illinois open to public travel with the exception of : 1,111.87 miles of ramps and 46.38 miles of collector-distributors. : The five highway systems included in the tables and defined below are not ide...

Discussion of teleomorphic and anamorphic Ascomycetous yeasts and yeast-like taxa

USDA-ARS?s Scientific Manuscript database

The relationship of ascomycetous yeasts with other members of the ascomycete fungi (Ascomycota) has been controversial for over 100 years. Because yeasts are morphologically simple, it was proposed that they represent primitive forms of ascomycetes (e.g., Guilliermond 1912). Alternatively, the ide...

Energy Monitoring in Gins - 2013 Update

USDA-ARS?s Scientific Manuscript database

Energy, comprised of electricity and fuel, is the second largest source of variable costs for cotton gins, after labor. Few studies of gin energy use have been conducted recently and none have monitored energy use continuously throughout the ginning season. More detailed information is needed to ide...

21 CFR 812.35 - Supplemental applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (including manufacturing changes) that do not constitute a significant change in design or basic principles... reliable information such as clinical information gathered during a trial or marketing. (B) Credible... investigator(s), and/or the data gathered during the clinical trial or marketing. (iv) Notice of IDE change...

21 CFR 814.104 - Original applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the Center for Biologics Evaluation and Research, send this information to the Document Control Center... and Research, send this information to the Central Document Control Room, Center for Drug Evaluation... device under an approved IDE) is available to treat or diagnose the disease or condition. The application...

Orthogonal Assessment of Biotherapeutic Glycosylation: A Case Study Correlating N-Glycan Core Afucosylation of Herceptin with Mechanism of Action.

PubMed

Upton, Rosie; Bell, Leonard; Guy, Colin; Caldwell, Paul; Estdale, Sian; Barran, Perdita E; Firth, David

2016-10-18

In the development of therapeutic antibodies and biosimilars, an appropriate biopharmaceutical CMC control strategy that connects critical quality attributes with mechanism of action should enable product assessment at an early stage of development in order to mitigate risk. Here we demonstrate a new analytical workflow using trastuzumab which comprises "middle-up" analysis using a combination of IdeS and the endoglycosidases EndoS and EndoS2 to comprehensively map the glycan content. Enzymatic cleavage between the two N-acetyl glucosamine residues of the chitobiose core of N-glycans significantly simplifies the oligosaccharide component enabling facile distinction of GlcNAc from GlcNAc with core fucose. This approach facilitates quantitative determination of total Fc-glycan core-afucosylation, which was in turn correlated with receptor binding affinity by surface plasmon resonance and in vitro ADCC potency with a cell based bioassay. The strategy also quantifies Fc-glycan occupancy and the relative contribution from high mannose glycans.

IDE spatio-temporal impact fluxes and high time-resolution studies of multi-impact events and long-lived debris clouds

NASA Technical Reports Server (NTRS)

Mulholland, J. Derral; Singer, S. Fred; Oliver, John P.; Weinberg, Jerry L.; Cooke, William J.; Kassel, Philip C.; Wortman, Jim J.; Montague, Nancy L.; Kinard, William H.

1991-01-01

During the first 12 months of the Long Duration Exposure Facility (LDEF) mission, the Interplanetary Dust Experiment (IDE) recorded over 15,000 total impacts on six orthogonal faces with a time resolution on the order of 15 to 20 seconds. When combined with the orbital data and the stabilized configuration of the spacecraft, this permits a detailed analysis of the micro-particulate environment. The functional status of each of the 459 detectors was monitored every 2.4 hours, and post-flight analyses of these data has now permitted an evaluation of the effective active detection area as a function of time, panel by panel and separately for the two sensitivity levels. Thus, total impacts were transformed into areal fluxes, and are presented here for the first time. Also discussed are possible effects of these fluxes on previously announced results: apparent debris events, meteor stream detections, and beta meteoroids in observationally significant numbers.

Analysis of the proteolysis of bioactive peptides using a peptidomics approach

PubMed Central

Kim, Yun-Gon; Lone, Anna Mari; Saghatelian, Alan

2014-01-01

Identifying the peptidases that inactivate bioactive peptides (e.g. peptide hormones and neuropeptides) in mammals is an important unmet challenge. This protocol describes a recent approach that combines liquid chromatography-mass spectrometry peptidomics to identify endogenous cleavage sites of a bioactive peptide, the subsequent biochemical purification of a candidate peptidase based on these cleavage sites, and validation of the candidate peptidase’s role in the physiological regulation of the bioactive peptide by examining a peptidase knockout mouse. We highlight successful application of this protocol to discover that insulin-degrading enzyme (IDE) regulates physiological calcitonin gene-related peptide (CGRP) levels and detail the key stages and steps in this approach. This protocol requires 7 days of work; however, the total time for this protocol is highly variable because of its dependence on the availability of biological reagents, namely purified enzymes and knockout mice. The protocol is valuable because it expedites the characterization of mammalian peptidases, such as IDE, which in certain instances can be used to develop novel therapeutics. PMID:23949379

Study of concentration of HPV DNA probe immobilization for cervical cancer detection based IDE biosensor

NASA Astrophysics Data System (ADS)

Roshila, M. L.; Hashim, U.; Azizah, N.

2016-07-01

This paper mainly illustrates regarding the detection process of Human Papillomavirus (HPV) DNA probe. HPV is the most common virus that infected to human by a sexually transmitted virus. The most common high-risk HPV are 16 and 18. Interdigitated electrode (IDE) device used as based of Titanium Dioxide (TiO2) acts as inorganic surface, where by using APTES as a linker between inorganic surface and organic surface. A strategy of rapid and sensitive for the HPV detection was proposed by integrating simple DNA extraction with a gene of DNA. The extraction of the gene of DNA will make an efficiency of the detection process. It will depend on the sequence of the capture probes and the way to support their attached. The fabrication, surface modification, immobilization and hybridization processes are characterized by current voltage (I-V) measurement by using KEITHLEY 6487. This strategy will perform a good sensitivity of HPV detection.

A MEMS-based Benzene Gas Sensor with a Self-heating WO3 Sensing Layer

PubMed Central

Ke, Ming-Tsun; Lee, Mu-Tsun; Lee, Chia-Yen; Fu, Lung-Ming

2009-01-01

In the study, a MEMS-based benzene gas sensor is presented, consisting of a quartz substrate, a thin-film WO3 sensing layer, an integrated Pt micro-heater, and Pt interdigitated electrodes (IDEs). When benzene is present in the atmosphere, oxidation occurs on the heated WO3 sensing layer. This causes a change in the electrical conductivity of the WO3 film, and hence changes the resistance between the IDEs. The benzene concentration is then computed from the change in the measured resistance. A specific orientation of the WO3 layer is obtained by optimizing the sputtering process parameters. It is found that the sensitivity of the gas sensor is optimized at a working temperature of 300 °C. At the optimal working temperature, the experimental results show that the sensor has a high degree of sensitivity (1.0 KΩ ppm−1), a low detection limit (0.2 ppm) and a rapid response time (35 s). PMID:22574052

Characterization of recombinant monoclonal antibody variants detected by hydrophobic interaction chromatography and imaged capillary isoelectric focusing electrophoresis.

PubMed

King, Cory; Patel, Rekha; Ponniah, Gomathinayagam; Nowak, Christine; Neill, Alyssa; Gu, Zhenyu; Liu, Hongcheng

2018-05-15

In-depth characterization of the commonly observed variants is critical to the successful development of recombinant monoclonal antibody therapeutics. Multiple peaks of a recombinant monoclonal antibody were observed when analyzed by hydrophobic interaction chromatography and imaged capillary isoelectric focusing. The potential modification causing the heterogeneity was localized to F(ab')2 region by analyzing the antibody after IdeS digestion using hydrophobic interaction chromatography. LC-MS analysis identified asparagine deamidation as the root cause of the observed multiple variants. While the isoelectric focusing method is expected to separate deamidated species, the similar profile observed in hydrophobic interaction chromatography indicates that the single site deamidation caused differences in hydrophobicity. Forced degradation demonstrated that the susceptible asparagine residue is highly exposed, which is expected as it is located in the light chain complementarity determining region. Deamidation of this single site decreased the mAb binding affinity to its specific antigen. Copyright © 2018 Elsevier B.V. All rights reserved.

Dual-Use Transducer for Use with a Boundary-Stiffened Panel and Method of Using the Same

NASA Technical Reports Server (NTRS)

Schiller, Noah H. (Inventor); Cabell, Randolph H. (Inventor)

2011-01-01

A transducer for use with a boundary-stiffened panel has an inter-digitated electrode (IDE) and a piezoelectric wafer portion positioned therebetween. The IDE and/or the wafer portion are triangular, with one edge or side aligned with a boundary edge of the panel. The transducer generates and transmits an output force to the panel in response to an input voltage signal from a sensor, which can be another transducer as described above or an accelerometer. A controller can generate an output force signal in response to the input voltage signal to help cancel the input voltage signal. A method of using the transducer minimizes vibration in the panel by connecting multiple transducers around a perimeter thereof. Motion is measured at different portions of the panel, and a voltage signal determined from the motion is transmitted to the transducers to generate an output force at least partially cancelling or damping the motion.

A novel microwave sensor to detect specific biomarkers in human cerebrospinal fluid and their relationship to cellular ischemia during thoracoabdominal aortic aneurysm repair.

PubMed

Fok, M; Bashir, M; Fraser, H; Strouther, N; Mason, A

2015-04-01

Thoraco-abdominal aneurysms (TAAA) represents a particularly lethal vascular disease that without surgical repair carries a dismal prognosis. However, there is an inherent risk from surgical repair of spinal cord ischaemia that can result in paraplegia. One method of reducing this risk is cerebrospinal fluid (CSF) drainage. We believe that the CSF contains clinically significant biomarkers that can indicate impending spinal cord ischaemia. This work therefore presents a novel measurement method for proteins, namely albumin, as a precursor to further work in this area. The work uses an interdigitated electrode (IDE) sensor and shows that it is capable of detecting various concentrations of albumin (from 0 to 100 g/L) with a high degree of repeatability at 200 MHz (R(2) = 0.991) and 4 GHz (R(2) = 0.975).

Input Decimated Ensembles

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Oza, Nikunj C.; Clancy, Daniel (Technical Monitor)

2001-01-01

Using an ensemble of classifiers instead of a single classifier has been shown to improve generalization performance in many pattern recognition problems. However, the extent of such improvement depends greatly on the amount of correlation among the errors of the base classifiers. Therefore, reducing those correlations while keeping the classifiers' performance levels high is an important area of research. In this article, we explore input decimation (ID), a method which selects feature subsets for their ability to discriminate among the classes and uses them to decouple the base classifiers. We provide a summary of the theoretical benefits of correlation reduction, along with results of our method on two underwater sonar data sets, three benchmarks from the Probenl/UCI repositories, and two synthetic data sets. The results indicate that input decimated ensembles (IDEs) outperform ensembles whose base classifiers use all the input features; randomly selected subsets of features; and features created using principal components analysis, on a wide range of domains.

Hyperspectral image reconstruction for x-ray fluorescence tomography

DOE PAGES

Gürsoy, Doǧa; Biçer, Tekin; Lanzirotti, Antonio; ...

2015-01-01

A penalized maximum-likelihood estimation is proposed to perform hyperspectral (spatio-spectral) image reconstruction for X-ray fluorescence tomography. The approach minimizes a Poisson-based negative log-likelihood of the observed photon counts, and uses a penalty term that has the effect of encouraging local continuity of model parameter estimates in both spatial and spectral dimensions simultaneously. The performance of the reconstruction method is demonstrated with experimental data acquired from a seed of arabidopsis thaliana collected at the 13-ID-E microprobe beamline at the Advanced Photon Source. The resulting element distribution estimates with the proposed approach show significantly better reconstruction quality than the conventional analytical inversionmore » approaches, and allows for a high data compression factor which can reduce data acquisition times remarkably. In particular, this technique provides the capability to tomographically reconstruct full energy dispersive spectra without compromising reconstruction artifacts that impact the interpretation of results.« less

75 FR 71688 - Certain New Chemicals; Receipt and Status Information

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

... polyalkylene oxide. P-10-0575 09/27/10 12/25/10 Eastman Kodak (S) Polymer used in (G) Methacrylic acid Company. manufacture of polymer with imaging media/ isoalkylmethacrylam products; for ide, export. arylmethacrylate...) industrial coatings. Alkylenealkanedioic acid, polymer with alkenylbenzene and alkenenitrile, ammonium salt...

76 FR 70152 - Pilot Program for Early Feasibility Study Investigational Device Exemption Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-10

...] Pilot Program for Early Feasibility Study Investigational Device Exemption Applications AGENCY: Food and... feasibility study investigational device exemption (IDE) applications. The pilot program will conform to the... Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.'' Under the pilot...

A Test of Genetic Algorithms in Relevance Feedback.

ERIC Educational Resources Information Center

Lopez-Pujalte, Cristina; Guerrero Bote, Vicente P.; Moya Anegon, Felix de

2002-01-01

Discussion of information retrieval, query optimization techniques, and relevance feedback focuses on genetic algorithms, which are derived from artificial intelligence techniques. Describes an evaluation of different genetic algorithms using a residual collection method and compares results with the Ide dec-hi method (Salton and Buckley, 1990…

Age-related energy values of meat and bone meal for broiler chickens.

PubMed

Adeola, O; Anwar, M N; Abdollahi, M R; Ravindran, V

2018-07-01

Six hundred and eighty-four male Ross 308 broiler chicks were used to test the null hypothesis that post hatching age between day 0 and 21 does not affect utilization of energy in meat and bone meal (MBM). There were 6 replicate cages in each of 12 treatments consisting of 3 test diets (0, 40, or 80 g MBM/kg diets) at 4 feeding ages post hatching (day 0 to 7, 6 to 11, 10 to 16, or 15 to 21 post hatching) for a total of 72 cages in a randomized complete block design. Birds were assigned to the 12 treatments on day 0, fed a standard starter diet until they were switched to the test diets on day 0, 6, 10, or 15, and the number of birds per cage for day 0 to 7, 6 to 11, 10 to 16, or 15 to 21 were 12, 10, 8, or 8, respectively. Excreta were collected during the last 3 days of each feeding age post hatching and ileal digesta on the last day of each age. There was no interaction between dietary MBM level and feeding age post hatching for any of the response criteria. Weight gain and gain-to-feed ratio improved linearly (P < 0.001) with increasing dietary MBM and, expectedly, there was an increase (P < 0.001) in weight gain and a reduction (P < 0.001) in gain-to-feed ratio with bird feeding age post hatching. Ileal digestible energy (IDE), apparent metabolizable energy (AME), and nitrogen-corrected AME (AMEn) of the diet linearly increased (P < 0.001) with increasing dietary MBM. There were linear increases in dietary IDE (P < 0.05), AME (P < 0.001), and AMEn (P < 0.001) with bird feeding age post hatching. The IDE, ME, and MEn of MBM were determined by the regression procedure. During day 0 to 7, 6 to 11, 10 to 16, or 15 to 21, energy values increased (P < 0.05) with age and the respective IDE of MBM were 2.852, 2.962, 2.927, or 2.959 kcal/g DM. Corresponding ME of MBM were 2.909, 3.125, 3.083, or 3.075 kcal/g DM and those of MEn were 2.687, 2.887, 2.839, or 2.845 kcal/g DM. These results show that energy values of MBM increase with age post hatching and suggest the same energy value of MBM should not be used in formulating diets of broiler chickens during the first 3 weeks post hatching.

Coerência espectroscópica de famílias de asteróides

NASA Astrophysics Data System (ADS)

Mothé Diniz, T.; Roig, F. V.

2003-08-01

As Famílias de asteróides são caracterizadas como agrupamentos de objetos provenientes da quebra por colisão de corpos precursores. Desta forma, seus membros devem preservar relações genéticas que podem ser traduzidas sob a análise de suas características espectrais. Neste trabalho é apresentado o primeiro estudo espectroscópico de todas as famílias de asteróides do cinturão principal. Para tal, a divisão em famílias foi refeita utilizando-se o método HCM com uma base de elementos próprios analíticos (Knezevic e Milani, Jun 2001) e para o estudo espectroscópico foram utilizadas diversas campanhas de observação espectroscópica, tais o S3OS2 e o SMASSII, bem como outros dados disponíveis na literatura. A homogeneidade espectroscópica de cada família foi avaliada através da verificação das classes espectroscópicas presentes, bem como da comparação destes espectros com os de objetos de fundo, localizados na vizinhança da família. Vinte e duas famílias foram analisadas (as que possuíam mais do que 3 membros com espectro) e, dentre as principais conclusões pode-se citar a homogeneidade espectroscópica e, provavelmente mineralógica das famílias de Vesta, Eunomia, Hoffmeister, Dora, Merxia, Agnia, Koronis e Veritas. Esta última em particular, foi tida como uma família não homogênea espectroscopicamente em trabalho anterior (Di Martino et al. 1997). Outro resultado interessante é, por um lado, a aparente falta de homogeneidade dos membros da família de Eos, e por outro sua forte distinção dos objetos de fundo. O oposto ocorre na família de Themis, esta apresentando-se espectroscopicamente compatível com os objetos de fundo, mas com grande homogeneidade taxonômica entre seus membros. Algumas das famílias apresentam asteróides "intrusos" (objetos cujas características físicas não são compatíveis com aquelas dos membros da família) que, de modo geral desaparecem ao se considerarem níveis mais baixos de corte para a divisão da família no HCM, sem prejuízo para o agrupamento dos demais membros.

The impact of plant-based antimicrobials on sensory properties of organic leafy greens

USDA-ARS?s Scientific Manuscript database

Plant extracts and essential oils are well known for their antibacterial activity. However, studies concerning their effect on the organoleptic properties of treated foods are limited. The objective was to study the sensory attributes of organic leafy greens treated with plant antimicrobials and ide...

Chinese National Strategy of Total War

DTIC Science & Technology

2008-06-01

Cyber Warfare Michael J. Good, BA Major, USA June 2008 APPROVED FOR PUBLIC RELEASE; DISTRIBUTION IS...who allowed me into the Cyber Warfare , my fellow students in the Cyber Warfare IDE program who have been great friends and mentors, and my fellow...Hackers and Other Cyber Criminals .............................................................................41 PLA Cyber Warfare

BIRD SPECIES ASSEMBLAGES AS INDICATORS OF BIOLOGICAL INTEGRITY IN GREAT BASIN RANGELAND

EPA Science Inventory

The study evaluates the potential for bird species assemblages to serve as indicators of biological integrity of rangelands in the Great Basin in much the same way that fish and invertebrate assemblages have been used as indicators in aquatic environments. Our approach was to ide...

BISPHENOL-A AND PHTHALATE ESTERS: POTENTIAL SOURCES OF RESIN COMPONENTS IN THE EVERYDAY ENVIRONMENTS OF PRESCHOOL CHILDREN

EPA Science Inventory

The Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) study examined the aggregate exposures of 257 preschool children to pollutants commonly found in their everyday environments. A primary objective of the CTEPP study was to ide...

Modeling a molecular initiating event to population effects: A case study of aromatase inhibition in fathead minnows

EPA Science Inventory

An adverse outcome pathway (AOP) conceptually links a molecular initiating event with measureable key events at higher levels of biological organization that ultimately result in an adverse outcome. Development of an AOP requires experimental data and scientific expertise to ide...

Forming Student Online Teams for Maximum Performance

ERIC Educational Resources Information Center

Olson, Joel D.; Ringhand, Darlene G.; Kalinski, Ray C.; Ziegler, James G.

2015-01-01

What is the best way to assign graduate business students to online team-based projects? Team assignments are frequently made on the basis of alphabet, time zones or previous performance. This study reviews personality as an indicator of student online team performance. The personality assessment IDE (Insights Discovery Evaluator) was administered…

A Dialogue with Foxfire's Hilton Smith, and IDE's George Wood.

ERIC Educational Resources Information Center

Hands On, 1994

1994-01-01

The executive director of the Foxfire Fund and the codirector of the Institute for Democracy in Education discuss collaborative strategies for promoting democratic approaches to education, the history and current context of democratic education, and the importance of empowering teachers to implement student-centered democratic education. (LP)

21 CFR 812.19 - Address for IDE correspondence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and Radiological Health, Document Mail Center, 10903 New Hampshire Ave., Bldg. 66, rm. G609, Silver Spring, MD 20993-0002. (2) For devices regulated by the Center for Biologics Evaluation and Research, send it to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and...

Implementing Simulation Design of Experiments and Remote Execution on a High Performance Computing Cluster

DTIC Science & Technology

2007-09-01

example, an application developed in Sun’s Netbeans [2007] integrated development environment (IDE) uses Swing class object for graphical user... Netbeans Version 5.5.1 [Computer Software]. Santa Clara, CA: Sun Microsystems. Process Modeler Version 7.0 [Computer Software]. Santa Clara, Ca

Small Boat and Swarm Defense: A Gap Study

DTIC Science & Technology

2008-09-01

25 1. Java......................................................................................................25 2. The NetBeans ...Figure 12. Overview of Java program development (Zakhour 2006)...............................26 Figure 13. NetBeans IDE generating new “Hello World...Application (Zakhour 2006) ..27 Figure 14. Example source code generation using NetBeans for the “Hello World” application (Zakhour 2006

Polyphenol oxidase inhibitor(s) from German cockroach (Blattella germanica) extract

USDA-ARS?s Scientific Manuscript database

An extract from German cockroach appears effective in inhibiting browning on apples and potatoes. Successful identification of inhibitor(s) of PPO from German cockroach would be useful to the fruit and vegetable segments of the food industry, due to the losses they incur from enzymatic browning. Ide...

Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR CAT)

DTIC Science & Technology

2016-12-01

Preservation and Resuscitation (EPR) was developed to rapidly preserve the organism during ischemia, using hypothermia, drugs , and fluids, to “ buy time...Device Exemption (IDE) from the Food and Drug Administration (FDA). Our trial is complicated by the fact that both fluids and equipment are to be used

Ready Set. . .Authoring Systems to Get You Started on Interactive Video Design.

ERIC Educational Resources Information Center

Rhodes, Dent M.; Azbell, Janet White

1986-01-01

Evaluates four authoring systems used to develop computer aided interactive video: The Instructor, InfoWriter, IDeAS, and ProCAL2. The information provided includes hardware requirements, compatibility with videotape and/or videodisc, instructional options available, user data-management capabilities, procedures for logging tapes, and access for…

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

PubMed

Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Abdullah, Maizaton Atmadini; Basri, Hamidon

2017-11-01

Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of a Behavioral Intervention Strategy for Adoption and Maintenance of a Physically Active Lifestyle: The Italian Diabetes and Exercise Study 2 (IDES_2): A Randomized Controlled Trial.

PubMed

Balducci, Stefano; D'Errico, Valeria; Haxhi, Jonida; Sacchetti, Massimo; Orlando, Giorgio; Cardelli, Patrizia; Vitale, Martina; Bollanti, Lucilla; Conti, Francesco; Zanuso, Silvano; Nicolucci, Antonio; Pugliese, Giuseppe

2017-11-01

Adherence to physical activity (PA) recommendations is hampered by the lack of effective strategies to promote behavior change. The Italian Diabetes and Exercise Study 2 (IDES_2) is a randomized controlled trial evaluating a novel behavioral intervention strategy for increasing PA and decreasing sedentary time (SED-time) in patients with type 2 diabetes. The study randomized 300 physically inactive and sedentary patients with type 2 diabetes 1:1 to receive theoretical and practical counseling once yearly for 3 years (intervention group [INT]) or standard care (control group [CON]). Here, we report the 4-month effects on objectively (accelerometer) measured daily light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time, and cardiovascular risk factors. LPA and MVPA both increased, and SED-time decreased in both groups, although changes were significantly more marked in INT participants (approximately twofold for LPA and SED-time and approximately sixfold for MVPA). A significant reduction in HbA 1c was observed only in INT subjects. An increase in LPA >0.92 h · day -1 and in MVPA >7.33 min · day -1 and a decrease in SED-time >1.05 h · day -1 were associated with an average decrease in HbA 1c of ∼1% and also with significant improvements in fasting glucose, body weight, waist circumference, and hs-CRP. Changes in PA and SED-time were independent predictors of improvements in HbA 1c . This behavioral intervention is effective in the short term for increasing LPA and MVPA and reducing SED-time. Significant improvements in cardiometabolic risk profiles were observed in subjects experiencing the most pronounced changes in PA and SED-time, even if below the recommended level. © 2017 by the American Diabetes Association.

Gene-Centric Analysis of Serum Cotinine Levels in African and European American Populations

PubMed Central

Hamidovic, Ajna; Goodloe, Robert J; Bergen, Andrew W; Benowitz, Neal L; Styn, Mindi A; Kasberger, Jay L; Choquet, Helene; Young, Taylor R; Meng, Yan; Palmer, Cameron; Pletcher, Mark; Kertesz, Stefan; Hitsman, Brian; Spring, Bonnie; Jorgenson, Eric

2012-01-01

To date, most genetic association studies of tobacco use have been conducted in European American subjects using the phenotype of smoking quantity (cigarettes per day). However, smoking quantity is a very imprecise measure of exposure to tobacco smoke constituents. Analyses of alternate phenotypes and populations may improve our understanding of tobacco addiction genetics. Cotinine is the major metabolite of nicotine, and measuring serum cotinine levels in smokers provides a more objective measure of nicotine dose than smoking quantity. Previous genetic association studies of serum cotinine have focused on individual genes. We conducted a genetic association study of the biomarker in African American (N=365) and European American (N=315) subjects from the Coronary Artery Risk Development in Young Adults study using a chip containing densely-spaced tag SNPs in ∼2100 genes. We found that rs11187065, located in the non-coding region (intron 1) of insulin-degrading enzyme (IDE), was the most strongly associated SNP (p=8.91 × 10−6) in the African American cohort, whereas rs11763963, located on chromosome 7 outside of a gene transcript, was the most strongly associated SNP in European Americans (p=1.53 × 10−6). We then evaluated how the top variant association in each population performed in the other group. We found that the association of rs11187065 in IDE was also associated with the phenotype in European Americans (p=0.044). Our top SNP association in European Americans, rs11763963 was non-polymorphic in our African American sample. It has been previously shown that psychostimulant self-administration is reduced in animals with lower insulin because of interference with dopamine transmission in the brain reward centers. Our finding provides a platform for further investigation of this, or additional mechanisms, involving the relationship between insulin and self-administered nicotine dose. PMID:22089314

Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease

PubMed Central

Nalivaeva, Natalia N.; Belyaev, Nikolai D.; Kerridge, Caroline; Turner, Anthony J.

2014-01-01

Abnormal elevation of amyloid β-peptide (Aβ) levels in the brain is the primary trigger for neuronal cell death specific to Alzheimer’s disease (AD). It is now evident that Aβ levels in the brain are manipulable due to a dynamic equilibrium between its production from the amyloid precursor protein (APP) and removal by amyloid clearance proteins. Clearance can be either enzymic or non-enzymic (binding/transport proteins). Intriguingly several of the main amyloid-degrading enzymes (ADEs) are members of the M13 peptidase family (neprilysin (NEP), NEP2 and the endothelin converting enzymes (ECE-1 and -2)). A distinct metallopeptidase, insulin-degrading enzyme (IDE), also contributes to Aβ degradation in the brain. The ADE family currently embraces more than 20 members, both membrane-bound and soluble, and of differing cellular locations. NEP plays an important role in brain function terminating neuropeptide signals. Its decrease in specific brain areas with age or after hypoxia, ischaemia or stroke contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP (and other genes) by the APP intracellular domain (AICD) and its dependence on the cell type and APP isoform expression suggest possibilities for selective manipulation of NEP gene expression in neuronal cells. We have also observed that another amyloid-clearing protein, namely transthyretin (TTR), is also regulated in the neuronal cell by a mechanism similar to NEP. Dependence of amyloid clearance proteins on histone deacetylases and the ability of HDAC inhibitors to up-regulate their expression in the brain opens new avenues for developing preventive strategies in AD. PMID:25278875

Role of anionic charges of osmoregulated periplasmic glucans of Salmonella enterica Serovar Typhimurium SL1344 in mice virulence

USDA-ARS?s Scientific Manuscript database

Osmoregulated periplasmic glucans (OPGs) are important periplasmic constituents of Salmonella spp. and are required for optimal growth in hypoosmotic environments such as irrigation and vegetable wash waters as well as for mice virulence. opgB gene of Salmonella enterica serovar Typhimurium was ide...

A Dynamic Analysis of the Medium Tank Battalion. Volume I

DTIC Science & Technology

1978-06-01

best available copy. W. KEY WORDS (Cortinue an reverse oIde If necessary And Identifty block number) CONSTRUCTION; PLANNING; MANAGEMENT; MODELS...unit, with 64K, 8-bit bytes, (2) Dual-disk drive, 2 Discs at 262K, 8-bit bytes, (3) Cathode Ray Tube Console and Keyboard, (4) High- speed printer, (5

CDPKs are dual-specificity protein kinases and tyrosine autophosphorylation attenuates kinase activity

USDA-ARS?s Scientific Manuscript database

Calcium-dependent protein kinases (CDPKs or CPKs) are classified as serine/threonine protein kinases but we made the surprising observation that soybean CDPK' and several Arabidopsis isoforms (AtCPK4 and AtCPK34) could also autophosphorylate on tyrosine residues. In studies with His6-GmCDPK', we ide...

The taming of the prairie: A century of agricultural research at the Northern Great Plains Research Laboratory

USDA-ARS?s Scientific Manuscript database

Nearly a century after Congress authorized the Northern Great Plains Research Laboratory, it had approximately 35 employees and an annual budget of 3.4 million dollars. The long history of research accomplishments from the Laboratory have been well accepted by the agricultural community and have ide...

The Organizational and the Interpersonal in an International Development Education Project.

ERIC Educational Resources Information Center

Bhola, H. S.

The organizational aspects of the process of innovation diffusion and the planned change and development as applied to an appraisal of international development education (IDE) are examined in this paper. The document begins by describing how effective organizations and institutions should be planned and structured to produce planned change. It…

Investigating the microstructure of keratin extracted from wool: peptide sequence (MALDI-TOF/TOF) and protein conformation (FTIR)

USDA-ARS?s Scientific Manuscript database

Keratin was extracted from wool by reduction with 2-mercaptoethanol. It was isolated as intact keratin and characterized by its similar molecular weight, protein composition, and secondary structure to native keratin. Gel electrophoresis patterns and MALDI-TOF/TOF peptide sequences provided the ide...

