Sample records for exemption ide process

  1. 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...

  2. 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

  3. 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

  4. 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...

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Performing clinical studies involving hernia mesh devices: what every investigator should know about the FDA investigational device exemption (IDE) process.

    PubMed

    Ashar, B S; Dang, J M; Krause, D; Luke, M C

    2011-12-01

    The FDA's Center for Devices and Radiological Health (CDRH) is responsible for providing reasonable assurance of safety and effectiveness of all medical devices marketed within the US. To date, CDRH has cleared numerous hernia mesh devices for general use, but has not cleared/approved any mesh devices intended for certain specific uses, such as for infected wounds, hernia prevention, biofilm reduction, or prevention of adhesions. CDRH is requesting that manufacturers seeking specific hernia mesh device labeling claims consult with the Agency to determine the level of evidence necessary for justifying such claims.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-β by affecting insulin-degrading enzyme.

    PubMed

    Grimm, Marcus O W; Mett, Janine; Stahlmann, Christoph P; Haupenthal, Viola J; Blümel, Tamara; Stötzel, Hannah; Grimm, Heike S; Hartmann, Tobias

    2016-12-01

    Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to be highly beneficial in Alzheimer's disease (AD). AD pathology is closely linked to an overproduction and accumulation of amyloid-β (Aβ) peptides as extracellular senile plaques in the brain. Total Aβ levels are not only dependent on its production by proteolytic processing of the amyloid precursor protein (APP), but also on Aβ-clearance mechanisms, including Aβ-degrading enzymes. Here we show that the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase Aβ-degradation by affecting insulin-degrading enzyme (IDE), the major Aβ-degrading enzyme secreted into the extracellular space of neuronal and microglial cells. The identification of the molecular mechanisms revealed that EPA directly increases IDE enzyme activity and elevates gene expression of IDE. DHA also directly stimulates IDE enzyme activity and affects IDE sorting by increasing exosome release of IDE, resulting in enhanced Aβ-degradation in the extracellular milieu. Apart from the known positive effect of DHA in reducing Aβ production, EPA and DHA might ameliorate AD pathology by increasing Aβ turnover.

  7. 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.

  8. 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.

  9. 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.

  10. M6-C artificial disc placement.

    PubMed

    Coric, Domagoj; Parish, John; Boltes, Margaret O

    2017-01-01

    There has been a steady evolution of cervical total disc replacement (TDR) devices over the last decade resulting in surgical technique that closely mimics anterior cervical discectomy and fusion as well as disc design that emphasizes quality of motion. The M6-C TDR device is a modern-generation artificial disc composed of titanium endplates with tri-keel fixation as well as a polyethylene weave with a polyurethane core. Although not yet approved by the FDA, M6-C has finished a pilot and pivotal US Investigational Device Exemption (IDE) study. The authors present the surgical technique for implantation of a 2-level M6-C cervical TDR device. The video can be found here: https://youtu.be/rFEAqINLRCo .

  11. Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity.

    PubMed

    Shin, Hye Jin; Kim, Chonsaeng; Cho, Sungchan

    2018-04-20

    Nucleoside analogs have been frequently identified as antiviral agents. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. Nucleoside analogs generally interfere with cellular nucleos(t)ide synthesis pathways, resulting in the depletion or imbalance of (d)NTP pools. Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. The precise crosstalk between these two independent processes remains to be determined. Nonetheless, we summarize the current knowledge of nucleos(t)ide synthesis inhibition-related innate immunity and propose it as a newly emerging antiviral mechanism of nucleoside analogs.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Molecular Basis for the Recognition and Cleavages of IGF-II, TGF-[alpha], and Amylin by Human Insulin-Degrading Enzyme

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

    Guo, Qing; Manolopoulou, Marika; Bian, Yao

    2010-02-11

    Insulin-degrading enzyme (IDE) is involved in the clearance of many bioactive peptide substrates, including insulin and amyloid-{beta}, peptides vital to the development of diabetes and Alzheimer's disease, respectively. IDE can also rapidly degrade hormones that are held together by intramolecular disulfide bond(s) without their reduction. Furthermore, IDE exhibits a remarkable ability to preferentially degrade structurally similar peptides such as the selective degradation of insulin-like growth factor (IGF)-II and transforming growth factor-{alpha} (TGF-{alpha}) over IGF-I and epidermal growth factor, respectively. Here, we used high-accuracy mass spectrometry to identify the cleavage sites of human IGF-II, TGF-{alpha}, amylin, reduced amylin, and amyloid-{beta} bymore » human IDE. We also determined the structures of human IDE-IGF-II and IDE-TGF-{alpha} at 2.3 {angstrom} and IDE-amylin at 2.9 {angstrom}. We found that IDE cleaves its substrates at multiple sites in a biased stochastic manner. Furthermore, the presence of a disulfide bond in amylin allows IDE to cut at an additional site in the middle of the peptide (amino acids 18-19). Our amylin-bound IDE structure offers insight into how the structural constraint from a disulfide bond in amylin can alter IDE cleavage sites. Together with NMR structures of amylin and the IGF and epidermal growth factor families, our work also reveals the structural basis of how the high dipole moment of substrates complements the charge distribution of the IDE catalytic chamber for the substrate selectivity. In addition, we show how the ability of substrates to properly anchor their N-terminus to the exosite of IDE and undergo a conformational switch upon binding to the catalytic chamber of IDE can also contribute to the selective degradation of structurally related growth factors.« less

  2. 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.

  3. 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.

  4. Expression of metalloprotease insulin-degrading enzyme (insulysin) in normal and malignant human tissues

    PubMed Central

    Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

    2013-01-01

    Background Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30:73; 2007). Materials and Methods Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed. Conclusions We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer’s disease and diabetes but not in cancer. PMID:18813847

  5. Proteolysis of mature HIV-1 p6 Gag protein by the insulin-degrading enzyme (IDE) regulates virus replication in an Env-dependent manner.

    PubMed

    Hahn, Friedrich; Schmalen, Adrian; Setz, Christian; Friedrich, Melanie; Schlößer, Stefan; Kölle, Julia; Spranger, Robert; Rauch, Pia; Fraedrich, Kirsten; Reif, Tatjana; Karius-Fischer, Julia; Balasubramanyam, Ashok; Henklein, Petra; Fossen, Torgils; Schubert, Ulrich

    2017-01-01

    There is a significantly higher risk for type II diabetes in HIV-1 carriers, albeit the molecular mechanism for this HIV-related pathology remains enigmatic. The 52 amino acid HIV-1 p6 Gag protein is synthesized as the C-terminal part of the Gag polyprotein Pr55. In this context, p6 promotes virus release by its two late (L-) domains, and facilitates the incorporation of the viral accessory protein Vpr. However, the function of p6 in its mature form, after proteolytic release from Gag, has not been investigated yet. We found that the mature p6 represents the first known viral substrate of the ubiquitously expressed cytosolic metalloendopeptidase insulin-degrading enzyme (IDE). IDE is sufficient and required for degradation of p6, and p6 is approximately 100-fold more efficiently degraded by IDE than its eponymous substrate insulin. This observation appears to be specific for HIV-1, as p6 proteins from HIV-2 and simian immunodeficiency virus, as well as the 51 amino acid p9 from equine infectious anaemia virus were insensitive to IDE degradation. The amount of virus-associated p6, as well as the efficiency of release and maturation of progeny viruses does not depend on the presence of IDE in the host cells, as it was shown by CRISPR/Cas9 edited IDE KO cells. However, HIV-1 mutants harboring IDE-insensitive p6 variants exhibit reduced virus replication capacity, a phenomenon that seems to depend on the presence of an X4-tropic Env. Furthermore, competing for IDE by exogenous insulin or inhibiting IDE by the highly specific inhibitor 6bK, also reduced virus replication. This effect could be specifically attributed to IDE since replication of HIV-1 variants coding for an IDE-insensitive p6 were inert towards IDE-inhibition. Our cumulative data support a model in which removal of p6 during viral entry is important for virus replication, at least in the case of X4 tropic HIV-1.

  6. 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

  7. Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues.

    PubMed

    Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

    2008-10-01

    Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and breast cancer tissue. Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed Western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Applying the four IDE-directed antibodies, we demonstrated IDE expression at the protein level, by means of immunoblotting and immunocytochemistry, in each of the tumor cell lines analyzed. Insulin-degrading enzyme protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in each of the cell lines and tissues assessed. In conclusion, we performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells thus extending our knowledge on the cellular and tissue distribution of IDE, an enzyme which to date has mainly been studied in connection with Alzheimer's disease and diabetes but not in cancer.

  8. 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.

  9. 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.

  10. Notch signaling proteins HES-1 and Hey-1 bind to insulin degrading enzyme (IDE) proximal promoter and repress its transcription and activity: Implications for cellular Aβ metabolism

    PubMed Central

    Leal, María C.; Surace, Ezequiel I.; Holgado, María P.; Ferrari, Carina C.; Tarelli, Rodolfo; Pitossi, Fernando; Wisniewski, Thomas; Castaño, Eduardo M.; Morelli, Laura

    2012-01-01

    Cerebral amyloid β (Aβ) accumulation is pathogenically associated with sporadic Alzheimer’s disease (SAD). BACE-1 is involved in Aβ generation while insulin-degrading enzyme (IDE) partakes in Aβ proteolytic clearance. Vulnerable regions in AD brains show increased BACE-1 protein levels and enzymatic activity while the opposite occurs with IDE. Another common feature in SAD brains is Notch1 overexpression. Here we demonstrate an increase in mRNA levels of Hey-1, a Notch target gene, and a decrease of IDE transcripts in the hippocampus of SAD brains as compared to controls. Transient transfection of Notch intracellular domain (NICD) in N2aSW cells, mouse neuroblastoma cells (N2a) stably expressing human amyloid precursor protein (APP) Swedish mutation, reduce IDE mRNA levels, promoting extracellular Aβ accumulation. Also, NICD, HES-1 and Hey-1 overexpression result in decreased IDE proximal promoter activity. This effect was mediated by 2 functional sites located at −379/−372 and −310 −303 from the first translation start site in the −575/−19 (556 bp) fragment of IDE proximal promoter. By site-directed mutagenesis of the IDE promoter region we reverted the inhibitory effect mediated by NICD transfection suggesting that these sites are indeed responsible for the Notch-mediated inhibition of the IDE gene expression. Intracranial injection of the Notch ligand JAG-1 in Tg2576 mice, expressing the Swedish mutation in human APP, induced overexpression of HES-1 and Hey-1 and reduction of IDE mRNA levels, respectively. Our results support our theory that a Notch-dependent IDE transcriptional modulation may impact on Aβ metabolism providing a functional link between Notch signaling and the amyloidogenic pathway in SAD. PMID:22036964

  11. 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

  12. 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.

  13. Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

    PubMed

    Tundo, Grazia; Ciaccio, Chiara; Sbardella, Diego; Boraso, Mariaserena; Viviani, Barbara; Coletta, Massimiliano; Marini, Stefano

    2012-01-01

    The deposition of β-amyloid (Aβ) into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD). Insulin-degrading-enzyme (IDE) is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Somatostatin Modulates Insulin-Degrading-Enzyme Metabolism: Implications for the Regulation of Microglia Activity in AD

    PubMed Central

    Tundo, Grazia; Ciaccio, Chiara; Sbardella, Diego; Boraso, Mariaserena; Viviani, Barbara; Coletta, Massimiliano; Marini, Stefano

    2012-01-01

    The deposition of β-amyloid (Aβ) into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD). Insulin-degrading-enzyme (IDE) is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity. PMID:22509294

  19. 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

  20. 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.

  1. 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.

  2. Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease.

    PubMed

    Dorfman, Verónica Berta; Pasquini, Laura; Riudavets, Miguel; López-Costa, Juan José; Villegas, Andrés; Troncoso, Juan Carlos; Lopera, Francisco; Castaño, Eduardo Miguel; Morelli, Laura

    2010-10-01

    Alzheimer's disease (AD) is characterized by amyloid beta (A beta) accumulation in the brain and is classified as familial early-onset (FAD) or sporadic late-onset (SAD). Evidences suggest that deficits in the brain expression of insulin degrading enzyme (IDE) and neprilysin (NEP), both proteases involved in amyloid degradation, may promote A beta deposition in SAD. We studied by immunohistochemistry IDE and NEP cortical expression in SAD and FAD samples carrying the E280A presenilin-1 missense mutation. We showed that IDE, a soluble peptidase, is linked with aggregated A beta 40 isoform while NEP, a membrane-bound protease, negatively correlates with amyloid angiopathy and its expression in the senile plaques is independent of aggregated amyloid and restricted to SAD cases. NEP, but not IDE, is over-expressed in dystrophic neurites, both proteases are immunoreactive in activated astrocytes but not in microglia and IDE was the only one detected in astrocytes of white matter from FAD cases. Collectively, our results support the notion that gross conformational changes involved in the modification from "natively folded-active" to "aggregated-inactive" IDE and NEP may be a relevant pathogenic mechanism in SAD. (c) 2008 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. 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

  6. 49 CFR 543.7 - Processing an exemption petition.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Processing an exemption petition. 543.7 Section... § 543.7 Processing an exemption petition. (a) NHTSA processes any complete petition. If a manufacturer submits a petition that does not contain all the information required by this part, NHTSA informs the...

  7. 29 CFR 780.806 - Exempt ginning limited to first processing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... cottonseed, is not exempt under section 13(b)(15). It is not first processing of the seed cotton; rather, it... 29 Labor 3 2013-07-01 2013-07-01 false Exempt ginning limited to first processing. 780.806 Section... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT...

  8. 29 CFR 780.806 - Exempt ginning limited to first processing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... cottonseed, is not exempt under section 13(b)(15). It is not first processing of the seed cotton; rather, it... 29 Labor 3 2012-07-01 2012-07-01 false Exempt ginning limited to first processing. 780.806 Section... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT...

  9. 29 CFR 780.806 - Exempt ginning limited to first processing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... cottonseed, is not exempt under section 13(b)(15). It is not first processing of the seed cotton; rather, it... 29 Labor 3 2011-07-01 2011-07-01 false Exempt ginning limited to first processing. 780.806 Section... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT...

  10. 29 CFR 780.806 - Exempt ginning limited to first processing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... cottonseed, is not exempt under section 13(b)(15). It is not first processing of the seed cotton; rather, it... 29 Labor 3 2010-07-01 2010-07-01 false Exempt ginning limited to first processing. 780.806 Section... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT...

  11. 29 CFR 780.806 - Exempt ginning limited to first processing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... cottonseed, is not exempt under section 13(b)(15). It is not first processing of the seed cotton; rather, it... 29 Labor 3 2014-07-01 2014-07-01 false Exempt ginning limited to first processing. 780.806 Section... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT...

  12. 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)

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 9.4T Human MRI: Preliminary Results

    PubMed Central

    Vaughan, Thomas; DelaBarre, Lance; Snyder, Carl; Tian, Jinfeng; Akgun, Can; Shrivastava, Devashish; Liu, Wanzahn; Olson, Chris; Adriany, Gregor; Strupp, John; Andersen, Peter; Gopinath, Anand; van de Moortele, Pierre-Francois; Garwood, Michael; Ugurbil, Kamil

    2014-01-01

    This work reports the preliminary results of the first human images at the new high-field benchmark of 9.4T. A 65-cm-diameter bore magnet was used together with an asymmetric 40-cm-diameter head gradient and shim set. A multichannel transmission line (transverse electromagnetic (TEM)) head coil was driven by a programmable parallel transceiver to control the relative phase and magnitude of each channel independently. These new RF field control methods facilitated compensation for RF artifacts attributed to destructive interference patterns, in order to achieve homogeneous 9.4T head images or localize anatomic targets. Prior to FDA investigational device exemptions (IDEs) and internal review board (IRB)-approved human studies, preliminary RF safety studies were performed on porcine models. These data are reported together with exit interview results from the first 44 human volunteers. Although several points for improvement are discussed, the preliminary results demonstrate the feasibility of safe and successful human imaging at 9.4T. PMID:17075852

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Inhibition of Insulin Degrading Enzyme and Insulin Degradation by UV-Killed Lactobacillus acidophilus.

