Software engineering capability for Ada (GRASP/Ada Tool)

Science.gov (United States)

Cross, James H., II

1995-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada Source code. A new Motif compliant graphical user interface has been developed for the GRASP/Ada prototype.

Monuments on Gemiler Ada and Karacaören Ada

OpenAIRE

Masuda, Tomoyuki

1995-01-01

Contents : 1. Church I on Gemiler Ada, 2. Church II on Gemiler Ada, 3. Church III on Gemiler Ada, 4. Church IV on Gemiler Ada, 5. Basilica on Karacaören Ada, 6. Painted Tomb on Karacaören Ada, 7. The Baptistery and the Chronology of Construction of the Karacaören Ada Basilica Complex, 8. Ölüdeniz Beach Basilica, 9. Iskender Basilica on Ölüdeniz Lagoon, 10. Mustafa Basilica near Beştaş Cove.

Classic-Ada(TM)

Science.gov (United States)

Valley, Lois

1989-01-01

The SPS product, Classic-Ada, is a software tool that supports object-oriented Ada programming with powerful inheritance and dynamic binding. Object Oriented Design (OOD) is an easy, natural development paradigm, but it is not supported by Ada. Following the DOD Ada mandate, SPS developed Classic-Ada to provide a tool which supports OOD and implements code in Ada. It consists of a design language, a code generator and a toolset. As a design language, Classic-Ada supports the object-oriented principles of information hiding, data abstraction, dynamic binding, and inheritance. It also supports natural reuse and incremental development through inheritance, code factoring, and Ada, Classic-Ada, dynamic binding and static binding in the same program. Only nine new constructs were added to Ada to provide object-oriented design capabilities. The Classic-Ada code generator translates user application code into fully compliant, ready-to-run, standard Ada. The Classic-Ada toolset is fully supported by SPS and consists of an object generator, a builder, a dictionary manager, and a reporter. Demonstrations of Classic-Ada and the Classic-Ada Browser were given at the workshop.

CLIPS/Ada: An Ada-based tool for building expert systems

Science.gov (United States)

White, W. A.

1990-01-01

Clips/Ada is a production system language and a development environment. It is functionally equivalent to the CLIPS tool. CLIPS/Ada was developed in order to provide a means of incorporating expert system technology into projects where the use of the Ada language had been mandated. A secondary purpose was to glean information about the Ada language and its compilers. Specifically, whether or not the language and compilers were mature enough to support AI applications. The CLIPS/Ada tool is coded entirely in Ada and is designed to be used by Ada systems that require expert reasoning.

GRASP/Ada 95: Reverse Engineering Tools for Ada

Science.gov (United States)

Cross, James H., II

1996-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped an algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD), and a new visualization for a fine-grained complexity metric called the Complexity Profile Graph (CPG). By synchronizing the CSD and the CPG, the CSD view of control structure, nesting, and source code is directly linked to the corresponding visualization of statement level complexity in the CPG. GRASP has been integrated with GNAT, the GNU Ada 95 Translator to provide a comprehensive graphical user interface and development environment for Ada 95. The user may view, edit, print, and compile source code as a CSD with no discernible addition to storage or computational overhead. The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada 95 source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. The current update has focused on the design and implementation of a new Motif compliant user interface, and a new CSD generator consisting of a tagger and renderer. The Complexity Profile Graph (CPG) is based on a set of functions that describes the context, content, and the scaling for complexity on a statement by statement basis. When combined graphicafly, the result is a composite profile of complexity for the program unit. Ongoing research includes the development and refinement of the associated functions, and the development of the CPG generator prototype. The current Version 5.0 prototype provides the capability for the user to generate CSDs and CPGs from Ada 95 source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for

Separation of porcine parvovirus from bovine serum albumin using PEG-salt aqueous two-phase system.