The Tuition Advance Fund: An Analysis Prepared for Boston University.

ERIC Educational Resources Information Center

Botsford, Keith

Three models for anlayzing the Tuition Advance Fund (TAF) are examined. The three models are: projections by the Institute for Demographic and Economic Studies (IDES), projections by Data Resources, Inc. (DRI), and the Tuition Advance Fund Simulation (TAFSIM) models from Boston University. Analysis of the TAF is based on enrollment, price, and…

Interactive Distance e-Learning for Isolated Communities: The Policy Footprint

ERIC Educational Resources Information Center

Crump, Stephen; Twyford, Kylie; Littler, Margaret

2008-01-01

This paper provides information on the policy strand of an investigation into the Australian Research Council Linkage research project into "interactive distance e-learning" [IDeL] following the introduction in New South Wales and in the Northern Territory of Australia of satellite-supported two-way broad-band internet services for…

The Learning and Productivity Benefits to Student Programmers from Real-World Development Environments

ERIC Educational Resources Information Center

Debuse, Justin C. W.; Lawley, Meredith

2012-01-01

Existing research and practice in software development environments shows no clear consensus on the most appropriate development tools to use; these may range from simple text editors through teaching-oriented examples to full commercial integrated development environments (IDEs). This study addresses this gap by examining student perceptions of…

Extending Orthogonal and Nearly Orthogonal Latin Hypercube Designs for Computer Simulation and Experimentation

DTIC Science & Technology

2006-12-01

The code was initially developed to be run within the netBeans IDE 5.04 running J2SE 5.0. During the course of the development, Eclipse SDK 3.2...covers the results from the research. Chapter V concludes and recommends future research. 4 netBeans

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.212 - Medicare Coverage IDE study criteria.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Medicare coverage of items and services described in § 405.211, a Category A (Experimental) or Category B...) The study design is methodologically appropriate and the anticipated number of enrolled subjects is... CFR parts 50, 56, and 812 and 45 CFR part 46. (7) Where appropriate, the study is not designed to...

QUANTIFYING AGGREGATE CHLORPYRIFOS EXPOSURE AND DOSE TO CHILDREN USING A PHYSICALLY-BASED TWO-STAGE MONTE CARLO PROBABILISTIC MODEL

EPA Science Inventory

To help address the Food Quality Protection Act of 1996, a physically-based, two-stage Monte Carlo probabilistic model has been developed to quantify and analyze aggregate exposure and dose to pesticides via multiple routes and pathways. To illustrate model capabilities and ide...

78 FR 15931 - Sunshine Act Meeting; Request for Comments on Draft Evaluation of Recommended Practice on Fatigue...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

... Evaluation of Recommended Practice on Fatigue Risk Management Systems for Personnel in the Refining and... and Health Administration: 2001-05-I-DE-1 (Process Safety Management coverage of atmospheric storage tanks); 2005-04-I-TX-9 (Process Safety Management requirement for organizational management of change...

MALDI, AP/MALDI and ESI techniques for the MS detection of amyloid [beta]-peptides

NASA Astrophysics Data System (ADS)

Grasso, Giuseppe; Mineo, Placido; Rizzarelli, Enrico; Spoto, Giuseppe

2009-04-01

Amyloid [beta]-peptides (A[beta]s) are involved in several neuropathological conditions such as Alzheimer's disease and considerable experimental evidences have emerged indicating that different proteases play a major role in regulating the accumulation of A[beta]s in the brain. Particularly, insulin-degrading enzyme (IDE) has been shown to degrade A[beta]s at different cleavage sites, but the experimental results reported in the literature and obtained by mass spectrometry methods are somehow fragmentary. The detection of A[beta]s is often complicated by solubility issues, oxidation artifacts and spontaneous aggregation/cleavage and, in order to rationalize the different reported results, we analyzed A[beta]s solutions by three different MS approaches: matrix assisted laser desorption ionization-time of flight (MALDI-TOF), atmospheric pressure (AP) MALDI ion trap and electrospray ionization (ESI) ion trap. Differences in the obtained results are discussed and ESI is chosen as the most suitable MS method for A[beta]s detection. Finally, cleavage sites produced by interaction of A[beta]s with IDE are identified, two of which had never been reported in the literature.

Spectroscopic Analysis of Desiccation-Induced Alterations of the Chlorophyllide Transformation Pathway in Etiolated Barley Leaves1

PubMed Central

Le Lay, Pascaline; Böddi, Béla; Kovacevic, Dragan; Juneau, Philippe; Dewez, David; Popovic, Radovan

2001-01-01

Effects of water deficit on the chlorophyllide (Chlide) transformation pathway were studied in etiolated barley (Hordeum vulgare) leaves by analyzing absorption spectra and 77-K fluorescence spectra deconvoluted in components. Chlide transformations were examined in dehydrated leaves exposed to a 35-ms saturating flash triggering protochlorophyllide (Pchlide) and Chlide transformation processes. During the 90 min following the flash, we found that dehydration induced modifications of Chlide transformations, but no effect on Pchlide phototransformation into Chlide was observed. During this time, content of NADPH-Pchlide oxydoreductase in leaves did not change. Chlide transformation process in dehydrated leaves was characterized by the alteration of the Shibata shift process, by the appearance of a new Chlide species emitting at 692 nm, and by the favored formation of Chl(ide) A668F676. The formation of Chl(ide) A668F676, so-called “free Chlide,” was probably induced by disaggregation of highly aggregated Chlide complexes. Here, we offer evidence for the alteration of photoactive Pchlide regeneration process, which may be caused by the desiccation-induced inhibition of Pchlide synthesis. PMID:11553748

Integrated digital error suppression for improved detection of circulating tumor DNA

PubMed Central

Kurtz, David M.; Chabon, Jacob J.; Scherer, Florian; Stehr, Henning; Liu, Chih Long; Bratman, Scott V.; Say, Carmen; Zhou, Li; Carter, Justin N.; West, Robert B.; Sledge, George W.; Shrager, Joseph B.; Loo, Billy W.; Neal, Joel W.; Wakelee, Heather A.; Diehn, Maximilian; Alizadeh, Ash A.

2016-01-01

High-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy. However, low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity. To overcome these limitations, we introduce an approach for integrated digital error suppression (iDES). Our method combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules. Individually, these two methods each improve the sensitivity of cancer personalized profiling by deep sequencing (CAPP-Seq) by ~3 fold, and synergize when combined to yield ~15-fold improvements. As a result, iDES-enhanced CAPP-Seq facilitates noninvasive variant detection across hundreds of kilobases. Applied to clinical non-small cell lung cancer (NSCLC) samples, our method enabled biopsy-free profiling of EGFR kinase domain mutations with 92% sensitivity and 96% specificity and detection of ctDNA down to 4 in 105 cfDNA molecules. We anticipate that iDES will aid the noninvasive genotyping and detection of ctDNA in research and clinical settings. PMID:27018799

Blowpipe Mineralogy for Physics/Environment: Highest-Possible-Tc SuperConductor (Beyond: (but via!!!) MgB2, Cuprates, Pnictides) Quest; BOTH PERMANENT FOREVER Carb-IDES SOLID-State Sequestration AND Drought(s)-Elimination

NASA Astrophysics Data System (ADS)

Segler, Kurt; Williams, Wendell; Siegel, Edward

2011-03-01

Detailed are old blowpipe new applications: charcoal-block reduction of borates to yield ("N-NW" of MgB2) Overhauser-[PR 35,1,411(1987); Intl.J.Mod.Phys.1, 2 & 4, 927(1987)]-"land" predicted high-EST-POSSIBLE Tc SC "LiD2"; very-early: Siegel[Phys.Stat.Sol.(a)11,45(1972);Semiconductors.and Insulators 5: 39,47,62(1979)] carb-IDES SOLID-state phase-TRANSITIONED CHEMICALLY-REDOX"-REACTED STABLE PERMANENT LONG-term NOT "CO2" BUT C-sequestration: PROFITABLE "Grab and Sell" TRUMPS "cap and trade"!!!; Mott alloying/vertical metal-insulator transitions in "borax-(GLASS)-beads"; and very-earlySiegel [{3rd Intl.Conf.Alt.Energy }(1980)-vol.5/p.459!!!] "FLYING-WATER" Hindenberg-effect (H2-UP;H2O-DOWN) via Hydrogen-maximal-Archimedes-buoyancy "chemical-rain-in-pipelines", only via Siegel proprietary "magnetic-hydrogen-valve"(MHV): Renewables-Hydrogen-Water flexible versatile agile scaleable retrofitable integrated operating-system for PERMANENT drought(s)-elimination FOREVER!!!

Fast-Response, Sensitivitive and Low-Powered Chemosensors by Fusing Nanostructured Porous Thin Film and IDEs-Microheater Chip

PubMed Central

Dai, Zhengfei; Xu, Lei; Duan, Guotao; Li, Tie; Zhang, Hongwen; Li, Yue; Wang, Yi; Wang, Yuelin; Cai, Weiping

2013-01-01

The chemiresistive thin film gas sensors with fast response, high sensitivity, low power consumption and mass-produced potency, have been expected for practical application. It requires both sensitive materials, especially exquisite nanomaterials, and efficient substrate chip for heating and electrical addressing. However, it is challenging to achieve repeatable microstructures across the films and low power consumption of substrate chip. Here we presented a new sensor structure via the fusion of metal-oxide nanoporous films and micro-electro-mechanical systems (MEMS)-based sensing chip. An interdigital-electrodes (IDEs) and microheater integrated MEMS structure is designed and employed as substrate chip to in-situ fabricate colloidal monolayer template-induced metal-oxide (egg. SnO2) nanoporous sensing films. This fused sensor demonstrates mW-level low power, ultrafast response (~1 s), and parts-per-billion lever detection for ethanol gas. Due to the controllable template strategy and mass-production potential, such micro/nano fused high-performance gas sensors will be next-generation key miniaturized/integrated devices for advanced practical applications. PMID:23591580

Increasing Diversity in the Earth Sciences (IDES) - An Oregon Effort

NASA Astrophysics Data System (ADS)

de Silva, S. L.; Duncan, R. A.; Wright, D. J.; de Silva, L.; Guerrero, E. F.

2011-12-01

The IDES (Increasing Diversity in Earth Sciences) Program is the first partnership of its kind in the state of Oregon targeted at broadening participation in the Earth Science enterprise. Funded by the National Science Foundation Opportunities to Enhance Diversity in the Geosciences program (NSF-OEDG), this partnership involves community colleges, a research university with major strengths in Earth Science research and education and an institutionalized commitment to enhancing diversity, state and federal agencies, centers of informal education, and the Oregon Space Grant Consortium, IDES has two integrated goals: 1) to increase the number of students from under-represented groups who pursue careers in Earth Science research and education, and 2) to strengthen the understanding of Earth Sciences and their relevance to society among broad and diverse segments of the population. Built around the best practices of tiered mentoring, interactive student cohort, research and education internships, and financial support, this 4-year program recruits 10 to 12 students (mainly rising juniors) each year from science majors at Oregon State University and five Oregon community colleges. The program is reaching its goals by: a) training participants in the application of geospatial to Earth Science problems of personal relevance b) immersing participants in a two-year mentored research project that involves summer internships with academic units, state and federal agencies, and centers for informal education in Oregon. c) exposing, educating, and involving participants in the breadth of Earth Science careers through contact with Earth Science professionals through mentors, a professional internship, and a learning community that includes a speaker series. d) instilling an understanding of context and relevance of the Earth Science Enterprise to the participants, their families, their communities, and the general public. We report on the first two years of this program during which 20 participants have been involved and significant feedback has been received.

Effects of preincubation of eggs and activation medium on the percentage of eyed embryos in ide (Leuciscus idus), an externally fertilizing fish.

PubMed

Siddique, Mohammad Abdul Momin; Linhart, Otomar; Krejszeff, Sławomir; Żarski, Daniel; Król, Jarosław; Butts, Ian Anthony Ernest

2016-03-15

Standardization of fertilization protocols is crucial for improving reproductive techniques for externally fertilizing fish in captive breeding. Therefore, the objectives of this study were to determine the effects of preincubation of eggs and activation medium on the percentage of eyed embryos for ide (Leuciscus idus). Pooled eggs from five females were preincubated in three different activating media for 0, 30, 60, 90, and 120 seconds and then fertilized by pooled sperm from five males. At the eyed-egg stage, the percentage of viable embryos was later calculated. Results showed that preincubation time was significant for the freshwater activation medium (P < 0.001), such that the percentage of eyed embryos declined across the preincubation time gradient. Additionally, there was an effect on the percentage of eyed embryos when eggs were incubated with Woynarovich solution (P < 0.001), such that a decline was detected at 90 seconds, whereas no effect was detected for the saline water medium. Activating medium had a significant effect on the percentage of eyed embryos for each preincubation time (P < 0.05). More precisely, freshwater produced the lowest percentage of eyed embryos at all preincubation times (ranged from 1.9% at 120 seconds to 43.6% at 0 seconds), whereas saline water and Woynarovich solution produced the highest percentage of eyed embryos at 0 seconds and 30 seconds before incubation. Woynarovich solution produced the highest percentage of eyed embryos at 60 seconds (65.26%), whereas saline water produced the highest percentage at 90 seconds (68.37%). No difference was detected between saline water and Woynarovich solution at 120 seconds. Examination of sperm traits showed no impact of activating medium on computer assisted sperm analysis parameters. Together, these results suggest that saline water or Woynarovich solution improve fertilization rate in ide during IVF; thus, these media are useful for standardizing fertilization protocols and controlled reproduction for this species. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study

PubMed Central

2012-01-01

Background Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD). Methods/design The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. Discussion The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies’ impact on clinical care and patients’ outcomes. PMID:23217181

THESIS-ABSTRACT Supplementation levels of exogenous alpha-amylase in broilers diets.

PubMed

Oliveira, H B; Silva, M I A; Mesquita, F R

2017-08-17

This study aimed to evaluate the supplementation levels of an exogenous alpha-amylase in broilers diets and compare two indicators in determining the diets energy. The experiment was divided into two parallel evaluations, being one of performance and the other of metabolism. In performance assay, 1,700 one-day-old Cobb-500 male chicks were used. The animals were distributed in 50 experimental plots and evaluated five treatments with ten replicates in a completely randomized design (CRD). The treatments were: a positive control (PC), a negative control (NC) and three alpha-amylase supplementation levels 200, 400 and 600 g/t, and the NC was formulated with 50 and 90 kcal of energy reduction in relation to the PC to the phases from 1 to 21 days and from 22 to 42 days, respectively. In the metabolism assay were used 240 animals, 150 birds for stage from 14 to 21 days and 90 birds to stage from 35 to 42 days of age and the treatments were the same as the performance assay, with six replicates per treatment in CRD. All diets of metabolism test contained the digestibility indicators Lipe ® (eucalyptus purified lignin) and chromic oxide (Cr 2 O 3 ), in concentrations of 0.05 and 1.0%, respectively. In the period from 1 to 21 days old, no significant differences were observed in weight gain (WG) (P > 0.05), however, feed intake (FI) was found higher by using 200 ppm of enzyme (P < 0.05) and better feed conversion (FC) with the PC (P < 0.05). From 22 to 42 days, no significant differences were observed on the WG (P > 0.05), but were observed lower FI and better FC to PC treatment (P < 0.05). In the period from 1 to 42 days of age, significant differences were also not observed on the WG (P > 0.05), but there was lower FI and better FC for the PC treatment (P < 0.05). The AMEn (apparent metabolizable energy corrected for nitrogen balance), determined using the total collection, reaffirmed the values ​​calculated for the PC and NC with intermediate data obtained from the enzyme use (200, 400 and 600 ppm). Comparing the total collection using Lipe ® and Cr 2 O 3 , a correlation was observed only for the PC results, that were always higher, and for the NC results, that were lower for the three methodologies. For IDE (ileal digestible energy), determined by Cr 2 O 3, significant differences were observed (P < 0.05) and it presented higher values in the PC treatment and lower values in the NC. In IDE determining by Lipe ® , significant was observed (P < 0.05), showing higher value in the PC treatment. It is concluded that in the metabolism assessments, exogenous alpha-amylase tested was effective in increasing the metabolizable energy (ME), however, not enough to be equivalent to the ME of PC treatment, a result that was better expressed in the total collection, AMEn by Lipe ® and IDE by Lipe ® methodologies. The performance results reflect the superiority of PC treatment, pointing enzyme limitation to supply the energy deficit practiced in this work.

Elemental analyses of hypervelocity microparticle impact sites on Interplanetary Dust Experiment sensor surfaces

NASA Technical Reports Server (NTRS)

Simon, Charles G.; Hunter, J. L.; Griffis, D. P.; Misra, V.; Ricks, D. A.; Wortman, Jim J.; Brownlee, D. E.

1993-01-01

The Interplanetary Dust Experiment (IDE) had over 450 electrically active ultra-high purity metal-oxide-silicon impact detectors located on the six primary sides of the Long Duration Exposure Facility (LDEF). Hypervelocity microparticles (approximately 0.2 to approximately 100 micron diameter) that struck the active sensors with enough energy to break down the 0.4 or 1.0 micron thick SIO2 insulator layer separating the silicon base (the negative electrode), and the 1000 A thick surface layer of aluminum (the positive electrode) caused electrical discharges that were recorded for the first year of orbit. The high purity Al-SiO2-Si substrates allowed detection of trace (ppm) amounts of hypervelocity impactor residues. After sputtering through a layer of surface contamination, secondary ion mass spectrometry (SIMS) was used to create two-dimensional elemental ion intensity maps of microparticle impact sites on the IDE sensors. The element intensities in the central craters of the impacts were corrected for relative ion yields and instrumental conditions and then normalized to silicon. The results were used to classify the particles' origins as 'manmade,' 'natural,' or 'indeterminate.' The last classification resulted from the presence of too little impactor residue, analytical interference from high background contamination, the lack of information on silicon and aluminum residues, or a combination of these circumstances. Several analytical 'blank' discharges were induced on flight sensors by pressing down on the sensor surface with a pure silicon shard. Analyses of these blank discharges showed that the discharge energy blasts away the layer of surface contamination. Only Si and Al were detected inside the discharge zones, including the central craters of these features. Thus far a total of 79 randomly selected microparticle impact sites from the six primary sides of the LDEF have been analyzed: 36 from tray C-9 (Leading (ram), or East, side), 18 from tray C-3 (Trailing (wake), or West, side), 12 from tray B-12 (North side), 4 from tray D-6 (South side), 3 from tray H-11 (Space end), and 6 from tray G-10 (Earth end). Residue from manmade debris was identified in craters on all trays. (Aluminum oxide particle residues were not detectable on the Al/Si substrates.) These results were consistent with the IDE impact record which showed highly variable long term microparticle impact flux rates on the West, Space and Earth sides of the LDEF which could not be ascribed to astronomical variability of micrometeorite density. The IDE record also showed episodic bursts of microparticle impacts on the East, North, and South sides of the satellite, denoting passage through orbital debris clouds or rings.

Elemental Analyses of Hypervelocity Microparticle Impact Sites on Interplanetary Dust Experiment Sensor Surfaces

NASA Technical Reports Server (NTRS)

Simon, C. G.; Hunter, J. L.; Griffis, D. P.; Misra, V.; Ricks, D. A.; Wortman, J. J.; Brownlee, D. E.

1992-01-01

The Interplanetary Dust Experiment (IDE) had over 450 electrically active ultra-high purity metal-oxide-silicon impact detectors located on the six primary sides of the Long Duration Exposure Facility (LDEF). Hypervelocity microparticles (approximately 0.2 to approximately 100 micron diameter) that struck the active sensors with enough energy to breakdown the 0.4 or 1.0 micron thick SiO2 insulator layer separating the silicon base (the negative electrode), and the 1000 A thick surface layer of aluminum (the positive electrode) caused electrical discharges that were recorded for the first year of orbit. The high purity Al-SiO2-Si substrates allowed detection of trace (ppm) amounts of hypervelocity impactor residues. After sputtering through a layer of surface contamination, secondary ion mass spectrometry (SIMS) was used to create two-dimensional elemental ion intensity maps of microparticle sites on the IDE sensors. The element intensities in the central craters of the impacts were corrected for relative ion yields and instrumental conditions and then normalized to silicon. The results classification resulted from the particles' origins as 'manmade', 'natural', or 'indeterminate'. The last classification resulted from the presence of too little impactor residue, analytical interference from high background contamination, the lack of information on silicon and aluminum residues, or a combination of these circumstances. Several analytical 'blank' discharges were induced on flight sensors by pressing down on the sensor surface with a pure silicon shard. Analyses of these blank discharges showed that the discharge energy blasts away the layer of surface contamination. Only Si and Al were detected inside the discharge zones, including the central craters, of these features. Thus far, a total of 79 randomly selected microparticle impact sites from the six primary sides of the LDEF were analyzed: 36 from tray C-9 (Leading (ram), or east, side), 18 from tray C-3 (Trailing (wake), or west, side), 12 from tray B-12 (north side), 4 from tray D-6 (south side), 3 from tray H-11 (space end), and 6 from tray G-10 (earth end). Residue from manmade debris was identified in craters on all trays (aluminum oxide particle residues were not detectable on the Al/Si substrates). These results were consistent with the IDE impact record which showed highly variable long term microparticle impact flux rates on the west, space, and Earth sides of the LDEF which could not be ascribed to astronomical variability of micrometeorite density. The IDE record also showed episodic bursts of microparticle impacts on the east, north, and south sides of the satellite, denoting passage through orbital debris clouds or rings.

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study

PubMed Central

Xu, Wei-Li; Pedersen, Nancy L.; Keller, Lina; Kalpouzos, Grégoria; Wang, Hui-Xin; Graff, Caroline; Winblad, Bengt; Bäckman, Lars; Fratiglioni, Laura

2015-01-01

Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people. PMID:26173052

Development of a 63K SNP array for Gossypium and high-density mapping of intra- and inter-specific populations of cotton (G. hirsutum L.)

USDA-ARS?s Scientific Manuscript database

High-throughput genotyping arrays provide a standardized resource for crop research communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), candidate marker and quantitative trait loci (QTL) ide...

Medication Management Assessment for Older Adults in the Community

ERIC Educational Resources Information Center

Orwig, Denise; Brandt, Nicole; Gruber-Baldini, Ann L.

2006-01-01

Purpose: The purpose of this study was to describe the Medication Management Instrument for Deficiencies in the Elderly (MedMaIDE) and to provide results of reliability and validity testing. Design and Methods: Participants were 50 older adults, aged 65 and older, who lived in the community, took at least one prescription medication, and were then…

77 FR 71601 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-03

... in certain circumstances, e.g., recall of the device, the occurrence of unanticipated adverse effects... Annual Reporting Burden \\1\\ Number of Average Activity/21 CFR Section Number of responses per Total annual burden per Total hours respondents respondent responses response Waivers--812.10 1 1 1 1 1 IDE...

Research on Mathematics Learning at the "Center of Individual Development and Adaptive Education" (IDeA)--An Introduction

ERIC Educational Resources Information Center

Krummheuer, Götz

2013-01-01

In 2008, the research center "Individual Development and Adaptive Education" was constituted by the Goethe University, the German Institute for International Educational Research, and the Sigmund Freud Institute, all located in Frankfurt am Main, Germany (http://www.idea-frankfurt.eu). The research of the center focuses on the…

Distributed Architecture for the Object-Oriented Method for Interoperability

DTIC Science & Technology

2003-03-01

Collaborative Environment. ......................121 Figure V-2. Distributed OOMI And The Collaboration Centric Paradigm. .....................123 Figure V...of systems are formed into a system federation to resolve differences in modeling. An OOMI Integrated Development Environment (OOMI IDE) lends ...space for the creation of possible distributed systems is partitioned into User Centric systems, Processing/Storage Centric systems, Implementation

Idee Per Consolidare Le Abilita In Matematica. Ideas for Strengthening Mathematics Skills. Italian Edition.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Bilingual Education.

Presented is an overview of some specific schemes that have been used successfully by teachers throughout New York State to strengthen basic mathematics skills. Components offer ideas that have been successful with primary, intermediate, and secondary students. The contents of this Italian language edition are identical to the English language and…

A single base pair in the right terminal domain of Tomato planta macho viroid is a virulence determinant factor on tomato

USDA-ARS?s Scientific Manuscript database

Tomato planta macho viroid (TPMVd), including isolates previously designated as Mexican papita viroid (MPVd), causes serious disease on tomatoes in North America. Two predominant variants, sharing 93.8% sequence identity, incited distinct severe (MPVd-S) or mild (MPVd-M) symptoms on tomato. To ide...

Interviews with College Students: Evaluating Computer Programming Environments for Introductory Courses

ERIC Educational Resources Information Center

Uysal, Murat Pasa

2014-01-01

Different methods, strategies, or tools have been proposed for teaching Object Oriented Programming (OOP). However, it is still difficult to introduce OOP to novice learners. The problem may be not only adopting a method or language, but also use of an appropriate integrated development environment (IDE). Therefore, the focus should be on the…

Interactive Distance e-Learning for Isolated Communities: Starting and Finishing the Jigsaw

ERIC Educational Resources Information Center

Crump, Stephen; Boylan, Colin

2008-01-01

This paper provides information on the background to the two pilot investigations into "interactive distance e-learning" [IDeL] following the introduction in New South Wales and in the Northern Territory of Australia of satellite-supported two-way broad-band internet services for school-age and adult distance education. The context is…

The Biomechanical Role of Scaffolds in Augmented Rotator Cuff Tendon Repairs

DTIC Science & Technology

2012-01-01

failure loads of a human dermal allograft rotator cuff augmentation. Arthroscopy 2008;24:20-4. doi:10.1016/j.arthro.2007.07.013 5. Bartolozzi A...of the cuff. J Bone Joint Surg Am 1991;73-A:982-9. 17. Ide J, Maeda S, Takagi K. A comparison of arthroscopic and open rotator cuff repair. Arthroscopy

A Practical Guide to the Technology and Adoption of Software Process Automation

DTIC Science & Technology

1994-03-01

IDE’s integration of Software through Pictures, CodeCenter, and FrameMaker ). However, successful use of in- tegrated tools, as reflected in actual...tool for a specific platform. Thus, when a Work Context calls for a word processor, the weaver.tis file can be set up to call FrameMaker for the Sun4

Analysis of Liquid Rocket Tankage

DTIC Science & Technology

1975-04-01

pitting and essencially no attack of’ the base metal. The internal surfacees showed some shallow pitting and discoloration which 28 were less severe than...301 STAINLESS STEEL. spoIclus Cur FROM PARENT KETAL AND W=O JOINTS Oil A2IDE CRYOPORMNT OLTIATZ 0’ .% OFFSET TOS ILE YI AID 5 LOCATION"UNDOU S?1C1M N

Nassi-Schneiderman Diagram in HTML Based on AML

ERIC Educational Resources Information Center

Menyhárt, László

2013-01-01

In an earlier work I defined an extension of XML called Algorithm Markup Language (AML) for easy and understandable coding in an IDE which supports XML editing (e.g. NetBeans). The AML extension contains annotations and native language (English or Hungarian) tag names used when coding our algorithm. This paper presents a drawing tool with which…

Explaining the Mathematical Creativity of a Young Boy: An Interdisciplinary Venture between Mathematics Education and Psychoanalysis

ERIC Educational Resources Information Center

Krummheuer, Götz; Leuzinger-Bohleber, Marianne; Müller-Kirchof, Marion; Münz, Melanie; Vogel, Rose

2013-01-01

First results of the project "Mathematical Creativity of Children at Risk" (MaKreKi) will be presented. The project is conducted in the interdisciplinary research center "Individual Development and Adaptive Education of Children at Risk" (IDeA [http://www.idea-frankfurt.eu; accessed 7 June 2013]). Combining a…

Near field communication (NFC) model for arduino uno based security systems office system

NASA Astrophysics Data System (ADS)

Chairunnas, A.; Abdurrasyid, I.

2018-03-01

Currently, many offices or companies that start growing rapidly in a company or office should have a very limited room to enter only people entitled to enter the room and use the facilities contained in it, for example, Files in it must have many files and documents very important because to reduce the abuse of files and irresponsible person. Because it will be made room door security system by using Near Field Communication on android smartphone. Software used is Arduino IDE. The tools used in this system are Arduino Uno R3, NFC shield, pear sensor, bell, led, servo, 16 × 2 LCD, and Near Field Communication (NFC) in android smartphone. This system runs based on 2 inputs of a new technology that is Near Field Communication (NFC) in android smartphone. And also use pear sensor to detect unauthorized person entering the room. If the correct password is entered then the door will open and the pear sensor will light off if wrong then the bell will light up.

Comparison principle for impulsive functional differential equations with infinite delays and applications

NASA Astrophysics Data System (ADS)

Li, Xiaodi; Shen, Jianhua; Akca, Haydar; Rakkiyappan, R.

2018-04-01

We introduce the Razumikhin technique to comparison principle and establish some comparison results for impulsive functional differential equations (IFDEs) with infinite delays, where the infinite delays may be infinite time-varying delays or infinite distributed delays. The idea is, under the help of Razumikhin technique, to reduce the study of IFDEs with infinite delays to the study of scalar impulsive differential equations (IDEs) in which the solutions are easy to deal with. Based on the comparison principle, we study the qualitative properties of IFDEs with infinite delays , which include stability, asymptotic stability, exponential stability, practical stability, boundedness, etc. It should be mentioned that the developed results in this paper can be applied to IFDEs with not only infinite delays but also persistent impulsive perturbations. Moreover, even for the special cases of non-impulsive effects or/and finite delays, the criteria prove to be simpler and less conservative than some existing results. Finally, two examples are given to illustrate the effectiveness and advantages of the proposed results.

Supervised exercise training counterbalances the adverse effects of insulin therapy in overweight/obese subjects with type 2 diabetes.

PubMed

Balducci, Stefano; Zanuso, Silvano; Cardelli, Patrizia; Salerno, Gerardo; Fallucca, Sara; Nicolucci, Antonio; Pugliese, Giuseppe

2012-01-01

To examine the effect of supervised exercise on traditional and nontraditional cardiovascular risk factors in sedentary, overweight/obese insulin-treated subjects with type 2 diabetes from the Italian Diabetes Exercise Study (IDES). The study randomized 73 insulin-treated patients to twice weekly supervised aerobic and resistance training plus structured exercise counseling (EXE) or to counseling alone (CON) for 12 months. Clinical and laboratory parameters were assessed at baseline and at the end of the study. The volume of physical activity was significantly higher in the EXE versus the CON group. Values for hemoglobin A(1c), BMI, waist circumference, high-sensitivity C-reactive protein, blood pressure, LDL cholesterol, and the coronary heart disease risk score were significantly reduced only in the EXE group. No major adverse events were observed. In insulin-treated subjects with type 2 diabetes, supervised exercise is safe and effective in improving glycemic control and markers of adiposity and inflammation, thus counterbalancing the adverse effects of insulin on these parameters.