    PubMed

    Neyazi, Nadia; Motevaseli, Elahe; Khorramizadeh, Mohammad Reza; Mohammadi Farsani, Taiebeh; Nouri, Zahra; Nasli Esfahani, Ensieh; Ghahremani, Mohammad Hossein

    2018-05-11

    Probiotics have beneficial effects on management of type 2 diabetes (T2D). The major hallmarks of T2D are insulin deficiency and insulin resistance which emphasize insulin therapy in onset of disease. Lactobacilli such as Lactobacillus acidophilus ( L. acidophilus ) have well known properties on prevention of T2D and insulin resistance but not on insulin degradation. Insulin-degrading enzyme (IDE) degrades insulin in the human body. We studied the effects of cell-free supernatant (CFS) and ultraviolet (UV)-killed L. acidophilus (ATCC 314) on IDE activity and insulin degradation in vitro. Cell growth inhibition by CFS and UV-killed L. acidophilus (ATCC 314) was studied and Western blotting and a fluoregenic assay was performed to determine IDE expression and its activity, respectively. Insulin degradation was evaluated by sandwich enzyme-linked immunosorbent assay(ELISA). IDE expression and activity was reduced by CFS and UV-killed L. acidophilus (ATCC 314). Although, decreased enzyme expression and activity was not significant for CFS in contrast to MRL (MRS with same pH as CFS). Also, reduction in IDE activity was not statistically considerable when compared to IDE expression. Insulin degradation was increased by CFS but decreased by UV-killed L. acidophilus (ATCC 314).

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. CoINcIDE: A framework for discovery of patient subtypes across multiple datasets.

    PubMed

    Planey, Catherine R; Gevaert, Olivier

    2016-03-09

    Patient disease subtypes have the potential to transform personalized medicine. However, many patient subtypes derived from unsupervised clustering analyses on high-dimensional datasets are not replicable across multiple datasets, limiting their clinical utility. We present CoINcIDE, a novel methodological framework for the discovery of patient subtypes across multiple datasets that requires no between-dataset transformations. We also present a high-quality database collection, curatedBreastData, with over 2,500 breast cancer gene expression samples. We use CoINcIDE to discover novel breast and ovarian cancer subtypes with prognostic significance and novel hypothesized ovarian therapeutic targets across multiple datasets. CoINcIDE and curatedBreastData are available as R packages.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 29 CFR 779.347 - Exemption limited to “recognized retail establishment”; factories not exempt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Exemption limited to ârecognized retail establishmentâ... Retail or Service Establishments Engaging in Manufacturing and Processing Activities; Section 13(a)(4) § 779.347 Exemption limited to “recognized retail establishment”; factories not exempt. The section 13(a...

  15. 29 CFR 779.347 - Exemption limited to “recognized retail establishment”; factories not exempt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Exemption limited to ârecognized retail establishmentâ... Retail or Service Establishments Engaging in Manufacturing and Processing Activities; Section 13(a)(4) § 779.347 Exemption limited to “recognized retail establishment”; factories not exempt. The section 13(a...

  16. 29 CFR 779.347 - Exemption limited to “recognized retail establishment”; factories not exempt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Exemption limited to ârecognized retail establishmentâ... Retail or Service Establishments Engaging in Manufacturing and Processing Activities; Section 13(a)(4) § 779.347 Exemption limited to “recognized retail establishment”; factories not exempt. The section 13(a...

  17. 29 CFR 779.347 - Exemption limited to “recognized retail establishment”; factories not exempt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Exemption limited to ârecognized retail establishmentâ... Retail or Service Establishments Engaging in Manufacturing and Processing Activities; Section 13(a)(4) § 779.347 Exemption limited to “recognized retail establishment”; factories not exempt. The section 13(a...

  18. 10 CFR 490.308 - Process for granting exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Process for granting exemptions. 490.308 Section 490.308 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel... exemption to the Office of Energy Efficiency and Renewable Energy, U.S. Department of Energy, EE-33, 1000...

  19. 10 CFR 490.308 - Process for granting exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Process for granting exemptions. 490.308 Section 490.308 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel... exemption to the Office of Energy Efficiency and Renewable Energy, U.S. Department of Energy, EE-33, 1000...

  20. 10 CFR 490.308 - Process for granting exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Process for granting exemptions. 490.308 Section 490.308 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel... exemption to the Office of Energy Efficiency and Renewable Energy, U.S. Department of Energy, EE-33, 1000...

  1. 10 CFR 490.308 - Process for granting exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Process for granting exemptions. 490.308 Section 490.308 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel... exemption to the Office of Energy Efficiency and Renewable Energy, U.S. Department of Energy, EE-33, 1000...

  2. Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines.

    PubMed

    Weirich, Gregor; Mengele, Karin; Yfanti, Christina; Gkazepis, Apostolos; Hellmann, Daniela; Welk, Anita; Giersig, Cecylia; Kuo, Wen-Liang; Rosner, Marsha Rich; Tang, Wei-Jen; Schmitt, Manfred

    2008-11-01

    Immunohistochemical evidence of ubiquitous distribution of the metalloprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cells is presented. Immunohistochemical staining was performed on a multi-organ tissue microarray (pancreas, lung, kidney, central/peripheral nervous system, liver, breast, placenta, myocardium, striated muscle, bone marrow, thymus, and spleen) and on a cell microarray of 31 tumor cell lines of different origin, as well as trophoblast cells and normal blood lymphocytes and granulocytes. IDE protein was expressed in all the tissues assessed and all the tumor cell lines except for Raji and HL-60. Trophoblast cells and granulocytes, but not normal lymphocytes, were also IDE-positive.

  3. Immunohistochemical evidence for ubiquitous distribution of metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines

    PubMed Central

    Weirich, Gregor; Mengele, Karin; Yfanti, Christina; Gkazepis, Apostolos; Hellmann, Daniela; Welk, Anita; Giersig, Cecylia; Kuo, Wen-Liang; Rosner, Marsha Rich; Tang, Wei-Jen; Schmitt, Manfred

    2013-01-01

    Immunohistochemical evidence for ubiquitous distribution of metalloprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cells is presented. Immunohistochemical staining was performed on a multi-organ tissue microarray (pancreas, lung, kidney, central/peripheral nervous system, liver, breast, placenta, myocardium, striated muscle, bone marrow, thymus, spleen) and on a cell microarray encompassing 31 tumor cell lines of different origin plus trophoblast cells, and normal blood lymphocytes and granulocytes. IDE protein is expressed by all of the tissues assessed and in all of the tumor cell lines except Raji and HL-60; trophoblast cells and granulocytes but not normal lymphocytes are also IDE-positive. PMID:18783335

  4. Agricultural Handling and Processing Industries; Data Pertinent to an Evaluation of Overtime Exemptions Available under the Fair Labor Standards Act. Volume I.

    ERIC Educational Resources Information Center

    Wage and Labor Standards Administration (DOL), Washington, DC.

    This report covers the major agricultural handling and processing industries qualifying for partial overtime exemption under the Fair Labor Standards Act and evaluates the need for such exemptions. Questionnaires which were sent to firms in various processing industries provide data on nearly 4,000 processors. The results show that existing…

  5. 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...

  6. 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.

  7. The Food and Drug Administration and pragmatic clinical trials of marketed medical products

    PubMed Central

    Anderson, Monique L; Griffin, Joseph; Goldkind, Sara F; Zeitler, Emily P; Wing, Liz; Al-Khatib, Sana M; Sherman, Rachel E

    2015-01-01

    Pragmatic clinical trials (PCTs) can help answer questions of comparative effectiveness for interventions routinely used in medical practice. PCTs may examine outcomes of one or more marketed medical products, and they are heterogeneous in design and risk. The Food and Drug Administration (FDA) is charged with protecting the rights, safety, and welfare of individuals enrolled in clinical investigations, as well as assuring the integrity upon which approval of medical products are made. The FDA has broad jurisdiction over drugs and medical devices (whether or not they are approved for marketing), and as such, clinical investigations of these products are subject to applicable FDA regulations. While many PCTs will meet the criteria for an exemption from the requirements for an investigational new drug application (IND) or investigational device exemption (IDE), in general all clinical investigations of medical products that fall under FDA jurisdiction must adhere to regulations for informed consent and review by an institutional review board (IRB). We are concerned that current FDA requirements for obtaining individual informed consent may deter or delay the conduct of PCTs intended to develop reliable evidence of comparative safety and effectiveness of approved medical products that are regulated by the FDA. Under current regulations, there are no described mechanisms to alter or waive informed consent to make it less burdensome or more practicable for low-risk PCTs. We recommend that the FDA establish a risk-based approach to obtaining informed consent in PCTs that would facilitate the conduct of PCTs without compromising the protection of enrolled individuals or the integrity of the resulting data. PMID:26374684

  8. Use of Fees to Discourage Nonmedical Exemptions to School Immunization Laws in US States

    PubMed Central

    Omer, Saad B.

    2016-01-01

    Recent outbreaks of vaccine-preventable diseases in the United States have renewed public discourse about state vaccine mandates for children entering schools. With acknowledgment of the challenge of eliminating religious and philosophical exemptions in most states, some have proposed instead to impose additional administrative burdens for parents seeking such exemptions. We review the use of taxes, fines, and fees as financial disincentives in public health. We argue that adding processing fees to a comprehensive set of administrative requirements for obtaining exemptions will avoid the use of taxpayer funding for exemption processing and will help tilt the balance of convenience in favor of vaccination. PMID:26691132

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 40 CFR 180.7 - Petitions proposing tolerances or exemptions for pesticide residues in or on raw agricultural...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Petitions proposing tolerances or exemptions for pesticide residues in or on raw agricultural commodities or processed foods. 180.7 Section 180... proposing tolerances or exemptions for pesticide residues in or on raw agricultural commodities or processed...

  14. 40 CFR 180.7 - Petitions proposing tolerances or exemptions for pesticide residues in or on raw agricultural...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Petitions proposing tolerances or exemptions for pesticide residues in or on raw agricultural commodities or processed foods. 180.7 Section 180... proposing tolerances or exemptions for pesticide residues in or on raw agricultural commodities or processed...

  15. 9 CFR 590.610 - Criteria for exemption.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.610 Criteria for exemption. Any plant processing egg products may qualify for... required for official egg products plants as are contained in §§ 590.500 through 590.580, and such exempted...

  16. 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.

  17. 9 CFR 590.650 - Exempted plant registration number.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

  18. 9 CFR 590.650 - Exempted plant registration number.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 29 CFR 779.347 - Exemption limited to “recognized retail establishment”; factories not exempt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... under the exemption are custom tailor shops, candy shops, ice cream parlors, bakeries, drug stores, optometrist establishments, retail ice plants and other local retail establishments which make or process the...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 14 CFR 298.22 - Processing by the Department.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PROCEEDINGS) ECONOMIC REGULATIONS EXEMPTIONS FOR AIR TAXI AND COMMUTER AIR CARRIER OPERATIONS Registration for Exemption by Air Taxi Operators § 298.22 Processing by the Department. After examination of the OST Form...

  16. 14 CFR 298.22 - Processing by the Department.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... PROCEEDINGS) ECONOMIC REGULATIONS EXEMPTIONS FOR AIR TAXI AND COMMUTER AIR CARRIER OPERATIONS Registration for Exemption by Air Taxi Operators § 298.22 Processing by the Department. After examination of the OST Form...

  17. 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

  18. Test Marketing Exemption (TME) for New Chemical Review under TSCA

    EPA Pesticide Factsheets

    Under section 5 of TSCA, EPA established an exemption for certain chemicals that are manufactured (including imported) for test marketing. You can learn more here about the requirements of this exemption, along with the review and submission process.

  19. 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.

  20. 7 CFR 1170.9 - Price reporting exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Any manufacturer that processes and markets less than 1 million pounds of butter per calendar year is exempt from reporting butter sales as specified in § 1170.8(b). (c) Any manufacturer that processes and...

  1. 7 CFR 1170.9 - Price reporting exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Any manufacturer that processes and markets less than 1 million pounds of butter per calendar year is exempt from reporting butter sales as specified in § 1170.8(b). (c) Any manufacturer that processes and...

  2. 7 CFR 1170.9 - Price reporting exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Any manufacturer that processes and markets less than 1 million pounds of butter per calendar year is exempt from reporting butter sales as specified in § 1170.8(b). (c) Any manufacturer that processes and...

  3. 7 CFR 1170.9 - Price reporting exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Any manufacturer that processes and markets less than 1 million pounds of butter per calendar year is exempt from reporting butter sales as specified in § 1170.8(b). (c) Any manufacturer that processes and...

  4. 7 CFR 1170.9 - Price reporting exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Any manufacturer that processes and markets less than 1 million pounds of butter per calendar year is exempt from reporting butter sales as specified in § 1170.8(b). (c) Any manufacturer that processes and...

  5. 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…

  6. 78 FR 46617 - Vogtle Electric Generating Station, Units 3 and 4; Southern Nuclear Operating Company; Change to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ...-92, issued to the licensee. The exemption is required by Paragraph A.4 of Section VIII, ``Processes... reduction in standardization caused by the exemption; and F. The exemption will not result in a significant...

  7. 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

  8. Efficient programming of human eye conjunctiva-derived induced pluripotent stem (ECiPS) cells into definitive endoderm-like cells.

    PubMed

    Massumi, Mohammad; Hoveizi, Elham; Baktash, Parvaneh; Hooti, Abdollah; Ghazizadeh, Leili; Nadri, Samad; Pourasgari, Farzaneh; Hajarizadeh, Athena; Soleimani, Masoud; Nabiuni, Mohammad; Khorramizadeh, Mohammad R

    2014-03-10

    Due to pluripotency of induced pluripotent stem (iPS) cells, and the lack of immunological incompatibility and ethical issues, iPS cells have been considered as an invaluable cell source for future cell replacement therapy. This study was aimed first at establishment of novel iPS cells, ECiPS, which directly reprogrammed from human Eye Conjunctiva-derived Mesenchymal Stem Cells (EC-MSCs); second, comparing the inductive effects of Wnt3a/Activin A biomolecules to IDE1 small molecule in derivation of definitive endoderm (DE) from the ECiPS cells. To that end, first, the EC-MSCs were transduced by SOKM-expressing lentiviruses and characterized for endogenous expression of embryonic markers Then the established ECiPS cells were induced to DE formation by Wnt3a/Activin A or IDE1. Quantification of GSC, Sox17 and Foxa2 expression, as DE-specific markers, in both mRNA and protein levels revealed that induction of ECiPS cells by either Wnt3a/Activin A or IDE1 could enhance the expression level of the genes; however the levels of increase were higher in Wnt3a/Activin A induced ECiPS-EBs than IDE1 induced cells. Furthermore, the flow cytometry analyses showed no synergistic effect between Activin A and Wnt3a to derive DE-like cells from ECiPS cells. The comparative findings suggest that although both Wnt3a/Activin A signaling and IDE1 molecule could be used for differentiation of iPS into DE cells, the DE-inducing effect of Wnt3a/Activin A was statistically higher than IDE1. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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.

  10. 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.

  11. 9 CFR 590.680 - Approval of labeling for egg products processed in exempted egg products processing plants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Approval of labeling for egg products processed in exempted egg products processing plants. 590.680 Section 590.680 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF...

  12. 9 CFR 590.680 - Approval of labeling for egg products processed in exempted egg products processing plants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Approval of labeling for egg products processed in exempted egg products processing plants. 590.680 Section 590.680 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF...

  13. 31 CFR 132.4 - Exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Exemptions. 132.4 Section 132.4 Money and Finance: Treasury Regulations Relating to Money and Finance PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING § 132.4 Exemptions. (a) Automated clearing house systems. The participants processing a...

  14. 9 CFR 381.11 - Exemptions based on religious dietary laws.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Exemptions based on religious dietary... OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION... Exemptions based on religious dietary laws. (a) Any person who slaughters, processes, or otherwise handles...

  15. 9 CFR 381.11 - Exemptions based on religious dietary laws.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Exemptions based on religious dietary... OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION... Exemptions based on religious dietary laws. (a) Any person who slaughters, processes, or otherwise handles...