Science.gov (United States)

Vijayaragavan, K Saagar; Zahid, Amna; Young, Jonathan W; Heldt, Caryn L

2014-09-15

Vaccine production faces a challenge in adopting conventional downstream processing steps that can efficiently purify large viral particles. Some major issues that plague vaccine purification are purity, potency, and quality. The industry currently considers 30% as an acceptable virus recovery for a vaccine purification process, including all downstream processes, whereas antibody recovery from CHO cell culture is generally around 80-85%. A platform technology with an improved virus recovery would revolutionize vaccine production. In a quest to fulfill this goal, we have been exploring aqueous two-phase systems (ATPSs) as an optional mechanism to purify virus. ATPS has been unable to gain wide implementation mainly due to loss of virus infectivity, co-purification of proteins, and difficulty of polymer recycling. Non-enveloped viruses are chemically resistant enough to withstand the high polymer and salt concentrations that are required for effective ATPS separations. We used infectious porcine parvovirus (PPV), a non-enveloped, DNA virus as a model virus to test and develop an ATPS separation method. We successfully tackled two of the three main disadvantages of ATPS previously stated; we achieved a high infectious yield of 64% in a PEG-citrate ATPS process while separating out the main contaminate protein, bovine serum albumin (BSA). The most dominant forces in the separation were biomolecule charge, virus surface hydrophobicity, and the ATPS surface tension. Highly hydrophobic viruses are likely to benefit from the discovered ATPS for high-purity vaccine production and ease of implementation. Copyright © 2014 Elsevier B.V. All rights reserved.

Update of GRASP/Ada reverse engineering tools for Ada

Science.gov (United States)

Cross, James H., II

1993-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional pretty printed Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype CSD generator (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3,e two update phases were completed. Update'92 focused on the initial analysis of evaluation data collected from software engineering students at Auburn University and the addition of significant enhancements to the user interface. Update'93 (the current update) focused on the statistical analysis of the data collected in the previous update and preparation of Version 3.4 of the prototype for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical

PEG and mPEG-anthracene induce DNA condensation and particle formation.

Science.gov (United States)

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2011-08-18

In this study, we investigated the binding of DNA with poly(ethylene glycol) (PEG) of different sizes and compositions such as PEG 3350, PEG 6000, and mPEG-anthracene in aqueous solution at physiological conditions. The effects of size and composition on DNA aggregation and condensation as well as conformation were determined using Fourier transform infrared (FTIR), UV-visible, CD, fluorescence spectroscopic methods and atomic force microscopy (AFM). Structural analysis showed moderate complex formation for PEG 3350 and PEG 6000 and weaker interaction for mPE-anthracene-DNA adducts with both hydrophilic and hydrophobic contacts. The order of ± stability of the complexes formed is K(PEG 6000) = 1.5 (±0.4) × 10(4) M(-1) > K(PEG 3350) = 7.9 (±1) × 10(3) M(-1) > K(m(PEG-anthracene))= 3.6 (±0.8) × 10(3) M(-1) with nearly 1 bound PEG molecule per DNA. No B-DNA conformational changes were observed, while DNA condensation and particle formation occurred at high PEG concentration.

Physicochemical characterization of 3,6-diHydroxyflavone binding BSA immobilized on PEG-coated silver nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Voicescu, Mariana, E-mail: voicescu@icf.ro [Institute of Physical Chemistry “Ilie Murgulescu” of the Romanian Academy (Romania); Ionescu, Sorana [University of Bucharest, Department of Physical Chemistry (Romania); Calderon-Moreno, Jose M. [Institute of Physical Chemistry “Ilie Murgulescu” of the Romanian Academy (Romania); Nistor, Cristina L. [National R& D Institute for Chemistry and Petrochemistry ICECHIM, Polymer Department (Romania)

2017-02-15

Studies based on silver nanoparticles (SNPs) and polyethylene glycols (PEGs) are mainly in the pharmaceutical field, with PEG as good “vehicle” to transport protein-based drugs. In this work, physicochemical characteristics of 3,6-diHydroxyflavone (3,6-diHF) binding bovine serum albumin (BSA) on PEG (Tween20, L64, and Myrj52)-coated SNPs have been investigated by steady-state and time-resolved fluorescence spectroscopy. These interactions give rise to the formation of intermolecular and intramolecular H bonds. As a subject of interest, the effect of temperature (30–60 °C) on the H bonds was studied by steady-state fluorescence. The size distribution and zeta potential of SNPs were determined by dynamic light scattering (DLS). Scanning electron microscopy (SEM) analysis revealed the spherical nature of particles with average diameter ~40–80 nm. The structure, stability, dynamics, and conformational changes in adsorbed BSA protein on the PEG-coated SNPs surface have been also investigated by steady-state/lifetime fluorescence and circular dichroism spectroscopy. The results have relevance in the oxidative stress and drug delivery processes.