Production and Characterization of an Avian Ricin Antitoxin

DTIC Science & Technology

1992-01-15

naturally -occurring plant and/or bacterial toxins as biological threat agents, effective antitoxins are needed for either piophylactic or causal...system, an avian antitoxin against the potent phytotoxin , ricin. will be developed and evaluated. The production of therapeutic antibodies in avian...Dynatech). PolyacrylmIde gel electrophoresis (PAGE): Acrylamide gels were prepared according to methods described by Laemmli ( Nature . 227. 1970) and

77 FR 73662 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... received by the Agency under the Pre-IDE program over the past 10 years. Based on FDA's experience with the... rate and reach a steady state of approximately 2,544 submissions per year. FDA estimates from past... annual estimate of 2,544 submissions is based on experienced trends over the past several years. FDA's...

Status of the core and the mini core collections for the U.S. gemrplasm collection of peanut

USDA-ARS?s Scientific Manuscript database

To maximize their usefulness, core and mini core collections should be dynamic. The peanut core collection was developed in the early 1990's, and the mini core was developed in the late 1990's. Research has shown that these collections can be used to improve the efficiency and effectiveness of ide...

Configuring Eclipse for GMAT Builds: Instructions for Windows Users, Rev. 0.3

NASA Technical Reports Server (NTRS)

Conway, Darrel J.

2007-01-01

This document provides instructions about how to configure the Eclipse IDE to build GMAT on Windows based PCs. The current instructions are preliminary; the Windows builds using Eclipse are currently a bit crude. These instructions are intended to give you enough information to get Eclipse setup to build wxWidgets based executables in general, and GMAT in particular.

Embedding Secure Coding Instruction into the IDE: Complementing Early and Intermediate CS Courses with ESIDE

ERIC Educational Resources Information Center

Whitney, Michael; Lipford, Heather Richter; Chu, Bill; Thomas, Tyler

2018-01-01

Many of the software security vulnerabilities that people face today can be remediated through secure coding practices. A critical step toward the practice of secure coding is ensuring that our computing students are educated on these practices. We argue that secure coding education needs to be included across a computing curriculum. We are…

Should we feed animals to feed people? An optimization-based evaluation of environmental, economic, and health aspects of human diets in the United States

USDA-ARS?s Scientific Manuscript database

Given global pressure to improve food security, there is increasing interest in the question of whether we should feed animals to feed humans. Another question is whether there is sufficient domestically produced food to meet a population’s nutrient requirements. A linear programming approach to ide...

JPRS Report, East Europe.

DTIC Science & Technology

1989-10-26

violence and dictatorship and their substitution by a humanistic ide- ology of democratic socialism. If we want to avoid groping about politically...the association to maintain regular and good relations with political parties and governmental institutions. This is because the existential ...is the humanistic ; it proclaims what pertains to the individual to be sacred and declares that the rules of arithmetic cannot be applied to human

A rapid approach for characterization of thiol-conjugated antibody-drug conjugates and calculation of drug-antibody ratio by liquid chromatography mass spectrometry.

PubMed

Firth, David; Bell, Leonard; Squires, Martin; Estdale, Sian; McKee, Colin

2015-09-15

We present the demonstration of a rapid "middle-up" liquid chromatography mass spectrometry (LC-MS)-based workflow for use in the characterization of thiol-conjugated maleimidocaproyl-monomethyl auristatin F (mcMMAF) and valine-citrulline-monomethyl auristatin E (vcMMAE) antibody-drug conjugates. Deconvoluted spectra were generated following a combination of deglycosylation, IdeS (immunoglobulin-degrading enzyme from Streptococcus pyogenes) digestion, and reduction steps that provide a visual representation of the product for rapid lot-to-lot comparison-a means to quickly assess the integrity of the antibody structure and the applied conjugation chemistry by mass. The relative abundance of the detected ions also offer information regarding differences in drug conjugation levels between samples, and the average drug-antibody ratio can be calculated. The approach requires little material (<100 μg) and, thus, is amenable to small-scale process development testing or as an early component of a complete characterization project facilitating informed decision making regarding which aspects of a molecule might need to be examined in more detail by orthogonal methodologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Nanostructure Engineered Chemical Sensors for Hazardous Gas and Vapor Detection

NASA Technical Reports Server (NTRS)

Li, Jing; Lu, Yijiang

2005-01-01

A nanosensor technology has been developed using nanostructures, such as single walled carbon nanotubes (SWNTs) and metal oxides nanowires or nanobelts, on a pair of interdigitated electrodes (IDE) processed with a silicon based microfabrication and micromachining technique. The IDE fingers were fabricated using thin film metallization techniques. Both in-situ growth of nanostructure materials and casting of the nanostructure dispersions were used to make chemical sensing devices. These sensors have been exposed to hazardous gases and vapors, such as acetone, benzene, chlorine, and ammonia in the concentration range of ppm to ppb at room temperature. The electronic molecular sensing in our sensor platform can be understood by electron modulation between the nanostructure engineered device and gas molecules. As a result of the electron modulation, the conductance of nanodevice will change. Due to the large surface area, low surface energy barrier and high thermal and mechanical stability, nanostructured chemical sensors potentially can offer higher sensitivity, lower power consumption and better robustness than the state-of-the-art systems, which make them more attractive for defense and space applications. Combined with MEMS technology, light weight and compact size sensors can be made in wafer scale with low cost.

Protocols for the analytical characterization of therapeutic monoclonal antibodies. II - Enzymatic and chemical sample preparation.

PubMed

Bobaly, Balazs; D'Atri, Valentina; Goyon, Alexandre; Colas, Olivier; Beck, Alain; Fekete, Szabolcs; Guillarme, Davy

2017-08-15

The analytical characterization of therapeutic monoclonal antibodies and related proteins usually incorporates various sample preparation methodologies. Indeed, quantitative and qualitative information can be enhanced by simplifying the sample, thanks to the removal of sources of heterogeneity (e.g. N-glycans) and/or by decreasing the molecular size of the tested protein by enzymatic or chemical fragmentation. These approaches make the sample more suitable for chromatographic and mass spectrometric analysis. Structural elucidation and quality control (QC) analysis of biopharmaceutics are usually performed at intact, subunit and peptide levels. In this paper, general sample preparation approaches used to attain peptide, subunit and glycan level analysis are overviewed. Protocols are described to perform tryptic proteolysis, IdeS and papain digestion, reduction as well as deglycosylation by PNGase F and EndoS2 enzymes. Both historical and modern sample preparation methods were compared and evaluated using rituximab and trastuzumab, two reference therapeutic mAb products approved by Food and Drug Administration (FDA) and European Medicines Agency (EMA). The described protocols may help analysts to develop sample preparation methods in the field of therapeutic protein analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome.

PubMed

Schupf, Nicole; Lee, Annie; Park, Naeun; Dang, Lam-Ha; Pang, Deborah; Yale, Alexander; Oh, David Kyung-Taek; Krinsky-McHale, Sharon J; Jenkins, Edmund C; Luchsinger, José A; Zigman, Warren B; Silverman, Wayne; Tycko, Benjamin; Kisselev, Sergey; Clark, Lorraine; Lee, Joseph H

2015-10-01

We examined the contribution of candidates genes for Alzheimer's disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aβ40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1). Copyright © 2015 Elsevier Inc. All rights reserved.

ChromaStarPy: A Stellar Atmosphere and Spectrum Modeling and Visualization Lab in Python

NASA Astrophysics Data System (ADS)

Short, C. Ian; Bayer, Jason H. T.; Burns, Lindsey M.

2018-02-01

We announce ChromaStarPy, an integrated general stellar atmospheric modeling and spectrum synthesis code written entirely in python V. 3. ChromaStarPy is a direct port of the ChromaStarServer (CSServ) Java modeling code described in earlier papers in this series, and many of the associated JavaScript (JS) post-processing procedures have been ported and incorporated into CSPy so that students have access to ready-made data products. A python integrated development environment (IDE) allows a student in a more advanced course to experiment with the code and to graphically visualize intermediate and final results, ad hoc, as they are running it. CSPy allows students and researchers to compare modeled to observed spectra in the same IDE in which they are processing observational data, while having complete control over the stellar parameters affecting the synthetic spectra. We also take the opportunity to describe improvements that have been made to the related codes, ChromaStar (CS), CSServ, and ChromaStarDB (CSDB), that, where relevant, have also been incorporated into CSPy. The application may be found at the home page of the OpenStars project: http://www.ap.smu.ca/OpenStars/.

Ensemble Eclipse: A Process for Prefab Development Environment for the Ensemble Project

NASA Technical Reports Server (NTRS)

Wallick, Michael N.; Mittman, David S.; Shams, Khawaja, S.; Bachmann, Andrew G.; Ludowise, Melissa

2013-01-01

This software simplifies the process of having to set up an Eclipse IDE programming environment for the members of the cross-NASA center project, Ensemble. It achieves this by assembling all the necessary add-ons and custom tools/preferences. This software is unique in that it allows developers in the Ensemble Project (approximately 20 to 40 at any time) across multiple NASA centers to set up a development environment almost instantly and work on Ensemble software. The software automatically has the source code repositories and other vital information and settings included. The Eclipse IDE is an open-source development framework. The NASA (Ensemble-specific) version of the software includes Ensemble-specific plug-ins as well as settings for the Ensemble project. This software saves developers the time and hassle of setting up a programming environment, making sure that everything is set up in the correct manner for Ensemble development. Existing software (i.e., standard Eclipse) requires an intensive setup process that is both time-consuming and error prone. This software is built once by a single user and tested, allowing other developers to simply download and use the software

Blowpipe Mineralogy for Physics/Environment: Highest-Possible-Tc SC Quest; BOTH PERMANENT FOREVER Carb-IDES SOLID-State Sequestration AND Drought(s)-Elimination

NASA Astrophysics Data System (ADS)

Segler, Kurt; Williams, W.; Siegel, E.

2010-03-01

Detailed are old blowpipe[Kraus,Hunt,Ramsdell, Mineralogy (1936)] new applications:charcoal-block reduction of borates to yield (``N-NW'' of MgB2) Overhauser-[PR 35,1,411(1987); Intl.J.Mod.Phys.1,2 & 4,927(1987)]-``land'' predicted high-EST- POSSIBLE Tc SC ˜ ``LiD2''; very-early: Siegel[Phys.Stat.Sol.(a) 11,45(1972);Semiconductors & Insulators 5: 39,47,62(1979)] carb- IDES SOLID-state phase-TRANSITIONED CHEMICALLY-REDOX"-REACTED STABLE PERMANENT LONG-term STRATEGY, NOT ``CO2" BUT NON-gas Carbon-``ELEMENT"-sequestration: PROFITABLE MARKETABLE SALEABLE VALUABLE USEFUL ``Grab and Sell" TRUMPS ``cap and trade"!!!; Mott alloying/vertical metal-insulator transitions in ``borax-(GLASS)- beads"; and very-early Siegel [3rd Intl.Conf.Alt.Energy,Hemi- sphere/Springer(1980)-vol.5/p.459] ``FLYING-WATER" ``Hindenberg- effect"(H2-UP;H2O-DOWN) via H2-maximal-Archimedes-buoyancy ``chemical-rain-in-piplines", only via Siegel GMR enabled diffusive-magnetoresistance(DMR)enabled Siegel proprietary ``magnetic-H-valve": Renewables-H2-H2O purposely flexible versatile agile scaleable retrofitable integrated operating- system for PERMANENT drought(s)-elimination FOREVER!!!

Advances in high-resolution synchrotron micro-XANES for constraining the redox evolution of terrestrial and extraterrestrial magma

NASA Astrophysics Data System (ADS)

Lanzirotti, A.; Sutton, S. R.; Dyar, M. D.; McCanta, M. C.; Head, E.

2017-12-01

Quantifying the redox evolution of geological materials is of fundamental importance for understanding the evolution of the Earth and terrestrial planets. Microfocused, synchrotron X-ray Absorption Spectroscopy (XAS) provides direct, in-situ analyses of the valence state for elements that can be used as proxies for oxygen fugacity (Fe, V, Cr, Ti, S, Eu, and Ce). Such proxies span the entire fO2 range of solar system evolution, covering at least 16 log units. Recent technical improvements at the Advanced Photon Source 13-ID-E microspectroscopy beamline have improved the energy, spatial resolution and detection sensitivity for XAS. The application of multiple valence state oxybarometers to individual mineral grains is valuable as demonstrated in a study of Ti, V and Cr valence in olivine and pyroxene of the ungrouped achondrite NWA 7325 [1], results which yielded a very reduced fO2 estimate of IW-3 and suggested a likely origin of NWA 7325 in a parent body with similar redox conditions to the ureilite parent body. Simultaneously, we have made advances using multivariate prediction models to more precisely measure ever-smaller variations in elemental valence [2]. Applied to V XAS spectra in glasses, we have developed an MVA calibration model that directly relates the measured spectra to predicted fO2, improving the precision in calculating fO2 with more robust error analysis. These machine learning based algorithms also allow for XAS to be collected in an imaging modality to spatially map elemental redox states within samples. For example for imaging changes in Fe oxidation state in natural lunar picritic glasses [3] that may be related to magmatic degassing. This presentation highlights recent examples of this research at 13-ID-E, including application of Fe, S and V valence state oxybarometers in the analysis of terrestrial volcanic glasses and melt inclusions for looking at long term evolution of oxygen fugacity of magmas. [1] Sutton S. et al. (2017) GCA, 211, 115-132. [2] Dyar M. D et al. (2016) Amer. Mineral., 101, 744-748. [3] McCanta et al. (2017) Icarus, 285, 95-102.

Safety and efficacy of cryolipolysis for non‐invasive reduction of submental fat

PubMed Central

Burns, A. Jay; Zelickson, Brian D.

2015-01-01

Background and Objectives Cryolipolysis has previously received FDA clearance for fat reduction in the abdomen, flanks, and thighs. There is also interest in small volume fat reduction for areas such as the chin, knees, and axilla. This article reports the results of a cryolipolysis pivotal IDE study for reduction of submental fullness. Study Design/Material and Methods A prototype small volume vacuum applicator (CoolMini applicator, CoolSculpting System, ZELTIQ Aesthetics) was used to treat 60 subjects in the submental area. At each treatment visit, a single treatment cycle was delivered at −10°C for 60 minutes, the same temperature and duration used in current commercially‐available cryolipolysis vacuum applicators. At the investigator's discretion, an optional second treatment was delivered 6 weeks after the initial treatment. The primary efficacy endpoint was 80% correct identification of baseline photographs by independent physician review. The primary safety endpoint was monitoring incidence of device‐ and/or procedure‐related serious adverse events. Secondary endpoints included assessment of fat layer thickness by ultrasound and subject satisfaction surveys administered 12 weeks after final cryolipolysis treatment. Results Independent photo review from 3 blinded physicians found 91% correct identification of baseline clinical photographs. Ultrasound data indicated mean fat layer reduction of 2.0 mm. Patient questionnaires revealed 83% of subjects were satisfied, 80% would recommend submental cryolipolysis to a friend, 77% reported visible fat reduction, 77% felt that their appearance improved following the treatment, and 76% found the procedure to be comfortable. No device‐ or procedure‐related serious adverse events were reported. Conclusion The results of this clinical evaluation of 60 patients treated in a pivotal IDE study demonstrate that submental fat can be reduced safely and effectively with a small volume cryolipolysis applicator. Patient surveys revealed that submental cryolipolysis was well‐tolerated, produced visible improvement in the neck contour, and generated high patient satisfaction. These study results led to FDA clearance of cryolipolysis for submental fat treatment. Lasers Surg. Med. 48:3–13, 2016. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. PMID:26607045

Coxiella Burnetti Vaccine Development: Lipopolysaccharide Structural Analysis

DTIC Science & Technology

1989-12-29

linkage, branching, and sequence, by periodate oxidation, supercritical fluid chromatography , and mass spectrometry. These techniques combine to pro... Supercritical fluid chromatography of PFBAB labeled maltodextrin sample prepared as the acetate derivative. C-anopropyl SFC column using CO 2 as the...8217 ide the elements of a global approach to oligosaccharide structure. The utility of s"pr critical fluid chromatography for a determination of Lipid-A

Electronic Warfare for Cyber Warriors

DTIC Science & Technology

2008-06-01

This research paper provides complete course content for the AFIT EENG 509, Electronic Warfare class. It is intended as a replacement for the existing course and designed for Intermediate Developmental Education (IDE) students in the Cyber Warfare degree program. This course provides relevant academic courseware and study material to give cyber warriors an academic and operational perspective on electronic warfare and its integration in the cyber domain.

77 FR 70168 - Guidance for Industry and Food and Drug Administration Staff; The Content of Investigational...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-23

...The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ``The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems.'' FDA is issuing this guidance to inform industry and Agency staff of its recommendations for analytical and clinical performance studies to support premarket submissions for artificial pancreas systems.

What It Takes. Air Force Command of Joint Operations

DTIC Science & Technology

2009-01-01

Iraq Assistance Group IDE intermediate developmental education IO international organization ISAF International Security and Assistance Force ISR...Operations Table A.1—Continued Joint Task Force Mission/Operation Start End Service Command Rank JTF–Joint Area Support Group (JASG) Iraqi Freedom...be of interest to a wide group of Air Force personnel involved in the development and func- tion of the service’s command organizations, including

An Assessment of a Beowulf System for a Wide Class of Analysis and Design Software

NASA Technical Reports Server (NTRS)

Katz, D. S.; Cwik, T.; Kwan, B. H.; Lou, J. Z.; Springer, P. L.; Sterling, T. L.; Wang, P.

1997-01-01

A typical Beowulf system, such as the machine at the Jet Propulsion Laboratory (JPL), may comprise 16 nodes interconnected by 100 base T Fast Ethernet. Each node may include a single Inter Pentium Pro 200 MHz microprocessor, 128 MBytes of DRAM, 2.5 GBytes of IDE disk, and PCI bus backplane, and an assortment of other devices.

Area-Efficient Graph Layouts (for VLSI).

DTIC Science & Technology

1980-08-13

thle short side, then no rectangle is ew r generated x’.ho se aspect r~itho i s \\orse di ai aJ. ’I lie d i % ide-I mid -cimq tier clInt ruolIn in... Sutherland and Donald Oestrcichcr, "flow big should a printed circuit board be?," ILEEE, Transactions on Computers, Vol. C-22, May 1973, pp. 537-542. 22

Lagrangian Mixing in an Axisymmetric Hurricane Model

DTIC Science & Technology

2010-07-23

The MMR r is found by tak - ing the log of the time-series 6ρ(t)−A1, where A1 is 90% of the minimum value of6ρ(t), and the slope of the linear func...Advective mixing in a nondivergent barotropic hurricane model, Atmos. Chem. Phys., 10, 475 –497, doi:10.5194/acp-10- 475 -2010, 2010. Salman, H., Ide, K

76 FR 50663 - Effective Date of Requirement for Premarket Approval for Three Class III Preamendments Devices

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-16

... completion of a PDP is not filed by the latter of the two dates, and no IDE is in effect, the device is... availability of a preamendments class III devices strategy document. The strategy document set forth FDA's... approved PMA or a declared completed PDP is required to be in effect for any such devices on or before 180...

Beware the Ides of Coupland: Douglas Coupland's (Oh, so Very Canadian) Perspective on the Future and What It Means to Us

ERIC Educational Resources Information Center

Boyle-Taylor, Marilyn

2011-01-01

Douglas Coupland, a prolific author/artist/lecturer and now prognosticator, is in the forefront of the arts movement in both Canada and the US. His works, starting with his breakout novel "Generation X: Tales for an Accelerated Culture," have consistently worked as a bellwether of current perspectives and values, both noting our cultural…

Fine Scale Modeling and Forecasts of Upper Atmospheric Turbulence for Operational Use

DTIC Science & Technology

2014-11-30

Weather Center Digital Data Service (ADDS) fhttp://www.aviationweather.gov/adds, http://weather.aero/1 Graphical Turbulence Guidance product, GTG -2.5...analysis GTG - Graphical Turbulence Guidance HRMM - High Resolution Mesoscale/Microscale ICD - Interface Control Document IDE - Integrated Development...site (with GTG 2.5 data) http://www.aviationweather.gov/turbuience • ADDS Experimental site http://weather.aero/ • NCEP FNL data - http

Knowledge Based Consultation for Finite Element Structural Analysis.

DTIC Science & Technology

1980-05-01

Intelligence Finite Element Program Tutorial 20 ABSTRACT (Continue. on rees side If necessary and ide.n’ty b,’ bit,, k nionh.) In recent years, techniques of...involved in Artificial Intelligence at Stanford University developed the program MYCIN F2], for clinical consultation of diseases that require...and Rules The basic backward chaining logic, characteristic to Artificial Intelligence . approaching 1he problem of knowledge representation was

A New NASA Data Product: Tropospheric and Stratospheric Column Ozone in the Tropics Derived from TOMS Measurements

NASA Technical Reports Server (NTRS)

Ziemke, J. R.; Chandra, S.; Bhartia, P. K.

1999-01-01

Tropospheric column ozone (TCO) and stratospheric column ozone (SCO) gridded data in the tropics for 1979-present are now available from NASA Goddard Space Flight Center via either direct ftp, world-NN,ide-NN,eb, or electronic mail. This note provides a brief overview of the method used to derive the data set including validation and adjustments.

DHX9 regulates production of hepatitis B virus-derived circular RNA and viral protein levels

PubMed Central

Sekiba, Kazuma; Otsuka, Motoyuki; Ohno, Motoko; Kishikawa, Takahiro; Yamagami, Mari; Suzuki, Tatsunori; Ishibashi, Rei; Seimiya, Takahiro; Tanaka, Eri; Koike, Kazuhiko

2018-01-01

Hepatitis B virus (HBV) infection, which is a major health concern worldwide, can lead to liver cirrhosis and hepatocellular carcinoma. Although current nucleos(t)ide analogs efficiently inhibit viral reverse transcription and viral DNA load clinically, episomal viral covalently closed circular DNA (cccDNA) minichromosomes and transcripts from cccDNA continue to be expressed over the long term. We hypothesized that, under these conditions, viral transcripts may have biological functions involved in pathogenesis. Here, we show that the host protein DExH-box helicase 9 (DXH9) is associated with viral RNAs. We also show that viral-derived circular RNA is produced during HBV replication, and the amount is increased by knockdown of the DHX9 protein, which, in turn, results in decreased viral protein levels but does not affect the levels of HBV DNA. These phenomena were observed in the HBV-producing cell culture model and HBV mini-circle model mimicking HBV cccDNA, as well as in human primary hepatocytes infected with HBV. Based on these results, we conclude that, in HBV infection, the RNA binding factor DHX9 is a novel regulator of viral circular RNA and viral protein levels. PMID:29765512

Energy and nutrient utilization of broiler chickens fed corn-soybean meal and corn-based diets supplemented with xylanase.

PubMed

Stefanello, C; Vieira, S L; Carvalho, P S; Sorbara, J O B; Cowieson, A J

2016-08-01

A study was conducted to evaluate the effects of increased levels of a β-xylanase on energy and nutrient utilization of broiler chickens fed corn-soy diets. A total of 480 slow feathering Cobb × Cobb 500 male broilers were randomly distributed to 10 treatments having 8 replicates of 6 birds each. Birds were fed a common starter diet to d 14 post hatch (3,050 kcal/kg AMEn, 21.7% CP, 1.05% Ca, and 0.53% nPP). The experimental diets were provided afterwards until 25 d. Two experimental diets, a conventional corn/soy-based basal diet (CS) and the basal diet in which 40% of the diet was displaced by corn (CN), were fed as-is or supplemented with 50, 100, 150, or 200 fungal β-xylanase units (FXU)/kg. Dietary treatments were distributed factorially as a 2 × 5 arrangement. Samples of feed, excreta, and ileal digesta were analyzed for determination of ileal digestible energy (IDE), metabolizable energy, and total tract retention of protein and lipid. No interactions between diet and xylanase were observed. The CS diets had higher (P < 0.05) energy utilization and nutrient digestibility when compared to the CN diets. AMEn and IDE were improved (P < 0.05) by 192 and 145 kcal/kg, respectively, when diets were supplemented with 100 FXU/kg xylanase. The xylanase added to the CN diet led to quadratic increases (P < 0.05) in IDE (Y = - 0.014x(2) + 2.570x + 3,155; r(2) = 0.60) and in AMEn (Y = - 0.016x(2) + 3.982x + 3,155; r(2) = 0.68). Crude protein digestibility and AMEn were linearly increased (P < 0.05) when xylanase was added to the CN diet. In conclusion, energy utilization and digestibility of crude protein and dry matter increased with xylanase supplementation in corn/soy-based diets. When xylanase was tested in the CS diet, 92 and 124 FXU/kg maximized the energy release effect; however, the maximum energy response in the CN diet or corn was not achieved until 200 FXU/kg. © 2016 Poultry Science Association Inc.

Quantify Relation Between Age-Related Comorbidities and Quality-of-Life Measures Among HIV-Positive Active Duty U.S. Military

DTIC Science & Technology

2017-12-01

quality of life (HRQOL) in infected persons. HRQOL is driven by an individual’s health perceptions, physical functionality, and psychological well...functionality, and psychological well-being, and is influenced by community and environmental indicators. Studies of HRQOL are generally associated...Infectious Disease Clinical Research Program IDES Integrated Disability Evaluation System ID-IRB Infectious Disease - Institutional Review Board IQR

Friction Sensitivity of Primary Explosives

DTIC Science & Technology

1982-09-01

diffeomI from. Report) ISI. SUPPLEMENTARY NOTES It. KEY WORDS (Contflnuo on rvotr.. oldo. it nec~oaoty and Identify by block ri,uobr) Friction...friction senisitivity. Primary explosives RD 1333 lead azide, dextrinated lead azide, polyvinyl-alcohol (PVA)-lead a~.ide, colloidal lead azide, nocrnal lead...results for dextrinated lead azide duPont 52-127 13 4 A comparison of friction data at 10% probability of initiation 14 FIGURES 1 Working surfaces of BAM

Fluid Dynamic Analysis of Volcanic Tremor,

DTIC Science & Technology

1982-10-01

information regarding the fluid system Fiske (1969) Kilauea volcano : The 1967-68 summit configuration, tremor magnitudes and source loca- eruption...Koyanagi (1981) Deep volcanic tremor logicalSociety of America, vol. 40, p. 175-194. and magma ascent mechanism under Kilauea , Hawaii . Omori, F...dynamics Seismology Tremors Volcanoes 40 M\\ TlACT (amhue ai revers if5 neeeeiy md ide~Wify by block number) Low-frequency (< 10 Hz) volcanic earthquakes

ADA and C++ Business Case Analysis

DTIC Science & Technology

1991-07-01

executable mini-specs, to support import of existing code. Automated database population/change propagation. 9. Documentation generation: via FrameMaker ...Backplane. ii. 4GLS H-20 I I IDE/Software through Pictures (StP) 12 June 1991 iii. Interleaf and FrameMaker publishing. 13. Output formats: PostScript... FrameMaker , WordPerfect. 12. User interface: Menu and mouse, windowing, color, on-line help, undo. Database browser via forms/tables component later

Tool Integration and Environment Architectures

DTIC Science & Technology

1991-05-01

include the Interactive Development Environment (IDE) Software Through Pictures (STP), Sabre-C and FrameMaker coalition, and the Verdix Ada Development...System (VADS) APSE, which includes the VADS compiler and choices of CADRE Teamwork or STP and FrameMaker or Interleaf. The key characteristic of...remote procedure execution to achieve a simulation of a homoge- neous repository (i.e., a simulation that the data in a FrameMaker document resides in one

Microwave Radiation and Thermoregulation.

DTIC Science & Technology

1981-11-01

AD-Alll 244 JOHN B PIERCE FOUNDATION LAB NEW HAVEN CONN F/S 6/18 MICROWAVE RADIATION AND THERMOREGULATION .(U) NOV 81 E R ADAIR AFOSR-77-3420...KEY WORDS rCo ntinue on reverse ,ide if necessary end identify by block number) behavioral thermoregulation squirrel monkey autonomic thermoregulation ...GOVERNMENT ~ j ~3Approved f or public release TABLE OF CONTENTS Page SUMMARY 1 BACKGROUND 3 A. Temperature changes and thermoregulation 3 B. Basic data on

30. Photocopy of a photograph (original print in the collection ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

30. Photocopy of a photograph (original print in the collection of the New Hampshire Water Resources Board, Concord, New Hampshire) 1934, photographer unknown 3 1/4 X 4 5/8 inch negative INTAKE TO THE POWER CANAL AT DAM No. 5. IDE'S 'ROUND BUILDING' IN THE FREEMAN AND O'NEIL COMPLEX IS VISIBLE ON THE LEFT. - Claremont Village Industrial District, Between B, Claremont, Sullivan County, NH

A Problem-Solving Environment for Biological Network Informatics: Bio-Spice

DTIC Science & Technology

2007-06-01

user an environment to access software tools. The Dashboard is built upon the NetBeans Integrated Development Environment (IDE), an open source Java...based integration platform was demonstrated. During the subsequent six month development cycle, the first version of the NetBeans based Bio-SPICE...frameworks (OAA, NetBeans , and Systems Biology Workbench (SBW)[15]), it becomes possible for Bio-SPICE tools to truly interoperate. This interoperation

Infrared Laser and Reaction Rate Study

DTIC Science & Technology

1976-02-01

Chamberlain, H. Fetterman , H. M. Foley, P. L. Kelley, H. Kildal, D. C. Lorents, R. Novick, R. Osgood, C K. Rhodes, M. Ruderman, H. Schlossberg...excited vibrational states. Experimental work by Bischel, Kelly, and Rhodes50 on 34 CH F confirms this fi iding. In unpublished work, Fetterman ... Fetterman , 51 MMMMMMI U..> sy^tcs in the f,r-lnfrarod and subminimoter regions that operate by op.ioal pulping. in this region, .here

BOKP: A DNA Barcode Reference Library for Monitoring Herbal Drugs in the Korean Pharmacopeia

PubMed Central

Liu, Jinxin; Shi, Linchun; Song, Jingyuan; Sun, Wei; Han, Jianping; Liu, Xia; Hou, Dianyun; Yao, Hui; Li, Mingyue; Chen, Shilin

2017-01-01

Herbal drug authentication is an important task in traditional medicine; however, it is challenged by the limitations of traditional authentication methods and the lack of trained experts. DNA barcoding is conspicuous in almost all areas of the biological sciences and has already been added to the British pharmacopeia and Chinese pharmacopeia for routine herbal drug authentication. However, DNA barcoding for the Korean pharmacopeia still requires significant improvements. Here, we present a DNA barcode reference library for herbal drugs in the Korean pharmacopeia and developed a species identification engine named KP-IDE to facilitate the adoption of this DNA reference library for the herbal drug authentication. Using taxonomy records, specimen records, sequence records, and reference records, KP-IDE can identify an unknown specimen. Currently, there are 6,777 taxonomy records, 1,054 specimen records, 30,744 sequence records (ITS2 and psbA-trnH) and 285 reference records. Moreover, 27 herbal drug materials were collected from the Seoul Yangnyeongsi herbal medicine market to give an example for real herbal drugs authentications. Our study demonstrates the prospects of the DNA barcode reference library for the Korean pharmacopeia and provides future directions for the use of DNA barcoding for authenticating herbal drugs listed in other modern pharmacopeias. PMID:29326593

Design and fabricate multi channel microfluidic mold on top of glass slide using SU-8

NASA Astrophysics Data System (ADS)

Azman, N. A. N.; Rajapaksha, R. D. A. A.; Uda, M. N. A.; Hashim, U.