  16. 9 CFR 381.11 - Exemptions based on religious dietary laws.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Exemptions based on religious dietary... OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION... Exemptions based on religious dietary laws. (a) Any person who slaughters, processes, or otherwise handles...

  17. 9 CFR 381.11 - Exemptions based on religious dietary laws.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Exemptions based on religious dietary... OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION... Exemptions based on religious dietary laws. (a) Any person who slaughters, processes, or otherwise handles...

  18. 29 CFR 780.504 - Basic conditions of exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Employment or Agricultural Employees in Processing Shade-Grown Tobacco; Exemption From Minimum Wage and... 29 Labor 3 2010-07-01 2010-07-01 false Basic conditions of exemption. 780.504 Section 780.504 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS...

  19. 29 CFR 784.149 - Typical operations that may qualify for exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... THE FAIR LABOR STANDARDS ACT APPLICABLE TO FISHING AND OPERATIONS ON AQUATIC PRODUCTS Exemptions Provisions Relating to Fishing and Aquatic Products Processing, Freezing, and Curing § 784.149 Typical operations that may qualify for exemption. Such operations as transporting the specified aquatic products to...

  20. 29 CFR 784.149 - Typical operations that may qualify for exemption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... THE FAIR LABOR STANDARDS ACT APPLICABLE TO FISHING AND OPERATIONS ON AQUATIC PRODUCTS Exemptions Provisions Relating to Fishing and Aquatic Products Processing, Freezing, and Curing § 784.149 Typical operations that may qualify for exemption. Such operations as transporting the specified aquatic products to...

  1. 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.

  2. 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.

  3. 40 CFR 763.173 - Exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... prohibitions imposed by § 763.165, § 763.167, or § 763.169 may file an application for an exemption. Persons whose exemption applications are approved by the Agency may manufacture, import, process, or distribute in commerce the banned product as specified in the Agency's approval of the application. No applicant...

  4. 9 CFR 590.640 - Application for exemption; approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.640 Application for exemption; approval. Any person desiring to process egg..., a Supervisory Egg Products Inspector will make a survey and inspection of the premises and plant to...

  5. 29 CFR 780.405 - Exemption is direct and does not mean activities are agriculture.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... agriculture. 780.405 Section 780.405 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture or Irrigation That Is Exempted From the Overtime Pay...

  6. 29 CFR 780.405 - Exemption is direct and does not mean activities are agriculture.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... agriculture. 780.405 Section 780.405 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture or Irrigation That Is Exempted From the Overtime Pay...

  7. 29 CFR 780.405 - Exemption is direct and does not mean activities are agriculture.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... agriculture. 780.405 Section 780.405 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture or Irrigation That Is Exempted From the Overtime Pay...

  8. 29 CFR 780.405 - Exemption is direct and does not mean activities are agriculture.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... agriculture. 780.405 Section 780.405 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture or Irrigation That Is Exempted From the Overtime Pay...

  9. 29 CFR 780.405 - Exemption is direct and does not mean activities are agriculture.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... agriculture. 780.405 Section 780.405 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture or Irrigation That Is Exempted From the Overtime Pay...

  10. 40 CFR 180.7 - Petitions proposing tolerances or exemptions for pesticide residues in or on raw agricultural...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... exemptions for pesticide residues in or on raw agricultural commodities or processed foods. 180.7 Section 180.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.7 Petitions...

  11. 40 CFR 180.7 - Petitions proposing tolerances or exemptions for pesticide residues in or on raw agricultural...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... exemptions for pesticide residues in or on raw agricultural commodities or processed foods. 180.7 Section 180.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.7 Petitions...

  12. 40 CFR 180.7 - Petitions proposing tolerances or exemptions for pesticide residues in or on raw agricultural...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... exemptions for pesticide residues in or on raw agricultural commodities or processed foods. 180.7 Section 180.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.7 Petitions...

  13. 9 CFR 590.650 - Exempted plant registration number.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Exempted plant registration number. 590.650 Section 590.650 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

  14. 9 CFR 590.650 - Exempted plant registration number.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Exempted plant registration number. 590.650 Section 590.650 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

  15. 9 CFR 590.650 - Exempted plant registration number.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Exempted plant registration number. 590.650 Section 590.650 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

  16. 9 CFR 590.640 - Application for exemption; approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.640 Application for exemption; approval. Any person desiring to process egg..., a Supervisory Egg Products Inspector will make a survey and inspection of the premises and plant to...

  17. 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

  18. 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

  19. 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...

  20. 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

  1. 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

  2. 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

  3. 21 CFR 1308.35 - Exemption of certain cannabis plant material, and products made therefrom, that contain...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exemption of certain cannabis plant material, and... ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Exempt Cannabis Plant... cannabis plant material, and products made therefrom, that contain tetrahydrocannabinols. (a) Any processed...

  4. 21 CFR 1308.35 - Exemption of certain cannabis plant material, and products made therefrom, that contain...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exemption of certain cannabis plant material, and... ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Exempt Cannabis Plant... cannabis plant material, and products made therefrom, that contain tetrahydrocannabinols. (a) Any processed...

  5. 21 CFR 1308.35 - Exemption of certain cannabis plant material, and products made therefrom, that contain...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exemption of certain cannabis plant material, and... ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Exempt Cannabis Plant... cannabis plant material, and products made therefrom, that contain tetrahydrocannabinols. (a) Any processed...

  6. 29 CFR 780.815 - Basic conditions of exemption; second part, processing of sugar beets, sugar-beet molasses...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sugar beets, sugar-beet molasses, sugarcane, or maple sap. 780.815 Section 780.815 Labor Regulations... Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap into Sugar or Syrup... Quantities § 780.815 Basic conditions of exemption; second part, processing of sugar beets, sugar-beet...

  7. 29 CFR 780.815 - Basic conditions of exemption; second part, processing of sugar beets, sugar-beet molasses...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... sugar beets, sugar-beet molasses, sugarcane, or maple sap. 780.815 Section 780.815 Labor Regulations... Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap into Sugar or Syrup... Quantities § 780.815 Basic conditions of exemption; second part, processing of sugar beets, sugar-beet...

  8. 29 CFR 780.815 - Basic conditions of exemption; second part, processing of sugar beets, sugar-beet molasses...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... sugar beets, sugar-beet molasses, sugarcane, or maple sap. 780.815 Section 780.815 Labor Regulations... Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap into Sugar or Syrup... Quantities § 780.815 Basic conditions of exemption; second part, processing of sugar beets, sugar-beet...

  9. 29 CFR 780.815 - Basic conditions of exemption; second part, processing of sugar beets, sugar-beet molasses...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sugar beets, sugar-beet molasses, sugarcane, or maple sap. 780.815 Section 780.815 Labor Regulations... Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap into Sugar or Syrup... Quantities § 780.815 Basic conditions of exemption; second part, processing of sugar beets, sugar-beet...

  10. 29 CFR 780.815 - Basic conditions of exemption; second part, processing of sugar beets, sugar-beet molasses...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... sugar beets, sugar-beet molasses, sugarcane, or maple sap. 780.815 Section 780.815 Labor Regulations... Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap into Sugar or Syrup... Quantities § 780.815 Basic conditions of exemption; second part, processing of sugar beets, sugar-beet...

  11. 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

  12. 29 CFR 780.522 - Nonprocessing employees.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Nonprocessing employees. 780.522 Section 780.522 Labor... Agricultural Employees in Processing Shade-Grown Tobacco; Exemption From Minimum Wage and Overtime Pay Requirements Under Section 13(a)(14) Exempt Processing § 780.522 Nonprocessing employees. Only those employees...

  13. 40 CFR Appendix Xiii to Part 266 - Mercury Bearing Wastes That May Be Processed in Exempt Mercury Recovery Units

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... are exempt mercury-bearing materials with less than 500 ppm of 40 CFR Part 261, appendix VIII organic... tank sludge 13. Mercury cell process solids 14. Recoverable levels of mercury contained in soil [59 FR...

  14. 40 CFR Appendix Xiii to Part 266 - Mercury Bearing Wastes That May Be Processed in Exempt Mercury Recovery Units

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... are exempt mercury-bearing materials with less than 500 ppm of 40 CFR Part 261, appendix VIII organic... tank sludge 13. Mercury cell process solids 14. Recoverable levels of mercury contained in soil [59 FR...

  15. 40 CFR Appendix Xiii to Part 266 - Mercury Bearing Wastes That May Be Processed in Exempt Mercury Recovery Units

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... are exempt mercury-bearing materials with less than 500 ppm of 40 CFR Part 261, appendix VIII organic... tank sludge 13. Mercury cell process solids 14. Recoverable levels of mercury contained in soil [59 FR...

  16. 40 CFR Appendix Xiii to Part 266 - Mercury Bearing Wastes That May Be Processed in Exempt Mercury Recovery Units

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... are exempt mercury-bearing materials with less than 500 ppm of 40 CFR Part 261, appendix VIII organic... tank sludge 13. Mercury cell process solids 14. Recoverable levels of mercury contained in soil [59 FR...

  17. 40 CFR Appendix Xiii to Part 266 - Mercury Bearing Wastes That May Be Processed in Exempt Mercury Recovery Units

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... are exempt mercury-bearing materials with less than 500 ppm of 40 CFR Part 261, appendix VIII organic... tank sludge 13. Mercury cell process solids 14. Recoverable levels of mercury contained in soil [59 FR...

  18. 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.

  19. 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.

  20. Gene expression levels as endophenotypes in genome-wide association studies of Alzheimer disease

    PubMed Central

    Zou, F.; Carrasquillo, M. M.; Pankratz, V. S.; Belbin, O.; Morgan, K.; Allen, M.; Wilcox, S. L.; Ma, L.; Walker, L. P.; Kouri, N.; Burgess, J. D.; Younkin, L. H.; Younkin, Samuel G.; Younkin, C. S.; Bisceglio, G. D.; Crook, J. E.; Dickson, D. W.; Petersen, R. C.; Graff-Radford, N.; Younkin, Steven G.; Ertekin-Taner, N.

    2010-01-01

    Background: Late-onset Alzheimer disease (LOAD) is a common disorder with a substantial genetic component. We postulate that many disease susceptibility variants act by altering gene expression levels. Methods: We measured messenger RNA (mRNA) expression levels of 12 LOAD candidate genes in the cerebella of 200 subjects with LOAD. Using the genotypes from our LOAD genome-wide association study for the cis-single nucleotide polymorphisms (SNPs) (n = 619) of these 12 LOAD candidate genes, we tested for associations with expression levels as endophenotypes. The strongest expression cis-SNP was tested for AD association in 7 independent case-control series (2,280 AD and 2,396 controls). Results: We identified 3 SNPs that associated significantly with IDE (insulin degrading enzyme) expression levels. A single copy of the minor allele for each significant SNP was associated with ∼twofold higher IDE expression levels. The most significant SNP, rs7910977, is 4.2 kb beyond the 3′ end of IDE. The association observed with this SNP was significant even at the genome-wide level (p = 2.7 × 10−8). Furthermore, the minor allele of rs7910977 associated significantly (p = 0.0046) with reduced LOAD risk (OR = 0.81 with a 95% CI of 0.70-0.94), as expected biologically from its association with elevated IDE expression. Conclusions: These results provide strong evidence that IDE is a late-onset Alzheimer disease (LOAD) gene with variants that modify risk of LOAD by influencing IDE expression. They also suggest that the use of expression levels as endophenotypes in genome-wide association studies may provide a powerful approach for the identification of disease susceptibility alleles. GLOSSARY AD = Alzheimer disease; CI = confidence interval; GWAS = genome-wide association study; LOAD = late-onset Alzheimer disease; mRNA = messenger RNA; OR = odds ratio; SNP = single nucleotide polymorphism. PMID:20142614

  1. 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

  2. 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/.

  3. 10 CFR 490.204 - Process for granting exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Process for granting exemptions. 490.204 Section 490.204 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Mandatory State...) Alternative fuels that meet the normal requirements and practices of the principal business of the State fleet...

  4. 10 CFR 490.204 - Process for granting exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Process for granting exemptions. 490.204 Section 490.204 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Mandatory State...) Alternative fuels that meet the normal requirements and practices of the principal business of the State fleet...

  5. 10 CFR 490.204 - Process for granting exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Process for granting exemptions. 490.204 Section 490.204 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Mandatory State...) Alternative fuels that meet the normal requirements and practices of the principal business of the State fleet...

  6. 10 CFR 490.204 - Process for granting exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Process for granting exemptions. 490.204 Section 490.204 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Mandatory State...) Alternative fuels that meet the normal requirements and practices of the principal business of the State fleet...

  7. 76 FR 11830 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... Effectiveness of Proposed Rule Change to Eliminate Duplicative Filings Under FINRA Rule 9610(a) February 25... the proposed change will make the process of seeking exemptive relief more efficient by eliminating... the efficiency of the exemptive relief process by eliminating duplicative filings and providing...

  8. 40 CFR 750.11 - Filing of petitions for exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Any person seeking an exemption from the PCB manufacturing ban imposed by section 6(e)(3)(A) of TSCA... to: (1) PCB use, which includes storage for use or reuse, manufacture, processing related to...., Washington, DC 20460-0001. (2) PCB disposal, which includes cleanup, storage for disposal, processing related...

  9. 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…

  10. 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…

  11. 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

  12. 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…

  13. 9 CFR 590.100 - Specific exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... inspection of processing operations in section 5(a) of the Act: Provided, That the conditions for exemption... limited to bakeries, restaurants, and other food processors, without continuous inspection, of certain...

  14. 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

  15. 29 CFR 780.322 - Is employed on the same farm as his parent or persons standing in the place of his parent.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND... “employed on the same farm” are accorded their natural meaning with the usual caution, however, that as in the case of all other exemptions, the exemptive language is to be construed narrowly. (See § 780.2...

  16. 29 CFR 780.322 - Is employed on the same farm as his parent or persons standing in the place of his parent.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND... “employed on the same farm” are accorded their natural meaning with the usual caution, however, that as in the case of all other exemptions, the exemptive language is to be construed narrowly. (See § 780.2...

  17. 29 CFR 780.322 - Is employed on the same farm as his parent or persons standing in the place of his parent.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND... “employed on the same farm” are accorded their natural meaning with the usual caution, however, that as in the case of all other exemptions, the exemptive language is to be construed narrowly. (See § 780.2...

  18. 29 CFR 780.322 - Is employed on the same farm as his parent or persons standing in the place of his parent.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND... “employed on the same farm” are accorded their natural meaning with the usual caution, however, that as in the case of all other exemptions, the exemptive language is to be construed narrowly. (See § 780.2...

  19. 29 CFR 780.322 - Is employed on the same farm as his parent or persons standing in the place of his parent.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND... “employed on the same farm” are accorded their natural meaning with the usual caution, however, that as in the case of all other exemptions, the exemptive language is to be construed narrowly. (See § 780.2...

  20. Supreme Court Rejects Coach's Plea, Exempts NCAA from Constitution's Due-Process Requirement.

    ERIC Educational Resources Information Center

    Lederman, Douglas

    1989-01-01

    The Supreme Court ruled that the National Collegiate Athletic Association is not a governmental entity, enhancing the NCAA's powers by exempting it from constitutional guarantees that governments must act according to due process of law. A dichotomy between the ability of universities to implement NCAA penalties is seen. (MLW)

  1. 40 CFR 63.1094 - What waste streams are exempt from the requirements of this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CATEGORIES (CONTINUED) National Emission Standards for Ethylene Manufacturing Process Units: Heat Exchange... section are exempt from this subpart. (a) Waste in the form of gases or vapors that is emitted from process fluids. (b) Waste that is contained in a segregated storm water sewer system. Waste Requirements ...