Physicochemical characterization of 3,6-diHydroxyflavone binding BSA immobilized on PEG-coated silver nanoparticles

Science.gov (United States)

Voicescu, Mariana; Ionescu, Sorana; Calderon-Moreno, Jose M.; Nistor, Cristina L.

2017-02-01

Studies based on silver nanoparticles (SNPs) and polyethylene glycols (PEGs) are mainly in the pharmaceutical field, with PEG as good "vehicle" to transport protein-based drugs. In this work, physicochemical characteristics of 3,6-diHydroxyflavone (3,6-diHF) binding bovine serum albumin (BSA) on PEG (Tween20, L64, and Myrj52)-coated SNPs have been investigated by steady-state and time-resolved fluorescence spectroscopy. These interactions give rise to the formation of intermolecular and intramolecular H bonds. As a subject of interest, the effect of temperature (30-60 °C) on the H bonds was studied by steady-state fluorescence. The size distribution and zeta potential of SNPs were determined by dynamic light scattering (DLS). Scanning electron microscopy (SEM) analysis revealed the spherical nature of particles with average diameter 40-80 nm. The structure, stability, dynamics, and conformational changes in adsorbed BSA protein on the PEG-coated SNPs surface have been also investigated by steady-state/lifetime fluorescence and circular dichroism spectroscopy. The results have relevance in the oxidative stress and drug delivery processes.

Experiment and model for the viscosities of MEA-PEG400, DEA-PEG400 and MDEA-PEG400 aqueous solutions

International Nuclear Information System (INIS)

Fu, Dong; Zhang, Pan; Du, LeiXia; Dai, Jing

2014-01-01

Highlights: • The viscosities of the amine-PEG400 aqueous solutions were measured. • The experiments were modeled satisfactorily by using the Weiland equation. • The effect of mass fractions of amine and PEG400 on the viscosity was illustrated. • The temperature dependence of the viscosity was demonstrated. - Abstract: The viscosities (η) of poly(ethylene oxide)400 (PEG400), monoethanolamine (MEA)-PEG400, diethanolamine (DEA)-PEG400 and N-methyldiethanolamine (MDEA)-PEG400 aqueous solutions were measured by using the NDJ-5S digital rotational viscometer. A thermodynamic equation was used to model the viscosities and the calculated results are satisfactory. The effects of temperature, mass fractions of amines and PEG400 on the viscosities were demonstrated on the basis of experiments and calculations

Evaluating pleural ADA, ADA2, IFN-γ and IGRA for diagnosing tuberculous pleurisy.

Science.gov (United States)

Keng, Li-Ta; Shu, Chin-Chung; Chen, Jason Yao-Ping; Liang, Sheng-Kai; Lin, Ching-Kai; Chang, Lih-Yu; Chang, Chia-Hao; Wang, Jann-Yuan; Yu, Chong-Jen; Lee, Li-Na

2013-10-01

Conventional methods for diagnosing tuberculous pleurisy (TB pleurisy) are either invasive or have a long turn-around-time. Performances of pleural adenosine deaminase (ADA), ADA2, interferon-gamma (IFN-γ), and interferon-gamma release assays (IGRA) as diagnostic tools for TB pleurisy were evaluated. Eighty-eight patients with lymphocyte-predominant pleural exudates between June 2010 and March 2011, including 31 with clinically diagnosed TB pleurisy, were prospectively studied. Pleural ADA and ADA2 activity were measured by colorimetric method, IFN-γ levels by enzyme-linked immuno-sorbent assay, and IGRA by enzyme-linked immuno-spot (T-SPOT.TB) assay. Pleural ADA, ADA2, and IFN-γ levels, but not the proportion of positive T-SPOT.TB assay, were significantly higher in patients with TB pleurisy than in those without TB pleurisy. The area under the receiver-operating-characteristic (ROC) curve was 0.920, 0.893, 0.875, and 0.544 for IFN-γ, ADA2, ADA, and T-SPOT.TB assay, respectively. The combination of ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL yielded a specificity of 100%. Pleural ADA, ADA2 and IFN-γ, but not T-SPOT.TB assay, are all sensitive and specific for TB pleurisy. In patients with lymphocyte-predominant pleural exudates, ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL in pleural effusion imply a very high probability of TB pleurisy. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Analysis of serum adenosine deaminase (ADA) and ADA1 and ADA2 isoenzyme activities in HIV positive and HIV-HBV co-infected patients.