2017-09-01

Microfluidic is the study of fluid in microscale. Microfluidics provides miniaturized fluidic networks for processing and analyzing liquids in the nanoliter to milliliter range. Microfluidic device comprises of some essential segments or structure that are micromixer, microchannel and microchamber. The SU-8 mold is known as the most used technique in microfluidic fabrication due to the characteristic of very gooey polymer that can be spread over a thickness. In this study, in order to reduce the fabrication cost, the development and fabrication of SU-8 mold is replace by using a glass plate instead of silicon wafer which is used in the previous research. We designed a microfluidic chip for use with an IDE sensors to conduct multiplex detection of multiple channels. The microfluidic chip was designed to include multiplex detection for pathogen that consists of multiple channels of simultaneous results. The multi-channel microfluidic chip was designed, including the fluid outlet and inlet. A multi-channel microfluidic chip was used for pathogen detection. This paper sum up the fabrication of lab SU-8 mold using glass slide.

The BBN (Bolt Beranek and Newman) Knowledge Acquisition Project. Phase 1. Functional Description; Test Plan.

DTIC Science & Technology

1987-05-01

Computers . " Symbolics. Inc. 8. Carnegie Group. Inc KnoiledgeCraft Carnegie Group, Inc.. 1985. .- 9. Moser, Margaret, An Overviev of NIKL. Section of BBN...ORGANIZATION NAME AND ADDRESS I0. PROGRAM ELEMENT. PROJECT. TASK BBN Laboratories Inc. AREAAWoRIUNTNUMER_ 10 Moulton St. Cambridge, MA 02238 It...knowledge representation, expert systems; strategic computing , . A 20 ABSTRACT (Contnue an r rerse ide If neceaesary and Identify by block number) This

Joint Typhoon Warning Center (JTWC92) Model.

DTIC Science & Technology

1992-05-01

Report Date. 13. Report Type and Dates Covered. I May 1992 IFinal - Contractor Report 4. Title and Subtitle. 5. FL iding Numbers. Final Report Joint...National Hurricane Center, Coral Gables, FL , 44 pp. I Neumann, C.J. and C.J. McAdie, 1991: A Revised National Hurricane Center NHC83 Model NHC90. NOAA...STATISTICAL-DYNAMICAL MODELS: HISTORICAL PERSPECTIVE The earliest known attempt at statistical-dynamical modeling is credi- ted to Veigas , (1966) for

Possible New Irdome Materials for Transmission to 4.5-5 Micrometers.

DTIC Science & Technology

1978-02-01

transmission completel to 5 microns and it has quite a high index or fraction. Several nitrides may be possible candidates with silicon nitride currently...receiving some consideration.1 However, it only transmits to 4.5 microns and also has a fairly high index or fraction. Many mixed nitride compounds are...should meet the IR transmission requirements but these generally have high indices of fraction . Many sulf ides, other chalcogenides, and semi-conductors

Microdesigning of Lightweight/High Strength Ceramic Materials.

DTIC Science & Technology

1987-08-30

if applicable) AFSSR NC Grant No. AFOSR-83-0375 8c. ADDRESS( Cft , State. and ZIP Code) 10 SOURCE OF FUNDING NUMBERS Bd.40PROGRAMO IPROJECT I TASK...The Adsorption of Pohmethacrvfic Acid from Solut.on.- Ph.D. Thesis . Polytechnic Institute of Brooklyn (1961). I5. R. J. Hunter. Zeta Potential in...Hasz. ’Surface Reactions and Electrical Double Layer Properties of Ceramic Ox. ides in Aqueous Solution,* M.S. Thesis . Massachusetts Institute of

The Feasibility of Implementing Multicommand Software Functions on a Microcomputer Network.

DTIC Science & Technology

1979-10-01

studies 20 ABSTRACT fConllnuo on revete &Ide it necessary and Identify by block number) ’This report presents the results of a study of design...considerations for hybrid monitor systems for distributed microcomputer networks. The objective of the study was to determine the feasibility of such monitor...Management Informa- tion and Computer Sciences. The study was one task on a project bentitled "The Feasibility of Implementing Multicommand Software

Summary of SEI Accomplishments for Software Development and Research

DTIC Science & Technology

1990-01-01

and Validation is ollered at Mississippi State University, East Tennessee State University, and the University of Minnesota, Duluth. Software Project...Project final report and helping Hecrcules prepare a presentation for the February AdJaJ[ J (. Work has begun on the final lessons-learned report. 10...and Solutions in the DoD software community. The Technology Applications Functlion prot ides a link between DoD mission-critical 0 000000 appictin J

Models of Cerebral System Mechanics.

DTIC Science & Technology

1986-07-20

Hirsch, A.E. (1971) Tolerances for cerebral concussion from head impact and whiplash in primates. J. Biomech. 4:13-21. Pamidi, M.R. and Advani, S.H. (1978...elastic element (PAMIDI and ADVANI, 1978). In the literature on the mechanics of head impacts, the skull was ide- alized to be a rigid sphere with an...of the living cranium. J. Amer. Osteo. Assoc., 70, 928-945. GOLDSMITH, W. (1972) Biomechanics of head injuries. In Biomechanics: Its Foundations and

The Soviet Union and Iraq Since 1968.

DTIC Science & Technology

1980-07-01

had outlived its usefulness and had itself become a threat to the regime’s authority. Kassem turned on it and attempted to restrict its political ... Kassem had studiously avoided: They began to eliminate the ICP physically as a political force. By one estimate 3,000 party members were killed.IlJ This...ide It mne@*aip and identir by block uwober) USSR Foreign Aid IRAQ Political Science Arms Control Foreign Policy Military Assistance International

Polar-Auroral Charging of the Space Shuttle and EVA (Extravehicular Activity) Astronaut

DTIC Science & Technology

1987-05-01

meteorological sacellftes confirm that charging aee occur and provIde values for the environmental parameters contributing to the chaging (1). The...Shuttla is not considered to be at risk from arc-discharge because it was desigeed to vithatand direct li4htnl.ag atrikes and has extensive redundancy...Perticina Environment Branch of the charging of the Air Force Defense maceozological sate~llte Prcgram C(’kiSP) spacecraft and thi- environmental

X3D-Earth: Full Globe Coverage Utilizing Multiple Dataset

DTIC Science & Technology

2010-09-01

DtedNvtProcessor Class ..................................................128 Figure 63. Subversion Checkout in Netbeans ...to the Ant build.xml file within a NetBeans Project: <target name=“moveToHamming” depends=““> <scp todir=“user@hamming.uc.nps.edu:/work/user/DTED...This task was generated using the NetBeans IDE (can be downloaded at www.netbeans.org). The task was then executed within NetBeans . This type of

Identifying and Solving the Real Problems Facing the Integrated Disability Evaluation System (IDES)

DTIC Science & Technology

2013-06-14

future. Statistics from the Defense and Veterans Brain Injury Center reveal that, from 2000 to mid 2012, 34 there were 244,217 medical diagnoses...of Traumatic Brain Injury, of which 46,795 were moderate to severe/penetrating. While 84 percent of those injuries were not deployment related, such...injuries represent a significant issue for the health of the force (Defense and Veterans Brain Injury Center 2012). Similarly, a 2010 Congressional

High-Performance Wireless Ammonia Gas Sensors Based on Reduced Graphene Oxide and Nano-Silver Ink Hybrid Material Loaded on a Patch Antenna.

PubMed

Wu, Bian; Zhang, Xingfei; Huang, Beiju; Zhao, Yutong; Cheng, Chuantong; Chen, Hongda

2017-09-09

Reduced graphene oxide (rGO) has been studied as a resistive ammonia gas sensor at room temperature. The sensitive hybrid material composed of rGO and nano-silver ink (Ag-ink) was loaded on a microstrip patch antenna to realize high-performance wireless ammonia sensors. The material was investigated using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Firstly, interdigital electrodes (IDEs) printed on the polyethylene terephthalate (PET) by direct printing were employed to measure the variation of resistance of the sensitive material with the ammonia concentration. The results indicated the response of sensor varied from 4.25% to 14.7% under 15-200 ppm ammonia concentrations. Furthermore, the hybrid material was loaded on a microstrip patch antenna fabricated by a conventional printed circuit board (PCB) process, and a 10 MHz frequency shift of the sensor antenna could be observed for 200 ppm ammonia gas. Finally, the wireless sensing property of the sensor antenna was successfully tested using the same emitted antenna outside the gas chamber with a high gain of 5.48 dBi, and an increased reflection magnitude of the emitted antenna due to the frequency mismatch of the sensor antenna was observed. Therefore, wireless ammonia gas sensors loaded on a patch antenna have significant application prospects in the field of Internet of Things (IoTs).

High-Performance Wireless Ammonia Gas Sensors Based on Reduced Graphene Oxide and Nano-Silver Ink Hybrid Material Loaded on a Patch Antenna

PubMed Central

Zhang, Xingfei; Huang, Beiju; Zhao, Yutong; Cheng, Chuantong; Chen, Hongda

2017-01-01

Reduced graphene oxide (rGO) has been studied as a resistive ammonia gas sensor at room temperature. The sensitive hybrid material composed of rGO and nano-silver ink (Ag-ink) was loaded on a microstrip patch antenna to realize high-performance wireless ammonia sensors. The material was investigated using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Firstly, interdigital electrodes (IDEs) printed on the polyethylene terephthalate (PET) by direct printing were employed to measure the variation of resistance of the sensitive material with the ammonia concentration. The results indicated the response of sensor varied from 4.25% to 14.7% under 15–200 ppm ammonia concentrations. Furthermore, the hybrid material was loaded on a microstrip patch antenna fabricated by a conventional printed circuit board (PCB) process, and a 10 MHz frequency shift of the sensor antenna could be observed for 200 ppm ammonia gas. Finally, the wireless sensing property of the sensor antenna was successfully tested using the same emitted antenna outside the gas chamber with a high gain of 5.48 dBi, and an increased reflection magnitude of the emitted antenna due to the frequency mismatch of the sensor antenna was observed. Therefore, wireless ammonia gas sensors loaded on a patch antenna have significant application prospects in the field of Internet of Things (IoTs). PMID:28891928

Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial.

PubMed

Perez-Molina, José A; Rubio, Rafael; Rivero, Antonio; Pasquau, Juan; Suárez-Lozano, Ignacio; Riera, Melcior; Estébanez, Miriam; Santos, Jesús; Sanz-Moreno, José; Troya, Jesús; Mariño, Ana; Antela, Antonio; Navarro, Jordi; Navarro, José; Esteban, Herminia; Moreno, Santiago

2015-07-01

Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir-ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed. In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488. Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047). In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. Bristol Myers-Squibb and Fundación SEIMC-GESIDA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel Serum Biomarkers Detected by Protein Array in Polycystic Ovary Syndrome with Low Progesterone Level.

PubMed

Zheng, Qin; Zhou, Feifei; Cui, Xinyuan; Liu, Mulin; Li, Yulin; Liu, Shuai; Tan, Jichun; Yan, Qiu

2018-01-01

Polycystic ovary syndrome (PCOS), characterized by female infertility and metabolic abnormalities, is one of the most common endocrine disorders. The etiology of PCOS remains unknown. The comprehensive analysis of protein alterations in PCOS patients is meaningful for identifying diagnostic biomarkers of PCOS. Here, we explored the clinical value of serum proteins as novel biomarkers to detect PCOS with low progesterone level. A total of 43 patients with PCOS and 30 healthy women were enrolled. Protein array was used to detect the variations of serum proteins between PCOS patients and healthy women. The level of five serum proteins was further confirmed by ELISA and western blot. The human ovarian granulosa cells (KGN) was cultured to examine the underlying mechanism of PCOS. CCK8 assay and western blot were carried out to evaluate the alterations in proliferative ability, TUNEL assay and DAPI staining to detect the apoptosis of KGN cells. Among the 507 proteins, we identified 76 differentially expressed serum proteins (≧1.5 fold), with 40 elevated and 36 decreased proteins. Moreover, 47 proteins were newly reported in PCOS. The alterations in the five significantly decreased proteins (EREG, inhibin βA, IDE, PDGF-D and KNG1) were further confirmed by ELISA and western blot. The level of these proteins were directly associated with the low progesterone, and the expression could be upregulated by progesterone. EREG and inhibin βA also promoted the proliferation and inhibited the apoptosis of ovarian granulosa cells. The study highlights that serum proteins are differentially expressed in PCOS patients and healthy women, and EREG and inhibin βA levels are upregulated by progesterone, which are correlated with ovarian functions. The study suggests that EREG and inhibin βA may be applied as novel potential biomarkers for PCOS with low progesterone level. © 2018 The Author(s). Published by S. Karger AG, Basel.

Spreading speeds for plant populations in landscapes with low environmental variation.

PubMed

Gilbert, Mark A; Gaffney, Eamonn A; Bullock, James M; White, Steven M

2014-12-21

Characterising the spread of biological populations is crucial in responding to both biological invasions and the shifting of habitat under climate change. Spreading speeds can be studied through mathematical models such as the discrete-time integro-difference equation (IDE) framework. The usual approach in implementing IDE models has been to ignore spatial variation in the demographic and dispersal parameters and to assume that these are spatially homogeneous. On the other hand, real landscapes are rarely spatially uniform with environmental variation being very important in determining biological spread. This raises the question of under what circumstances spatial structure need not be modelled explicitly. Recent work has shown that spatial variation can be ignored for the specific case where the scale of landscape variation is much smaller than the spreading population׳s dispersal scale. We consider more general types of landscape, where the spatial scales of environmental variation are arbitrarily large, but the maximum change in environmental parameters is relatively small. We find that the difference between the wave-speeds of populations spreading in a spatially structured periodic landscape and its homogenisation is, in general, proportional to ϵ(2), where ϵ governs the degree of environmental variation. For stochastically generated landscapes we numerically demonstrate that the error decays faster than ϵ. In both cases, this means that for sufficiently small ϵ, the homogeneous approximation is better than might be expected. Hence, in many situations, the precise details of the landscape can be ignored in favour of spatially homogeneous parameters. This means that field ecologists can use the homogeneous IDE as a relatively simple modelling tool--in terms of both measuring parameter values and doing the modelling itself. However, as ϵ increases, this homogeneous approximation loses its accuracy. The change in wave-speed due to the extrinsic (landscape) variation can be positive or negative, which is in contrast to the reduction in wave-speed caused by intrinsic stochasticity. To deal with the loss of accuracy as ϵ increases, we formulate a second-order approximation to the wave-speed for periodic landscapes and compare both approximations against the results of numerical simulation and show that they are both accurate for the range of landscapes considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

An angiotensin-(1–7) peptidase in the kidney cortex, proximal tubules, and human HK-2 epithelial cells that is distinct from insulin-degrading enzyme

PubMed Central

Wilson, Bryan A.; Cruz-Diaz, Nildris; Marshall, Allyson C.; Pirro, Nancy T.; Su, Yixin; Gwathmey, TanYa M.; Rose, James C.

2015-01-01

Angiotensin 1–7 [ANG-(1–7)] is expressed within the kidney and exhibits renoprotective actions that antagonize the inflammatory, fibrotic, and pro-oxidant effects of ANG II. We previously identified an peptidase that preferentially metabolized ANG-(1–7) to ANG-(1–4) in the brain medulla and cerebrospinal fluid (CSF) of sheep (Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. J Neurochem 130: 313–323, 2014); thus the present study established the expression of the peptidase in the kidney. Utilizing a sensitive HPLC-based approach, we demonstrate a peptidase activity that hydrolyzed ANG-(1–7) to ANG-(1–4) in the sheep cortex, isolated tubules, and human HK-2 renal epithelial cells. The peptidase was markedly sensitive to the metallopeptidase inhibitor JMV-390; human HK-2 cells expressed subnanomolar sensitivity (IC50 = 0.5 nM) and the highest specific activity (123 ± 5 fmol·min−1·mg−1) compared with the tubules (96 ± 12 fmol·min−1·mg−1) and cortex (107 ± 9 fmol·min−1·mg−1). The peptidase was purified 41-fold from HK-2 cells; the activity was sensitive to JMV-390, the chelator o-phenanthroline, and the mercury-containing compound p-chloromercuribenzoic acid (PCMB), but not to selective inhibitors against neprilysin, neurolysin and thimet oligopeptidase. Both ANG-(1–7) and its endogenous analog [Ala1]-ANG-(1–7) (alamandine) were preferentially hydrolyzed by the peptidase compared with ANG II, [Asp1]-ANG II, ANG I, and ANG-(1–12). Although the ANG-(1–7) peptidase and insulin-degrading enzyme (IDE) share similar inhibitor characteristics of a metallothiolendopeptidase, we demonstrate marked differences in substrate specificity, which suggest these peptidases are distinct. We conclude that an ANG-(1–7) peptidase is expressed within the renal proximal tubule and may play a potential role in the renal renin-angiotensin system to regulate ANG-(1–7) tone. PMID:25568136

Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)

PubMed Central

Watashi, Koichi; Sluder, Ann; Daito, Takuji; Matsunaga, Satoko; Ryo, Akihide; Nagamori, Shushi; Iwamoto, Masashi; Nakajima, Syo; Tsukuda, Senko; Borroto-Esoda, Katyna; Sugiyama, Masaya; Tanaka, Yasuhito; Kanai, Yoshikatsu; Kusuhara, Hiroyuki; Mizokami, Masashi; Wakita, Takaji

2014-01-01

Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration <0.2 μM. Conclusion: This study provides a proof of concept for the novel strategy to identify anti-HBV agents by targeting the candidate HBV receptor, NTCP, using CsA as a structural platform. (Hepatology 2014;59:1726–1737) PMID:24375637

Study of the Engine Bird Ingestion Experience of the Boeing 737 Aircraft (October 1986- September 1988)

DTIC Science & Technology

1990-05-01

IBADAN, NIGERIA N FON 1382fIZ IBIZA, SPAIN N FON 124 220 ICT WICHITA, KA, USA N YES 10698 6220 toA IDANO FALLS, 10, USA N ’WES 2190 27’S6IDE I NOORE...NACEIO, ALAGOAS, BRAZIL S FGK 978 1646 MDE MEDELLIN , COLOMBIA N FGN 312 312 1I0 MAKURDI, NIGERIA N FGN 730 695 MDK MBANDACA, ZAIRE N FGN 416 522 100

Floating Breakwaters: State-of-the-Art Literature Review.

DTIC Science & Technology

1981-10-01

transmission Mooring loads 20. / . 20. STR ACT (Continue on reverse ide If necessary and Identify by block number) A multitude of conceptual models of...are designed by finding the ultimate lateral resistance of the pile-soil system and increasing the lateral mooring load , Ft, by a fac- tor of safety...Fs, to determine the design lateral load on the pile. The ultimate lateral resistance of the anchor pile is reached when either the passive strength of

Artificial Intelligence: An Analysis of Potential Applications to Training, Performance Measurement, and Job Performance Aiding.

DTIC Science & Technology

1983-09-01

AD-Ali33 592 ARTIFICIAL INTELLIGENCE: AN ANALYSIS OF POTENTIAL 1/1 APPLICATIONS TO TRAININ..(U) DENVER RESEARCH INST CO JRICHARDSON SEP 83 AFHRL-TP...83-28 b ’ 3 - 4. TITLE (aied Suhkie) 5. TYPE OF REPORT & PERIOD COVERED ARTIFICIAL INTEL11GENCE: AN ANALYSIS OF Interim POTENTIAL APPLICATIONS TO...8217 sde if neceseamy end ides*f by black naumber) artificial intelligence military research * computer-aided diagnosis performance tests computer

Semiconductor Alloy Theory.

DTIC Science & Technology

1986-01-14

0.15 0.352 GaPAs) 3.5 191 0.10 0.11 0.307 In(As,SbJ 6.8 635 0.52 0.79 0.840 Ga(As,Sb) 7.6 924 0.53 0.94 0.844 AI(As,Sb) 8.1 1030 0.56 0.78 0.810 - ln(PSb...to prov ide good estimiates, of the mixing enthalpies *T, /T 2 is plotted against bi8 ) alone, the FPT points are fl of pseudobinaryN alloys. The

Integration of an Apple II Plus Computer into an Existing Dual Axis Sun Tracker System.

DTIC Science & Technology

1984-06-01

Identify by block number) S, tpec l Sun Tracker System Solar Energy Apple II Plus Computer 20. ABSTRACT (’ ntlnue on reveree ide If neceesery end...14 4. Dual Axis Sun Tracker (Side View) ----------------- 15 5. Solar Tracker System Block Diagram ---------------- 17 6. Plug Wiring Diagram for Top...sources will be competitive. Already many homes have solar collectors and other devices designed to decrease the consumption of gas, oil, and

Flood Control, Mississippi River, La Crosse, Wisconsin.

DTIC Science & Technology

1975-10-01

end SuP.,tifle) S TYPE OF REPORT & PERIOD COVEkr FINAL ENVIRONMENTAL IMPACT STATEMENT FLOOD CONTROL MISSISSIPPI RIVER LA CROSSE, WISCONSIN Pinal FIq 6...PERFORMING ORG. REPORT NUMBER 7. AUTHOR(e) 0 CONTRACT OR GRANT NUMBER( s ) 9 PERFORMING ORGANIZATION NAME AND ADrRESS 10. PROGRAM ELEMENT. PROJECT, T...rev s eflA ff r,,.e.. ind IdeInify by block rnmber) "-The proposed action is a flood control project consisting of levees, road raises, flood wall

Computer Program User’s Manual for FIREFINDER Digital Topographic Data Verification Library Dubbing System. Volume II. Dubbing.

DTIC Science & Technology

1982-01-29

N - Nw .VA COMPUTER PROGRAM USER’S MANUAL FOR . 0FIREFINDER DIGITAL TOPOGRAPHIC DATA VERIFICATION LIBRARY DUBBING SYSTEM VOLUME II DUBBING 29 JANUARY...Digital Topographic Data Verification Library Dubbing System, Volume II, Dubbing 6. PERFORMING ORG. REPORT NUMER 7. AUTHOR(q) S. CONTRACT OR GRANT...Software Library FIREFINDER Dubbing 20. ABSTRACT (Continue an revWee *Ide II necessary end identify by leek mauber) PThis manual describes the computer

Scientific Studies of the High-Latitude Ionosphere with the Ionosphere Dynamics and ElectroDynamics - Data Assimilation (IDED-DA) Model

DTIC Science & Technology

2014-09-23

conduct simulations with a high-latitude data assimilation model. The specific objectives are to study magnetosphere-ionosphere ( M -I) coupling processes...based on three physics-based models, including a magnetosphere-ionosphere ( M -I) electrodynamics model, an ionosphere model, and a magnetic...inversion code. The ionosphere model is a high-resolution version of the Ionosphere Forecast Model ( IFM ), which is a 3-D, multi-ion model of the ionosphere

"Bonjour History": Materials and Ideas for Teaching Louisiana's Cajun History = "Bonjour l'Histoire": Quelques Idees, Deux ou Trois Activites, et Plusieurs Materiaux pour l'Enseignement de l'Histoire des Cadiens en Louisiane.

ERIC Educational Resources Information Center

Mounier, Brenda

The goals of this teacher's guidebook and videotape are designed to incorporate Acadian (Cajun) history into the 4th grade social studies curriculum and the 4th and 5th grade Louisiana 30-minute daily French programs and French immersion programs. Another goal is to create an awareness, appreciation, and understanding of Acadian history in…

On-Site Fuel Cell Energy Systems: The U.S. Air Force Field Test Demonstration Plan.

DTIC Science & Technology

1980-12-01

Continue on reverse -, de if necessary and identify by block number) Fuel cells Cogererati on Energy conversion ABSTRACT (Continue an reverse ide If...fuel electrode, water at the oxygen electrode, and to act as a mechanical barrier between the two gases to prevent mixing and direct combustion . When the...possibility of more effective utilization of hydrocarbon fuels, especially when compared with the alternative heat engine combustion technologies. Figure 12

Mathematical Capture of Human Data for Computer Model Building and Validation

DTIC Science & Technology

2014-04-03

weapon. The Projectile, the VDE , and the IDE weapons had effects of financial loss for the targeted participant, while the MRAD yielded its own...for LE, Centroid and TE for the baseline and The VDE weapon conditions since p-values exceeded α. All other conditions rejected the null...hypothesis except the LE for VDE weapon. The K-S Statistics were correspondingly lower for the measures that failed to reject the null hypothesis. The CDF

Ammonium Nitrate as an Oxidant for Composite Propellants. Part 1. Preliminary Considerations

DTIC Science & Technology

1954-09-01

obtainable with a sirple amonium nitrate / fucl mixture is about 223 sec. The advantage of using oxygenated fuels is calculated for cases where, because of...Propulsion Laboratory have used ammonium nitrate and mixtures of arnonium nitrate and ammonium perchloratc as the oxidant /in COi IDE ,T )kL/ D ISCRT&T...previously considered are giver and also a curve for amnonium nitrate / polyvinyl alcohol mixtures. Amonium pcrchlorate/polyisobutenc is inclu£cd for

AFHRL Annual Report FY 81.

DTIC Science & Technology

1981-01-01

iiruI. sulihrur~. arid comtiije iii-aro’ d~ namny rallier- than slin’. ’I’ll(-% nralt oilwulf-d’’I’r tip li[’ I Lahioraiorn s R&D~ I) rezar ’ I .I s...XI)- \\093) 2831. fl’/I. ide anfgle’ ifi/lifil P pIc v"isuafl s.Iovin. Xf1lfM.- TH-81-51. \\D - \\105l 50I8. Idrn ). It.. & kaii r. J. F.. Ii rffflafif

Critical Thinking Skills of U.S. Air Force Senior and Intermediate Developmental Education Students

DTIC Science & Technology

2016-02-16

SAASS), and Air War College (AWC). T-tests indicated no statistically significant difference in the CT skills of the sample of ACSC and AWC students...hypothesis that there was no statistically significant difference in the CT skills of IDE and SDE students. SAASS, as a more selective advanced studies...potential to develop CT skills, concluding, “students in the experimental group performed at a statistically significantly higher level than students in

An IDeA for enhancing undergraduate research at rural primarily undergraduate institutions.

PubMed

Sens, Donald A; Cisek, Karen L; Conway, Pat; Doze, Van A

2017-09-01

This study documents the efforts of the North Dakota (ND) IDeA Networks of Biomedical Research Excellence (INBRE) program to assist in the development of undergraduate research programs at four state-supported primarily undergraduate institutions (PUIs) in ND. The study was initiated in the 2004-2005 academic year and continues to the present. The study shows that gaining initial institutional support for undergraduate research was assisted by providing salary support for faculty involved in undergraduate research. Once research was ongoing, each institution evolved their own unique plan for the use of support from the ND INBRE. Undergraduate student researchers have prepared, presented, and defended their research results on 188 unique posters since initiation of the program, with many posters being presented at more than one meeting. PUI faculty have authored 35 peer-reviewed manuscripts. Evaluation has shown that over 95% of the undergraduate students performing research matriculated with their bachelor's degree. Career choices of 77.2% of these graduates was determined, and 37% pursued a career in the health professions. Of the students not pursuing a post-baccalaureate degree, 81.2% chose careers directly linked to science. The study reinforces the concept that undergraduate research can be performed directly on the PUI campus and be of value in preparing the next generation of health professionals in research, service, and teaching. Copyright © 2017 the American Physiological Society.

Carbon Nanotube Based Chemical Sensors for Space and Terrestrial Applications

NASA Technical Reports Server (NTRS)

Li, Jing; Lu, Yijiang

2009-01-01

A nanosensor technology has been developed using nanostructures, such as single walled carbon nanotubes (SWNTs), on a pair of interdigitated electrodes (IDE) processed with a silicon-based microfabrication and micromachining technique. The IDE fingers were fabricated using photolithography and thin film metallization techniques. Both in-situ growth of nanostructure materials and casting of the nanostructure dispersions were used to make chemical sensing devices. These sensors have been exposed to nitrogen dioxide, acetone, benzene, nitrotoluene, chlorine, and ammonia in the concentration range of ppm to ppb at room temperature. The electronic molecular sensing of carbon nanotubes in our sensor platform can be understood by intra- and inter-tube electron modulation in terms of charge transfer mechanisms. As a result of the charge transfer, the conductance of p-type or hole-richer SWNTs in air will change. Due to the large surface area, low surface energy barrier and high thermal and mechanical stability, nanostructured chemical sensors potentially can offer higher sensitivity, lower power consumption and better robustness than the state-of-the-art systems, which make them more attractive for defense and space applications. Combined with MEMS technology, light weight and compact size sensors can be made in wafer scale with low cost. Additionally, a wireless capability of such a sensor chip can be used for networked mobile and fixed-site detection and warning systems for military bases, facilities and battlefield areas.

Antiviral efficacy of entecavir in nucleos(t)ide-naïve patients of Black/African descent with chronic hepatitis B.

PubMed

Jeffers, L; Van Rensburg, C J; Banks, A; Schechter, M; Schmidt, S J; Hu, W; Llamoso, C; Parana, R

2014-01-01

This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies. © 2013 John Wiley & Sons Ltd.