  2. Marketing approval for the lithotripter.

    PubMed

    Nightingale, S L; Young, F E

    1986-01-01

    In December 1984, the Food and Drug Administration (FDA) granted Dornier Systems (FRG) approval to market the external shock wave lithotripter (ESWL) in the USA. The Medical Device Amendments of the Food, Drug, and Cosmetic Act require that the FDA evaluate the safety and effectiveness of medical devices intended for commercial distribution in the U.S. Such evaluation includes basic scientific studies, animal testing, and investigational studies in human subjects, culminating in a judgment concerning acceptable risks in terms of anticipated benefits, and whether the device is effective for its intended use. Prior to human studies in West Germany, Dornier had evaluated the destruction of stones of varying composition, measured the rate and energy of stone destruction, and tested blood samples and lymphocyte cultures exposed to shock waves. In addition, studies in both rats and dogs had demonstrated the feasibility of the technique and evidence of safety. Such data are provided by manufacturers when applying for an investigational device exemption (IDE) from the FDA, which permits clinical studies in humans; such studies also require the approval of an Institutional Review Board. The FDA approved Dornier's IDE, allowing human investigational use of the ESWL in facilities in the U.S., conducted concurrently with similar studies in West Germany. Upon completion of clinical trials, data acquired in vitro, in laboratory animals, and in human investigations are submitted to the FDA for a premarked approval application (PMAA). The Agency was given 6 months to make a decision, taking into consideration the recommendation of an advisory panel of experts from outside the Agency who had reviewed the same data. In its evaluation of the ESWL for safety and effectiveness, the FDA considered the question of alternative practices and procedures to treat nephrolithiasis, including percutaneous nephrolithotomy and open surgical procedures, and the adverse effects of such procedures. Clinical data available at the time of review for approval included reports of treatment of 667 patients in West German centers, and 327 patients treated in three U.S. facilities. Dornier and the FDA initiated discussions concerning the labeling of the device and a postmarketing surveillance plan. These were completed and marketing approval for the ESWL was granted.

  3. 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.

  4. 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

  5. 47 CFR 1.1204 - Exempt ex parte presentations and proceedings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... decision-making process, unless it fits within another exemption not requiring disclosure (e.g., foreign... to avoid interference with an investigation, a determination will be made in the discretion of the...

  6. 47 CFR 1.1204 - Exempt ex parte presentations and proceedings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... process, unless it fits within another exemption not requiring disclosure (e.g., foreign affairs). The... to avoid interference with an investigation, a determination will be made in the discretion of the...

  7. 47 CFR 1.1204 - Exempt ex parte presentations and proceedings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... decision-making process, unless it fits within another exemption not requiring disclosure (e.g., foreign... to avoid interference with an investigation, a determination will be made in the discretion of the...

  8. 47 CFR 1.1204 - Exempt ex parte presentations and proceedings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... decision-making process, unless it fits within another exemption not requiring disclosure (e.g., foreign... to avoid interference with an investigation, a determination will be made in the discretion of the...

  9. 29 CFR 780.915 - “Place of first processing.”

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Fruit and Vegetable Harvest Transportation; Exemption From Overtime Pay Requirements Under Section 13(b)(16) Exempt Operations on Fruits Or Vegetables § 780.915 “Place of first processing.” Under section 13(b)(16) the fruits or vegetables may be transported to only two types of places. One is a “place of...

  10. 40 CFR 763.173 - Exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT ASBESTOS Prohibition of the Manufacture, Importation, Processing, and Distribution in Commerce of Certain Asbestos... Pennsylvania Ave., NW., Washington, DC 20460, ATTENTION: Asbestos Exemption. For information regarding the...

  11. 16 CFR 802.60 - Acquisitions by securities underwriters.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 EXEMPTION RULES § 802.60... underwriter, in the ordinary course of business, and in the process of underwriting, shall be exempt from the...

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Information to be Submitted with 2016 Renewable Fuel Standard (RFS) Small Refinery Hardship Exemption Requests

    EPA Pesticide Factsheets

    This December 6, 2016 letter from EPA provides information about the petition submission process for small refineries seeking exemptions from their 2016 RFS obligations, including financial and other information necessary for evaluation.

  4. 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.

  5. 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

  6. 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.

  7. 50 CFR 453.01 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.01 Purpose. This part prescribes the procedures to be used by the Endangered Species Committee when examining applications for exemption from section 7(a)(2) of the Endangered Species Act of...

  8. 50 CFR 453.01 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.01 Purpose. This part prescribes the procedures to be used by the Endangered Species Committee when examining applications for exemption from section 7(a)(2) of the Endangered Species Act of...

  9. 50 CFR 453.01 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.01 Purpose. This part prescribes the procedures to be used by the Endangered Species Committee when examining applications for exemption from section 7(a)(2) of the Endangered Species Act of...

  10. 50 CFR 453.01 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.01 Purpose. This part prescribes the procedures to be used by the Endangered Species Committee when examining applications for exemption from section 7(a)(2) of the Endangered Species Act of...

  11. 50 CFR 453.01 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.01 Purpose. This part prescribes the procedures to be used by the Endangered Species Committee when examining applications for exemption from section 7(a)(2) of the Endangered Species Act of...

  12. 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.

  13. Notification: Evaluation of EPA’s Federal Insecticide, Fungicide, and Rodenticide Act Section 18 Emergency Exemptions

    EPA Pesticide Factsheets

    Project #OPE-FY17-0024, August 21, 2017. The EPA OIG plans to begin preliminary research on the emergency exemption process used by the EPA’s Office of Chemical Safety and Pollution Prevention’s Office of Pesticide Programs.

  14. Enhancing Coordination and Communication with States on Review and Approval of Aquifer Exemption Requests

    EPA Pesticide Factsheets

    The memorandum in the link provided is for Underground Injection Control (UIC) program managers and is intended to promote a consistent and predictable process for the review of aquifer exemption requests under the Safe Drinking Water Act (SDWA).

  15. 29 CFR 780.501 - Statutory provision.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Agricultural Employees in Processing Shade-Grown Tobacco; Exemption From Minimum Wage and Overtime Pay... Labor Standards Act exempts from the minimum wage requirements of section 6 of the Act and from the... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL...

  16. 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.

  17. Enhancing Coordination and Communication with States on Review and Approval of Aquifer Exemption Requests Under SDWA

    EPA Pesticide Factsheets

    The memorandum in the link provided is for Underground Injection Control (UIC) program managers and is intended to promote a consistent and predictable process for the review of aquifer exemption requests under the Safe Drinking Water Act (SDWA).

  18. 78 FR 41117 - Virgil C. Summer Nuclear Station, Units 2 and 3; South Carolina Electric and Gas; Change to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ... VIII, ``Processes for Changes and Departures,'' Appendix D to 10 CFR Part 52 to allow the licensee to... reduction in standardization caused by the exemption; and F. the exemption will not result in a significant...

  19. 78 FR 32278 - Vogtle Electric Generating Station, Units 3 and 4; Southern Nuclear Operating Company; Change to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    ... Paragraph A.4 of Section VIII, ``Processes for Changes and Departures,'' Appendix D to 10 CFR part 52 to... standardization caused by the exemption; and F. the exemption will not result in a significant decrease in the...

  20. 40 CFR 725.428 - Requirements for the Tier II exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SUBSTANCES CONTROL ACT REPORTING REQUIREMENTS AND REVIEW PROCESSES FOR MICROORGANISMS General Exemptions for... material meets the criteria under § 725.421. (c) Adequate physical containment and control technologies are used. The criteria listed under § 725.422 for physical containment and control technologies of...

  1. 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.

  2. Mandatory influenza vaccination of health care workers: translating policy to practice.

    PubMed

    Babcock, Hilary M; Gemeinhart, Nancy; Jones, Marilyn; Dunagan, W Claiborne; Woeltje, Keith F

    2010-02-15

    Influenza vaccination of health care workers has been recommended since 1984. Multiple strategies to enhance vaccination rates have been suggested, but national rates have remained low. BJC HealthCare is a large Midwestern health care organization with approximately 26,000 employees. Because organizational vaccination rates remained below target levels, influenza vaccination was made a condition of employment for all employees in 2008. Medical or religious exemptions could be requested. Predetermined medical contraindications include hypersensitivity to eggs, prior hypersensitivity reaction to influenza vaccine, and history of Guillan-Barré syndrome. Medical exemption requests were reviewed by occupational health nurses and their medical directors. Employees who were neither vaccinated nor exempted by 15 December 2008 were not scheduled for work. Employees still not vaccinated or exempt by 15 January 2009 were terminated. Overall, 25,561 (98.4%) of 25,980 active employees were vaccinated. Ninety employees (0.3%) received religious exemptions, and 321 (1.2%) received medical exemptions. Eight employees (0.03%) were not vaccinated or exempted. Reasons for medical exemption included allergy to eggs (107 [33%]), prior allergic reaction or allergy to other vaccine component (83 [26%]), history of Guillan-Barré syndrome (15 [5%]), and other (116 [36%]), including 14 because of pregnancy. Many requests reflected misinformation about the vaccine. A mandatory influenza vaccination campaign successfully increased vaccination rates. Fewer employees sought medical or religious exemptions than had signed declination statements during the previous year. A standardized medical exemption request form would simplify the request and review process for employees, their physicians, and occupational health and will be used next year.

  3. 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

  4. 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

  5. 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

  6. 77 FR 29755 - Advisory Group to the Internal Revenue Service Tax Exempt and Government Entities Division (TE/GE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ...; Washington, DC. Issues to be discussed relate to Employee Plans, Exempt Organizations, and Government Entities. Reports from five ACT subgroups cover the following topics: Employee Plans: --Analysis and Recommendations Regarding the Scope of the Employee Plans Examination Process [[Page 29756

  7. 29 CFR 780.606 - Interpretation of term “agriculture.”

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.606 Interpretation of term “agriculture.” Section 3(f) of the Act, which defines...

  8. 29 CFR 780.606 - Interpretation of term “agriculture.”

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.606 Interpretation of term “agriculture.” Section 3(f) of the Act, which defines...

  9. 29 CFR 780.606 - Interpretation of term “agriculture.”

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.606 Interpretation of term “agriculture.” Section 3(f) of the Act, which defines...

  10. 29 CFR 780.606 - Interpretation of term “agriculture.”

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.606 Interpretation of term “agriculture.” Section 3(f) of the Act, which defines...

  11. 29 CFR 780.606 - Interpretation of term “agriculture.”

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.606 Interpretation of term “agriculture.” Section 3(f) of the Act, which defines...

  12. 49 CFR 1150.36 - Exempt construction of connecting track.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... environmental issues have been raised or discovered during the environmental review process, the Board shall... significant environmental issues have been raised or discovered, the Board, through the Director of the Office... environmental issues cannot be made prior to the date that the exemption authority would otherwise become...

  13. 40 CFR 63.775 - Reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... operator of a glycol dehydration unit subject to this subpart that is exempt from the control requirements for glycol dehydration unit process vents in § 63.765, is exempt from all reporting requirements for....0 or higher and documentation stating why the TEG dehydration unit must operate using the alternate...

  14. 7 CFR 205.101 - Exemptions and exclusions from certification.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... products as “organic” but whose gross agricultural income from organic sales totals $5,000 or less annually... from such operations shall not be used as ingredients identified as organic in processed products... organic ingredients by total weight of the finished product (excluding water and salt) is exempt from the...

  15. 10 CFR 490.204 - Process for granting exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Alternative fuels that meet the normal requirements and practices of the principal business of the State fleet... requirements and practices of the principal business of the State fleet are not available for purchase or lease... must be accompanied with supporting documentation. (c) Exemptions are granted for one model year only...

  16. Labor Certifications

    ERIC Educational Resources Information Center

    Kaye, Allen E.

    1978-01-01

    The U.S. Immigration and Nationality Act requires that those aliens who wish to obtain U.S. immigrant visas and who intend to be permanently employed here to obtain a certification from the U.S. Secretary of Labor. Certain aliens are exempt from this requirement. Those not exempt must follow the labor certification process. (NQ)

  17. 29 CFR 780.503 - What determines the application of the exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 780.503 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF... STANDARDS ACT Employment or Agricultural Employees in Processing Shade-Grown Tobacco; Exemption From Minimum Wage and Overtime Pay Requirements Under Section 13(a)(14) Introductory § 780.503 What determines the...

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Design architecture of double spiral interdigitated electrode with back gate electrode for biosensor application

    NASA Astrophysics Data System (ADS)

    Fathil, M. F. M.; Arshad, M. K. Md.; Hashim, U.; Ruslinda, A. R.; Gopinath, Subash C. B.; M. Nuzaihan M., N.; Ayub, R. M.; Adzhri, R.; Zaki, M.; Azman, A. H.

    2016-07-01

    This paper presents the preparation method of photolithography chrome mask design used in fabrication process of double spiral interdigitated electrode with back gate biasing based biosensor. By learning the fabrication process flow of the biosensor, the chrome masks are designed through drawing using the AutoCAD software. The overall width and length of the device is optimized at 7.0 mm and 10.0 mm, respectively. Fabrication processes of the biosensor required three chrome masks, which included back gate opening, spiral IDE formation, and passivation area formation. The complete chrome masks design will be sent for chrome mask fabrication and for future use in biosensor fabrication.

  6. 40 CFR 180.1225 - Decanoic acid; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., breweries, wineries, beverage and food processing plants. [68 FR 7939, Feb. 19, 2003; 68 FR 17308, Apr. 9... AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD... acid (up to 170 ppm per application) on food contact surfaces such as equipment, pipelines, tanks, vats...

  7. 47 CFR 1.1204 - Exempt ex parte presentations and proceedings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... presentation is authorized by statute or by the Commission's rules to be made without service, see, e.g., § 1... decision-making process, unless it fits within another exemption not requiring disclosure (e.g., foreign... license; (9) The presentation is made pursuant to an express or implied promise of confidentiality to...

  8. 29 CFR 780.803 - Basic conditions of exemption; first part, ginning of cotton.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... cotton. 780.803 Section 780.803 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... FAIR LABOR STANDARDS ACT Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet... Section 13(b)(15) Introductory § 780.803 Basic conditions of exemption; first part, ginning of cotton...

  9. 29 CFR 780.803 - Basic conditions of exemption; first part, ginning of cotton.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... cotton. 780.803 Section 780.803 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... FAIR LABOR STANDARDS ACT Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet... Section 13(b)(15) Introductory § 780.803 Basic conditions of exemption; first part, ginning of cotton...

  10. 29 CFR 780.803 - Basic conditions of exemption; first part, ginning of cotton.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... cotton. 780.803 Section 780.803 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... FAIR LABOR STANDARDS ACT Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet... Section 13(b)(15) Introductory § 780.803 Basic conditions of exemption; first part, ginning of cotton...

  11. 29 CFR 780.803 - Basic conditions of exemption; first part, ginning of cotton.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... cotton. 780.803 Section 780.803 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... FAIR LABOR STANDARDS ACT Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet... Section 13(b)(15) Introductory § 780.803 Basic conditions of exemption; first part, ginning of cotton...

  12. 29 CFR 780.803 - Basic conditions of exemption; first part, ginning of cotton.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... cotton. 780.803 Section 780.803 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... FAIR LABOR STANDARDS ACT Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet... Section 13(b)(15) Introductory § 780.803 Basic conditions of exemption; first part, ginning of cotton...

  13. 40 CFR 63.2251 - What are the requirements for the routine control device maintenance exemption?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the routine control device maintenance exemption? (a) You may request a routine control device..., explain why the maintenance cannot be accomplished during process shutdowns, describe how you plan to make... device is used to control a green rotary dryer, tube dryer, rotary strand dryer, or pressurized refiner...

  14. 76 FR 42004 - Privacy Act of 1974: Implementation of Exemptions; Department of Homeland Security Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-18

    ... compromise the objectivity or fairness of the testing or examination process.'' Exemptions from these..., for the following reasons: (a) From subsection (c)(3) (Accounting for Disclosures) because release of the accounting of disclosures could alert the subject of an investigation of an actual or potential...

  15. 40 CFR 180.1122 - Inert ingredients of semiochemical dispensers; exemptions from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1122 Inert ingredients of semiochemical... (including the monomers, plasticizers, dispersing agents, antioxidants, UV protectants, stabilizers, and... commodity (RAC) or processed foods/feeds derived from the commodity by virtue of its proximity to the RAC or...

  16. 40 CFR 180.1122 - Inert ingredients of semiochemical dispensers; exemptions from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1122 Inert ingredients of semiochemical... (including the monomers, plasticizers, dispersing agents, antioxidants, UV protectants, stabilizers, and... commodity (RAC) or processed foods/feeds derived from the commodity by virtue of its proximity to the RAC or...