Science.gov (United States)

Khodadadi, Iraj; Abdi, Mohammad; Ahmadi, Abbas; Wahedi, Mohammad Saleh; Menbari, Shahoo; Lahoorpour, Fariba; Rahbari, Rezgar

2011-08-01

To determine adenosine deaminase (ADA) activity as a possible diagnostic marker in HIV and HIV-HBV co-infected patients. Blood samples were collected from 72 healthy, 33 HIV positive and 30 HIV-HBV co-infected subjects. Blood CD4+ cell count was recorded and serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total ADA, and ADA1 and ADA2 isoenzyme activities were determined. Serum ALT, AST, total ADA and ADA2 isoenzyme activities were significantly higher in HIV positive and HIV-HBV co-infected groups compare to the control (pADA activities (R(2)=0.589, pADA was significantly increased in HIV and HIV-HBV co-infections. Therefore, because of its low cost and simplicity to perform, ADA activity might be considered as a useful diagnostic tool among the other markers in these diseases. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

ADA5/SPT20 links the ADA and SPT genes, which are involved in yeast transcription.

OpenAIRE

Marcus, G A; Horiuchi, J; Silverman, N; Guarente, L

1996-01-01

In this report we described the cloning and characterization of ADA5, a gene identified by resistance to GAL4-VP16-mediated toxicity. ADA5 binds directly to the VP16 activation domain but not to a transcriptionally defective VP16 double point mutant. Double mutants with mutations in ada5 and other genes (ada2 or ada3) isolated by resistance to GAL4-VP16 grow like ada5 single mutants, suggesting that ADA5 is in the same pathway as the other ADA genes. Further, ADA5 cofractionates and coprecipi...

Effect of PEG and mPEG-anthracene on tRNA aggregation and particle formation.

Science.gov (United States)

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2012-01-09

Poly(ethylene glycol) (PEG) and its derivatives are synthetic polymers with major applications in gene and drug delivery systems. Synthetic polymers are also used to transport miRNA and siRNA in vitro. We studied the interaction of tRNA with several PEGs of different compositions, such as PEG 3350, PEG 6000, and mPEG-anthracene under physiological conditions. FTIR, UV-visible, CD, and fluorescence spectroscopic methods as well as atomic force microscopy (AFM) were used to analyze the PEG binding mode, the binding constant, and the effects of polymer complexation on tRNA stability, aggregation, and particle formation. Structural analysis showed that PEG-tRNA interaction occurs via RNA bases and the backbone phosphate group with both hydrophilic and hydrophobic contacts. The overall binding constants of K(PEG 3350-tRNA)= 1.9 (±0.5) × 10(4) M(-1), K(PEG 6000-tRNA) = 8.9 (±1) × 10(4) M(-1), and K(mPEG-anthracene)= 1.2 (±0.40) × 10(3) M(-1) show stronger polymer-RNA complexation by PEG 6000 and by PEG 3350 than the mPEG-anthracene. AFM imaging showed that PEG complexes contain on average one tRNA with PEG 3350, five tRNA with PEG 6000, and ten tRNA molecules with mPEG-anthracene. tRNA aggregation and particle formation occurred at high polymer concentrations, whereas it remains in A-family structure.

Ada 9X overview

Science.gov (United States)

Weller, David G.

1992-01-01

The current version of Ada has been an ANSI standard since 1983. In 1988, the Ada Joint Program Office was tasked with reevaluating the language and proposing changes to the standard. Since that time, the world has seen a tremendous explosion in object-oriented languages, as well as other growing fields such as distributed computing and support for very large software systems. The speaker will discuss new features being added to the next version of Ada, currently called Ada 9X, and what transition issues must be considered for current Ada projects.

Exosome purification based on PEG-coated Fe3O4 nanoparticles.