The neuropsychology of the schizo-obsessive subtype of schizophrenia: a new analysis.

PubMed

Patel, D D; Laws, K R; Padhi, A; Farrow, J M; Mukhopadhaya, K; Krishnaiah, R; Fineberg, N A

2010-06-01

Interest in the neuro-cognitive profile of patients with schizophrenia and co-morbid obsessive compulsive disorder (schizo-OCD) is rising in response to reports of high co-morbidity rates. Whereas schizophrenia has been associated with global impairment in a wide range of neuro-cognitive domains, OCD is associated with specific deficits featuring impaired performance on tasks of motor and cognitive inhibition involving frontostriatal neuro-circuitry. We compared cognitive function using the CANTAB battery in patients with schizo-OCD (n=12) and a schizophrenia group without OCD symptoms (n=16). The groups were matched for IQ, gender, age, medication, and duration of illness. The schizo-OCD patients made significantly more errors on a task of attentional set-shifting (ID-ED set-shift task). By contrast, no significant differences emerged on the Stockings of Cambridge task, the Cambridge Gamble Task or the Affective Go/NoGo tasks. No correlation emerged between ID-ED performance and severity of schizophrenia, OCD or depressive symptoms, consistent with neurocognitive impairment holding trait rather than state-marker status. Schizo-obsessives also exhibited a trend toward more motor tics emphasizing a neurological contribution to the disorder.ConclusionOur findings reveal a more severe attentional set-shifting deficit and neurological abnormality that may be fundamental to the neuro-cognitive profile of schizo-OCD. The clinical implications of these impairments merit further exploration in larger studies.

Climate change in the classroom: Reaching out to middle school students through science and math suitcase lessons

NASA Astrophysics Data System (ADS)

Jacobo, A. C.; Collay, R.; Harris, R. N.; de Silva, L.

2011-12-01

We have formed a link between the Increasing Diversity in Earth Sciences (IDES) program with the Science and Math Investigative Learning Experiences (SMILE) program, both at Oregon State University. The IDES mission is to strengthen the understanding of Earth Sciences and their relevance to society among broad and diverse segments of the population and the SMILE mission is to provide science and math enrichment for underrepresented and other educationally underserved students in grades 4-12. Traditionally, underserved schools do not have enough time or resources to spend on science and mathematics. Furthermore, numerous budget cuts in many Oregon school districts have negatively impacted math and science cirriculum. To combat this trend we have designed suitcase lessons in climate change that can be carried to a number of classrooms. These lesson plans are scientifically rich and economically attractive. These lessons are designed to engage students in math and science through climate change presentations, group discussions, and hands-on activities. Over the past year we have familiarized ourselves with the academic ability of sixth and seventh graders through in-class observation in Salem Oregon. One of the suit case lessons we developed focuses on climate change by exploring the plight of polar bears in the face of diminishing sea ice. Our presentation will report the results of this activity.

Executive functioning in people with obsessive-compulsive personality traits: evidence of modest impairment.

PubMed

García-Villamisar, Domingo; Dattilo, John

2015-06-01

Investigations of executive dysfunctions among people with obsessive-compulsive personality disorders (OCPD) have yielded inconsistent results. The authors speculate that obsessive-compulsive personality traits (OCPT) from a nonclinical population may be associated with specific executive dysfunctions relative to working memory, attentional set-shifting, and planning. A sample consisting of 79 adults (39 females, 40 males) was divided into high and low scorers on the Personality Diagnostic Questionnaire-4 (PDQ-4; Hyler, 1994). In addition, these participants were interviewed using the SCID-II (First, Spitzer, Gibbon & Williams, 1997) to confirm the presence of symptoms of obsessive-compulsive personality. Participants completed a battery of executive tasks associated with the Cambridge Neuropsychological Test Automated Battery (CANTAB), including Spatial Working Memory, Intradimensional/Extradimensional (ID/ED), Attentional Set-Shifting, and Stockings of Cambridge. Also, self-report measures of executive functions as well as of anxiety and depressive symptoms were administered. The analysis of covariance revealed significant differences between participants with OCPT and controls on the Spatial Working Memory tasks, ID/ED tasks, Stockings of Cambridge, and the Dysexecutive Questionnaire (DEX). Nevertheless, there were no significant differences in the number of problems solved in minimum movements. These results suggest that executive dysfunctions are present in people with prominent OCPT and that there is a high convergence between clinical and ecological measures of executive functions in people with obsessive personality traits.

The detection of organic solvent vapor by using polymer coated chemocapacitor sensor

NASA Astrophysics Data System (ADS)

Rusdiarna Indrapraja, Apik; Rivai, Muhammad; Arifin, Achmad; Purwanto, Djoko

2017-05-01

A chemocapacitor consists of planar interdigital electrodes (IDE) made by two comb electrodes on a substrate. A dielectric film was applied on the electrodes in which the absorbed vapor will modify its permittivity. This study has fabricated chemocapacitor with the IDE distance of 0.5 mm, while the dielectric film was a sensitive layer consisting of a polymeric material. The deposition of the polymeric film was accomplished by drop casting. A sensor array consisting of four chemocapacitors coated with different polymers namely PEG-1540, PEG-20M, PEG-6000, and PVP was used to obtain the pattern of shift in the capacitance. The integrated circuit AD7746 was used as the capacitance to-digital converter (CDC). The organic solvents of ethanol, benzene, and aceton were used as the vapor samples in this experiment. The results showed that the change in the capacitance value increases proportionally to the concentration of vapour where sensors coated with PEG-1540 and PVP have higher sensitivity, i.e. 0.0028pF/part per thousand and 0.0027pF/part per thousand, respectively. Based on the capacitance to digital conversion capabilities, the system provides there solution of 0.4084ppm. The sensor array could produce a different pattern for each of the vapor sample. The Neural Network pattern recognition system could identify the type of vapor automatically with the root mean square error of 10-5

Regression method-derived energy value of dried egg albumen for broiler chickens.

PubMed

Hancock, S; Zhang, F; Adeola, O

2018-05-01

The energy value of dried egg albumen (DEA) for broiler chickens was determined with male Ross 708 broilers. Birds were fed a common broiler starter diet from day 0 to 17 and experimental diets from day 17 to 22 post hatching. A total of 192 birds was allotted to 3 diets in a randomized complete block design with 8 replicate cages per diet and 8 birds per cage. The experiment used a corn-soybean meal reference diet and 2 test diets which the DEA was added at 50 or 100 g/kg to partially replace the energy source in the reference diet. The analyzed DM of DEA was 934 g/kg, and the respective analyzed gross energy and CP were 5,310 kcal and 894 g/kg DM. Addition of DEA to the reference diet linearly increased (P < 0.01) ileal DM digestibility, ileal energy digestibility, and ileal digestible energy (IDE), metabolizable energy (ME), and nitrogen-corrected metabolizable energy (MEn), whereas the effect on N retention was quadratic (P < 0.05). The IDE, ME, MEn of DEA values determined by the regression method were 4,777, 4,966, and 4,750 kcal/kg DM, respectively. In conclusion, the current study demonstrated that between 89 and 94% of the gross energy in dried egg albumen is utilized by broiler chickens.

Genomic Basis of Adaptive Evolution: The Survival of Amur Ide (Leuciscus waleckii) in an Extremely Alkaline Environment

PubMed Central

Xu, Jian; Li, Jiong-Tang; Jiang, Yanliang; Peng, Wenzhu; Yao, Zongli; Chen, Baohua; Jiang, Likun; Feng, Jingyan; Ji, Peifeng; Liu, Guiming; Liu, Zhanjiang; Tai, Ruyu; Dong, Chuanju; Sun, Xiaoqing; Zhao, Zi-Xia; Zhang, Yan; Wang, Jian; Li, Shangqi; Zhao, Yunfeng; Yang, Jiuhui; Sun, Xiaowen; Xu, Peng

2017-01-01

The Amur ide (Leuciscus waleckii) is a cyprinid fish that is widely distributed in Northeast Asia. The Lake Dali Nur population inhabits one of the most extreme aquatic environments on Earth, with an alkalinity up to 50 mmol/L (pH 9.6), thus providing an exceptional model with which to characterize the mechanisms of genomic evolution underlying adaptation to extreme environments. Here, we developed the reference genome assembly for L. waleckii from Lake Dali Nur. Intriguingly, we identified unusual expanded long terminal repeats (LTRs) with higher nucleotide substitution rates than in many other teleosts, suggesting their more recent insertion into the L. waleckii genome. We also identified expansions in genes encoding egg coat proteins and natriuretic peptide receptors, possibly underlying the adaptation to extreme environmental stress. We further sequenced the genomes of 10 additional individuals from freshwater and 18 from Lake Dali Nur populations, and we detected a total of 7.6 million SNPs from both populations. In a genome scan and comparison of these two populations, we identified a set of genomic regions under selective sweeps that harbor genes involved in ion homoeostasis, acid-base regulation, unfolded protein response, reactive oxygen species elimination, and urea excretion. Our findings provide comprehensive insight into the genomic mechanisms of teleost fish that underlie their adaptation to extreme alkaline environments. PMID:28007977

Comparative metabolism and elimination of acetanilide compounds by rat.

PubMed

Davison, K L; Larsen, G L; Feil, V J

1994-10-01

1. 14C-labelled propachlor, alachlor, butachlor, metolachlor, methoxypropachlor and some of their mercapturic acid pathway metabolites (MAP) were given to rat either by gavage or by perfusion into a renal artery. MAP metabolites were isolated from bile and urine. 2. Rat gavaged with propachlor and methoxypropachlor eliminated 14C mostly in urine, whereas rat gavaged with alachlor, butachlor and metolachlor eliminated 14C about equally divided between urine and faeces. When bile ducts were cannulated, the gavaged rat eliminated most of the 14C in bile for all compounds. The amount of 14C in bile from the propachlor-gavaged rat was less than that for the other acetanilides, with the difference being in the urine. 3. The mercapturic acid metabolites 2-methylsulphinyl-N-(1-methylhydroxyethyl)-N-phenylacetam ide and 2-methylsulphinyl-N-(1-methylmethoxyethyl)-N-phenylacetam ide were isolated from the urine and bile of the methoxypropachlor-gavaged rat. 4. Bile was the major route for 14C elimination when MAP metabolites of alachlor, butachlor and metolachlor were perfused into a renal artery. Urine was the major route for 14C elimination when MAP metabolites of propachlor and methoxypropachlor were perfused. Mercapturic acid conjugates were major metabolites in bile and urine when MAP metabolites were perfused. 5. We conclude that alkyl groups on the phenyl portion of the acetanilide causes biliary elimination to be favoured over urinary elimination.

Determinação de elementos próprios dos asteróides troianos: comparação entre as teorias semi-analítica e sintética

NASA Astrophysics Data System (ADS)

Roig, F.; Beaugé, C.

2003-08-01

Além do cálculo semi-analítico de elementos próprios dos asteróides Troianos (Beaugé & Roig 2001, Icarus 153, 391), recentemente foi apresentado um novo conjunto destes elementos próprios determinado através de uma teoria sintética (Knenezevic & Milani 2003, comunicação pessoal). As bases de dados contendo estas determinações estão disponiveis na pagina web do Asteroid Dynamical Site (http://hamilton.dm.unipi.it/cgi-bin/astdys/astibo). Nesta comunicação apresentamos os primeiros resultados de um estudo comparativo entre ambos conjuntos de elementos próprios, analisando suas vantagens e desvantagens, assim como os limites de precisão de cada conjunto. Mostramos que os elementos próprios sintéticos são mais precisos que os smi-analíticos para grandes amplitudes de libração do ângulo s = l-lJup, embora acontece o contrario para os corpos cuja amplitude de libração é muito pequena. Finalmente discutimos a influencia destes erros na determinação de familias de asteroides e da estrutura resonante em torno dos pontos Lagrangeanos L4 e L5.

MOFs for the Sensitive Detection of Ammonia: Deployment of fcu-MOF Thin Films as Effective Chemical Capacitive Sensors.

PubMed

Assen, Ayalew H; Yassine, Omar; Shekhah, Osama; Eddaoudi, Mohamed; Salama, Khaled N

2017-09-22

This work reports on the fabrication and deployment of a select metal-organic framework (MOF) thin film as an advanced chemical capacitive sensor for the sensing/detection of ammonia (NH 3 ) at room temperature. Namely, the MOF thin film sensing layer consists of a rare-earth (RE) MOF (RE-fcu-MOF) deposited on a capacitive interdigitated electrode (IDE). Purposely, the chemically stable naphthalene-based RE-fcu-MOF (NDC-Y-fcu-MOF) was elected and prepared/arranged as a thin film on a prefunctionalized capacitive IDE via the solvothermal growth method. Unlike earlier realizations, the fabricated MOF-based sensor showed a notable detection sensitivity for NH 3 at concentrations down to 1 ppm, with a detection limit appraised to be around 100 ppb (at room temperature) even in the presence of humidity and/or CO 2 . Distinctly, the NDC-Y-fcu-MOF based sensor exhibited the required stability to NH 3 , in contrast to other reported MOFs, and a remarkable detection selectivity toward NH 3 vs CH 4 , NO 2 , H 2 , and C 7 H 8 . The NDC-Y-fcu-MOF based sensor exhibited excellent performance for sensing ammonia for simulated breathing system in the presence of the mixture of carbon dioxide and/or humidity (water vapor), with no major alteration in the detection signal.

Retrospective analysis of a case series of patients with traumatic injuries to the craniocervical junction.

PubMed

Esteves, Luiz Adriano; Joaquim, Andrei Fernandes; Tedeschi, Helder

2016-01-01

To evaluate the correlation between the treatment, the characteristics of the lesions and the clinical outcome of patients with traumatic injuries to the craniocervical junction. This was a retrospective study of patients treated conservatively or surgically between 2010 and 2013 with complete data sets. We analyzed 37 patients, 73% were men with mean age of 41.7 years. Of these, 32% were submitted to initial surgical treatment and 68% received conservative treatment. Seven (29%) underwent surgery subsequently. In the surgical group, there were seven cases of odontoid type II fractures, two cases of fracture of posterior elements of the axis, one case of C1-C2 dislocation with associated fractured C2, one case of occipitocervical dislocation, and one case of combined C1 and C2 fractures, and facet dislocation. Only one patient had neurological déficit that improved after treatment. Two surgical complications were seen: a liquoric fistula and one surgical wound infection (reaproached). In the group treated conservatively, odontoid fractures (eight cases) and fractures of the posterior elements of C2 (five cases) were more frequent. In two cases, in addition to the injuries of the craniocervical junction, there were fractures in other segments of the spine. None of the patients who underwent conservative treatment presented neurological deterioration. Although injuries of craniocervical junction are relatively rare, they usually involve fractures of the odontoid and the posterior elements of the axis. Our results recommend early surgical treatment for type II odontoid fractures and ligament injuries, the conservative treatment for other injuries. Avaliar a correlação entre o tratamento, as características das lesões e o resultado clínico em pacientes com lesões traumáticas na junção craniocervical. Estudo retrospectivo de pacientes maiores de 18 anos tratados de forma conservadora ou cirúrgica, entre 2010 e 2013. Foram analisados 37 pacientes, 73% eram do sexo masculino e a média de idade foi de 41,7 anos. Inicialmente 32% dos pacientes foram submetidos a tratamento cirúrgico, e 68% foram submetidos a tratamento conservador. Sete pacientes (29%) do grupo conservador foram submetidos posteriormente à cirurgia. No grupo cirúrgico, houve sete casos de fratura de odontóide tipo II, dois casos de fratura de elementos posteriores do áxis, um caso de luxação C1-C2, um caso de deslocamento occipito-cervical e um caso de fraturas de C1 e C2 e luxação facetária. Um paciente apresentava déficit neurológico, melhorando após o tratamento. Houve duas complicações pós-cirúrgicas, uma fístula liquórica e uma infecção de ferida operatória (reabordada). No grupo conservador, predominaram as fraturas do odontóide (oito) e dos elementos posteriores de C2 (cinco). Em dois casos, havia também fraturas em outros segmentos da coluna. Nenhum dos pacientes deste grupo apresentou deterioração neurológica. As lesões da junção craniocervical são raras, sendo mais frequentes as fraturas do odontóide e dos elementos posteriores do áxis. Nossos resultados recomendam o tratamento cirúrgico precoce para os pacientes com fraturas do odontóide tipo II e lesões ligamentares, e tratamento conservador para os demais pacientes.

Detection of human immunodeficiency virus type 1 (HIV-1) Tat protein by aptamer-based biosensors

NASA Astrophysics Data System (ADS)

Hashim, Uda; Fatin, M. F.; Ruslinda, A. R.; Gopinath, Subash C. B.; Uda, M. N. A.

2017-03-01

A study was conducted to detect the human immunodeficiency virus (HIV-1) Tat protein using interdigitated electrodes. The measurements and images of the IDEs' finger gaps and the images of chitosan-carbon nanotubes deposited on top of the interdigitated electrodes were taken using the Scanning Electron Microscope. The detection of HIV-1 Tat protein was done using split aptamers and aptamer tail. Biosensors were chosen as diagnostic equipment due to their rapid diagnostic capabilities.

Cyber ACTS/SAASS: A Second Year of Command and Staff College for the Future Leaders of Our Cyber Forces

DTIC Science & Technology

2009-01-01

objectives. The Air Force is struggling to determine the best way of developing offensive and defensive capabilities for cyber warfare . Our warfighting...education (IDE) cyber warfare program at the Air Force Institute of Technology (AFIT), located at Wright-Patterson AFB, Ohio. I propose that the Air...Force create a two-year professional military education (PME) path consisting of ACSC followed by AFIT’s cyber warfare program, paralleling the current path of ACSC followed by SAASS.

ANAM4 TBI Reaction Time-Based Tests have Prognostic Utility for Acute Concussion

DTIC Science & Technology

2013-07-01

Canadian Football League season. Clin J Sport Med 2000; 10(1); 9-14. 19. Gerberich SG, Priest JD, Boen JR, Sträub CP, Maxwell RE; Concussion incidences and...Cumulative effects associated with recurrent concussion in collegiate football players; the NCAA Concussion Study. JAMA 2003; 290( 19); 2549-55. 21. Zemper...Iverson GL, Ide T, Maroon J; Examining concussion rates and return to play in high school football players wearing newer helmet technology; a three-year

Scales of Hydrogen-Bonding Workshop Held in London, England on 1-3 July 1987

DTIC Science & Technology

1987-07-03

medium (a perfluorinated compound , FC-75), hoping to attain the basicity of CF3 CH2OH and (CF 3.2CHOH. The frequency shifts of the 3818 cm v(OH) band of...bond basicity for nonassoclated compounds , pro.ided that the reference acids in each case led toi*values that were almost the same - around 65". ’ 1...experimental measurements JOSE-LOUIS M. ABBOUD * The hydrogen-bonding basicity of oxygen and sulphur compounds MICHAEL H. ABRAHAM, PRISCILLA L

Development of a Web-Based Distributed Interactive Simulation (DIS) Environment Using JavaScript

DTIC Science & Technology

2014-09-01

scripting that let users change or interact with web content depending on user input, which is in contrast with server-side scripts such as PHP, Java and...transfer, DIS usually broadcasts or multicasts its PDUs based on UDP socket. 3. JavaScript JavaScript is the scripting language of the web, and all...IDE) for developing desktop, mobile and web applications with JAVA , C++, HTML5, JavaScript and more. b. Framework The DIS implementation of

Analysis of the Suspended H-Waveguide and Other Related Dielectric Waveguide Structures.

DTIC Science & Technology

1983-01-01

energy is concentrated in the disc. In the substrate regions, the fields decay extremely fast. Consequently, the removal of the dielectric substrates...ado re erse ide i f ne oeeary e d IdO tif’ I V Week 110m mke ) 0 In this thesis, the field and propagation characceristicshof’many dielectric waveguide...propagation co*stants and the field distribu- tions of a newly developed suspended H-woveguide based on the mode matching techniques is described. The d

The SEEDs of Planet Formation: Indirect Signatures of Giant Planets in Transitional Disks

NASA Technical Reports Server (NTRS)

Grady, Carol; Currie, T.

2012-01-01

We live in a planetary system with 2 gas giant planets, and as a resu lt of RV, transit, microlensing, and transit timing studies have ide ntified hundreds of giant planet candidates in the past 15 years. Su ch studies have preferentially concentrated on older, low activity So lar analogs, and thus tell us little about .when, where, and how gian t planets form in their disks, or how frequently they form in disks associated with intermediate-mass stars.

Sterblichkeit: der paradoxe Kunstgriff des Lebens - Eine Betrachtung vor dem Hintergrund der modernen Biologie

NASA Astrophysics Data System (ADS)

Verbeek, Bernhard

Leben gibt es auf der Erde seit fast 4 Mio. Jahren, trotz allen Katastrophen. Die Idee des Lebens scheint unsterblich. Der Tod aber offenbar auch. Jedes Lebewesen ist davon bedroht, ja für Menschen und andere "höhere“ Lebewesen ist er im Lebensprogramm eingebaut - todsicher. Diese Tatsache ist alles andere als selbstverständlich. Ist sie überhaupt kompatibel mit dem Prinzip der Evolution, nach dem der am besten Angepasste überlebt?

Kopf

NASA Astrophysics Data System (ADS)

Goldschmid, Alfred; Maier, Wolfgang; Olsson, Lennart; Piekarski, Nadine

Die Evolution des Wirbeltierkopfes ist ein klassisches Problemfeld der vergleichend en Morphologie. Bereits J.W. von Goethe (1749-1832) und L. Oken (1779-1851) vertraten die Idee eines aus Segmenten bestehenden Schädels. Die Segmente sollten umgewandelten Wirbeln entsprechen; später wurden auch die Hirnnerven den segmentalen Spinalnerven des Rumpfes gleichgesetzt — Vorstellungen, die vor allem gegen Ende des 19. Jh. auf massive Ablehnung stießen. Die moderne Entwicklungsbiologie zei gt jedoch, dass zumindest Teile des Kopfes in ihrer Entwicklung eine deutliche Segmentierung aufweisen.

Testing Cobol Programs by Mutation. Volume II. CMS 1 System Documentation,

DTIC Science & Technology

1980-02-01

8217 LOOP MVth a’ solution was to enebese the macn depesi- 1F rumen Tom dent imes ide a apeelal type of mdulo called a G aaraadom(2); device maul* (see...software status register can be modified at will, while the required, but as an additional benefit, Modula contents of the buffer can be dealt with as...language. The requirements are stringent and usu- Dick up the contents of the address by Indirect ally the work Is never completed, an the uses for

76 FR 80948 - Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

...The Food and Drug Administration (FDA) is extending the comment period for the notice that appeared in the Federal Register of Thursday, November, 10, 2011 (76 FR 70151). In the notice, FDA requested comments on the draft guidance that has been developed to promote the initiation of clinical investigations to evaluate the medical devices under FDA's Investigational Device Exemptions (IDE) regulations. The Agency is taking this action to allow interested persons additional time to submit comments.

Development of an On-Demand, Generic, Drug-Delivery System

DTIC Science & Technology

1985-08-06

systems Two systems were evaluated for CO2 evolution. The first of these was an enzymatic system based on urea and urease . The second system was based...PHM 84 Research pH Meter was used te monitor pH. Solutions of various buffer concen- trations and pHs were prepared for each buffer system. One urease ...Measurement of carbon dio~ide production was accomplished using the apparatus shown in Figure 2. Carbon dioxide was generated by putting a urease tablet in the

Space WARC 1985 - Legal Issues and Implications.

DTIC Science & Technology

1984-01-01

public releoa.I |_Distribution Unlimited DISTRIBUTION STATEMENT ACCESSION FOR NTIS GRAM! DTIC TAB UNANNOUNCED E] JUSTIFICATION 3LC r DISTRIBUTIOND...EXHAUSTED. -7 77 7-7 77 .1- *~AD-A 150 972 "A INSTRUCTIONS____ 1.RGOVT AC(,.iN~.~j~ RECIPIENT’S CATALOG NUMBER * ~AFIT/CI/NR 85-9T IO EOT&PRO OEE r ...reere ide if neceeeesy anid identiy by bock numbas,) 20. ABSTRACT (Continue orn revere. sid. If nocep--ty end idetify by bla~ck r --mbsr) ATTACHED FORM

Design and Integration of a Three Degrees-of-Freedom Robotic Vehicle with Control Moment Gyro for the Autonomous Multi-Agent Physically Interacting Spacecraft (AMPHIS) Testbed

DTIC Science & Technology

2006-09-01

required directional control for each thruster due to their high precision and equivalent power and computer interface requirements to those for the...Universal Serial Bus) ports, LPT (Line Printing Terminal) and KVM (Keyboard-Video- Mouse) interfaces. Additionally, power is supplied to the computer through...of the IDE cable to the Prometheus Development Kit ACC-IDEEXT. Connect a small drive power connector from the desktop ATX power supply to the ACC

Heat Exchanger Cleaning in Support of Ocean Thermal Energy Conversion (OTEC) - Electronics Subsystems.

DTIC Science & Technology

1980-12-01

exchangers . The performance of heat exchangers will therefore decide the ultimate success or failure of OTEC . BACKGROUND Hardware development in support...8217AD-AG9 216 NAVAL COASTAL SYSTEMS CENTER PANAMA CITY FL F/S 13/10 HEAT EXCHANGER CLEANING IN SUPPORT OF OCEAN THERMAL ENERGY CONV"-ETC(U) DEC 80 D F...block minI ber) Heat Exchangers Chlorination Cleaning Electronics Thermal Energy Conversion 2%AISTRACT (Centhmes en; rewwe ide it neseer end iftefb Op

Validating Network Security Policies via Static Analysis of Router ACL Configuration

DTIC Science & Technology

2006-12-01

this research effort. A. SOFTWARE IMPLEMENTATION The system software was created with Java, using NetBeans IDE 5.0 [12]. NetBeans is a free, open...11. P. Gupta, and N. McKeown (2001), Algorithms for Packet Classification, IEEE Network, vol. 15, issue 2, pp. 24-32. 12, NetBeans (2006), Welcome to... NetBeans , http://www.netbeans.org, last accessed on 25 November 2006. 13. IANA.org (2006), Port Numbers, http://www.iana.org/assignments/port

Modeling Airport Ground Operations using Discrete Event Simulation (DES) and X3D Visualization

DTIC Science & Technology

2008-03-01

scenes. It is written in open-source Java and XML using the Netbeans platform, which gave the features of being suitable as standalone applications...and as a plug-in module for the Netbeans integrated development environment (IDE). X3D Graphics is the tool used for the elaboration the creation of...process is shown in Figure 2. To 20 create a new event graph in Viskit, first, Viskit tool must be launched via Netbeans or from the executable

Facilities Maintenance in the U.S. Navy

DTIC Science & Technology

1986-01-01

Row’a9IVI s..Nl,I I~de 14. 11111116104 It. safeI MeAI. 5,124 AN (:lgnd) JOHN SMITH I765 IIf Figure 111-1 Work Request is EMIROENCY/SERVICE WORK...Eliminate fire, health and active life of less than 3 years safety hazards o Infrequently or only partially o Patch and reinforce instead used of...safety or health hazards and to permit reactivation within the period prescribed under mobili- zation plans o Surplus facilities a Fliminate fire, safety

Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease.

PubMed

McClean, Paula L; Hölscher, Christian

2014-01-01

Type 2 diabetes is a risk factor in the development of Alzheimer's disease (AD). It has been shown that insulin signalling is desensitised in the brains of AD patients. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and long-lasting analogues such as liraglutide (Victoza(®)) are on the market as type 2 diabetes treatments. We have previously shown that liraglutide improved cognitive function, reduced amyloid plaque deposition, inflammation, overall APP and oligomer levels and enhanced LTP when injected peripherally for two months in 7 month old APPswe/PS1ΔE9 (APP/PS1) mice. This showed that liraglutide has preventive effects at the early stage of AD development. The current study investigated whether Liraglutide would have restorative effects in late-stage Alzheimer's disease in mice. Accordingly, 14-month-old APP/PS1 and littermate control mice were injected with Liraglutide (25 nmol/kg bw) ip. for 2 months. Spatial memory was improved by Liraglutide-treatment in APP/PS1 mice compared with APP/PS1 saline-treated mice. Overall plaque load was reduced by 33%, and inflammation reduced by 30%, while neuronal progenitor cell count in the dentate gyrus was increased by 50%. LTP was significantly enhanced in APP/PS1 liraglutide-treated mice compared with APP/PS1 saline mice, corroborated with increased synapse numbers in hippocampus and cortex. Total brain APP and beta-amyloid oligomer levels were reduced in Liraglutide-treated APP/PS1 mice while IDE levels were increased. These results demonstrate that Liraglutide not only has preventive properties, but also can reverse some of the key pathological hallmarks of AD. Liraglutide is now being tested in clinical trials in AD patients. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. Copyright © 2013 Elsevier Ltd. All rights reserved.

A five years study of antiviral effect of entecavir in Chinese chronic hepatitis B patients.

PubMed

Liu, Kehui; Xiang, Xiaogang; Bao, Rebecca; Chen, Rong; Liu, Yunye; Xie, Jingdong; Guo, Qing; Bao, Shisan; Xie, Qing; Wang, Hui

2016-07-01

Entecavir (ETV) is a potent viral replication inhibitor for chronic hepatitis B (CHB) patients. To investigate the efficacy of ETV in Chinese nucleos(t)ide(NA)-experienced CHB patients. Among 89 CHB patients with ETV monotherapy for ≥6 months, 33/89 (37%) or 56/89 (73%) were NA-naïve or NA-experienced. During a median follow-up of 5.75 years, all NA-naïve CHB patients achieved VR without genotypic ETV-resistance. However, VR was observed in 50/56 (~90%) of NA-experienced CHB patients during a median follow-up of 4.75 years. Antiviral efficacy was not reduced in patients with previous lamivudine (LAM) with/without LAM-resistance (HR 0.465; 95% CI 0.196-1.100; p > 0.05) (HR 0.472; 95% CI 0.205-1.091; p > 0.05). Patients with a primary treatment failure to adefovir (ADV) had a reduced probability of achieving VR compared to NA-naïve (HR 0.496; 95% CI 0.287-0.857; p < 0.01). Previous ADV-experienced patients with a partial VR (HR 1.253; 95% CI 0.429-3.665; p > 0.05) did not influence antiviral response to ETV. The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistance. ETV may still be an option in ADV-experienced patients with a partial VR, but not advised in patients with a primary treatment failure to ADV.