  17. 21 CFR 701.9 - Exemptions from labeling requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) COSMETICS COSMETIC LABELING General Provisions § 701.9 Exemptions from labeling requirements. (a) Except as provided by paragraphs (b) and (c) of this section, a shipment or other delivery of a cosmetic... establishment where such cosmetic is to be processed, labeled, or repacked; or (2) In case such person is not...

  18. 21 CFR 701.9 - Exemptions from labeling requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) COSMETICS COSMETIC LABELING General Provisions § 701.9 Exemptions from labeling requirements. (a) Except as provided by paragraphs (b) and (c) of this section, a shipment or other delivery of a cosmetic... establishment where such cosmetic is to be processed, labeled, or repacked; or (2) In case such person is not...

  19. 21 CFR 701.9 - Exemptions from labeling requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) COSMETICS COSMETIC LABELING General Provisions § 701.9 Exemptions from labeling requirements. (a) Except as provided by paragraphs (b) and (c) of this section, a shipment or other delivery of a cosmetic... establishment where such cosmetic is to be processed, labeled, or repacked; or (2) In case such person is not...

  20. 21 CFR 701.9 - Exemptions from labeling requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) COSMETICS COSMETIC LABELING General Provisions § 701.9 Exemptions from labeling requirements. (a) Except as provided by paragraphs (b) and (c) of this section, a shipment or other delivery of a cosmetic... establishment where such cosmetic is to be processed, labeled, or repacked; or (2) In case such person is not...

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 29 CFR 780.106 - Employment in “primary” agriculture is farming regardless of why or where work is performed.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Employment in âprimaryâ agriculture is farming regardless... DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT General Scope of Agriculture Exemption...

  7. 29 CFR 780.106 - Employment in “primary” agriculture is farming regardless of why or where work is performed.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Employment in âprimaryâ agriculture is farming regardless... DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT General Scope of Agriculture Exemption...

  8. 29 CFR 780.106 - Employment in “primary” agriculture is farming regardless of why or where work is performed.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Employment in âprimaryâ agriculture is farming regardless... DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT General Scope of Agriculture Exemption...

  9. 29 CFR 780.106 - Employment in “primary” agriculture is farming regardless of why or where work is performed.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Employment in âprimaryâ agriculture is farming regardless... DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT General Scope of Agriculture Exemption...

  10. 29 CFR 780.106 - Employment in “primary” agriculture is farming regardless of why or where work is performed.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Employment in âprimaryâ agriculture is farming regardless... DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT General Scope of Agriculture Exemption...

  11. 40 CFR 761.80 - Manufacturing, processing and distribution in commerce exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 16823-0048 (PDE-41.2). (6) Radian Corp., Austin, TX 78766 (PDE-182.1). (7) Restek Corporation... petitioner(s) an exemption for 1 year to export PCBs for use in small quantities for research and development: (1) Accu-Standard, New Haven, CT. 06503. (2) ManTech, Research Triangle Park, NC 27709. (d) The...

  12. 40 CFR 761.80 - Manufacturing, processing and distribution in commerce exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 16823-0048 (PDE-41.2). (6) Radian Corp., Austin, TX 78766 (PDE-182.1). (7) Restek Corporation... petitioner(s) an exemption for 1 year to export PCBs for use in small quantities for research and development: (1) Accu-Standard, New Haven, CT. 06503. (2) ManTech, Research Triangle Park, NC 27709. (d) The...

  13. 40 CFR 761.80 - Manufacturing, processing and distribution in commerce exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 16823-0048 (PDE-41.2). (6) Radian Corp., Austin, TX 78766 (PDE-182.1). (7) Restek Corporation... petitioner(s) an exemption for 1 year to export PCBs for use in small quantities for research and development: (1) Accu-Standard, New Haven, CT. 06503. (2) ManTech, Research Triangle Park, NC 27709. (d) The...

  14. 40 CFR 761.80 - Manufacturing, processing and distribution in commerce exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 16823-0048 (PDE-41.2). (6) Radian Corp., Austin, TX 78766 (PDE-182.1). (7) Restek Corporation... petitioner(s) an exemption for 1 year to export PCBs for use in small quantities for research and development: (1) Accu-Standard, New Haven, CT. 06503. (2) ManTech, Research Triangle Park, NC 27709. (d) The...

  15. 40 CFR 761.80 - Manufacturing, processing and distribution in commerce exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 16823-0048 (PDE-41.2). (6) Radian Corp., Austin, TX 78766 (PDE-182.1). (7) Restek Corporation... petitioner(s) an exemption for 1 year to export PCBs for use in small quantities for research and development: (1) Accu-Standard, New Haven, CT. 06503. (2) ManTech, Research Triangle Park, NC 27709. (d) The...

  16. 40 CFR Appendix Xii to Part 266 - Nickel or Chromium-Bearing Materials that may be Processed in Exempt Nickel-Chromium Recovery...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...

  17. 40 CFR Appendix Xii to Part 266 - Nickel or Chromium-Bearing Materials that may be Processed in Exempt Nickel-Chromium Recovery...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...

  18. 40 CFR Appendix Xii to Part 266 - Nickel or Chromium-Bearing Materials that may be Processed in Exempt Nickel-Chromium Recovery...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...

  19. 40 CFR Appendix Xii to Part 266 - Nickel or Chromium-Bearing Materials that may be Processed in Exempt Nickel-Chromium Recovery...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...

  20. 40 CFR Appendix Xii to Part 266 - Nickel or Chromium-Bearing Materials that may be Processed in Exempt Nickel-Chromium Recovery...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...

  1. 78 FR 55657 - Privacy Act of 1974: Implementation of Exemptions; Department of Homeland Security Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-11

    ... making a final eligibility decision, TSA will advise the applicant that the FBI criminal record discloses... maintain the element of unpredictability for security purposes. Accordingly, persons who have been enrolled... processes, the applicable exemptions may be waived on a case-by-case basis. A notice of system of records...

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Maternal Lead Exposure Induces Down-regulation of Hippocampal Insulin-degrading Enzyme and Nerve Growth Factor Expression in Mouse Pups.

    PubMed

    Li, Xing; Li, Ning; Sun, Hua Lei; Yin, Jun; Tao, Yu Chang; Mao, Zhen Xing; Yu, Zeng Li; Li, Wen Jie; Bogden, John D

    2017-03-01

    Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life. This study was aimed to investigate the effects of lead exposure of pregnant mice on the expressions of insulin-degrading enzyme (IDE) and nerve growth factor (NGF) in the hippocampus of their offspring. Blood samples were collected from the tail vein, and after anesthetizing the pups, the brain was excised on postnatal day 21. Lead concentrations were determined by graphite furnace atomic absorption spectrophotometry, and the expressions of IDE and NGF were determined by immunohistochemistry and Western blotting. Results showed that the reduction in IDE and NGF expression in the hippocampus of pups might be associated with impairment of learning and memory and dementia induced by maternal lead exposure during pregnancy and lactation. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  7. 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.

  8. The IRS looks closely at homes for the aging. Organizations must be prepared to face increased scrutiny on tax-exempt status and financing.

    PubMed

    Peregrine, M W

    1994-06-01

    Tax-exempt status has long been perceived as appropriate for the traditional retirement home (i.e., congregate housing and life-care facility), which serves the elderly and typically experiences low profit margins. An organization that is both organized and operated exclusively for religious, charitable, scientific, literary, or educational purposes or for testing for public safety may qualify for tax-exempt status under Internal Revenue Code section 501(c)(3). The Internal Revenue Service uses the generic term "homes for the aging" to include all forms of retirement housing facilities (except nursing homes that solely provide the highest level of nursing care). A home for the aging that qualifies under section 501(c)(3) (through satisfaction of the organizational and operational tests) will qualify for charitable status for federal tax purposes if it operates to satisfy the following basic needs of aged persons: suitable housing, healthcare, and financial security. In general, not-for-profit organizations recognized as exempt under code section 501(c)(3) may be eligible for tax-exempt financing to develop a home for the aging through the issuance of tax-exempt bonds. Effective tax-exemption planning is a necessary part of the business planning process by sophisticated not-for-profit organizations that own and operate (or desire to own and operate) charitable homes for the aging and similar housing facilities serving the elderly. The benefits of exempt status remain attractive for many such organizations. The challenge of obtaining and maintaining that status is becoming far more burdensome.

  9. 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

  10. 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.

  11. 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.

  12. Public service quality improvements: a case for exemption from IRB review of public administration research.

    PubMed

    Jordan, Sara R

    2014-01-01

    Should the exemption from Institutional Review Board (IRB) evaluations currently in place for quality improvements research be extended to public administration research that addresses questions of improving the quality of public service delivery? As a means to both reduce the level of disdain held by a group of social science researchers for IRBs and to reduce the cost of review for minimal risk studies, I argue here that much of the current public administration research should also be exempted from normal processes of review by IRBs on the basis of their similarity to Quality Improvements (QI) research, a category of studies already granted exemption. This argument dovetails provisions currently in place for studies of public service and public benefit, but reframes these exemptions in the language of "quality improvements," which may be a more comfortable language for IRBs concerned to demonstrate compliance for review of all fields. To expedite this argument into the practices of IRBs, I included a checklist that researchers could use to self-identify their studies as QI, not research as such.

  13. Potential impacts of imposing methyl bromide phaseout on US strawberry growers: a case study of a nomination for a critical use exemption under the Montreal Protocol.

    PubMed

    Norman, Catherine S

    2005-04-01

    The Montreal Protocol on Substances that Deplete the Ozone Layer requires developed countries to phaseout methyl bromide production and non-quarantine uses by 2005 and developing countries to do the same by 2015. Exemptions to phaseout have been significant in slowing the process of abatement; many countries have applied for exemptions for some uses, partly on grounds that phaseout is economically infeasible. Data on the US strawberry market are used to investigate grower costs arising from substitution away from methyl bromide, the impact of trends in and characteristics of the demand for fresh strawberries, and characteristics of trade with countries not yet required to eliminate use of the compound. It appears that actual net costs to growers will be much smaller than the simple increase in production costs cited in the US nomination for exemption.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. The scope of the conscience-based exemption in Section 4(1) of the Abortion Act 1967: Doogan and Wood v NHS Greater Glasgow Health Board [2013] CSIH 36.

    PubMed

    Neal, Mary

    2014-01-01

    Doogan is a judgment of the Inner House of the Scottish Court of Session in an action brought by two midwives ('petitioners' at first instance and 'reclaimers' on appeal) for judicial review of a decision by Greater Glasgow and Clyde Health Board ('respondents'). At issue in the litigation was the scope of the conscience-based exemption contained in section 4(1) of the Abortion Act 1967, which included consideration of where the burden of managing the exemption should fall. The court of first instance (Outer House) had held that section 4(1), which exempts people with a conscientious objection from having to 'participate in any treatment authorised by this Act', ought to be read in light of section 1, which was the authorising provision. On the analysis adopted by the Outer House, any activity which was not unlawful before the 1967 Act came into force, and which therefore did not require to be authorised by section 1, was not covered by section 4(1). Roles which consisted of 'supervision, delegation, and support' were held not to fall within the scope of section 4(1) for this reason. The Inner House rejected the argument that the scope of the exemption in section 4(1) must be coextensive with the scope of the authorisation in section 1, and held that section 4(1) covered the 'whole process of treatment' given for the purpose of terminating a pregnancy. For the Inner House, therefore, 'supervision, delegation, and support' of staff directly involved in the abortion process did constitute the kind of 'participation' that a person could be exempted from under section 4(1). Moreover, the court took the view that the reclaimers' interpretation of section 4(1) was also to be preferred in terms of its likely management consequences. The appeal succeeded, and the Health Board has begun the process of appealing to the UK Supreme Court. © The Author [2014]. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. 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.

  5. 29 CFR 780.816 - Processing of specific commodities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap... processing of sugar beets, sugar-beet molasses, sugarcane, or maple sap is within the exemption. Operations...

  6. 29 CFR 780.816 - Processing of specific commodities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap... processing of sugar beets, sugar-beet molasses, sugarcane, or maple sap is within the exemption. Operations...

  7. 29 CFR 780.816 - Processing of specific commodities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap... processing of sugar beets, sugar-beet molasses, sugarcane, or maple sap is within the exemption. Operations...

  8. 29 CFR 780.816 - Processing of specific commodities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap... processing of sugar beets, sugar-beet molasses, sugarcane, or maple sap is within the exemption. Operations...

  9. 29 CFR 780.816 - Processing of specific commodities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Employment in Ginning of Cotton and Processing of Sugar Beets, Sugar-Beet Molasses, Sugarcane, or Maple Sap... processing of sugar beets, sugar-beet molasses, sugarcane, or maple sap is within the exemption. Operations...

  10. SDI-based business processes: A territorial analysis web information system in Spain

    NASA Astrophysics Data System (ADS)

    Béjar, Rubén; Latre, Miguel Á.; Lopez-Pellicer, Francisco J.; Nogueras-Iso, Javier; Zarazaga-Soria, F. J.; Muro-Medrano, Pedro R.

    2012-09-01

    Spatial Data Infrastructures (SDIs) provide access to geospatial data and operations through interoperable Web services. These data and operations can be chained to set up specialized geospatial business processes, and these processes can give support to different applications. End users can benefit from these applications, while experts can integrate the Web services in their own business processes and developments. This paper presents an SDI-based territorial analysis Web information system for Spain, which gives access to land cover, topography and elevation data, as well as to a number of interoperable geospatial operations by means of a Web Processing Service (WPS). Several examples illustrate how different territorial analysis business processes are supported. The system has been established by the Spanish National SDI (Infraestructura de Datos Espaciales de España, IDEE) both as an experimental platform for geoscientists and geoinformation system developers, and as a mechanism to contribute to the Spanish citizens knowledge about their territory.

  11. 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

  12. Leptin inhibits amyloid β-protein degradation through decrease of neprilysin expression in primary cultured astrocytes.

    PubMed

    Yamamoto, Naoki; Tanida, Mamoru; Ono, Yoko; Kasahara, Rika; Fujii, Yuko; Ohora, Kentaro; Suzuki, Kenji; Sobue, Kazuya

    2014-02-28

    Pathogenesis of Alzheimer's disease (AD) is characterized by accumulation of extracellular deposits of amyloid β-protein (Aβ) in the brain. The steady state level of Aβ in the brain is determined by the balance between its production and removal; the latter occurring through egress across blood and CSF barriers as well as Aβ degradation. The major Aβ-degrading enzymes in the brain are neprilysin (NEP) and insulin-degrading enzyme (IDE), which may promote Aβ deposition in patients with sporadic late-onset AD. Epidemiological studies have suggested an inverse relationship between the adipocytokine leptin levels and the onset of AD. However, the mechanisms underlying the relationship remain uncertain. We investigated whether leptin is associated with Aβ degradation by inducing NEP and IDE expression within primary cultured astrocytes. Leptin significantly decreased the expression of NEP but not IDE in a concentration- and time-dependent manner through the activation of extracellular signal-regulated kinase (ERK) in cultured rat astrocytes. Furthermore, leptin inhibited the degradation of exogenous Aβ in primary cultured astrocytes. These results suggest that leptin suppresses Aβ degradation by NEP through activation of ERK. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. ABC's of monitoring federal tax exemption.

    PubMed

    Sanborn, A B; MacKelvie, C F

    1988-10-01

    Congress and the Internal Revenue Service (IRS) are taking a close look at the Internal Revenue Code (IRC) as it applies to Catholic institutions' activities. Although most Catholic institutions' exempt status is secured by reserved power organizational characteristics, it would behoove healthcare leaders to become familiar with the tax system and the IRS operation and, if necessary, make appropriate accommodations. They should understand what triggers an IRS audit and the audit process itself. The IRS subjects exempt institutions to organizational and operational tests. It deems that a healthcare entity is organized exclusively for an exempt (and charitable) purpose when that entity's articles of incorporation: 1. Limit the organization's purposes to charitable purposes. 2. Limit the organizations's activities to those which further its exempt purposes only, with other purposes furthered in only an insubstantial way. 3. Limit activities to those specified in IRC Section 501(c)(3). 4. Limit distribution of the organization's assets on dissolution to another organization with a like or similar exempt purpose. 5. Limit legislative and bar political activities Although most Catholic healthcare entities are "tax managed" conservatively, from an operational perspective, they often enter into transactions that the IRS considers "red flags." Some of these "red flag" transactions involve: Joint venture operations. Physician recruitment and physician handling plans. Rental/lease arrangements. Defined compensation plans. Hospital productivity plans. Profit-sharing plans. Contingent compensation arrangements. Acquisition, mergers, and divestitures. Taxable subsidiaries and unrelated business income.