Science.gov (United States)

Chang, Ming; Chang, Yaw-Jen; Chao, Pei Yu; Yu, Qing

2018-01-01

Cancer cells secrete many exosomes, which facilitate metastasis and the later growth of cancer. For early cancer diagnosis, the detection of exosomes is a crucial step. Exosomes exist in biological fluid, such as blood, which contains various proteins. It is necessary to remove the proteins in the biological fluid to avoid test interference. This paper presented a novel method for exosome isolation using Fe3O4 magnetic nanoparticles (MNPs), which were synthesized using the chemical co-precipitation method and then coated with polyethylene glycol (PEG). The experimental results showed that the diameter of the PEG-coated Fe3O4 nanoparticles was about 20 nm, while an agglomerate of MNPs reached hundreds of nanometers in size. In the protein removal experiments, fetal bovine serum (FBS) was adopted as the analyte for bioassays of exosome purification. PEG-coated Fe3O4 MNPs reduced the protein concentration in FBS to 39.89% of the original solution. By observing a particle size distribution of 30~200 nm (the size range of various exosomes), the exosome concentrations were kept the same before and after purification. In the gel electrophoresis experiments, the bands of CD63 (~53 kDa) and CD9 (~22 kDa) revealed that exosomes existed in FBS as well as in the purified solution. However, the bands of the serum albumins (~66 kDa) and the various immunoglobulins (around 160 ~ 188 kDa) in the purified solution's lane explained that most proteins in FBS were removed by PEG-coated Fe3O4 MNPs. When purifying exosomes from serum, protein removal is critical for further exosome investigation. The proposed technique provides a simple and effective method to remove proteins in the serum using the PEG-coated Fe3O4 MNPs.

The development of a program analysis environment for Ada: Reverse engineering tools for Ada

Science.gov (United States)

Cross, James H., II

1991-01-01

The Graphical Representations of Algorithms, Structures, and Processes for Ada (GRASP/Ada) has successfully created and prototyped a new algorithm level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and thus improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under the Virtual Memory System (VMS) on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. In Phase 3 of the project, the prototype was prepared for limited distribution (GRASP/Ada Version 3.0) to facilitate evaluation. The user interface was extensively reworked. The current prototype provides the capability for the user to generate CSD from Ada source code in a reverse engineering mode with a level of flexibility suitable for practical application.

ART-Ada design project, phase 2

Science.gov (United States)

Lee, S. Daniel; Allen, Bradley P.

1990-01-01

Interest in deploying expert systems in Ada has increased. An Ada based expert system tool is described called ART-Ada, which was built to support research into the language and methodological issues of expert systems in Ada. ART-Ada allows applications of an existing expert system tool called ART-IM (Automated Reasoning Tool for Information Management) to be deployed in various Ada environments. ART-IM, a C-based expert system tool, is used to generate Ada source code which is compiled and linked with an Ada based inference engine to produce an Ada executable image. ART-Ada is being used to implement several expert systems for NASA's Space Station Freedom Program and the U.S. Air Force.

Near-infrared (1550 nm) in vivo bioimaging based on rare-earth doped ceramic nanophosphors modified with PEG-b-poly(4-vinylbenzylphosphonate)

Science.gov (United States)

Kamimura, Masao; Kanayama, Naoki; Tokuzen, Kimikazu; Soga, Kohei; Nagasaki, Yukio

2011-09-01

A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO3H2) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y2O3 nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO3H2 (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO3H2 was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection.A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate

Ada To X-Window Bindings

Science.gov (United States)

Souleles, Dean

1993-01-01

Ada to X-Window Bindings computer program developed to provide Ada programmers with complete interfaces to Xt Intrinsics and OSF Motif toolkits. Provides "Ada view" of some mostly C-language programming libraries. Package of software written in Ada and C languages.

Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: tetra-conjugation or PEG as the linker.

Science.gov (United States)

Li, Chunju; Lin, Qixun; Wang, Jun; Shen, Lijuan; Ma, Guanghui; Su, Zhiguo; Hu, Tao

2012-12-31

Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. Copyright © 2012 Elsevier B.V. All rights reserved.