Is it possible to stop nucleos(t)ide analogue treatment in chronic hepatitis B patients?

PubMed Central

Moreno-Cubero, Elia; del Arco, Robert T Sánchez; Peña-Asensio, Julia; de Villalobos, Eduardo Sanz; Míquel, Joaquín; Larrubia, Juan Ramón

2018-01-01

Chronic hepatitis B (CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue (NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus (HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen (HBsAg), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBsAg loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBsAg seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure a close follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host’s immune system. Viral parameters that have been described as good predictors of response in HBeAg(+) cases, have proven useless in HBeAg(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups. PMID:29740199

Stop codons in the hepatitis B surface proteins are enriched during antiviral therapy and are associated with host cell apoptosis

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

Colledge, Danielle; Soppe, Sally; Yuen, Lilly

Premature stop codons in the hepatitis B virus (HBV) surface protein can be associated with nucleos(t)ide analogue resistance due to overlap of the HBV surface and polymerase genes. The aim of this study was to determine the effect of the replication of three common surface stop codon variants on the hepatocyte. Cell lines were transfected with infectious HBV clones encoding surface stop codons rtM204I/sW196*, rtA181T/sW172*, rtV191I/sW182*, and a panel of substitutions in the surface proteins. HBsAg was measured by Western blotting. Proliferation and apoptosis were measured using flow cytometry. All three surface stop codon variants were defective in HBsAg secretion.more » Cells transfected with these variants were less proliferative and had higher levels of apoptosis than those transfected with variants that did not encode surface stop codons. The most cytopathic variant was rtM204I/sW196*. Replication of HBV encoding surface stop codons was toxic to the cell and promoted apoptosis, exacerbating disease progression. - Highlights: •Under normal circumstances, HBV replication is not cytopathic. •Premature stop codons in the HBV surface protein can be selected and enriched during nucleos(t)ide analogue therapy. •Replication of these variants can be cytopathic to the cell and promote apoptosis. •Inadequate antiviral therapy may actually promote disease progression.« less

Paternal identity impacts embryonic development for two species of freshwater fish.

PubMed

Siddique, Mohammad Abdul Momin; Linhart, Otomar; Krejszeff, Sławomir; Żarski, Daniel; Pitcher, Trevor E; Politis, Sebastian Nikitas; Butts, Ian Anthony Ernest

2017-05-01

Paternal, compared to maternal, contributions were believed to have only a limited influence on embryonic development and larval fitness traits in fishes. Therefore, the perspective of male influence on early life history traits has come under scrutiny. This study was conducted to determine parental effects on the rate of eyed embryos of Ide Leuciscus idus and Northern pike Esox lucius. Five sires and five dams from each species were crossed using a quantitative genetic breeding design and the resulting 25 sib groups of each species were reared to the embryonic eyed stage. We then partition variation in embryonic phenotypic performance to maternal, paternal, and parental interactions using the Restricted Maximum Likelihood (REML) model. Results showed that paternal, maternal, and the paternal×maternal interaction terms were highly significant for both species; clearly demonstrating that certain family combinations were more compatible than others. Paternal effects explained 20.24% of the total variance, which was 2-fold higher than the maternal effects (10.73%) in Ide, while paternal effects explained 18.9% of the total variance, which was 15-fold higher than the maternal effects (1.3%) in Northern pike. Together, these results indicate that male effects are of major importance during embryonic development for these species. Furthermore, this study demonstrates that genetic compatibility between sires and dams plays an important role and needs to be taken into consideration for reproduction of these and likely other economically important fish species. Copyright © 2016 Elsevier Inc. All rights reserved.

[Is there an essence of caring? A core of Nursing? Criticism of Katie Erikssons' "Vårdandets ide"].

PubMed

Nielsen, G; Larsen, B

1989-01-01

In her book "Vårdandets Ide" the Finnish nurse, Katie Eriksson puts forward the thesis, that all kind af caring activities do have a common core. To establish this thesis professor Eriksson introduces the Aristotelian notion of an essence: Different kinds of caring activities do have a common set of essential properties constituting the act of caring. In this article we submit a thesis to the contrary: There may exist no set of essential properties common to all kind of caring activities: The belief is induced in us, that there may exist some common core to all caring activities, because the same term, namely "caring", is being used as a general term to cover a wide field of very different kinds of activities. Instead of the traditional Aristotelian craving for generality issuing in the notion of an essence, we suggest the use of the more modern Wittgensteinian concept of a family resemblance: There may be no common core but a set of family resemblances among the different kinds of caring activities. Instead of an abstract philosophical search for the common core of caring activities, we propose nurses to look at the actual use of the term "to care", thereby circumscribing the subject matter of caring. It goes without saying, that this article contains a good deal of philosophical arguments including, of course, an introduction to some basic Aristotelian notions, fundamental distinctions in the theory of definition, and finally the Wittgensteinian concept of family resemblance.

Long-term Clinical Outcomes of Cervical Disc Arthroplasty: A Prospective, Randomized, Controlled Trial.

PubMed

Sasso, Willa R; Smucker, Joseph D; Sasso, Maria P; Sasso, Rick C

2017-02-15

Prospective, randomized, single-center, clinical trial. To prospectively examine the 7- and 10-year outcomes of cervical arthroplasty to anterior cervical discectomy and fusion (ACDF). Degeneration of the cervical discs causing radiculopathy is a frequent source of surgical intervention, commonly treated with ACDF. Positive clinical outcomes are associated with arthrodesis techniques, yet there remains a long-term concern for adjacent segment change. Cervical disc arthroplasty has been designed to mitigate some of the challenges associated with arthrodesis whereas providing for a similar positive neurological outcome. As data has been collected from numerous prospective US FDA IDE trials, longer term outcomes regarding adjacent segment change may be examined. As part of an FDA IDE trial, a single center collected prospective outcomes data on 47 patients randomized in a 1:1 ratio to ACDF or arthroplasty. Success of both surgical interventions remained high at the 10-year interval. Both arthrodesis and arthroplasty demonstrated statistically significant improvements in neck disability index, visual analog scale neck and arm pain scores at all intervals including 7- and 10-year periods. Arthroplasty demonstrated an advantage in comparison to arthrodesis as measured by final 10-year NDI score (8 vs. 16, P = 0.0485). Patients requiring reoperation were higher in number in the arthrodesis cohort (32%) in comparison with arthroplasty (9%) (P = 0.055). At 7 and 10 years, cervical arthroplasty compares favorably with ACDF as defined by standard outcomes scores in a highly selected population with radiculopathy. 1.

Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons

PubMed Central

RODRIGUEZ, Jesse S.; ZÜRCHER, Nicole R.; KEENAN, Kathryn E.; BARTLETT, Thad Q.; NATHANIELSZ, Peter W.; NIJLAND, Mark J.

2011-01-01

Objective We investigated effects of three weekly courses of fetal betamethasone (βM) exposure on motivation and cognition in juvenile baboon offspring utilizing the Cambridge Neuropsychological Test Automated Battery. Study design Pregnant baboons (Papio sp.) received two injections of saline control (C) or 175 μg/kg βM 24h apart at 0.6, 0.65 and 0.7 gestation. Offspring [Female (FC), n = 7 and Male (MC), n = 6; Female (FβM), n = 7 and Male (MβM), n = 5] were studied at 2.6–3.2 years with a progressive ratio test for motivation, simple discriminations (SD) and reversals (SR) for associative learning and rule change plasticity, and an intra-dimensional/extra-dimensional (IDED) set-shifting test for attention allocation. Results βM exposure decreased motivation in both sexes. In IDED testing, FβM made more errors in the SR [mean difference of errors (FβM minus MβM) = 20.2 ± 9.9; P≤0.05], compound discrimination [mean difference of errors = 36.3 ± 17.4; P≤0.05] and compound reversal [mean difference of errors = 58 ± 23.6; P<0.05] stages as compared to the MβM offspring. Conclusion This central nervous system developmental programming adds growing concerns of long-term effects of repeated fetal synthetic glucocorticoid exposure. In summary, behavioral effects observed show sex specific differences in resilience to multiple fetal βM exposures. PMID:21411054

Duck hepatitis B virus covalently closed circular DNA appears to survive hepatocyte mitosis in the growing liver

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

Reaiche-Miller, Georget Y.; Thorpe, Michael; Low, Huey Chi

Nucleos(t)ide analogues that inhibit hepatitis B virus (HBV) DNA replication are typically used as monotherapy for chronically infected patients. Treatment with a nucleos(t)ide analogue eliminates most HBV DNA replication intermediates and produces a gradual decline in levels of covalently closed circular DNA (cccDNA), the template for viral RNA synthesis. It remains uncertain if levels of cccDNA decline primarily through hepatocyte death, or if loss also occurs during hepatocyte mitosis. To determine if cccDNA survives mitosis, growing ducklings infected with duck hepatitis B virus (DHBV) were treated with the nucleoside analogue, Entecavir. Viremia was suppressed at least 10{sup 5}-fold, during amore » period when average liver mass increased 23-fold. Analysis of the data suggested that if cccDNA synthesis was completely inhibited, at least 49% of cccDNA survived hepatocyte mitosis. However, there was a large duck-to-duck variation in cccDNA levels, suggesting that low level cccDNA synthesis may contribute to this apparent survival through mitosis. - Highlights: • The hepatitis B virus nuclear template is covalently closed circular DNA (cccDNA). • cccDNA was studied during liver growth in duck hepatitis B virus infected ducks. • Virus DNA replication and new cccDNA synthesis were inhibited with Entecavir. • At least 49% of cccDNA appeared to survive hepatocyte mitosis. • Low level virus DNA synthesis may contribute to survival of cccDNA through mitosis.« less

A meta-analysis of comparative outcomes following cervical arthroplasty or anterior cervical fusion: results from 4 prospective multicenter randomized clinical trials and up to 1226 patients.

PubMed

McAfee, Paul C; Reah, Chris; Gilder, Kye; Eisermann, Lukas; Cunningham, Bryan

2012-05-15

Meta-analysis of 4 prospective randomized controlled Food and Drug Administration (FDA) Investigational Device Exemption (IDE) clinical trials. To maximize the information available from 4 IDE studies by analyzing the combined outcomes of cervical arthroplasty versus fusion at 24-month follow-up. To date, 4 randomized clinical trials have been completed in the United States under FDA IDE protocols to study cervical arthroplasty. Each trial reported arthroplasty to be at least as successful as fusion controls based on noninferiority trial designs. However, sample sizes in any given trial may not be sufficient to demonstrate superiority of treatment effect. Meta-analysis enables pooling of results from comparable trials, which may lead to more precise and statistically significant estimates of treatment effect. Four cervical arthroplasty randomized clinical trials with comparable enrollment criteria and outcome measures were conducted independently by 3 separate sponsors to study the following devices: Bryan, Prestige, ProDisc-C, and PCM cervical disc replacements. A total of 1608 patients were treated across 98 investigative sites. Data were available for 1352 treated patients, of which 1226 were evaluable at 24 months. Assessments included clinical success definitions based on neck disability index, maintenance or improvement of neurological status, subsequent surgery or intervention at the index level (survivorship), and a composite score comprising these as well as serious device-related adverse events. Trial endpoint comparisons were made at 24 months postoperatively. For each endpoint, a random-effects meta-analysis was performed to compare the success rates of cervical arthroplasty with anterior cervical discectomy and fusion (ACDF). Also, supportive frequentist and bayesian analyses were performed. The pooled primary overall success results indicated a statistically significant treatment effect favoring arthroplasty compared with ACDF. Overall success was achieved by 77.6% of the arthroplasty patients and by 70.8% of the ACDF patients (pooled odds ratio [OR]: 0.699, 95% confidence interval [CI]: 0.539-0.908, P = 0.007). The results of the individual subcomponent meta-analyses, all of which favored arthroplasty, were neck disability index success (OR: 0.786, 95% CI: 0.589-1.050, P = 0.103), neurological status (OR: 0.552, 95% CI: 0.364-0.835, P = 0.005), and survivorship (OR: 0.510, 95% CI: 0.275-0.946, P = 0.033). Only the survivorship endpoint suggested low heterogeneity. These findings suggest that cervical arthroplasty is superior to ACDF in overall success, neurological success, and survivorship outcomes at 24 months postoperatively.

Long term microparticle impact fluxes on LDEF determined from optical survey of Interplanetary Dust Experiment (IDE) sensors

NASA Technical Reports Server (NTRS)

Simon, C. G.; Oliver, J. P.; Cooke, W. J.; Downey, K. I.; Kassel, P. C.

1995-01-01

Many of the IDE metal-oxide-silicon (MOS) capacitor-discharge impact sensors remained active during the entire Long Duration Exposure Facility (LDEF) mission. An optical survey of impact sites on the active surfaces of these sensors has been extended to include all sensors from the low-flux sides of LDEF (i.e. the west or trailing side, the earth end, and the space end) and 5-7 active sensors from each LDEF's high-flux sides (i.e. the east or leading side, the south side, and the north side). This survey was facilitated by the presence of a relatively large (greater than 50 micron diameter) optical signature associated with each impact site on the active sensor surfaces. Of the approximately 4700 impacts in the optical survey data set, 84% were from particles in the 0.5 to 3 micron size range. An estimate of the total number of hypervelocity impacts on LDEF from particles greater than 0.5 micron diameter yields a value of approximately 7 x 10(exp 6). Impact feature dimensions for several dozen large craters on MOS sensors and germanium witness plates are also presented. Impact fluxes calculated from the IDE survey data closely matched surveys of similar size impacts (greater than or equal to 3 micron diameter craters in Al, or marginal penetrations of a 2.4 micron thick Al foil) by other LDEF investigators. Since the first year IDE data were electronically recorded, the flux data could be divided into three long term time periods: the first year, the entire 5.8 year mission, and the intervening 4.8 years (by difference). The IDE data show that there was an order of magnitude decrease in the long term microparticle impact flux on the trailing side of LDEF, from 1.01 to 0.098 x 10(exp -4) m(exp 2)/s, from the first year in orbit compared to years 2-6. The long term flux on the leading edge showed an increase from 8.6 to 11.2 x 10(exp -4) m(exp -2)/s over this same time period. (Short term flux increases up to 10,000 times the background rate were recorded on the leading side during LDEF's first year in orbit.) The overall east/west ratio was 44, but during LDEF's first year in orbit the ratio was 8.5, and during years 2-6 the ratio was 114. Long term microparticle impact fluxes on the space end decreased from 1.12 to 0.55 x 10(exp -4) m(exp -2)/s from the first year in orbit compared to years 2-6. The earth end showed the opposite trend with an increase from 0.16 to 0.38 x 10(exp -4) m(exp -2)/s. Fluxes on rows 6 and 12 decreased from 6.1 to 3.4 and 6.7 to 3.7 x 10(exp -4) m(exp -2)/s, respectively, over the same time periods. This resulted in space/earth microparticle impact flux ratios of 7.1 during the first year and 1.5 during years 2-6, while the south/north, space/north and space/south ratios remained constant at 1.1, 0.16 and 0.17, respectively, during the entire mission. This information indicates the possible identification of long term changes in discrete microparticle orbital debris component contributions to the total impact flux experienced by LDEF. A dramatic decrease in the debris population capable of striking the trailing side was detected that could possibly be attributed to the hiatus of western launch activity experienced from 1986-1989. A significant increase in the debris population that preferentially struck the leading side was also observed and could possibly be attributed to a single breakup event that occurred in September of 1986. A substantial increase in the microparticle debris population that struck the earth end of LDEF, but not the space end, was also detected and could possibly be the result of a single breakup event at low altitude. These results point to the importance of including discrete orbital debris component contribution changes in flux models in order to achieve accurate predictions of the microparticle environment that a particular spacecraft will experience in earth orbit. The only reliable, verified empirical measurements of these changes are reported in this paper. Further time-resolved in-situ measurements of these debris populations are needed to accurately assess model predictions and mitigation practices.

Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver

PubMed Central

Nakabori, Tasuku; Hikita, Hayato; Murai, Kazuhiro; Nozaki, Yasutoshi; Kai, Yugo; Makino, Yuki; Saito, Yoshinobu; Tanaka, Satoshi; Wada, Hiroshi; Eguchi, Hidetoshi; Takahashi, Takeshi; Suemizu, Hiroshi; Sakamori, Ryotaro; Hiramatsu, Naoki; Tatsumi, Tomohide; Takehara, Tetsuo

2016-01-01

Sodium taurocholate cotransporting polypeptide (NTCP) is a recently discovered hepatitis B virus (HBV) receptor. In the present study, we used TK-NOG mice with a humanized liver to examine the impact of endogenous NTCP expression on HBV infection. Upon inoculation with HBV, these mice exhibited clear viremia in 2 weeks, and serum HBV DNA levels gradually increased. The frequency of HBsAg-positive hepatocytes in the liver was 5.1 ± 0.6% at 2 weeks and increased with increasing HBV DNA levels, reaching 92.9 ± 2.8% at 10 to 12 weeks. In vivo siRNA-mediated NTCP knockdown before and after HBV inoculation significantly suppressed the levels of HBV replication and the frequency of HBsAg-positive hepatocytes at 2 weeks, whereas NTCP knockdown 13 weeks after infection did not affect these parameters. Similar to the humanized mouse livers in the early phase of HBV infection, human liver samples from chronic hepatitis B patients, especially those treated with nucleos(t)ide analogues, contained a considerable number of hepatocytes that were negative for the anti-HBs antibody. In conclusion, NTCP inhibition prevents the spread of HBV-infected hepatocytes in mice with a humanized liver. NTCP-targeted therapy has potential for regulating HBV infection in patients with chronic hepatitis B. PMID:27278060

Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP).

PubMed

Watashi, Koichi; Sluder, Ann; Daito, Takuji; Matsunaga, Satoko; Ryo, Akihide; Nagamori, Shushi; Iwamoto, Masashi; Nakajima, Syo; Tsukuda, Senko; Borroto-Esoda, Katyna; Sugiyama, Masaya; Tanaka, Yasuhito; Kanai, Yoshikatsu; Kusuhara, Hiroyuki; Mizokami, Masashi; Wakita, Takaji

2014-05-01

Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration <0.2 μM. This study provides a proof of concept for the novel strategy to identify anti-HBV agents by targeting the candidate HBV receptor, NTCP, using CsA as a structural platform. Copyright © 2014 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases.

A Rapid Dot Immunoassay for the Detection of Serum Antibodies to Eastern Equine Encephalomyelitis and Saint Louis Encephalitis Viruses in Sentinel Chickens

DTIC Science & Technology

1988-01-01

tion inhibition (HI) tests .6 uses a novel membrane, polyvinylydine difluor- EEE and SLE viruses are significant public ide (PVDF), and yields a...only 3 aged values between the two tests (Fig. 3). Vari- of 6 SLE virus-inoculated birds developed an- ability in EIA titer was observed with samples... SLE samples negative by EIA were location. Four serum samples from each of 3 also negative by DotIA. EEE-positive chickens were tested by EIA and A

Design for Flood Control, Wave Protection, and Prevention of Shoaling, Rogue River, Oregon. Hydraulic Model Investigation.

DTIC Science & Technology

1982-08-01

Gold Beach docks; a turning basin 10 ft deep, 150 ft wide, and 600 ft long adjacent to the decks; and revetment on the north bank extending approximately...jetty. A ga was left in thetbroan or to ft lde sctaW to arbor fatt.itie. 4. bsrye pPbla oaists beftten the logu River Ij4ties; slag 1 ide 4 f 0 south... revetments are also rubble-mound structures. Experience and experimental research have shown that considerable wave energy passes through the

Software Acquisition in the Age of Cyber Warfare

DTIC Science & Technology

2011-05-01

s c h o o l o f S Y S T E M S a n d L O G I S T I C S education service research Software Acquisition in the Age of Cyber Warfare Maj...DATE MAY 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Software Acquisition in the Age of Cyber Warfare 5a...AFIT Cyber 200/300 Courses Cyber Warfare IDE Program 34 Special Emphasis On… Enterprise Integration (Active Directory, PKI) Security

Proceedings of the NRDEC (Natick RD&E Center) Science Symposium Held on 2-4 June 1986 in Natick, Massachusetts. Volume 1

DTIC Science & Technology

1986-06-04

turbulence as a means of increasing the external heat transfer coefficient. To evaluate the various evaporator des igns, each evaporator in turn was plumbed...water was pumped through the i ns ide surface while air flowed around t he outs i de . The amount of heat being transferred could be calculated by...intercept, (infinite wate r flow), the inside heat transfer coefficient can be de termined. The heat transfer res istances of the evaporator material

76 FR 36542 - Draft Guidance for Industry and Food and Drug Administration Staff: The Content of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

...The Food and Drug Administration (FDA) is announcing the availability of the draft guidance document entitled ``Draft Guidance for Industry and Food and Drug Administration Staff: The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Low Glucose Suspend (LGS) Device Systems.'' This draft guidance document provides industry and Agency staff with recommendations that are intended to improve the safety and effectiveness of LGS Device Systems. This draft guidance is not final nor is it in effect at this time.

Lassa Fever Immune Plasma

DTIC Science & Technology

1988-07-31

cases are likely to be seen. Finally, further studies into the nature of the virus or viruses of LF are needed. Clinical experience suggests that there...OF ReIPRIt r ~M. u iav Is. PAGE COUNT Annual Rpnnrt T FROM 1,.1IR7 j ,O 30 lunB 88-7-31 22 1. SUPPUMENTARY NOTATION 17. COSATI CODES 10. SUSJECT...TERMS (Connimm on nwmw ,o neceiawt &W ide I No& num IELD IGROUP suS.GROUP Lassa fever Immunotherapy RA 1 06 1) 6 LLassa virus Liberia nf i Pl,:m haiman 19

[The role of free-radical oхidation for patogenesis of chronic generalization periodontitis in elderly age patients].

PubMed

Pinelis, Y I; Malezhik, M S; Malezhik, L P

2017-01-01

In old aged patients with chronic generalized periodontitis and cardiovascular diseases the level lipoperoxidation increased and antioхidation protection decreased in saliva and blood. After the course of treatment myocardial ischemia and diseases chronic periodontal inflammation the level of lipoperoхidation was changed insignificant accompanied with decreased of TBK-active substance in saliva and blood. Change of nitric oхide after by treatment was depended it initial level before treatment and often had an opposite orientation.

Towards a Framework for Generating Tests to Satisfy Complex Code Coverage in Java Pathfinder

NASA Technical Reports Server (NTRS)

Staats, Matt

2009-01-01

We present work on a prototype tool based on the JavaPathfinder (JPF) model checker for automatically generating tests satisfying the MC/DC code coverage criterion. Using the Eclipse IDE, developers and testers can quickly instrument Java source code with JPF annotations covering all MC/DC coverage obligations, and JPF can then be used to automatically generate tests that satisfy these obligations. The prototype extension to JPF enables various tasks useful in automatic test generation to be performed, such as test suite reduction and execution of generated tests.

Cultural Resources Survey at Historical Kaskaskia and Selected Portions of the Upper Mississippi River Shoreline from Miles 115.9 to 272.9, Illinois and Missouri.

DTIC Science & Technology

1985-04-01

Resources Group, Ltd. AREA & WORK UNIT NUMBERS 127 N. Washington Avenue Carbondale, Illinois 62901 11. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT...Ice President, and Mr. Keith Govro, Head, Ecology Department, provided assistance in the areas of project administration and fileld logistics. - The... area w as pr ov Ided by Mr. Her b Mey er, U niv er sity Photocomm un Icat Ion s, Southern Ill inois University. Mr. Meyer also contributed results of

Subsurface Conditions at Site 16 Lone Star Army Ammunition Plant, Texas

DTIC Science & Technology

1989-04-01

fully acceptable or appropriate. . . 35 . The intercepts of three st-faces with borings were analyzed to establish any inclinatio- fot comparison to...conspicuously steeper slope. 38. In descending southeastward, the ground water loses more than 13 ft of head in a horizontal distance of only about 35 ft...Extractables CLSS13*6- Vol. organic 24 CLSS13*5-N Metals 6.3 90 26 35 -7 CLSS 13*5-S Sulf ides CLSS13*5-MS Extractables CLSS13*5- Vol. organic 25 CLSS13*4-N

A Literature Review-Problem Definition Studies on Selected Toxic Chemicals. Volume 1. Occupational Health and Safety Aspects of Diesel Fuel and White Smoke Generated from It

DTIC Science & Technology

1978-04-01

properties heating oil :mammalian toxicity sampling ABSTRACT (Cotthum an to~" aid* if neoe...m mE ide .Ids bp block ,ninborj Literature is reviewed (75...mutations. Diesel fuel may be excreted from the body in the urine , or exhaled from the lungs. Persons who may be exposed to diesel fuel white smoke should be...37 VIII. Carcinogenicity, Mutagenicity, Teratogenicity 42 IX. Industrial Hygiene Practices and Standards 43 X. Sampling and Analytic Techniques 45

Advanced Operational Aviation Medicine Course (6th), Held at Centre de Medecine Aeronautique, Brussels, Belgium, 24-28 March 1980,

DTIC Science & Technology

1981-05-01

accolk au 10 bruit, decrescendo et laisse libre la miso et la tilisystole. 2) les souffles cardiopulsaonaires (souffle de Potaist) rencontris plus...climicion do so faire rapidement une id~e de Is diatensibilitL6 dui sya-A tome artLriel. IV - ZTUD88 CHROI0CARDIOGUAPIQLMS Pilque lea intervallos dui...nombro do trois, continuant d’atno pratiqudost .Lo test do Maator, Il consist. A fairs gravir A une cadence doonnd in scabeau do doux marches pendant

Continuous Non-Destructive Monitoring of Cell Health Using Impedance Based Interdigitated Electrode Structured Sensors

NASA Astrophysics Data System (ADS)

Paschero, Anna; McLoughlin, Eve; Moore, Eric

2011-06-01

This article examines some preliminary tests which were performed in order to evaluate the best electrode configuration (width and spacing) for cell culture analyses. Biochips packaged with indium tin oxide (ITO) interdigitated electrodes (IDEs) were used to perform impedance measurements on A549 cells cultured on the surface of the biochip. Several tests were carried out using a 10 mM solution of Sodium Chloride (NaCl), cell medium and the cell culture itself to characterize some of the configurations already fabricated in the facilities at Tyndall National Institute.

An Image Segmentation System Based on Thresholding.

DTIC Science & Technology

1978-12-01

referred to as tuoe gjj~ j flj t~zoe ~~~ errg r~ res p e c t i v e l y . Examples of these errors are provided in F ig ure 2 This figure also shows a...h it’ . IV& ’ I’~ I~~ t ’ dl St~ flt~ C t ~ t he ide ~ td ~ a’.’ en t p1 xe I i 0 0 ~ r ~ - c ~~ dI~ + ~~ — 2 I I~ r dr ~~ o — O r* . - ’ 0 — 0

Measurement of Radiative Surface Properties for Use of the Infrared Scanning Camera

DTIC Science & Technology

1976-02-01

i p t (ARO Contro l No. ARO-VKF-TR-75-91) was submit ted fo r publ ica t ion on June 24, 1975. AEDC-TR-76-11 CONTENTS 1.0 2.0 3.0 4.0...with a ca l c ium f luor ide (CaF2) p r i s m and is a s i n g l e - p a s s i n s t rumen t . The wavelength v e r s u s d r u m number ca l

Scandia-Stabilized Zirconia Coating for Composites.

DTIC Science & Technology

1990-04-03

are present as oxides, acids and as in U.S. Pat. No. 4,328,285, describes some of the prior free sulfur . art attempts to coat engine parts with ceramic...base Because vanadium pentoxide (V205 ) is an acidic ox- materials, and Siemers teaches using cerium oxide or ide, it reacts with Na2O (a highly...surfaces exposed to vanadium and compounds decreases with the V2Os/Na2O ratio from sulfur compound corrosion. Na2V 120 31 (most acidic ) to Na3VO4(least

Research on conceptual/innovative design for the life cycle

NASA Technical Reports Server (NTRS)

Cagan, Jonathan; Agogino, Alice M.

1990-01-01

The goal of this research is developing and integrating qualitative and quantitative methods for life cycle design. The definition of the problem includes formal computer-based methods limited to final detailing stages of design; CAD data bases do not capture design intent or design history; and life cycle issues were ignored during early stages of design. Viewgraphs outline research in conceptual design; the SYMON (SYmbolic MONotonicity analyzer) algorithm; multistart vector quantization optimization algorithm; intelligent manufacturing: IDES - Influence Diagram Architecture; and 1st PRINCE (FIRST PRINciple Computational Evaluator).

LDEF- 69 Months in Space. Second Post-Retrieval Symposium, Part 2

DTIC Science & Technology

1992-06-01

is the crater diameter at the foil surface. While no 5.77 year flux data is available for the IDE 0.4 gtm MOS sensors (due to power loss ), a first...velocity each ray with given direction and velocity is then weighted by a factor: k = v2 v*) with : v* = (v - V2sin 2 a)0. where v is the impact...space debris. This relative weight is the same for any debris size. Penetration Analysis To calculate the number of holes in the blankets a design or

Age-related energy values of bakery meal for broiler chickens determined using the regression method.

PubMed

Stefanello, C; Vieira, S L; Xue, P; Ajuwon, K M; Adeola, O

2016-07-01

A study was conducted to determine the ileal digestible energy (IDE), ME, and MEn contents of bakery meal using the regression method and to evaluate whether the energy values are age-dependent in broiler chickens from zero to 21 d post hatching. Seven hundred and eighty male Ross 708 chicks were fed 3 experimental diets in which bakery meal was incorporated into a corn-soybean meal-based reference diet at zero, 100, or 200 g/kg by replacing the energy-yielding ingredients. A 3 × 3 factorial arrangement of 3 ages (1, 2, or 3 wk) and 3 dietary bakery meal levels were used. Birds were fed the same experimental diets in these 3 evaluated ages. Birds were grouped by weight into 10 replicates per treatment in a randomized complete block design. Apparent ileal digestibility and total tract retention of DM, N, and energy were calculated. Expression of mucin (MUC2), sodium-dependent phosphate transporter (NaPi-IIb), solute carrier family 7 (cationic amino acid transporter, Y(+) system, SLC7A2), glucose (GLUT2), and sodium-glucose linked transporter (SGLT1) genes were measured at each age in the jejunum by real-time PCR. Addition of bakery meal to the reference diet resulted in a linear decrease in retention of DM, N, and energy, and a quadratic reduction (P < 0.05) in N retention and ME. There was a linear increase in DM, N, and energy as birds' ages increased from 1 to 3 wk. Dietary bakery meal did not affect jejunal gene expression. Expression of genes encoding MUC2, NaPi-IIb, and SLC7A2 linearly increased (P < 0.05) with age. Regression-derived MEn of bakery meal linearly increased (P < 0.05) as the age of birds increased, with values of 2,710, 2,820, and 2,923 kcal/kg DM for 1, 2, and 3 wk, respectively. Based on these results, utilization of energy and nitrogen in the basal diet decreased when bakery meal was included and increased with age of broiler chickens. © 2016 Poultry Science Association Inc.