  14. The 5-year cost-effectiveness of two-level anterior cervical discectomy and fusion or cervical disc replacement: a Markov analysis.

    PubMed

    Overley, Samuel C; McAnany, Steven J; Brochin, Robert L; Kim, Jun S; Merrill, Robert K; Qureshi, Sheeraz A

    2018-01-01

    Anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) are both acceptable surgical options for the treatment of cervical myelopathy and radiculopathy. To date, there are limited economic analyses assessing the relative cost-effectiveness of two-level ACDF versus CDR. The purpose of this study was to determine the 5-year cost-effectiveness of two-level ACDF versus CDR. The study design is a secondary analysis of prospectively collected data. Patients in the Prestige cervical disc investigational device exemption (IDE) study who underwent either a two-level CDR or a two-level ACDF were included in the study. The outcome measures were cost and quality-adjusted life years (QALYs). A Markov state-transition model was used to evaluate data from the two-level Prestige cervical disc IDE study. Data from the 36-item Short Form Health Survey were converted into utilities using the short form (SF)-6D algorithm. Costs were calculated from the payer perspective. QALYs were used to represent effectiveness. A probabilistic sensitivity analysis (PSA) was performed using a Monte Carlo simulation. The base-case analysis, assuming a 40-year-old person who failed appropriate conservative care, generated a 5-year cost of $130,417 for CDR and $116,717 for ACDF. Cervical disc replacement and ACDF generated 3.45 and 3.23 QALYs, respectively. The incremental cost-effectiveness ratio (ICER) was calculated to be $62,337/QALY for CDR. The Monte Carlo simulation validated the base-case scenario. Cervical disc replacement had an average cost of $130,445 (confidence interval [CI]: $108,395-$152,761) with an average effectiveness of 3.46 (CI: 3.05-3.83). Anterior cervical discectomy and fusion had an average cost of $116,595 (CI: $95,439-$137,937) and an average effectiveness of 3.23 (CI: 2.84-3.59). The ICER was calculated at $62,133/QALY with respect to CDR. Using a $100,000/QALY willingness to pay (WTP), CDR is the more cost-effective strategy and would be selected 61.5% of the time by the simulation. Two-level CDR and ACDF are both cost-effective strategies at 5 years. Neither strategy was found to be more cost-effective with an ICER greater than the $50,000/QALY WTP threshold. The assumptions used in the analysis were strongly validated with the results of the PSA. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. 7 CFR 906.120 - Fruit exempt from regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... juice, or preserved by any commercial process, including canning, freezing, dehydrating, drying, and the addition of chemical substances, or by fermentation. Fruit so processed, if handled in accordance with...

  16. True to form. The IRS' updated reporting rules for tax-exempt organizations could require full disclosure on community benefits, charity care.

    PubMed

    Evans, Melanie

    2007-06-04

    By mid-month, the IRS expects to unveil extensive changes to its Form 990 reporting rules for not-for-profits, which could further affect current disclosure or nondisclosure of tax-exempt hospitals' community benefits and charity care. Most hospitals welcome the revisions, but the legislative process to implement those reforms could be lengthy, says healthcare attorney Bernadette Broccolo, left.

  17. 40 CFR 799.5115 - Chemical testing requirements for certain chemicals of interest to the Occupational Safety and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...−3) applied to the skin. (For example, if the steady-state rate is 1 microgram × hr−1 × cm−2 and the... research and development (as described at 40 CFR 790.42(a)(5)). B. Persons who process (as defined at TSCA... to test or apply to EPA for an exemption from testing. The letter of intent to test or the exemption...

  18. Soil fumigation: The critical use exemption, quarantine pre-shipment rules, re-registration decision, and their effect on the 2012 growing season

    Treesearch

    Scott A. Enebak

    2012-01-01

    This article gives a brief history of the importance of methyl bromide in the production of forest tree seedlings in the southern United States and the timeline for the Montreal Protocol and Clean Air Act to phase out ozone depleting compounds. In addition, the process, steps used, and current status under the Critical Use Exemption and Quarantine Pre-shipment articles...

  19. Public Health and Politics: Using the Tax Code to Expand Advocacy.

    PubMed

    Gorovitz, Eric

    2017-03-01

    Protecting the public's health has always been an inherently political endeavor. The field of public health, however, is conspicuously and persistently absent from sustained, sophisticated engagement in political processes, particularly elections, that determine policy outcomes. This results, in large part, from widespread misunderstanding of rules governing how, and how much, public advocates working in tax-exempt organizations can participate in public policy development. This article briefly summarizes the rules governing public policy engagement by exempt organizations. It then describes different types of exempt organizations, and how they can work together to expand engagement. Next, it identifies several key mechanisms of policy development that public health advocates could influence. Finally, it suggests some methods of applying the tax rules to increase participation in these arenas.

  20. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

    PubMed Central

    Yui, Daishi; Nishida, Yoichiro; Nishina, Tomoko; Mogushi, Kaoru; Tajiri, Mio; Ishibashi, Satoru; Ajioka, Itsuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Murayama, Shigeo; Yokota, Takanori

    2015-01-01

    Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa -/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa -/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa -/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. PMID:26637123

  1. 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

  2. Hospital charge exemptions for the poor in Shandong, China.

    PubMed

    Meng, Qingyue; Sun, Qiang; Hearst, Norman

    2002-12-01

    Rapid economic changes in China have produced soaring hospital charges, a breakdown of the old social health insurance system, a resulting crisis in hospital affordability and renewed interest in mechanisms for discounts or exemptions from hospital charges for the poor. Little is known, however, about how effective such systems are in practice. We studied nine public hospitals in Shandong Province that offer discount or exemption mechanisms for the poor. Methods included document review, key informant interviews, detailed review of financial records and focus group discussions. These hospitals receive little government subsidy and must support themselves almost entirely through user fees. Hospital managers saw discount mechanisms primarily as marketing tools and designed them to limit their cost. Only a small fraction of hospital services were eligible for discount, and these were usually low cost or low utilization items. Discounts were generally 10-50% for selected items with very few services exempted from charge. The total value of discounts granted was 1% or less of total hospital operating budgets. Correct identification of indigents was a major difficulty for hospitals. Only a minority of indigents received discounts, the process was sometimes arbitrary and some who received discounts were not really poor. Government policies requiring discounts for the poor were vague and not enforced. The exemption programmes studied do not provide effective protection from hospital charges for the poor. To be effective, exemption mechanisms would likely require both financing and regulation by the government as well as an accurate way to identify the poor.

  3. User fee exemptions and excessive household spending for normal delivery in Burkina Faso: the need for careful implementation.

    PubMed

    Ben Ameur, Amal; Ridde, Valéry; Bado, Aristide R; Ingabire, Marie-Gloriose; Queuille, Ludovic

    2012-11-21

    In 2006, the Parliament of Burkina Faso passed a policy to reduce the direct costs of obstetric services and neonatal care in the country's health centres, aiming to lower the country's high national maternal mortality and morbidity rates. Implementation was via a "partial exemption" covering 80% of the costs. In 2008 the German NGO HELP launched a pilot project in two health districts to eliminate the remaining 20% of user fees. Regardless of any exemptions, women giving birth in Burkina Faso's health centres face additional expenses that often represent an additional barrier to accessing health services. We compared the total cost of giving birth in health centres offering partial exemption versus those with full exemption to assess the impact on additional out-of-pocket fees. A case-control study was performed to compare medical expenses. Case subjects were women who gave birth in 12 health centres located in the Dori and Sebba districts, where HELP provided full fee exemption for obstetric services and neonatal care. Controls were from six health centres in the neighbouring Djibo district where a partial fee exemption was in place. A random sample of approximately 50 women per health centre was selected for a total of 870 women. There was an implementation gap regarding the full exemption for obstetric services and neonatal care. Only 1.1% of the sample from Sebba but 17.5% of the group from Dori had excessive spending on birth related costs, indicating that women who delivered in Sebba were much less exposed to excessive medical expenses than women from Dori. Additional out-of-pocket fees in the full exemption health districts took into account household ability to pay, with poorer women generally paying less. We found that the elimination of fees for facility-based births benefits especially the poorest households. The existence of excessive spending related to direct costs of giving birth is of concern, making it urgent for the government to remove all direct fees for obstetric and neonatal care. However, the policy of completely abolishing user fees is insufficient; the implementation process must have a thorough monitoring system to reduce implementation gaps.

  4. 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.

  5. 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.

  6. 40 CFR 766.2 - Applicability and duration of this part.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... person who, at any time during the duration of this part, manufactures (and/or imports), or processes, a... effective date of this part. (3) Small manufacturers are exempt from reporting process and reaction...

  7. 40 CFR 766.2 - Applicability and duration of this part.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... person who, at any time during the duration of this part, manufactures (and/or imports), or processes, a... effective date of this part. (3) Small manufacturers are exempt from reporting process and reaction...

  8. 40 CFR 766.2 - Applicability and duration of this part.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... person who, at any time during the duration of this part, manufactures (and/or imports), or processes, a... effective date of this part. (3) Small manufacturers are exempt from reporting process and reaction...

  9. 40 CFR 766.2 - Applicability and duration of this part.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... person who, at any time during the duration of this part, manufactures (and/or imports), or processes, a... effective date of this part. (3) Small manufacturers are exempt from reporting process and reaction...

  10. 76 FR 37766 - Specified Commodities Imported Into the United States, Exempt From Import Regulations; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... as processing, charity, animal feed, seed, and distribution to relief agencies when those outlets are...; dates (other than dates for processing); walnuts; dried prunes (suspended); raisins; and hazelnuts...

  11. 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.

  12. Capital financing in prospective payment.

    PubMed

    Oszustowicz, R J; Dreachslin, J L

    1984-03-01

    In the era of prospective payment, arranging financing for hospital capital projects is expected to become even more complicated than under cost-based reimbursement systems. This article outlines the information needed for a bond issue in the prospective payment environment, defines the roles and duties of several external persons and organizations involved with planning a major capital financing, and provides an overview of the entire process. This article assumes for illustrative purposes that a tax-exempt bond issue is going to be used to finance a facility expansion. This method was chosen since over 70% of all major capital financing for hospitals use the tax-exempt bond as the principal vehicle for attracting the necessary debt to finance a major construction project. The tax-exempt bond issue also requires the most detail in documentation and legal provisions.

  13. 32 CFR 806.29 - Administrative processing of Air Force FOIA requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .../service/a nongovernment source (Exemption 4), records are part of the Air Force's decision-making process... explanation of the decision-making process for intra-agency documents denied under the deliberative process... specific “compelling need” or due process/humanitarian need is true and correct to the best of their...

  14. 45 CFR 612.4 - Processing requests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.4 Processing requests. (a) Monitoring of requests. The NSF Office of the... referred, unless such notification would disclose information otherwise exempt. ...

  15. 45 CFR 612.4 - Processing requests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.4 Processing requests. (a) Monitoring of requests. The NSF Office of the... referred, unless such notification would disclose information otherwise exempt. ...

  16. Multisclae heterogeneity of the 2011 Tohoku-oki earthquake by inversion

    NASA Astrophysics Data System (ADS)

    Aochi, H.; Ulrich, T.; Cornier, G.

    2012-12-01

    Earthquake fault heterogeneity is often studied on a set of subfaults in kinematic inversion, while it is sometimes described with spatially localized geometry. Aochi and Ide (EPS, 2011) and Ide and Aochi (submitted to Pageoph and AGU, 2012) apply a concept of multi-scale heterogeneity to simulate the dynamic rupture process of the 2011 Tohoku-oki earthquake, introducing circular patches of different dimension in fault fracture energy distribution. Previously the patches are given by the past moderate earthquakes in this region, and this seems to be consistent with the evolution process of this mega earthquake, although a few patches, in particular, the largest patch, had not been known previously. In this study, we try to identify patches by inversion. As demonstrated in several earthquakes including the 2010 Maule (M8.8) earthquake, it is possible to indentify two asperities of ellipse kinematically or dynamically (e.g. Ruiz and Madariaga, 2011, and so on). In the successful examples, different asperities are rather visible, separated in space. However the Tohoku-oki earthquake has hierarchical structure of heterogeneity. We apply the Genetic Algorithm to inverse the model parameters from the ground motions (K-net and Kik-net from NIED) and the high sampling GPS (GSI). Starting from low frequency ranges (> 50 seconds), we obtain an ellipse corresponding to M9 event located around the hypocenter, coherent with the previous result by Madariaga et al. (pers. comm.). However it is difficult to identify the second smaller with few constraints. This is mainly because the largest covers the entire rupture area and any smaller patch improves the fitting only for the closer stations. Again, this needs to introduce the multi-scale concept in inversion procedure. Instead of finding the largest one at first, we have to start to extract rather smaller moderate patches from the beginning of the record, following the rupture process.

  17. 76 FR 82277 - Nomination of Existing Marine Protected Areas to the National System of Marine Protected Areas

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ....S.S. YSD Exempt Site H.M.C.S. Saint Francis Exempt Site French Van Gilder Exempt Site [[Page 82279... Area Amanave Village Marine Protected Area Massachusetts Albert Gallatin Exempt Site Alice M. Colburn Exempt Site Alice M. Lawrence Exempt Site Ardandhu Exempt Site Barge and Crane Exempt Site California...

  18. 30 CFR 47.92 - Exemptions from labeling.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... COMMUNICATION (HazCom) Exemptions § 47.92 Exemptions from labeling. A hazardous chemical is exempt from subpart... Chemicals Exempt from Labeling Exemption Conditions for exemption Chemical substance, consumer product, hazardous substance, or pesticide When kept in its manufacturer's or supplier's original packaging labeled...

  19. 30 CFR 47.92 - Exemptions from labeling.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... COMMUNICATION (HazCom) Exemptions § 47.92 Exemptions from labeling. A hazardous chemical is exempt from subpart... Chemicals Exempt from Labeling Exemption Conditions for exemption Chemical substance, consumer product, hazardous substance, or pesticide When kept in its manufacturer's or supplier's original packaging labeled...

  20. 30 CFR 47.92 - Exemptions from labeling.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... COMMUNICATION (HazCom) Exemptions § 47.92 Exemptions from labeling. A hazardous chemical is exempt from subpart... Chemicals Exempt from Labeling Exemption Conditions for exemption Chemical substance, consumer product, hazardous substance, or pesticide When kept in its manufacturer's or supplier's original packaging labeled...

  1. 30 CFR 47.92 - Exemptions from labeling.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... COMMUNICATION (HazCom) Exemptions § 47.92 Exemptions from labeling. A hazardous chemical is exempt from subpart... Chemicals Exempt from Labeling Exemption Conditions for exemption Chemical substance, consumer product, hazardous substance, or pesticide When kept in its manufacturer's or supplier's original packaging labeled...

  2. 75 FR 6131 - Proposed Processed Raspberry Promotion, Research, and Information Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... promotion, research, and information program for processed raspberries. The proposed program, Processed... be exempt from the assessment. The proposed program would be implemented under the Commodity... implementation of the program prior to it going into effect. In addition, USDA is announcing that the referendum...

  3. Design of intelligent vehicle control system based on single chip microcomputer

    NASA Astrophysics Data System (ADS)

    Zhang, Congwei

    2018-06-01

    The smart car microprocessor uses the KL25ZV128VLK4 in the Freescale series of single-chip microcomputers. The image sampling sensor uses the CMOS digital camera OV7725. The obtained track data is processed by the corresponding algorithm to obtain track sideline information. At the same time, the pulse width modulation control (PWM) is used to control the motor and servo movements, and based on the digital incremental PID algorithm, the motor speed control and servo steering control are realized. In the project design, IAR Embedded Workbench IDE is used as the software development platform to program and debug the micro-control module, camera image processing module, hardware power distribution module, motor drive and servo control module, and then complete the design of the intelligent car control system.