Biodegradation of polyethylene glycol (PEG) in three tropical soils using radio labelled PEG

Energy Technology Data Exchange (ETDEWEB)

Abdalla, A.L. [Laboratory of Animal Nutrition, Centre for Nuclear Energy in Agriculture, University of Sao Paulo (CENA/USP), Piracicaba SP (Brazil)]. E-mail: abdalla@cena.usp.br; Regitano, J.B.; Tornisielo, V.L.; Marchese, L. [Laboratory of Ecotoxicology, Piracicaba SP (Brazil); Pecanha, M.R.S.R.; Vitti, D.M.S.S. [Laboratory of Animal Nutrition, Centre for Nuclear Energy in Agriculture, University of Sao Paulo (CENA/USP), Piracicaba SP (Brazil); Smith, T. [School of Agriculture, Policy and Development, University of Reading, Reading (United Kingdom)

2005-08-19

Polyethylene glycol (PEG) may be added to forage based diets rich in tannins for ruminant feeding because it binds to tannins and thus prevent the formation of potentially indigestible tannin-protein complexes. The objective of this work was to determine the in vitro biodegradation (mineralization, i.e., complete breakdown of PEG to CO{sub 2}) rate of PEG. {sup 14}C-Polyethylene glycol ({sup 14}C-PEG) was added to three different tropical soils (a sandy clay loam soil, SaCL; a sandy clay soil, SaC; and a sandy loam soil, SaL) and was incubated in Bartha flasks. Free PEG and PEG bound to tannins from a tannin rich local shrub were incubated under aerobic conditions for up to 70 days. The biodegradation assay monitored the {sup 14}CO{sub 2} evolved after degradation of the labelled PEG in the soils. After incubation, the amount of {sup 14}CO{sub 2} evolved from the {sup 14}C-PEG application was low. Higher PEG mineralization values were found for the soils with higher organic matter contents (20.1 and 18.6 g organic matter/kg for SaCL and SaC, respectively) than for the SaL soil (11.9 g organic matter/kg) (P < 0.05). The extent of mineralization of PEG after 70 days of incubation in the soil was significantly lower (P < 0.05) when it was added as bound to the browse tannin than in the free form (0.040 and 0.079, respectively). (author)

Ada training evaluation and recommendations from the Gamma Ray Observatory Ada Development Team

International Nuclear Information System (INIS)

1985-10-01

The Ada training experiences of the Gamma Ray Observatory Ada development team are related, and recommendations are made concerning future Ada training for software developers. Training methods are evaluated, deficiencies in the training program are noted, and a recommended approach, including course outline, time allocation, and reference materials, is offered

PEG Tube Placement

Directory of Open Access Journals (Sweden)

Saptarshi Biswas

2014-01-01

Full Text Available Percutaneous endoscopic gastrostomy (PEG has been used for providing enteral access to patients who require long-term enteral nutrition for years. Although generally considered safe, PEG tube placement can be associated with many immediate and delayed complications. Buried bumper syndrome (BBS is one of the uncommon and late complications of percutaneous endoscopic gastrostomy (PEG placement. It occurs when the internal bumper of the PEG tube erodes into the gastric wall and lodges itself between the gastric wall and skin. This can lead to a variety of additional complications such as wound infection, peritonitis, and necrotizing fasciitis. We present here a case of buried bumper syndrome which caused extensive necrosis of the anterior abdominal wall.

Ada in AI or AI in Ada. On developing a rationale for integration

Science.gov (United States)

Collard, Philippe E.; Goforth, Andre

1988-01-01

The use of Ada as an Artificial Intelligence (AI) language is gaining interest in the NASA Community, i.e., by parties who have a need to deploy Knowledge Based-Systems (KBS) compatible with the use of Ada as the software standard for the Space Station. A fair number of KBS and pseudo-KBS implementations in Ada exist today. Currently, no widely used guidelines exist to compare and evaluate these with one another. The lack of guidelines illustrates a fundamental problem inherent in trying to compare and evaluate implementations of any sort in languages that are procedural or imperative in style, such as Ada, with those in languages that are functional in style, such as Lisp. Discussed are the strengths and weakness of using Ada as an AI language and a preliminary analysis provided of factors needed for the development of criteria for the integration of these two families of languages and the environments in which they are implemented. The intent for developing such criteria is to have a logical rationale that may be used to guide the development of Ada tools and methodology to support KBS requirements, and to identify those AI technology components that may most readily and effectively be deployed in Ada.

PEG-asparaginase induced severe hypertriglyceridemia.