Impact of the INBRE summer student mentored research program on undergraduate students in Arkansas.

PubMed

McSweeney, Jean C; Hudson, Teresa J; Prince, Latrina; Beneš, Helen; Tackett, Alan J; Miller Robinson, Caroline; Koeppe, Roger; Cornett, Lawrence E

2018-03-01

The Institutional Development Award (IDeA) program, housed within the National Institute for General Medical Sciences, administers the Networks of Biomedical Research Excellence (INBRE) as a strategic mission to broaden the geographic distribution of National Institutes of Health (NIH) funding within the United States. Undergraduate summer student mentored research programs (SSMRP) are a common feature of INBRE programs and are designed to increase undergraduate student interest in research careers in the biomedical sciences. Little information is available about student perspectives on how these programs impact their choices relative to education and careers. Therefore, we conducted qualitative interviews with 20 participants from the Arkansas INBRE SSMRP in the years 2002-2012. Each telephone interview lasted 30-45 min. An interview guide with a broad "grand tour" question was used to elicit student perspectives on SSMRP participation. Interviews were digitally recorded, then transcribed verbatim, and the transcript checked for accuracy. Content analysis and constant comparison were used to identify nine themes that were grouped into three temporal categories: before, during, and after the SSMRP experience. Students viewed the experience as positive and felt it impacted their career choices. They emphasized the value of mentoring in the program, and some reported maintaining a relationship with the mentor after the summer experience ended. Students also valued learning new laboratory and presentation skills and felt their research experience was enhanced by meeting students and scientists with a wide range of career interests. These data suggest that the Arkansas INBRE and the NIH IDeA program are successfully meeting the goal of increasing interest in research among undergraduates.

Nanomolecular gas sensor architectures based on functionalized carbon nanotubes for vapor detection

NASA Astrophysics Data System (ADS)

Hines, Deon; Zhang, Henan; Rümmeli, Mark H.; Adebimpe, David; Akins, Daniel L.

2015-05-01

There is enormous interest in detection of simple & complex odors by mean of electronic instrumentation. Specifically, our work focuses on creating derivatized-nanotube-based "electronic noses" for the detection and identification of gases, and other materials. We have grafted single-walled carbon nanotubes (SWNTs) with an array of electron-donating and electron withdrawing moieties and have characterized some of the physicochemical properties of the modified nanotubes. Gas sensing elements have been fabricated by spin coating the functionalized nanotubes onto interdigitated electrodes (IDE's), creating an array of sensors. Each element in the sensor array can contain a different functionalized matrix. This facilitates the construction of chemical sensor arrays with high selectivity and sensitivity; a methodology that mimics the mammalian olfactory system. Exposure of these coated IDEs to organic vapors and the successful classification of the data obtained under DC monitoring, indicate that the system can function as gas sensors of high repeatability and selectivity for a wide range of common analytes. Since the detection of explosive materials is also of concern in this research, our next phase focuses on explosives such as, TNT, RDX, and Triacetone Triperoxide (TATP). Sensor data from individual detection are assessed on their own individual merits, after which they are amalgamated and reclassified to present each vapor as unique data point on a 2-dimensional map and with minimum loss of information. This approach can assist the nation's need for a technology to defeat IEDs through the use of methods that detect unique chemical signatures associated with explosive molecules and byproducts.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

PubMed

Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

2016-01-01

Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Mercury, Fatty Acids Content and Lipid Quality Indexes in Muscles of Freshwater and Marine Fish on the Polish Market. Risk Assessment of Fish Consumption.

PubMed

Łuczyńska, Joanna; Paszczyk, Beata; Nowosad, Joanna; Łuczyński, Marek Jan

2017-09-25

Mercury content and fatty acids in muscles of Perca fluviatilis L. (European perch), Leuciscus idus L. (ide), Cyprinus carpio L. (European or common carp), Oncorhynchus mykiss Walb. (rainbow trout), Platichthys flesus L. (European flounder). and Clupea harengus L. (bream) from the Polish market were investigated. The total mercury was processed with AAS. The fatty acids were analyzed by gas chromatography. The concentration of mercury in muscles varied from 0.006 to 0.138 mg/kg and decreased as follows: perch ≈ ide > flounder > herring ≈ bream ≈ rainbow trout > carp ( p ≤ 0.05). There were only significant positive correlations between body weight and mercury content in muscle tissue of carp (r = 0.878), flounder (r = 0.925) and herring (r = 0.982) ( p ≤ 0.05). The atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were calculated as follows 0.33-0.70 (IA), 0.16-0.31 (IT) and 13.01-33.22 (FLQ). Hypocholesterolemic (OFA) and hypercholesterolemic fatty acids (DFA) in muscles of fish ranged from 18.26 to 23.01 and from 73.91 to 78.46, respectively. In most cases, there were not significant correlations between size (body weight and total length) and fatty acids in the muscles of the examined fish ( p > 0.05). The Target Hazard Quotient (THQ) values were below 1, which shows that there is no non-carcinogenic health risk to the consumer by consuming the examined fish.

A MAGNIFIED GLANCE INTO THE DARK SECTOR: PROBING COSMOLOGICAL MODELS WITH STRONG LENSING IN A1689

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

Magaña, Juan; Motta, V.; Cárdenas, Victor H.

2015-11-01

In this paper we constrain four alternative models to the late cosmic acceleration in the universe: Chevallier–Polarski–Linder (CPL), interacting dark energy (IDE), Ricci holographic dark energy (HDE), and modified polytropic Cardassian (MPC). Strong lensing (SL) images of background galaxies produced by the galaxy cluster Abell 1689 are used to test these models. To perform this analysis we modify the LENSTOOL lens modeling code. The value added by this probe is compared with other complementary probes: Type Ia supernovae (SN Ia), baryon acoustic oscillations (BAO), and cosmic microwave background (CMB). We found that the CPL constraints obtained for the SL datamore » are consistent with those estimated using the other probes. The IDE constraints are consistent with the complementary bounds only if large errors in the SL measurements are considered. The Ricci HDE and MPC constraints are weak, but they are similar to the BAO, SN Ia, and CMB estimations. We also compute the figure of merit as a tool to quantify the goodness of fit of the data. Our results suggest that the SL method provides statistically significant constraints on the CPL parameters but is weak for those of the other models. Finally, we show that the use of the SL measurements in galaxy clusters is a promising and powerful technique to constrain cosmological models. The advantage of this method is that cosmological parameters are estimated by modeling the SL features for each underlying cosmology. These estimations could be further improved by SL constraints coming from other galaxy clusters.« less

Mercury, Fatty Acids Content and Lipid Quality Indexes in Muscles of Freshwater and Marine Fish on the Polish Market. Risk Assessment of Fish Consumption

PubMed Central

Łuczyńska, Joanna; Paszczyk, Beata; Nowosad, Joanna; Łuczyński, Marek Jan

2017-01-01

Mercury content and fatty acids in muscles of Perca fluviatilis L. (European perch), Leuciscus idus L. (ide), Cyprinus carpio L. (European or common carp), Oncorhynchus mykiss Walb. (rainbow trout), Platichthys flesus L. (European flounder). and Clupea harengus L. (bream) from the Polish market were investigated. The total mercury was processed with AAS. The fatty acids were analyzed by gas chromatography. The concentration of mercury in muscles varied from 0.006 to 0.138 mg/kg and decreased as follows: perch ≈ ide > flounder > herring ≈ bream ≈ rainbow trout > carp (p ≤ 0.05). There were only significant positive correlations between body weight and mercury content in muscle tissue of carp (r = 0.878), flounder (r = 0.925) and herring (r = 0.982) (p ≤ 0.05). The atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were calculated as follows 0.33–0.70 (IA), 0.16–0.31 (IT) and 13.01–33.22 (FLQ). Hypocholesterolemic (OFA) and hypercholesterolemic fatty acids (DFA) in muscles of fish ranged from 18.26 to 23.01 and from 73.91 to 78.46, respectively. In most cases, there were not significant correlations between size (body weight and total length) and fatty acids in the muscles of the examined fish (p > 0.05). The Target Hazard Quotient (THQ) values were below 1, which shows that there is no non-carcinogenic health risk to the consumer by consuming the examined fish. PMID:28946712

Neuropsychological and hypothalamic-pituitary-axis function in female patients with melancholic and non-melancholic depression.

PubMed

Michopoulos, Ioannis; Zervas, Iannis M; Pantelis, Chris; Tsaltas, Eleftheria; Papakosta, Vassiliki-Maria; Boufidou, Fotini; Nikolaou, Chrissoula; Papageorgiou, Charalambos; Soldatos, Costas R; Lykouras, Lefteris

2008-06-01

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

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

Song, Jun; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX; Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX

2010-02-26

Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4)more » which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.« less

ZnO Nanoparticles/Reduced Graphene Oxide Bilayer Thin Films for Improved NH3-Sensing Performances at Room Temperature

NASA Astrophysics Data System (ADS)

Tai, Huiling; Yuan, Zhen; Zheng, Weijian; Ye, Zongbiao; Liu, Chunhua; Du, Xiaosong

2016-03-01

ZnO nanoparticles and graphene oxide (GO) thin film were deposited on gold interdigital electrodes (IDEs) in sequence via simple spraying process, which was further restored to ZnO/reduced graphene oxide (rGO) bilayer thin film by the thermal reduction treatment and employed for ammonia (NH3) detection at room temperature. rGO was identified by UV-vis absorption spectra and X-ray photoelectron spectroscope (XPS) analyses, and the adhesion between ZnO nanoparticles and rGO nanosheets might also be formed. The NH3-sensing performances of pure rGO film and ZnO/rGO bilayer films with different sprayed GO amounts were compared. The results showed that ZnO/rGO film sensors exhibited enhanced response properties, and the optimal GO amount of 1.5 ml was achieved. Furthermore, the optimal ZnO/rGO film sensor showed an excellent reversibility and fast response/recovery rate within the detection range of 10-50 ppm. Meanwhile, the sensor also displayed good repeatability and selectivity to NH3. However, the interference of water molecules on the prepared sensor is non-ignorable; some techniques should be researched to eliminate the effect of moisture in the further work. The remarkably enhanced NH3-sensing characteristics were speculated to be attributed to both the supporting role of ZnO nanoparticles film and accumulation heterojunction at the interface between ZnO and rGO. Thus, the proposed ZnO/rGO bilayer thin film sensor might give a promise for high-performance NH3-sensing applications.

Active control of structures using macro-fiber composite (MFC)

NASA Astrophysics Data System (ADS)

Kovalovs, A.; Barkanov, E.; Gluhihs, S.

2007-12-01

This paper presents the use of macro-fiber composites (MFC) for vibration reduces of structures. The MFC consist of polyimid films with IDE-electrodes that are glued on the top and the bottom of rectangular piezoceramic fibers. The interdigitated electrodes deliver the electric field required to activate the piezoelectric effect in the fibers and allows to invoke the stronger longitudinal piezoelectric effect along the length of the fibers. When this actuator embedded in a surface or attached to flexible structures, the MFC actuator provides distributed solid-state deflection and vibration control. The major advantages of the piezoelectric fibre composite actuators are their high performance, flexibility, and durability when compared with the traditional piezoceramic (PZT) actuators. In addition, the ability of MFC devices to couple the electrical and mechanical fields is larger than in monolithic PZT. In this study, we showed the experimental results that an MFC could be used as actuator to find modal parameters and reduce vibration for structures such as an aluminium beam and metal music plate. Two MFC actuators were attached to the surfaces of test subjects. First MFC actuator used to supply a signal as exciter of vibration and second MFC show his application for reduction of vibration in the range of resonance frequencies. Experimental results of aluminium beam with MFC actuators compared with finite element model which modelled in ANSYS software. The applied voltage is modelled as a thermal load according to thermal analogy for MFC. The experimental and numerical results presented in this paper confirm the potential of MFC for use in the vibration control of structures.

Improvement of Depth Profiling into Biotissues Using Micro Electrical Impedance Spectroscopy on a Needle with Selective Passivation

PubMed Central

Yun, Joho; Kim, Hyeon Woo; Lee, Jong-Hyun

2016-01-01

A micro electrical impedance spectroscopy (EIS)-on-a-needle for depth profiling (μEoN-DP) with a selective passivation layer (SPL) on a hypodermic needle was recently fabricated to measure the electrical impedance of biotissues along with the penetration depths. The SPL of the μEoN-DP enabled the sensing interdigitated electrodes (IDEs) to contribute predominantly to the measurement by reducing the relative influence of the connection lines on the sensor output. The discrimination capability of the μEoN-DP was verified using phosphate-buffered saline (PBS) at various concentration levels. The resistance and capacitance extracted through curve fitting were similar to those theoretically estimated based on the mixing ratio of PBS and deionized water; the maximum discrepancies were 8.02% and 1.85%, respectively. Depth profiling was conducted using four-layered porcine tissue to verify the effectiveness of the discrimination capability of the μEoN-DP. The magnitude and phase between dissimilar porcine tissues (fat and muscle) were clearly discriminated at the optimal frequency of 1 MHz. Two kinds of simulations, one with SPL and the other with complete passivation layer (CPL), were performed, and it was verified that the SPL was advantageous over CPL in the discrimination of biotissues in terms of sensor output. PMID:28009845

Improvement of Depth Profiling into Biotissues Using Micro Electrical Impedance Spectroscopy on a Needle with Selective Passivation.

PubMed

Yun, Joho; Kim, Hyeon Woo; Lee, Jong-Hyun

2016-12-21

A micro electrical impedance spectroscopy (EIS)-on-a-needle for depth profiling (μEoN-DP) with a selective passivation layer (SPL) on a hypodermic needle was recently fabricated to measure the electrical impedance of biotissues along with the penetration depths. The SPL of the μEoN-DP enabled the sensing interdigitated electrodes (IDEs) to contribute predominantly to the measurement by reducing the relative influence of the connection lines on the sensor output. The discrimination capability of the μEoN-DP was verified using phosphate-buffered saline (PBS) at various concentration levels. The resistance and capacitance extracted through curve fitting were similar to those theoretically estimated based on the mixing ratio of PBS and deionized water; the maximum discrepancies were 8.02% and 1.85%, respectively. Depth profiling was conducted using four-layered porcine tissue to verify the effectiveness of the discrimination capability of the μEoN-DP. The magnitude and phase between dissimilar porcine tissues (fat and muscle) were clearly discriminated at the optimal frequency of 1 MHz. Two kinds of simulations, one with SPL and the other with complete passivation layer (CPL), were performed, and it was verified that the SPL was advantageous over CPL in the discrimination of biotissues in terms of sensor output.

Short- and long-term outcome of interferon therapy for chronic hepatitis B infection

PubMed Central

Seo, Yasushi; Yano, Yoshihiko

2014-01-01

Hepatitis B virus (HBV) infection is a serious clinical problem worldwide. Conventional interferon (IFN)-α has been approved for the treatment of chronic hepatitis B (CHB). Short-term studies have demonstrated that IFN-based therapy is moderately effective in inducing the loss of hepatitis e antigen (HBeAg) or seroconversion (30%-40%) in HBeAg-positive patients and also produces sustained HBV DNA suppression (20%-30%) in HBeAg-negative patients. Many studies have reported a correlation between the HBV genotype and response to IFN treatment. The highest response rate to IFN treatment was found in patients infected with HBV genotype A, followed by HBV genotypes B, C, and D. The long-term effect of IFN-α on CHB has not yet been elucidated. The ability of IFN-α treatment to prevent new cirrhosis, complications associated with cirrhosis, and development of hepatocellular carcinoma (HCC) is controversial. The beneficial effect of IFN-α treatment in reducing the development of HCC has mainly been observed in treatment responders who already have cirrhosis. These inconsistent findings may be attributed to the inevitable limitations of comparisons across studies, including differences in the baseline characteristics of the study and the moderate suppression of HBV replication by IFN-α relative to nucleoside/nucleos(t)ide analogs. PMID:25309065

Temporal and spatial behavior of pharmaceuticals in ...

EPA Pesticide Factsheets

The behavior of active pharmaceutical ingredients (APIs) in urban estuaries is not well understood. In this study, 15 high volume usage APIs were measured over a one year period throughout Narragansett Bay, RI, USA to determine factors controlling their concentration and distribution. Dissolved APIs ranged in concentration from not detected to 310 ng/L, with numerous APIs present at all sites and sampling periods. Eight APIs were present in suspended particulate material, ranging in concentration from <1 ng/g to 44 ng/g. Partitioning coefficients (Kds) were determined for APIs present in both the dissolved and particulate phases, with their range and variability remaining relatively constant during the study. Organic carbon normalization reduced the observed variability of several APIs to a small extent; however, other factors appear to play a role in controlling partitioning behavior. The continuous discharge of wastewater treatment plant effluents into upper Narragansett Bay resulted in sustained levels of APIs, resulting in a zone of “pseudo-persistence.” For most of the APIs, there was a strong relationship with salinity, indicating conservative behavior within the estuary. Short flushing times in Narragansett Bay coupled with APIs present primarily in the dissolved phase suggests that most APIs will be diluted and transported out of the estuary, with only small amounts of several compounds removed to and sequestered in sediments. This study ide

Type 1 Deiodinase Regulates ApoA-I Gene Expression and ApoA-I Synthesis Independent of Thyroid Hormone Signaling

PubMed Central

Liu, Jing; Hernandez-Ono, Antonio; Graham, Mark J.; Galton, Valerie Anne; Ginsberg, Henry N.

2016-01-01

Objective Plasma levels of high density lipoprotein cholesterol (HDLC) and apolipoprotein A-I (ApoA-I) are reduced in individuals with defective insulin signaling. Initial studies using liver-specific insulin receptor (InsR) knockout mice (LIRKO) identified reduced expression of Type 1 Deiodinase (Dio1) as a potentially novel link between defective hepatic insulin signaling and reduced expression of the ApoA-I gene. Our objective was to examine the regulation of ApoA-I expression by Dio1. Approach and Results Acute inactivation of InsR by adenoviral delivery of Cre recombinase to InsR floxed mice reduced HDLC and expression of both ApoA-I and Dio1. Overexpression of Dio1 in LIRKO restored HDLC and ApoA-I levels and increased the expression of ApoA-I. Dio1 knockout (D1KO) mice had very low expression of ApoA-I and reduced serum levels of HDLC and ApoA-I. Treatment of C57BL/6J mice with anti-sense to Dio1 reduced ApoA-I mRNA, HDLC, and serum ApoA-I. Hepatic 3,5,3′-triiodothyronine (T3) content was normal or elevated in LIRKO or D1KO mice. Knockdown of either InsR or Dio1 by siRNA in HepG2 cells decreased expression of ApoA-I as well as ApoA-I synthesis and secretion. siRNA knockdown of InsR or Dio1 decreased activity of a region of the ApoA-I promoter lacking thyroid hormone response elements (TREs) (Region B). Electrophoretic mobility shift assay demonstrated that reduced Dio1 expression decreased the binding of nuclear proteins to Region B. Conclusions Reductions in Dio1 expression reduce expression of ApoA-I in a T3/TRE independent manner. PMID:27150392

Type 1 Deiodinase Regulates ApoA-I Gene Expression and ApoA-I Synthesis Independent of Thyroid Hormone Signaling.

PubMed

Liu, Jing; Hernandez-Ono, Antonio; Graham, Mark J; Galton, Valerie Anne; Ginsberg, Henry N

2016-07-01

Plasma levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) are reduced in individuals with defective insulin signaling. Initial studies using liver-specific insulin receptor (InsR) knockout mice identified reduced expression of type 1 deiodinase (Dio1) as a potentially novel link between defective hepatic insulin signaling and reduced expression of the ApoA-I gene. Our objective was to examine the regulation of ApoA-I expression by Dio1. Acute inactivation of InsR by adenoviral delivery of Cre recombinase to InsR floxed mice reduced HDL-C and expression of both ApoA-I and Dio1. Overexpression of Dio1 in InsR knockout mice restored HDL-C and ApoA-I levels and increased the expression of ApoA-I. Dio1 knockout mice had low expression of ApoA-I and reduced serum levels of HDL-C and ApoA-I. Treatment of C57BL/6J mice with antisense to Dio1 reduced ApoA-I mRNA, HDL-C, and serum ApoA-I. Hepatic 3,5,3'-triiodothyronine content was normal or elevated in InsR knockout mice or Dio1 knockout mice. Knockdown of either InsR or Dio1 by siRNA in HepG2 cells decreased the expression of ApoA-I and ApoA-I synthesis and secretion. siRNA knockdown of InsR or Dio1 decreased activity of a region of the ApoA-I promoter lacking thyroid hormone response elements (region B). Electrophoretic mobility shift assay demonstrated that reduced Dio1 expression decreased the binding of nuclear proteins to region B. Reductions in Dio1 expression reduce the expression of ApoA-I in a 3,5,3'-triiodothyronine-/thyroid hormone response element-independent manner. © 2016 American Heart Association, Inc.

Regulation of SFRP-1 expression in the rat dental follicle.

PubMed

Liu, Dawen; Yao, Shaomian; Wise, Gary E

2012-01-01

Tooth eruption requires osteoclastogenesis and subsequent bone resorption. Secreted frizzled-related protein-1 (SFRP-1) negatively regulates osteoclastogenesis. Our previous studies indicated that SFRP-1 is expressed in the rat dental follicle (DF), with reduced expression at days 3 and 9 close to the times for the major and minor bursts of osteoclastogenesis, respectively; but it remains unclear as to what molecules contribute to its reduced expression at these critical times. Thus, it was the aim of this study to determine which molecules regulate the expression of SFRP-1 in the DF. To that end, the DF cells were treated with cytokines that are maximally expressed at days 3 or 9, and SFRP-1 expression was determined. Our study indicated that colony-stimulating factor-1 (CSF-1), a molecule maximally expressed in the DF at day 3, down-regulated SFRP-1 expression. As to endothelial monocyte-activating polypeptide II (EMAP-II), a highly expressed molecule in the DF at day 3, it had no effect on the expression of SFRP-1. However, when EMAP-II was knocked down by siRNA, the expression of SFRP-1 was elevated, and this elevated SFRP-1 expression could be reduced by adding recombinant EMAP-II protein. This suggests that EMAP-II maintained a lower level of SFRP-1 in the DF. TNF-α is a molecule maximally expressed at day 9, and this study indicated that it also down-regulated the expression of SFRP-1 in the DF cells. In conclusion, CSF-1 and EMAP-II may contribute to the reduced SFRP-1 expression seen on day 3, while TNF-α may contribute to the reduced SFRP-1 expression at day 9.

Reduced MUC4 expression is a late event in breast carcinogenesis and is correlated with increased infiltration of immune cells as well as promoter hypermethylation in invasive breast carcinoma.

PubMed

Cho, Jin Seong; Park, Min Ho; Lee, Ji Shin; Yoon, Jung Han

2015-01-01

Altered expression of MUC4 is associated with tumor progression and immune surveillance, but the potential involvement of MUC4 in breast carcinogenesis has not been rigorously assessed. Immunohistochemical staining with anti-MUC4 antibody was performed in a total of 324 patients with 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 invasive breast carcinoma (IBC) using tissue microarray. Immunohistochemical staining for CD8, CD57, and CD1a and methylation-specific polymerase chain reaction were also performed in IBC. Reduced MUC4 expression in IBC was significantly higher than in usual ductal hyperplasia and ductal carcinoma in situ (P<0.001 and P<0.01, respectively). Reduced MUC4 expression in IBC was significantly correlated with promoter hypermethylation (P<0.05). No association between MUC4 expression and patient outcomes was identified. Intratumoral CD8 T cells and stromal CD57 natural killer cells were significantly increased in the reduced MUC4 expression group compared with those in the normal expression group (P<0.01 and P<0.05, respectively). Our results suggest that tumor progression in breast epithelium is accompanied by reduced MUC4 protein expression. Reduced MUC4 expression correlates with increased tumor-infiltrating CD8 T and NK cells as well as promoter hypermethylation in IBC.

Computing Science and Statistics: Proceedings of the Symposium on the Interface: Computationally Intensive Methods in Statistics (20th) Held in Fairfax, Virginia on April 20-23, 1988

DTIC Science & Technology

1989-03-15

essence of the idea ycessible mtho forunrtandig eth- Tis tand thP ra) rm guh ide propet oaes nd d of e aessie meh bsd fooesadng asymptoti- isthe for s...network? This of Such empirical parametric model fitting is of course depends heavily on the class of net- course the essence of much of applied...smaller problems is the essence of graphical modeling. A model hy- attributes. Let e be the discrete joint outcome space for those N pergraph, g

76 FR 76166 - Draft Guidance for Industry and Food and Drug Administration Staff; the Content of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

...The Food and Drug Administration (FDA) is announcing the availability of the draft guidance document entitled ``Draft Guidance for Industry and FDA Staff: The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems.'' This draft guidance document provides industry and the Agency staff with guidelines for developing premarket submissions for artificial pancreas device systems, in particular, the Control-to-Range (CTR) and Control-to-Target (CTT) device systems. This draft guidance is not final nor is it in effect at this time.

Walter Odington's De etate mundi and the Pursuit of a Scientific Chronology in Medieval England.

PubMed

Nothaft, Carl Philipp

2016-01-01

This article deals with a forgotten treatise on the age of the world, written between 1308 and 1316 by Walter Odington, a monk of Evesham Abbey, otherwise known for his writings on alchemy and music theory. By tracing the sources and rationale behind Odington's arguments and comparing them with those of other medieval authors, the article attempts to shed new light on the state of chronological scholarship in England in the eleventh to fourteenth centuries, when astronomical and astrological methods were freely used to supplement or replace scriptural interpretation, yielding creative and unexpected results.

Metallurgical Examination of a Cast Turret Manufactured by the American Steel Foundries

DTIC Science & Technology

1945-03-28

ferrite and a structure stmlar to tempered bainite tnd fine carb ides. 4. The results of this investigatio l inCicate that the American Steel Foundries...1hirrot No 11Mufac t~redj~ t!Le American~ Steel Poidcries J.J Wil jr;I 4?1 ’JJ No. B171; 11000 Picral Structure simuilar to temnpered bainite Lavsociated wita fine carbides and ferrite patcha.. FIGM I ...examination has been conducted on two samples of the. cast turret to. 3171 for the Hedium Tank II4, maiufactured by the i.meriaan Steel Foundries, which

ARC-1994-AC94-0353-2B

NASA Image and Video Library

1994-07-01

Photo Artwork composite by JPL This depiction of comet Shoemaker-Levy 9 impacting Jupiter is shown from several perspectives. IMAGE B shows the perspective from Galileo spacecraft which can observe the impact point directly. For visual appeal, most of the large cometary fragments are shown close to one another in this image. At the time of Jupiter impact, the fragments will be separated from one another by serveral times the distances shown. This image was created by D.A. Seal of JPL's Mission Design Section using orbital computations provIded by P.W. Chodas and D.K. Yeomans of JPL's Navigation Section.

ARC-1994-AC94-0353-2A

NASA Image and Video Library

1994-07-01

Photo Artwork composite by JPL This depiction of comet Shoemaker-Levy 9 impacting Jupiter is shown from several perspectives. IMAGE A is shown from the perspective of Earth based observers. For visual appeal, most of the large cometary fragments are shown close to one another in this image. At the time of Jupiter impact, the fragments will be separated from one another by serveral times the distances shown. This image was created by D.A. Seal of JPL's Mission Design Section using orbital computations provIded by P.W. Chodas and D.K. Yeomans of JPL's Navigation Section.

ARC-1994-AC94-0353-2D

NASA Image and Video Library

1994-07-01

Photo Artwork composite by JPL This depiction of comet Shoemaker-Levy 9 impacting Jupiter is shown from several perspectives. IMAGE D depicts a generic view from Jupiter's south pole. For visual appeal, most of the large cometary fragments are shown close to one another in this image. At the time of Jupiter impact, the fragments will be separated from one another by serveral times the distances shown. This image was created by D.A. Seal of JPL's Mission Design Section using orbital computations provIded by P.W. Chodas and D.K. Yeomans of JPL's Navigation Section.

Capacitive Behavior of Single Gallium Oxide Nanobelt

PubMed Central

Cai, Haitao; Liu, Hang; Zhu, Huichao; Shao, Pai; Hou, Changmin

2015-01-01

In this research, monocrystalline gallium oxide (Ga2O3) nanobelts were synthesized through oxidation of metal gallium at high temperature. An electronic device, based on an individual Ga2O3 nanobelt on Pt interdigital electrodes (IDEs), was fabricated to investigate the electrical characteristics of the Ga2O3 nanobelt in a dry atmosphere at room temperature. The current-voltage (I-V) and I/V-t characteristics show the capacitive behavior of the Ga2O3 nanobelt, indicating the existence of capacitive elements in the Pt/Ga2O3/Pt structure. PMID:28793506

Suffodit inguina.

PubMed

Betzig, Laura

2014-01-01

When Julius Caesar was stabbed, 23 times, on the Ides of March, at least one of the daggers is supposed to have gone into his groin. He wasn't the last Roman to have his privates attacked. And he wasn't the last primate. In competition for sexual access, gonads are occasionally targeted: canine incisions in monkey and ape scrota are not uncommon; and rumors had a number of Roman emperors--from Caligula and Nero, to Galba, Vitellius, Domitian, Commodus, Caracalla, Elagabalus, to Balbinus, Pupienus and Valerian over the course of the third century crisis--done in with their genitals at risk, or with their genitals cut off.

Installation Restoration Program for Eglin AFB, Florida. Phase 2. Field Evaluation

DTIC Science & Technology

1984-09-01

of t jest l-iianja-erent pra-ct ices w .hien are discussed in Section D.5 5.1.4 Landfill L)-26 In Dotn NoveM( Der and tebruary samplI igs, ioX" results...to analy.ze 6rounawater samp los tronm La’nd ti I v)-ZIt for organional I ides in the base/ neut ral extractaLeI, organics section of the priority...the gasoline tank was not filled near wells or the van and any spillage was allowed to evaporate before moving the pump. During use, the pump was

Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial.