  4. 29 CFR 784.133 - “First processing.”

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Aquatic Products First Processing, Canning, Or Packing of Marine Products Under Section 13(a)(5) § 784.133 “First processing.” Processing connotes a change from the natural state of the marine product and first... preliminary operations as cleaning, washing, and grading of the marine products, though not exempt as first...

  5. 29 CFR 784.133 - “First processing.”

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Aquatic Products First Processing, Canning, Or Packing of Marine Products Under Section 13(a)(5) § 784.133 “First processing.” Processing connotes a change from the natural state of the marine product and first... preliminary operations as cleaning, washing, and grading of the marine products, though not exempt as first...

  6. 50 CFR 453.04 - Committee information gathering.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.04 Committee information gathering. (a) Written submissions...

  7. 50 CFR 453.04 - Committee information gathering.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.04 Committee information gathering. (a) Written submissions...

  8. 50 CFR 453.04 - Committee information gathering.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.04 Committee information gathering. (a) Written submissions...

  9. 50 CFR 453.02 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.02 Definitions. Definitions applicable to this part are contained in 50...

  10. 50 CFR 453.04 - Committee information gathering.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.04 Committee information gathering. (a) Written submissions...

  11. 50 CFR 453.04 - Committee information gathering.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.04 Committee information gathering. (a) Written submissions...

  12. 50 CFR 453.02 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.02 Definitions. Definitions applicable to this part are contained in 50...

  13. 50 CFR 453.02 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.02 Definitions. Definitions applicable to this part are contained in 50...

  14. 50 CFR 453.02 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.02 Definitions. Definitions applicable to this part are contained in 50...

  15. 50 CFR 453.02 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.02 Definitions. Definitions applicable to this part are contained in 50...

  16. 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.

  17. 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)

  18. Effects of user fee exemptions on the provision and use of maternal health services: a review of literature.

    PubMed

    Hatt, Laurel E; Makinen, Marty; Madhavan, Supriya; Conlon, Claudia M

    2013-12-01

    User fee removal has been put forward as an approach to increasing priority health service utilization, reducing impoverishment, and ultimately reducing maternal and neonatal mortality. However, user fees are a source of facility revenue in many low-income countries, often used for purchasing drugs and supplies and paying incentives to health workers. This paper reviews evidence on the effects of user fee exemptions on maternal health service utilization, service provision, and outcomes, including both supply-side and demand-side effects. We reviewed 19 peer-reviewed research articles addressing user fee exemptions and maternal health services or outcomes published since 1990. Studies were identified through a USAID-commissioned call for evidence, key word search, and screening process. Teams of reviewers assigned criteria-based quality scores to each paper and prepared structured narrative reviews. The grade of the evidence was found to be relatively weak, mainly from short-term, non-controlled studies. The introduction of user fee exemptions appears to have resulted in increased rates of facility-based deliveries and caesarean sections in some contexts. Impacts on maternal and neonatal mortality have not been conclusively demonstrated; exemptions for delivery care may contribute to modest reductions in institutional maternal mortality but the evidence is very weak. User fee exemptions were found to have negative, neutral, or inconclusive effects on availability of inputs, provider motivation, and quality of services. The extent to which user fee revenue lost by facilities is replaced can directly affect service provision and may have unintended consequences for provider motivation. Few studies have looked at the equity effects of fee removal, despite clear evidence that fees disproportionately burden the poor. This review highlights potential and documented benefits (increased use of maternity services) as well as risks (decreased provider motivation and quality) of user fee exemption policies for maternal health services. Governments should link user fee exemption policies with the replacement of lost revenue for facilities as well as broader health system improvements, including facility upgrades, ensured supply of needed inputs, and improved human resources for health. Removing user fees may increase uptake but will not reduce mortality proportionally if the quality of facility-based care is poor. More rigorous evaluations of both demand- and supply-side effects of mature fee exemption programmes are needed.

  19. Non-clinical and Pre-clinical Testing to Demonstrate Safety of the Barostim Neo Electrode for Activation of Carotid Baroreceptors in Chronic Human Implants

    PubMed Central

    Wilks, Seth J.; Hara, Seth A.; Ross, Erika K.; Nicolai, Evan N.; Pignato, Paul A.; Cates, Adam W.; Ludwig, Kip A.

    2017-01-01

    The Barostim neo™ electrode was developed by CVRx, Inc.to deliver baroreflex activation therapy (BAT)™ to treat hypertension and heart failure. The neo electrode concept was designed to deliver electrical stimulation to the baroreceptors within the carotid sinus bulb, while minimizing invasiveness of the implant procedure. This device is currently CE marked in Europe, and in a Pivotal (akin to Phase III) Trial in the United States. Here we present the in vitro and in vivo safety testing that was completed in order to obtain necessary regulatory approval prior to conducting human studies in Europe, as well as an FDA Investigational Device Exemption (IDE) to conduct a Pivotal Trial in the United States. Stimulated electrodes (10 mA, 500 μs, 100 Hz) were compared to unstimulated electrodes using optical microscopy and several electrochemical techniques over the course of 27 weeks. Electrode dissolution was evaluated by analyzing trace metal content of solutions in which electrodes were stimulated. Lastly, safety testing under Good Laboratory Practice guidelines was conducted in an ovine animal model over a 12 and 24 week time period, with results processed and evaluated by an independent histopathologist. Long-term stimulation testing indicated that the neo electrode with a sputtered iridium oxide coating can be stimulated at maximal levels for the lifetime of the implant without clinically significant dissolution of platinum or iridium, and without increasing the potential at the electrode interface to cause hydrolysis or significant tissue damage. Histological examination of tissue that was adjacent to the neo electrodes indicated no clinically significant signs of increased inflammation and no arterial stenosis as a result of 6 months of continuous stimulation. The work presented here involved rigorous characterization and evaluation testing of the neo electrode, which was used to support its safety for chronic implantation. The testing strategies discussed provide a starting point and proven framework for testing new neuromodulation electrode concepts to support regulatory approval for clinical studies. PMID:28824361

  20. 7 CFR 944.350 - Safeguard procedures for avocados, grapefruit, kiwifruit, olives, oranges, prune variety plums...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...

  1. 7 CFR 944.350 - Safeguard procedures for avocados, grapefruit, kiwifruit, olives, oranges, prune variety plums...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...

  2. 7 CFR 944.350 - Safeguard procedures for avocados, grapefruit, kiwifruit, olives, oranges, prune variety plums...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...

  3. 7 CFR 944.350 - Safeguard procedures for avocados, grapefruit, kiwifruit, olives, oranges, prune variety plums...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...

  4. 7 CFR 944.350 - Safeguard procedures for avocados, grapefruit, kiwifruit, olives, oranges, prune variety plums...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...

  5. 7 CFR 57.100 - Specific exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... processing in nonofficial plants, including but not limited to bakeries, restaurants, and other food... grading operations; (2) Hatcheries; (3) Transporters; (4) Laboratories, pharmaceutical companies; and (5...

  6. 11 CFR 9405.5 - Categories of exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... descriptions of manufacturing process, quality control methodology, and test results. The following procedures... lawful national security intelligence investigation, information furnished by a confidential source; (v...

  7. 11 CFR 9405.5 - Categories of exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... descriptions of manufacturing process, quality control methodology, and test results. The following procedures... lawful national security intelligence investigation, information furnished by a confidential source; (v...

  8. 11 CFR 9405.5 - Categories of exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... descriptions of manufacturing process, quality control methodology, and test results. The following procedures... lawful national security intelligence investigation, information furnished by a confidential source; (v...

  9. 11 CFR 9405.5 - Categories of exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... descriptions of manufacturing process, quality control methodology, and test results. The following procedures... lawful national security intelligence investigation, information furnished by a confidential source; (v...

  10. 50 CFR 453.06 - Additional Committee powers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.06 Additional Committee powers. (a) Secure information. Subject...

  11. 50 CFR 453.06 - Additional Committee powers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.06 Additional Committee powers. (a) Secure information. Subject...

  12. 50 CFR 453.06 - Additional Committee powers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.06 Additional Committee powers. (a) Secure information. Subject...

  13. 50 CFR 453.06 - Additional Committee powers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.06 Additional Committee powers. (a) Secure information. Subject...

  14. 50 CFR 453.06 - Additional Committee powers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.06 Additional Committee powers. (a) Secure information. Subject...

  15. 50 CFR 452.04 - Secretary's report.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS... benefits of the proposed action; (3) Discussing the nature and extent of the benefits of alternative...

  16. 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.

  17. 40 CFR 176.5 - Establishment of a time-limited tolerance or exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... authorizes an emergency exemption or a crisis exemption. EPA will consider establishing such a tolerance only... exemption, has stated its intention to issue a crisis exemption, or has issued a crisis exemption for a use...

  18. 76 FR 51431 - Prohibited Transaction Exemptions and Grant of Individual Exemptions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... DEPARTMENT OF LABOR Employee Benefits Security Administration Prohibited Transaction Exemptions and Grant of Individual Exemptions Notice of Technical Correction Prohibited Transaction Exemptions and Grant of Individual Exemptions Involving D-11468 and D-11469, The Krispy Kreme Doughnut...

  19. 7 CFR 989.60 - Exemption.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN... may designate such raisins as it deems appropriate for production, processing, and marketing research...

  20. 7 CFR 989.60 - Exemption.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN... may designate such raisins as it deems appropriate for production, processing, and marketing research...

  1. 7 CFR 989.60 - Exemption.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN... may designate such raisins as it deems appropriate for production, processing, and marketing research...

  2. 77 FR 62218 - Pacific Fishery Management Council; Public Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-12

    ... Management 1. NMFS Report 2. Exempted Fishing Permit (EFP) Process 3. Pacific Sardine Stock Assessment and... Groundfish Management Process) 3. Progress Report on Using Descending Devices to Mitigate Barotrauma in... Fishery Management Council; Public Meetings AGENCY: National Marine Fisheries Service (NMFS), National...

  3. The Asfora Bullet Cage System Shows Comparable Fusion Rate Success Versus Control Cage in Posterior Lumbar Interbody Fusion in a Randomized Clinical Trial.

    PubMed

    Morgan, Jeremy P; Miller, Ashley L; Thompson, Paul A; Asfora, Wilson T

    2016-04-01

    Low back pain and degeneration of the intervertebral disc are an integrated malady that affects millions of Americans. Cage devices used in association with posterior lumbar interbody fusion (PLIF) have been shown to be an effective approach in the treatment of a number of lower spine disorders attributed to degenerative disc disease (DDD). This study was undertaken as part of a U.S. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) study and compares the effectiveness of the Asfora Bullet Cage System (ABCS) to successfully fuse vertebra at one or two levels between L2 and S1 in patients with DDD to an FDA approved comparison device, the Medtronic-Sofamor Danek Inter Fix Threaded Fusion Device (MSDIFD). A total of 257 randomized participants were implanted with either the ABCS device (n = 132) or the MSDIFD device (n = 125) through an open posterior approach using autogenous local bone graft without the use of pedicle screws. Patients were evaluated prior to surgery and at the 24 month (24-M) visit for fusion status, deep tendon reflex status, sensory function, motor function, straight leg raise status, pain, disability, and device safety. Radiological evaluation and statistical analysis were performed by independent professionals. Evaluation of device success was performed at 24-M visit. From the original group of 257 patients, 59 were lost to follow-up. Primary measures of success at the 24-M visit involved pain and function, fusion, neurological status, and device-related adverse events measures. Pain and function improved in both (MSDIFD: 75.7 percent; ABCS: 82.6 percent). Fusion success with all radiographic points at 24-M visits was 79.4 percent MSDIFD and 88.2 percent ABCS. Neurological improvement was seen in both (MSDIFD: 77.0 percent; ABCS: 87.8 percent). One device-related grade 1 adverse event was reported in the MSDIFD group. Disc height preservation was equivalent for single level fusions (MSDIFD: 16.1 percent; ABCS: 20.0 percent) and second level fusions (MSDIFD: 10.7 percent; ABCS: 14.3 percent). General health and well-being improvement was the same (MSDIFD: 37.0 percent; ABCS: 40.0 percent). Subsequent fusion, up to 10 years, was equivalent (MSDIFD: 83.8 percent; ABCS: 91.2). Results for both devices were considered to be satisfactory, with a slight non-significant superiority for the ABCS. From the ABCS device FDA IDE sanctioned study and the review of the literature, we concluded that the Asfora Bullet Cage System is safe, effective and comparable to other interbody fusion devices which are used stand-alone or in conjunction with pedicle screws, rhBMP-2, or autogenous bone harvested from the iliac crest inserted through anterior, lateral or posterior approaches.

  4. 40 CFR 91.1011 - Submission of exemption requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) CONTROL OF EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Exclusion and Exemption of Marine SI Engines § 91.1011 Submission of exemption requests. Requests for exemption or further information concerning exemptions and/or the exemption request review procedure should be addressed to: Manager, Engine...

  5. 50 CFR 18.23 - Native exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND... receiving, storing, processing, and shipping materials; (3) A proposal for a system of bookkeeping and/or...

  6. 50 CFR 453.05 - Committee meetings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.05 Committee meetings. (a) The committee shall meet at the call of the...

  7. 50 CFR 453.05 - Committee meetings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.05 Committee meetings. (a) The committee shall meet at the call of the...

  8. 50 CFR 453.05 - Committee meetings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.05 Committee meetings. (a) The committee shall meet at the call of the...

  9. 50 CFR 453.05 - Committee meetings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.05 Committee meetings. (a) The committee shall meet at the call of the...

  10. 50 CFR 453.05 - Committee meetings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS ENDANGERED SPECIES COMMITTEE § 453.05 Committee meetings. (a) The committee shall meet at the call of the...

  11. 50 CFR 452.01 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS ENDANGERED SPECIES EXEMPTION PROCESS... Endangered Species Act. ... Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE...

  12. 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...

  13. 75 FR 4295 - Premanufacture Notification Exemption for Polymers; Amendment of Polymer Exemption Rule to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-27

    ... Premanufacture Notification Exemption for Polymers; Amendment of Polymer Exemption Rule to Exclude Certain Perfluorinated Polymers AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: EPA is amending the polymer exemption rule, which provides an exemption from the premanufacture notification (PMN...

  14. 75 FR 66423 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-28

    ... renewal of exemptions; request for comments. SUMMARY: FMCSA announces its decision to renew the exemptions... the exemptions for these commercial motor vehicle (CMV) drivers. DATES: This decision is effective... exemption (including renewals) are set out in 49 CFR part 381. Exemption Decision This notice addresses 13...

  15. 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.

  16. 76 FR 51879 - Definition of Solid Waste Disposal Facilities for Tax-Exempt Bond Purposes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... input for processing in some stage of a manufacturing or production process to produce a different end... and sold on the market as a material for input into manufacturing or production processes. The... production of any agricultural, commercial, consumer, or industrial product, provided that material qualified...

  17. 26 CFR 1.142(a)(6)-1 - Exempt facility bonds: solid waste disposal facilities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... section), or a recycling process (as defined in paragraph (d)(3) of this section). Absent an express... product within the meaning of paragraph (e) of this section. (3) Recycling process—(i) In general. The term recycling process means reconstituting, transforming, or otherwise processing solid waste into a...

  18. IRS proposes ruling on physician recruitment. How a hospital recruits physicians would affect its tax-exempt status.

    PubMed

    Griffith, G M

    1996-01-01

    On March 15, 1995, the Internal Revenue Service (IRS) announced a proposed revenue ruling stating how certain physician recruitment practices could be implemented without threatening hospitals' tax-exemption. As proposed, the IRS ruling would provide flexibility for recruitment incentives rather than a list of strict physician recruitment guidelines. The proposed ruling is not legally binding until issued in final form, and there is no deadline for finalizing it. In the meantime, however, the standards outlined in the proposed ruling reflect arrangements the IRS likely would approve, which should be an incentive for tax-exempt hospitals to follow reasonable physician recruitment practices. Assuming a hospital complies with other legal requirements such as fraud and abuse laws, it must answer two key tax-exempt status questions for its recruitment or retention package: Will the incentives result in a disguised distribution of profits from the operation of the organization? Is the total incentive package reasonable under all the facts and circumstances, both in absolute total value for physician(s) recruited and in relation to services required by the hospital and the community? The proposed ruling also provides guidance on basic documentation requirements and a process for approving recruitment arrangements.

  19. 46 CFR 28.60 - Exemption letter.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... VESSELS General Provisions § 28.60 Exemption letter. (a) Types of exemptions. (1) Specific exemption means... for an exemption of either type must be in writing, have specific reasons for the request, and be sent... vessel to which any exemption applies. (e) Right of appeal. Any person directly affected by a decision or...

  20. 77 FR 13691 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ..., ocular hypertension, retinal detachment, cataracts and corneal scaring. In most cases, their eye... Application of Multiple Regression Analysis of a Poisson Process,'' Journal of American Statistical...

  1. 29 CFR 780.118 - “Harvesting.”

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF... fruit, the stripping of bluegrass seed, and the digging up of shrubs and trees grown in a nursery... from their attachment to the soil or otherwise reduced to possession. For example, the processing of...

  2. 29 CFR 780.118 - “Harvesting.”

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF... fruit, the stripping of bluegrass seed, and the digging up of shrubs and trees grown in a nursery... from their attachment to the soil or otherwise reduced to possession. For example, the processing of...

  3. 29 CFR 780.118 - “Harvesting.”

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF... fruit, the stripping of bluegrass seed, and the digging up of shrubs and trees grown in a nursery... from their attachment to the soil or otherwise reduced to possession. For example, the processing of...

  4. 29 CFR 780.118 - “Harvesting.”

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF... fruit, the stripping of bluegrass seed, and the digging up of shrubs and trees grown in a nursery... from their attachment to the soil or otherwise reduced to possession. For example, the processing of...

  5. 29 CFR 780.118 - “Harvesting.”

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS EXEMPTIONS APPLICABLE TO AGRICULTURE, PROCESSING OF... fruit, the stripping of bluegrass seed, and the digging up of shrubs and trees grown in a nursery... from their attachment to the soil or otherwise reduced to possession. For example, the processing of...

  6. 22 CFR 51.53 - Refunds.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Fees § 51.53 Refunds. (a) The Department will refund the passport application fee and the security surcharge to any person exempt from payment of passport... expedited passport processing fee if the Department fails to provide expedited passport processing as...

  7. 22 CFR 51.53 - Refunds.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Fees § 51.53 Refunds. (a) The Department will refund the passport application fee and the security surcharge to any person exempt from payment of passport... expedited passport processing fee if the Department fails to provide expedited passport processing as...

  8. 22 CFR 51.53 - Refunds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Fees § 51.53 Refunds. (a) The Department will refund the passport application fee and the security surcharge to any person exempt from payment of passport... expedited passport processing fee if the Department fails to provide expedited passport processing as...

  9. 22 CFR 51.53 - Refunds.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Fees § 51.53 Refunds. (a) The Department will refund the passport application fee and the security surcharge to any person exempt from payment of passport... expedited passport processing fee if the Department fails to provide expedited passport processing as...

  10. 22 CFR 51.53 - Refunds.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Fees § 51.53 Refunds. (a) The Department will refund the passport application fee and the security surcharge to any person exempt from payment of passport... expedited passport processing fee if the Department fails to provide expedited passport processing as...

  11. 40 CFR 63.2250 - What are the general requirements?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., except during periods of process unit or control device startup, shutdown, and malfunction; prior to process unit initial startup; and during the routine control device maintenance exemption specified in... practice requirements are not operating, or during periods of startup, shutdown, and malfunction. Startup...

  12. 40 CFR 63.2250 - What are the general requirements?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., except during periods of process unit or control device startup, shutdown, and malfunction; prior to process unit initial startup; and during the routine control device maintenance exemption specified in... practice requirements are not operating, or during periods of startup, shutdown, and malfunction. Startup...

  13. 40 CFR 63.2250 - What are the general requirements?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., except during periods of process unit or control device startup, shutdown, and malfunction; prior to process unit initial startup; and during the routine control device maintenance exemption specified in... practice requirements are not operating, or during periods of startup, shutdown, and malfunction. Startup...

  14. 76 FR 24089 - Credit Risk Retention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-29

    ... Resecuritization Transactions D. Additional Exemptions E. Safe Harbor for Certain Foreign-Related Transactions VII..., when incentives are not properly aligned and there is a lack of discipline in the origination process... incentive problems among various parties involved in the process.\\8\\ \\7\\ Securitization may reduce the cost...

  15. 40 CFR 63.1326 - Batch process vents-recordkeeping provisions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutant Emissions: Group IV Polymers and Resins... requirements for Group 2 batch process vents that are exempt from the batch mass input limitation provisions...

  16. 76 FR 30717 - Notice Pursuant to Executive Order 12600 of Receipt of Freedom of Information Act (FOIA) Requests...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ...) COUNTRY CODE Not exempt under the FOIA. 15) BUS START DATE Not exempt under the FOIA. 16) FISCAL YEAR END... exempt under the FOIA. 71) PAST PERF POC (R2) Not exempt under the FOIA. 72) PAST PERF ST ADD (1) Not exempt under the FOIA. 73) PAST PERF ST ADD (2) Not exempt under the FOIA. 74) PAST PERF CITY Not exempt...

  17. 19 CFR 148.55 - Exemption for articles bearing American trademark.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... registered with the U.S. Patent and Trademark Office and recorded with Customs. The exemption may be applied... 19 Customs Duties 2 2010-04-01 2010-04-01 false Exemption for articles bearing American trademark... § 148.55 Exemption for articles bearing American trademark. (a) Application of exemption. An exemption...

  18. 17 CFR 250.3 - Exemption of certain banks.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Exemption of certain banks... Exemptions § 250.3 Exemption of certain banks. (a) General exemption. Subject to the provisions of § 250.6 and to the requirements contained in paragraph (c) of this section, any bank shall be exempt from any...

  19. 32 CFR 701.113 - PA exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... DOCUMENTS AFFECTING THE PUBLIC DON Privacy Program § 701.113 PA exemptions. (a) Exempt systems of records. 5... records that is filed in a non-exempt system of records retains its exempt status. (e) Types of exemptions.... They are: (i) “(k)(1)”: Information which is properly classified under E.O. in the interest of national...

  20. 18 CFR 4.103 - General provisions for case-specific exemption.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

  1. 18 CFR 4.103 - General provisions for case-specific exemption.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

  2. 18 CFR 4.103 - General provisions for case-specific exemption.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

  3. 18 CFR 4.103 - General provisions for case-specific exemption.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

  4. 18 CFR 4.103 - General provisions for case-specific exemption.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

  5. 40 CFR 166.45 - Duration of crisis exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Duration of crisis exemption. 166.45... EXEMPTION OF FEDERAL AND STATE AGENCIES FOR USE OF PESTICIDES UNDER EMERGENCY CONDITIONS Crisis Exemptions § 166.45 Duration of crisis exemption. A crisis exemption may be authorized for: (a) Only as long as is...

  6. 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.

  7. 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.

  8. 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.

  9. 29 CFR 784.117 - Combinations of exempt work.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Combinations of exempt work. 784.117 Section 784.117 Labor... Aquatic Products Principles Applicable to the Two Exemptions § 784.117 Combinations of exempt work. The combination of exempt work under sections 13(a)(5) and 13(b)(4), or one of these sections with exempt work...

  10. 19 CFR 148.53 - Exemption for tools of trade.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Exemption for tools of trade. 148.53 Section 148.53 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS Other Exemptions § 148.53 Exemption for tools of trade. (a) Exemption. Professional...

  11. 19 CFR 148.53 - Exemption for tools of trade.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Exemption for tools of trade. 148.53 Section 148.53 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS Other Exemptions § 148.53 Exemption for tools of trade. (a) Exemption. Professional...

  12. 19 CFR 148.53 - Exemption for tools of trade.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Exemption for tools of trade. 148.53 Section 148.53 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS Other Exemptions § 148.53 Exemption for tools of trade. (a) Exemption. Professional...

  13. 19 CFR 148.53 - Exemption for tools of trade.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Exemption for tools of trade. 148.53 Section 148.53 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS Other Exemptions § 148.53 Exemption for tools of trade. (a) Exemption. Professional...

  14. 75 FR 72868 - Qualification of Drivers; Exemption Renewals; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-26

    ... granting these exemptions will provide a level of safety that will be equivalent to, or greater than, the... exemption for a 2-year period if it finds ``such exemption would likely achieve a level of safety that is... conditions of the exemption; (2) the exemption has resulted in a lower level of safety than was maintained...

  15. 77 FR 74161 - Fisheries of the Exclusive Economic Zone Off Alaska; Allocating Bering Sea and Aleutian Islands...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ..., processors, and affected communities to request an exemption from regional delivery requirements. Federal... within the designated region; likewise, crab purchased with regionally designated individual processing... fishing and processing activity making regional delivery requirements untenable in some seasons. Amendment...

  16. 40 CFR 63.2250 - What are the general requirements?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... periods of process unit or control device startup, shutdown, and malfunction; prior to process unit initial startup; and during the routine control device maintenance exemption specified in § 63.2251. The... are not operating, or during periods of startup, shutdown, and malfunction. Startup and shutdown...

  17. 40 CFR 63.2250 - What are the general requirements?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... periods of process unit or control device startup, shutdown, and malfunction; prior to process unit initial startup; and during the routine control device maintenance exemption specified in § 63.2251. The... are not operating, or during periods of startup, shutdown, and malfunction. Startup and shutdown...

  18. 14 CFR 298.51 - Processing by the Department.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Processing by the Department. 298.51 Section 298.51 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS EXEMPTIONS FOR AIR TAXI AND COMMUTER AIR CARRIER OPERATIONS Commuter Air...

  19. 14 CFR 298.51 - Processing by the Department.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Processing by the Department. 298.51 Section 298.51 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS EXEMPTIONS FOR AIR TAXI AND COMMUTER AIR CARRIER OPERATIONS Commuter Air...

  20. 75 FR 57328 - Petitions for Exemption; Summary of Petitions Received

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-20

    ... more information on the rulemaking process, see the SUPPLEMENTARY INFORMATION section of this document..., except Federal holidays. FOR FURTHER INFORMATION CONTACT: Jan Thor, (425-227-2127), Standardization...

  1. 19 CFR 148.34 - Family grouping of exemptions for articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... which member of the family is the owner of the articles. However, a group exemption will not include an exemption for a family member not entitled to it in his own right, nor will a group exemption be applied to... will not be applied under the group exemption to alcoholic beverages. No exemptions allowable to a...

  2. State income tax policy and family size: fertility and the dependency exemption.

    PubMed

    Whittington, L A

    1993-10-01

    Data from the Panel Study on Income Dynamics, excluding the low income Survey of Economic Opportunity, were used to test an empirical model of the relationship between US state tax exemption values and tax rates for couples and fertility. Income is held constant so that the real tax exemption value is affected by changes in tax rates, the price level, or the statutory value of the exemption. Prior research by Whittington et al. found a positive relationship between births and the federal exemption between 1979-83 for 294 households. The tax value of the exemption varies widely across states. There are 41 states with substantial personal income taxes, while seven states have no state personal income taxes. A very limited tax on personal income is collected in Tennessee, New Hampshire, and Connecticut. Pennsylvania has no dependency exemption. The range in exemption varies from $1500 in Georgia to $300 in Alabama. Tax credits in lieu of exemptions vary from $6 in Arkansas to $85 in Oregon. Tax rates also vary across states. The value of the exemption lowers the cost of a child and is not constant over time. Six models are specified. Model 1 uses combined state and federal exemptions. Models 2 and 3 use a lagged combined exemption value of one and two years. Models 4 and 6 use state exemptions separated from federal exemptions. Model 5 uses a lag of one year, and model 6 uses a lag of two years. The estimation results of the conditional logit (Chamberlain) Model 1 show a negative and significant coefficient, which suggests that exemptions are not an incentive for births. In Models 2 and 3, the coefficient is positive and significant. In Model 4, the pattern of Model 1 holds except the sign is positive. In Models 5 and 6, the federal exemption is positive and significant, and the state exemption is negative and significant. When substitution is made with the means of the predicted values for the exemption, Models 1-4 all become positive and significant. In models with income as a constant, income reduces the impact of the dependency exemption on fertility. Neither state or federal exemptions are a determinant of fertility but serve as a policy tool for motivating average family size.

  3. 76 FR 71260 - Approval and Promulgation of Implementation Plans; Texas; Revisions to the New Source Review (NSR...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... natural gas 7/22/1998 6/17/1998 Repeal and readoption disapproval. processing, as Section treating, or 116... for Changes at Certain Natural Gas Processing, Treating, or Compression Facilities 1. What is the... the following grounds: This definition exempts changes at certain natural gas processing, treating, or...

  4. 37 CFR 102.34 - Specific exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... required by Executive order to be kept secret in the interest of the national defense and foreign policy... frustrating the investigatory process, to insure the proper functioning and integrity of law enforcement...

  5. 75 FR 37879 - Petitions for Exemption; Summary of Petitions Received

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ... more information on the rulemaking process, see the SUPPLEMENTARY INFORMATION section of this document... Federal holidays. FOR FURTHER INFORMATION CONTACT: Jan Thor, (425-227-2127), Standardization Branch, ANM...

  6. 75 FR 15771 - Petitions for Exemption; Summary of Petitions Received

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ... more information on the rulemaking process, see the SUPPLEMENTARY INFORMATION section of this document... Federal holidays. FOR FURTHER INFORMATION CONTACT: Jan Thor, (425-227-2127), Standardization Branch, ANM...

  7. 75 FR 26843 - Petition for Exemption; Summary of Petition Received

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... more information on the rulemaking process, see the SUPPLEMENTARY INFORMATION section of this document... Federal holidays. FOR FURTHER INFORMATION CONTACT: Jan Thor, (425-227-2127), Standardization Branch, ANM...

  8. 45 CFR 2508.19 - What Privacy Act exemptions or control of systems of records are exempt from disclosure?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false What Privacy Act exemptions or control of systems of records are exempt from disclosure? 2508.19 Section 2508.19 Public Welfare Regulations Relating to... ACT OF 1974 § 2508.19 What Privacy Act exemptions or control of systems of records are exempt from...

  9. 76 FR 12216 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-04

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 11 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  10. 77 FR 46153 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-02

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 48 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  11. 78 FR 51268 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ...-24015; FMCSA-2011-0024; FMCSA-2011-0102] Qualification of Drivers; Exemption Applications; Vision AGENCY... for comments. SUMMARY: FMCSA announces its decision to renew the exemptions from the vision... to exempt individuals from the vision requirement if the exemptions granted will not compromise...

  12. 78 FR 16035 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 5 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  13. 76 FR 70215 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 20 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  14. 77 FR 3554 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 6 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  15. 77 FR 52388 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ...-0231; FMCSA-2010-0082; FMCSA-2010-0114] Qualification of Drivers; Exemption Applications; Vision AGENCY... for comments. SUMMARY: FMCSA announces its decision to renew the exemptions from the vision... to exempt individuals from the vision requirement if the exemptions granted will not compromise...

  16. 75 FR 1451 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 13 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  17. 76 FR 44653 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-26

    ...-9258; FMCSA-2005-21254; FMCSA-2009-0121] Qualification of Drivers; Exemption Applications; Vision...; request for comments. SUMMARY: FMCSA announces its decision to renew the exemptions from the vision... to exempt individuals from the vision requirement if the exemptions granted will not compromise...

  18. 77 FR 36338 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-18

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 25 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  19. 76 FR 32017 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-02

    ...; Exemption Applications; Vision AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION... exemptions from the vision requirement in the Federal Motor Carrier Safety Regulations for 18 individuals. FMCSA has statutory authority to exempt individuals from the vision requirement if the exemptions...

  20. 76 FR 9865 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ...-7006; FMCSA-2006-25246; FMCSA-2006-26066] Qualification of Drivers; Exemption Applications; Vision...; request for comments. SUMMARY: FMCSA announces its decision to renew the exemptions from the vision... to exempt individuals from the vision requirement if the exemptions granted will not compromise...

Top