PubMed

Arribas, José R; Girard, Pierre-Marie; Landman, Roland; Pich, Judit; Mallolas, Josep; Martínez-Rebollar, María; Zamora, Francisco X; Estrada, Vicente; Crespo, Manuel; Podzamczer, Daniel; Portilla, Joaquín; Dronda, Fernando; Iribarren, José A; Domingo, Pere; Pulido, Federico; Montero, Marta; Knobel, Hernando; Cabié, André; Weiss, Laurence; Gatell, José M

2015-07-01

Our objective was to assess therapeutic non-inferiority of dual treatment with lopinavir-ritonavir and lamivudine to triple treatment with lopinavir-ritonavir plus two nucleos(t)ides for maintenance of HIV-1 viral suppression. In this randomised, open-label, non-inferiority trial, we recruited patients from 32 HIV units in hospitals in Spain and France. Eligible patients were HIV-infected adults (aged ≥18 years) with HIV-1 RNA of less than 50 copies per mL, for at least 6 months on triple treatment with lopinavir-ritonavir (twice daily) plus lamivudine or emtricitabine and a second nucleos(t)ide, with no resistance or virological failure to these drugs, and no positive hepatitis B serum surface antigen. Investigators at each centre randomly assigned patients (1:1; block size of four; stratified by time to suppression [<1 year or >1 year] and nadir CD4 cell count [<100 cells per μL or >100 cells per μL]; computer-generated random sequence) to continue triple treatment or switch to dual treatment (oral lopinavir 400 mg and oral ritonavir 100 mg twice daily plus oral lamivudine 300 mg once daily). The primary endpoint was response to treatment in the intention-to-treat population (all randomised patients) at 48 weeks. The non-inferiority margin was 12%. This study is registered with ClinicalTrials.gov, number NCT01471821. Between Oct 1, 2011, and April 1, 2013, we randomly assigned 250 participants to continue triple treatment (127 [51%] patients) or switch to dual treatment (123 [49%] patients). In the intention-to-treat population, 110 (86·6%) of 127 patients in the triple-treatment group responded to treatment versus 108 (87·8%) of 123 in the dual-treatment group (difference -1·2% [95% CI -9·6 to 7·3]; p=0·92), meeting the criteria for non-inferiority. Serious adverse events occurred in eight (7%) patients in the triple-treatment group and five (4%) in the dual-treatment group (p=0·515), and study drug discontinuations due to adverse events occurred in four (3%) in the triple-treatment group and one (1%) in the dual-treatment group (p=0·223). Dual treatment with lopinavir-ritonavir plus lamivudine has non-inferior therapeutic efficacy and is similarly tolerated to triple treatment. AbbVie and Red Temática Cooperativa de Investigación en Sida. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adjustable under-expression of yeast mating pathway proteins in Saccharomyces cerevisiae using a programmed ribosomal frameshift.

PubMed

Choi, Min-Yeon; Park, Sang-Hyun

2016-06-01

Experimental research in molecular biology frequently relies on the promotion or suppression of gene expression, an important tool in the study of its functions. Although yeast is among the most studied model systems with the ease of maintenance and manipulation, current experimental methods are mostly limited to gene deletion, suppression or overexpression of genes. Therefore, the ability to reduce protein expressions and then observing the effects would promote a better understanding of the exact functions and their interactions. Reducing protein expression is mainly limited by the difficulties associated with controlling the reduction level, and in some cases, the initial endogenous abundance is too low. For the under-expression to be useful as an experimental tool, repeatability and stability of reduced expression is important. We found that cis-elements in programmed -1 ribosomal frameshifting (-1RFS) of beet western yellow virus (BWYV) could be utilized to reduced protein expression in Saccharomyces cerevisiae. The two main advantages of using -1RFS are adjustable reduction rates and ease of use. To demonstrate the utility of this under-expression system, examples of reduced protein abundance were shown using yeast mating pathway components. The abundance of MAP kinase Fus3 was reduced to approximately 28-75 % of the wild-type value. Other MAP kinase mating pathway components, including Ste5, Ste11, and Ste7, were also under-expressed to verify that the -1RFS system works with different proteins. Furthermore, reduced Fus3 abundance altered the overall signal transduction outcome of the mating pathway, demonstrating the potential for further studies of signal transduction adjustment via under-expression.

Pioglitazone inhibits LOX-1 expression in human coronary artery endothelial cells by reducing intracellular superoxide radical generation.

PubMed

Mehta, Jawahar L; Hu, Bo; Chen, Jiawei; Li, Dayuan

2003-12-01

LOX-1, a novel lectin-like receptor for oxidized LDL (ox-LDL), is expressed in response to ox-LDL, angiotensin II (Ang II), tumor necrosis factor (TNF)-alpha, and other stress stimuli. It is highly expressed in atherosclerotic tissues. Peroxisome proliferator-activated receptor (PPAR)-gamma ligands, such as pioglitazone, exert antiatherosclerotic effects. This study examined the regulation of LOX-1 expression in human coronary artery endothelial cells (HCAECs) by pioglitazone. Fourth generation HCAECs were treated with ox-LDL, Ang II, or TNF-alpha with or without pioglitazone pretreatment. All 3 stimuli upregulated LOX-1 expression (mRNA and protein). Pioglitazone, in a concentration-dependent manner, reduced LOX-1 expression (P<0.01 versus ox-LDL, Ang II, or TNF-alpha alone). Ox-LDL, Ang II, and TNF-alpha each enhanced intracellular superoxide radical generation, and pioglitazone pretreatment reduced superoxide generation (P<0.01 versus ox-LDL, Ang II, or TNF-alpha). Furthermore, all 3 stimuli upregulated the expression of the transcription factors nuclear factor-kappaB and activator protein-1 (determined by electrophoretic mobility shift assay), and pioglitazone pretreatment reduced this expression (P<0.01 versus ox-LDL, Ang II, or TNF-alpha). To determine the biological significance of pioglitazone-mediated downregulation of LOX-1, we studied monocyte adhesion to ox-LDL-treated HCAECs. Pioglitazone reduced the adhesion of monocytes to activated HCAECs in a fashion similar to that produced by antisense to LOX-1 mRNA. These observations suggest that the PPAR-gamma ligand pioglitazone reduces intracellular superoxide radical generation and subsequently reduces the expression of transcription factors, expression of the LOX-1 gene, and monocyte adhesion to activated endothelium. The salutary effect of PPAR-gamma ligands in atherogenesis may involve the inhibition of LOX-1 and the adhesion of monocytes to endothelium.

Early mortality in acute promyelocytic leukemia: Potential predictors

PubMed Central

Chen, Can; Huang, Xilian; Wang, Kaile; Chen, Kuang; Gao, Danquan; Qian, Shenxian

2018-01-01

Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10–15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure. In the present study, published data was reviewed with a focus on the factors associated with early mortality. When treated with ATO as a primary treatment, the fms-like tyrosine kinase-internal tandem deletion has no impact on early mortality. Low lymphoid enhancer binding factor-1 expression may be a reliable marker for early mortality and the target of therapy if it could be proven by further studies. Cluster of differentiation (CD)56+ and CD34+/CD2+ may be candidates to select high-risk patients. The risk of early mortality in APL still cannot be predicted via the cell surface makers, despite multiple studies on their prognostic significance. Typically, a complex translocation did not alter the survival rate in patients with APL; however, if an abnormal karyotype [e.g., Ide(17), ZBTB16/RARα and STAT5B/RARα] appeared singularly or as part of a complex mutation, there is a high possibility of early mortality if clinicians are unable to identify or monitor it. PMID:29541170

Why Lumbar Artificial Disk Replacements (LADRs) Fail.

PubMed

Pettine, Kenneth; Ryu, Robert; Techy, Fernando

2017-07-01

A retrospective review of prospectively collected data. To determine why artificial disk replacements (ADRs) fail by examining results of 91 patients in FDA studies performed at a single investigational device exemption (IDE) site with minimum 2-year follow-up. Patients following lumbar ADR generally achieve their 24-month follow-up results at 3 months postoperatively. Every patient undergoing ADR at 1 IDE site by 2 surgeons was evaluated for clinical success. Failure was defined as <50% improvement in ODI and VAS or any additional surgery at index or adjacent spine motion segment. Three ADRs were evaluated: Maverick, 25 patients; Charité, 31 patients; and Kineflex, 35 patients. All procedures were 1-level operations performed at L4-L5 or L5-S1. Demographics and inclusion/exclusion criteria were similar and will be discussed. Overall clinical failure occurred in 26% (24 of 91 patients) at 2-year follow-up. Clinical failure occurred in: 28% (Maverick) (7 of 25 patients), 39% (Charité) (12 of 31 patients), and 14% (Kineflex) (5 of 35 patients). Causes of failure included facet pathology, 50% of failure patients (12 of 24). Implant complications occurred in 5% of total patients and 21% of failure patients (5 of 24). Only 5 patients went from a success to failure after 3 months. Only 1 patient went from a failure to success after a facet rhizotomy 1 year after ADR. Seventy-four percent of patients after ADR met strict clinical success after 2-year follow-up. The clinical success versus failure rate did not change from their 3-month follow-up in 85 of the 91 patients (93%). Overall clinical success may be improved most by patient selection and implant type.

A phase transition caught in mid-course: independent and concomitant analyses of the monoclinic and triclinic structures of (nBu4N)[Co(orotate)2(bipy)]·3H2O.

PubMed

Castro, Miguel; Falvello, Larry R; Forcén-Vázquez, Elena; Guerra, Pablo; Al-Kenany, Nuha A; Martínez, Gema; Tomás, Milagros

2017-09-01

The preparation and characterization of the n Bu 4 N + salts of two bis-orotate(2-) complexes of cobalt, namely bis(tetra-n-butylammonium) diaquabis(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-ide-6-carboxylato-κ 2 N 1 ,O 6 )cobalt(II) 1.8-hydrate, (C 16 H 36 N) 2 [Co(C 5 H 2 N 2 O 4 ) 2 (H 2 O) 2 ]·1.8H 2 O, (1), and tetra-n-butylammonium (2,2'-bipyridine-κ 2 N,N')bis(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-ide-6-carboxylato-κ 2 N 1 ,O 6 )cobalt(III) trihydrate, (C 16 H 36 N)[Co(C 5 H 2 N 2 O 4 ) 2 (C 10 H 8 N 2 )]·3H 2 O, (2), are reported. The Co III complex, (2), which is monoclinic at room temperature, presents a conservative single-crystal-to-single-crystal phase transition below 200 K, producing a triclinic twin. The transition, which involves a conformational change in one of the n Bu groups of the cation, is reversible and can be cycled. Both end phases have been characterized structurally and the system was also characterized structurally in a two-phase intermediate state, using single-crystal diffraction techniques, with both the monoclinic and triclinic phases present. Thermal analysis allows a rough estimate of the small energy content, viz. 0.25 kJ mol -1 , for both the monoclinic-to-triclinic transformation and the reverse transition, in agreement with the nature of the structural changes involving only the n Bu 4 N + cation.

Regulatory issues relating to therapies for periodontal regeneration.

PubMed

Singleton, D G; Torres-Cabassa, A

1997-03-01

The Food and Drug Administration (FDA) has regulated medical devices since May 1976, when the Medical Device Amendments were enacted. The clinical trial requirements for the marketing of periodontal regeneration devices have been dependent, in part, on the degree of their similarity to devices marketed prior to the legislative enactment date in terms of materials, indication statements, and labeling claims. Nonresorbable barriers were allowed to be marketed based on their equivalence to devices marketed prior to the enactment date based on biocompatability and clinical trial data under the premarket notification requirements section of the law. Bone filling materials such as hydroxyapatite were first marketed based on the finding of equivalence to predicate devices. Newer technologies such as bioabsorbable barriers have also been reviewed under the premarket notification provisions of the law, but manufacturers have been required to provide more extensive safety and effectiveness data to establish equivalence to pre-Amendments devices. Data to answer questions related to the potential toxicity of breakdown products, period of absorption, and ultimate clinical effectiveness needed to be answered prior to marketing. New devices that incorporate technologies that are not substantially equivalent to predicate devices must proceed through the premarket approval route to marketing. For new devices considered a potential significant risk to the patient population, clinical trials are conducted via the investigational device exemption (IDE) requirements that specify the means by which trials will proceed in order to protect the rights of patients. New devices of organic origin, such as bone morphogenic protein, have followed the premarket approval route with IDE requirements instituted as a condition for their path to the marketplace. Issues associated with immediate and long-term contact including potential toxicity, tumorigenicity, and sensitization need to be addressed with appropriate animal models.

Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.

PubMed

Velay, A; Jeulin, H; Eschlimann, M; Malvé, B; Goehringer, F; Bensenane, M; Frippiat, J-P; Abraham, P; Ismail, A M; Murray, J M; Combet, C; Zoulim, F; Bronowicki, J-P; Schvoerer, E

2016-05-01

For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence. © 2016 John Wiley & Sons Ltd.

Atherogenic properties of LDL particles after switching from Truvada or Kivexa plus lopinavir/r to lamivudine plus lopinavir/r: OLE-MET substudy.

PubMed

Saumoy, Maria; Tiraboschi, Juan M; Ordoñez-Llanos, Jordi; Ribera, Esteban; Domingo, Pere; Mallolas, Josep; Curto, Jordi; Gatell, Josep M; Podzamczer, Daniel

2017-03-01

The objective of this study was to determine the impact of tenofovir or abacavir discontinuation on low-density lipoprotein (LDL) phenotype and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in HIV-infected patients treated with lopinavir/ritonavir plus 2 nucleos(t)ide reverse transcriptase inhibitors (NRTI). Multicenter, open-label study. Patients were randomized to continue with lopinavir/ritonavir plus 2 NRTI (triple therapy) or to switch to lopinavir/ritonavir plus lamivudine (dual therapy). LDL phenotype (by gradient gel electrophoresis) and Lp-PLA2 (by 2-thio-PAF) were determined at baseline and week 48. Forty-four patients included (triple therapy n = 19, dual therapy n = 25): men 63.6%, age 41.5 years (25-61), Framingham score 4.9% (0.2-22). Tenofovir was part of the regimen in 28 (63.6%) patients. Dual therapy patients were younger (p = 0.013) and had lower baseline apolipoprotein A1 (p = 0.029). At week 48, there were no changes in standard lipid measurements, except ApoA1/Apo B, which increased in dual therapy (p = 0.038) with no differences between arms. At week 48, no change in LDL phenotype was found in either arm. No changes in total Lp-PLA2 activity or the relative distribution of LDL and HDL particles were found at week 48 in either arm. Discontinuing the third nucleos(t)ide, mainly tenofovir and abacavir, in a lopinavir/ritonavir-containing regimen was not associated with a deleterious effect on LDL phenotype nor in Lp-PLA2 activity.

Nanostructuring of Biosensing Electrodes with Nanodiamonds for Antibody Immobilization

PubMed Central

2015-01-01

While chemical vapor deposition of diamond films is currently cost prohibitive for biosensor construction, in this paper, we show that sonication-assisted nanostructuring of biosensing electrodes with nanodiamonds (NDs) allows harnessing the hydrolytic stability of the diamond biofunctionalization chemistry for real-time continuous sensing, while improving the detector sensitivity and stability. We find that the higher surface coverages were important for improved bacterial capture and can be achieved through proper choice of solvent, ND concentration, and seeding time. A mixture of methanol and dimethyl sulfoxide provides the highest surface coverage (33.6 ± 3.4%) for the NDs with positive zeta-potential, compared to dilutions of dimethyl sulfoxide with acetone, ethanol, isopropyl alcohol, or water. Through impedance spectroscopy of ND-seeded interdigitated electrodes (IDEs), we found that the ND seeds serve as electrically conductive islands only a few nanometers apart. Also we show that the seeded NDs are amply hydrogenated to be decorated with antibodies using the UV-alkene chemistry, and higher bacterial captures can be obtained compared to our previously reported work with diamond films. When sensing bacteria from 106 cfu/mL E. coliO157:H7, the resistance to charge transfer at the IDEs decreased by ∼38.8%, which is nearly 1.5 times better than that reported previously using redox probes. Further in the case of 108 cfu/mL E. coliO157:H7, the charge transfer resistance changed by ∼46%, which is similar to the magnitude of improvement reported using magnetic nanoparticle-based sample enrichment prior to impedance detection. Thus ND seeding allows impedance biosensing in low conductivity solutions with competitive sensitivity. PMID:24397797

3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy.

PubMed

Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul

2017-01-14

To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis ( P = 0.046) but also in those with decompensated cirrhosis ( P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume ( P = 0.002 and 0.005, respectively). Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.

Design and Characterization of a Sensorized Microfluidic Cell-Culture System with Electro-Thermal Micro-Pumps and Sensors for Cell Adhesion, Oxygen, and pH on a Glass Chip.

PubMed

Bonk, Sebastian M; Stubbe, Marco; Buehler, Sebastian M; Tautorat, Carsten; Baumann, Werner; Klinkenberg, Ernst-Dieter; Gimsa, Jan

2015-07-30

We combined a multi-sensor glass-chip with a microfluidic channel grid for the characterization of cellular behavior. The grid was imprinted in poly-dimethyl-siloxane. Mouse-embryonal/fetal calvaria fibroblasts (MC3T3-E1) were used as a model system. Thin-film platinum (Pt) sensors for respiration (amperometric oxygen electrode), acidification (potentiometric pH electrodes) and cell adhesion (interdigitated-electrodes structures, IDES) allowed us to monitor cell-physiological parameters as well as the cell-spreading behavior. Two on-chip electro-thermal micro-pumps (ETμPs) permitted the induction of medium flow in the system, e.g., for medium mixing and drug delivery. The glass-wafer technology ensured the microscopic observability of the on-chip cell culture. Connecting Pt structures were passivated by a 1.2 μm layer of silicon nitride (Si3N4). Thin Si3N4 layers (20 nm or 60 nm) were used as the sensitive material of the pH electrodes. These electrodes showed a linear behavior in the pH range from 4 to 9, with a sensitivity of up to 39 mV per pH step. The oxygen sensors were circular Pt electrodes with a sensor area of 78.5 μm(2). Their sensitivity was 100 pA per 1% oxygen increase in the range from 0% to 21% oxygen (air saturated). Two different IDES geometries with 30- and 50-μm finger spacings showed comparable sensitivities in detecting the proliferation rate of MC3T3 cells. These cells were cultured for 11 days in vitro to test the biocompatibility, microfluidics and electric sensors of our system under standard laboratory conditions.

Characterization of alanine to valine sequence variants in the Fc region of nivolumab biosimilar produced in Chinese hamster ovary cells.

PubMed

Li, Yantao; Fu, Tuo; Liu, Tao; Guo, Huaizu; Guo, Qingcheng; Xu, Jin; Zhang, Dapeng; Qian, Weizhu; Dai, Jianxin; Li, Bohua; Guo, Yajun; Hou, Sheng; Wang, Hao

2016-07-01

Nivolumab is a therapeutic fully human IgG4 antibody to programmed death 1 (PD-1). In this study, a nivolumab biosimilar, which was produced in our laboratory, was analyzed and characterized. Sequence variants that contain undesired amino acid sequences may cause concern during biosimilar bioprocess development. We found that low levels of sequence variants were detected in the heavy chain of the nivolumab biosimilar by ultra performance liquid chromatography (UPLC) and tandem mass spectrometry. It was further identified with UPLC-MS/MS by IdeS or trypsin digestion. The sequence variant was confirmed through addition of synthetic mutant peptide. Subsequently, the mixing base signal of normal and mutant sequence was detected through DNA sequencing. The relative levels of mutant A424V in the Fc region of the heavy chain have been detected and demonstrated to be 12.25% and 13.54%, via base peak intensity (BPI) and UV chromatography of the tryptic peptide mapping, respectively. A424V variant was also quantified by real-time PCR (RT-PCR) at the DNA and RNA level, which was 19.2% and 16.8%, respectively. The relative content of the mutant was consistent at the DNA, RNA and protein level, indicating that the A424V mutation may have little influence at transcriptional or translational levels. These results demonstrate that orthogonal state-of-the-art techniques such as LC- UV- MS and RT-PCR should be implemented to characterize recombinant proteins and cell lines for development of biosimilars. Our study suggests that it is important to establish an integrated and effective analytical method to monitor and characterize sequence variants during antibody drug development, especially for antibody biosimilar products.

[Double J stent removal's cost estimate using a re-sterilizable fibroscope in a French private structure].

PubMed

Almeras, C; Loison, G; Tollon, C; Gautier, J-R; Badoc, C; Cid, E; Sabatier, R; Zanoun, L; Brudo, L

2017-12-01

In front of the arrival of new devices intended to simplify the removal of double J stent, it poses the problem of the knowledge of the real cost of such an ablation under the current conditions of realization. This is a monocentric economic evaluation of cost and remuneration needed data-gathering of quotation (CCAM, GHS/SE, …), estimate of the associated costs of wear and damping of the endoscopic equipments (endoscopes, cables, …), estimate of the cost of sterilization, estimate of the associated costs to the intervention of staff (Auxiliary nurse [AS] and Nurse [IDE]) with timing of the various tasks. Quotation CCAM JCGE004 (48€) gives access to fixed price SE1 (73.71€ for private clinic, and 75.89€ for public institution) without hospitalization nor anaesthesia. The costs were reported to an act of single double J removal. Concerning the equipments: 4.42€HT for the fibroscopes, graspers, cable and light. The costs of sterilization were: 17.95€HT. The timed workforce's costs were: 7.61-9.51€ for AS and 9.92-10.84€ for IDE. The cost of consumable was about 1.37 €HT, by excluding the common base from the extractions (1.876€HT). The total costs in France in 2016 were thus about 47.4 to 50.496€ including all taxes. This estimate will be used certainly for reflection on the investments and the future studies of the economic impact of the new devices of extraction, by correlating it of course with the various maintenance contracts from each institution. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mutational Analysis of a Role for Salicylic Acid in Iron Metabolism of Mycobacterium smegmatis

PubMed Central

Adilakshmi, Tadepalli; Ayling, Peter D.; Ratledge, Colin

2000-01-01

The role of salicylic acid in iron metabolism was examined in two wild-type strains (mc2155 and NCIMB 8548) and three mutant strains (mc21292 [lacking exochelin], SM3 [lacking iron-dependent repressor protein IdeR] and S99 [a salicylate-requiring auxotroph derived in this study]) of Mycobacterium smegmatis. Synthesis of salicylate in SM3 was derepressed even in the presence of iron, as was synthesis of the siderophores exochelin, mycobactin, and carboxymycobactin. S99 was dependent on salicylate for growth and failed to grow with the three ferrisiderophores, suggesting that salicylate fulfills an additional function(s) other than being a precursor of mycobactin and carboxymycobactin. Salicylic acid at 100 μg/ml repressed the formation of a 29-kDa cell envelope protein (putative exochelin receptor protein) in S99 grown both iron deficiently and iron sufficiently. In contrast, synthesis of this protein was affected only under iron-limited conditions in the parent strain, mc2155, and remained unaltered in SM3, suggesting an interaction between the IdeR protein and salicylate. Thus, salicylate may also function as a signal molecule for recognition of cellular iron status. Growth of all strains and mutants with p-aminosalicylate (PAS) at 100 μg/ml increased salicylate accumulation between three- and eightfold under both iron-limited and iron-sufficient growth conditions and decreased mycobactin accumulation by 40 to 80% but increased carboxymycobactin accumulation by 50 to 55%. Thus, although PAS inhibited salicylate conversion to mycobactin, presumptively by blocking salicylate AMP kinase, PAS also interferes with the additional functions of salicylate, as its effect was heightened in S99 when the salicylate concentration was minimal. PMID:10629169

High-Resolution Graphene Films for Electrochemical Sensing via Inkjet Maskless Lithography.

PubMed

Hondred, John A; Stromberg, Loreen R; Mosher, Curtis L; Claussen, Jonathan C

2017-10-24

Solution-phase printing of nanomaterial-based graphene inks are rapidly gaining interest for fabrication of flexible electronics. However, scalable manufacturing techniques for high-resolution printed graphene circuits are still lacking. Here, we report a patterning technique [i.e., inkjet maskless lithography (IML)] to form high-resolution, flexible, graphene films (line widths down to 20 μm) that significantly exceed the current inkjet printing resolution of graphene (line widths ∼60 μm). IML uses an inkjet printed polymer lacquer as a sacrificial pattern, viscous spin-coated graphene, and a subsequent graphene lift-off to pattern films without the need for prefabricated stencils, templates, or cleanroom technology (e.g., photolithography). Laser annealing is employed to increase conductivity on thermally sensitive, flexible substrates [polyethylene terephthalate (PET)]. Laser annealing and subsequent platinum nanoparticle deposition substantially increases the electroactive nature of graphene as illustrated by electrochemical hydrogen peroxide (H 2 O 2 ) sensing [rapid response (5 s), broad linear sensing range (0.1-550 μm), high sensitivity (0.21 μM/μA), and low detection limit (0.21 μM)]. Moreover, high-resolution, complex graphene circuits [i.e., interdigitated electrodes (IDE) with varying finger width and spacing] were created with IML and characterized via potassium chloride (KCl) electrochemical impedance spectroscopy (EIS). Results indicated that sensitivity directly correlates to electrode feature size as the IDE with the smallest finger width and spacing (50 and 50 μm) displayed the largest response to changes in KCl concentration (∼21 kΩ). These results indicate that the developed IML patterning technique is well-suited for rapid, solution-phase graphene film prototyping on flexible substrates for numerous applications including electrochemical sensing.

Seismic evidence for deep fluid circulation in the overriding plate of subduction zones

NASA Astrophysics Data System (ADS)

Tauzin, B.; Reynard, B.; Bodin, T.; Perrillat, J. P.; Debayle, E.

2015-12-01

In subduction zones, non-volcanic tremors are associated with fluid circulations (Obara, 2002). Their sources are often located on the interplate boundary (Rogers and Dragert, 2003; Shelly et al, 2006; La Rocca, 2009), consistent with fluids released by the dehydration of subducted plates (Hacker et al., 2003). Reports of tremors in the overriding continental crust of several subduction zones in the world (Kao et al., 2005; Payero et al., 2008; Ide, 2012) suggest fluid circulation at shallower depths but potential fluid paths are poorly documented. Here we obtained seismic observations from receiver functions that evidence the close association between the shallow tremor zone, electrical conductivity, and tectonic features of the Cascadia overriding plate. A seismic discontinuity near 15 km depth in the crust of the overriding North American plate is attributed to the Conrad discontinuity. This interface is segmented, and its interruption is spatially correlated with conductive regions and shallow swarms of seismicity and non-volcanic tremors. These observations suggest that shallow fluid circulation, tremors and seismicity are controlled by fault zones limiting blocks of accreted terranes in the overriding plate (Brudzinski and Allen, 2007). These zones constitute fluid "escape" routes that may contribute unloading fluid pressure on the megathrust. Obara, K. (2002). Science, 296, 1679-1681. Rogers, G., & Dragert, H. (2003). Science, 300, 1942-1943. Shelly, D. R., et al. (2006). Nature, 442, 188-191. La Rocca, M., et al. (2009). Science, 323, 620-623. Kao, H., et al. (2005). Nature, 436, 841-844. Payero, J. S., et al. (2008). Geophysical Research Letters, 35. Ide, S. (2012). Journal of Geophysical Research: Solid Earth, 117. Brudzinski, M. R., & Allen, R. M. (2007). Geology, 35, 907-910.

Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

PubMed

Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

2006-06-01

Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells.

PubMed Central

Kondoh, N.; Yamada, T.; Kihara-Negishi, F.; Yamamoto, M.; Oikawa, T.

1998-01-01

To investigate the cell biological function of PU.1, a member of the Ets family of transcription factors, a vector capable of expressing the protein was transfected into HT1080 human fibrosarcoma cells. Exogenous expression of PU.1 in HT1080 cells reduced colony-forming efficiency but stimulated cell migration in soft agar, although it did not affect cell growth in adherent culture. Expression of the urokinase-type plasminogen activator (uPA) mRNA, which is known to be correlated with cell migration and invasion, was enhanced in PU.1 transfectants compared with mock transfectants. Run-on analysis demonstrated that uPA transcription was unaffected by PU.1, suggesting that this enhancement mainly occurs at a post-transcriptional level. On the other hand, treatment of HT1080 cells with the synthetic glucocorticoid dexamethasone (DEX; 10(-7) M) significantly reduced uPA gene expression at a transcriptional level. Furthermore, DEX inhibited cell migration in soft agar without affecting cell growth. These negative effects of DEX on uPA expression and cell migration were alleviated by the expression of PU.1 in HT1080 cells, whereas expression of the N-ras oncogene, which is responsible for maintenance of the transformed phenotypes in HT1080 cells, was unaffected by PU.1 expression or DEX treatment in the cells. Our results suggest that expression of PU.1 can stimulate uPA gene expression at the post-transcriptional level, which may subsequently lead to activation of cell motility and/or reduced cell-cell adhesion, but reduces anchorage-independent growth of HT1080 cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9743289

Thermophysical and Electronic Properties Information Analysis Center (TEPIAC). A Continuing Systematic Program on Data Tables of Thermophysical and Electronic Properties of Materials.

DTIC Science & Technology

1981-05-01

cermets, intermetallics, polymers, tomposites, elements, compounds, glasses , coatings, systems, materials, data 1tion. data evaluation, data analysis...intermetallics, glasses , ceramics, cermets, applied coatings, polymers, composites, and systems. The strategy of literature search has been to use both the...Tv i]3qTMt- I I [ 1 f-TL 1i 1: I 11c IQ I HT. Tsfl-)EN11R2 P- J 99’)~ 0 J917 V2O5 Vanadium Ox ide Li~~~~~~~~j ff T7AV~fi YJ rILLVL7T_(For

VAPOR PRESSURES, LIQUID MOLAR VOLUMES, VAPOR NON- IDEALITIES, AND CRITICAL PROPERTIES OF SOME FLUORINATED ETHERS: CF3OCF2OCF3, CF3OCF2 CF2H, c-CF2CF2CF2O, CF3OCF2H, AND CF3OCH3; AND OF CCl3F AND CF2ClH

EPA Science Inventory

Vapor pressures, compressibilities, expansivities, and molar volumes of the liquid phase have been measured between room temperature and the critical temperature for a series of fluorinated ethers: CF3OCF2OCF3, CF3OCF2CF2H, c-CF2CF2CF2O, CF3OCF2H, and CF3OCH3. Vapor-phase non-ide...