Science.gov (United States)

Galindo, Rodolfo J; Yoon, Justin; Devoe, Craig; Myers, Alyson K

2016-04-01

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

Righting the ADA

Science.gov (United States)

National Council on Disability, 2004

2004-01-01

Many Americans with disabilities feel that a series of negative court decisions is reducing their status to that of "second-class citizens," a status that the Americans with Disabilities Act (ADA) was supposed to remedy forever. In this report, the National Council on Disability (NCD), which first proposed the enactment of an ADA and…

Effect of cationic grafted copolymer structure on the encapsulation of bovine serum albumin

International Nuclear Information System (INIS)

Flynn, Nicholas; Topal, Ç. Özge; Hikkaduwa Koralege, Rangika S.; Hartson, Steve; Ranjan, Ashish; Liu, Jing; Pope, Carey; Ramsey, Joshua D.

2016-01-01

The aim of the present study was to evaluate a library of poly-L-lysine (PLL)-graft (g)-polyethylene glycol (PEG) copolymers for the ability to encapsulate effectively a model protein, bovine serum albumin (BSA), and to characterize the stability and protein function of the resulting nanoparticle. A library of nine grafted copolymers was produced by varying PLL molecular weight and PEG grafting ratio. Electrostatic self-assembly of the protein and the grafted copolymer drove encapsulation. The formation of protein/polymer nanoparticles with a core/shell structure was confirmed using PAGE, dynamic light scattering, and electron microscopy. Encapsulation of the BSA into nanoparticles was strongly dependent on the copolymer-to-protein mass ratio, PEG grafting ratio, and PLL molecular weight. A copolymer-to-protein mass ratio of 7:1 and higher was generally required for high levels of encapsulation, and under these conditions, no loss of protein activity was observed. Copolymer characteristics also influenced nanoparticle resistance to polyanions and protease degradation. The results indicate that a copolymer of 15–30 kDa PLL, with a PEG grafting ratio of 10:1, is most promising for protein delivery. - Highlights: • A 4–70 kDa range of PLL-g-PEG copolymers was able to encapsulate BSA into NPs. • Encapsulation of BSA by PLL-g-PEG not only retained but increased esterolytic activity. • NPs were stable against protease degradation and polyanion dissociation.

Effect of cationic grafted copolymer structure on the encapsulation of bovine serum albumin

Energy Technology Data Exchange (ETDEWEB)

Flynn, Nicholas [School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078 (United States); Topal, Ç. Özge [School of Mechanical and Aerospace Engineering, Oklahoma State University, Stillwater, OK 74078 (United States); Hikkaduwa Koralege, Rangika S. [School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078 (United States); Hartson, Steve [Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078 (United States); Ranjan, Ashish; Liu, Jing; Pope, Carey [Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Ramsey, Joshua D., E-mail: josh.ramsey@okstate.edu [School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078 (United States)

2016-05-01

The aim of the present study was to evaluate a library of poly-L-lysine (PLL)-graft (g)-polyethylene glycol (PEG) copolymers for the ability to encapsulate effectively a model protein, bovine serum albumin (BSA), and to characterize the stability and protein function of the resulting nanoparticle. A library of nine grafted copolymers was produced by varying PLL molecular weight and PEG grafting ratio. Electrostatic self-assembly of the protein and the grafted copolymer drove encapsulation. The formation of protein/polymer nanoparticles with a core/shell structure was confirmed using PAGE, dynamic light scattering, and electron microscopy. Encapsulation of the BSA into nanoparticles was strongly dependent on the copolymer-to-protein mass ratio, PEG grafting ratio, and PLL molecular weight. A copolymer-to-protein mass ratio of 7:1 and higher was generally required for high levels of encapsulation, and under these conditions, no loss of protein activity was observed. Copolymer characteristics also influenced nanoparticle resistance to polyanions and protease degradation. The results indicate that a copolymer of 15–30 kDa PLL, with a PEG grafting ratio of 10:1, is most promising for protein delivery. - Highlights: • A 4–70 kDa range of PLL-g-PEG copolymers was able to encapsulate BSA into NPs. • Encapsulation of BSA by PLL-g-PEG not only retained but increased esterolytic activity. • NPs were stable against protease degradation and polyanion dissociation.

Object-oriented programming with mixins in Ada

Science.gov (United States)

Seidewitz, ED

1992-01-01

Recently, I wrote a paper discussing the lack of 'true' object-oriented programming language features in Ada 83, why one might desire them in Ada, and how they might be added in Ada 9X. The approach I took in this paper was to build the new object-oriented features of Ada 9X as much as possible on the basic constructs and philosophy of Ada 83. The object-oriented features proposed for Ada 9X, while different in detail, are based on the same kind of approach. Further consideration of this approach led me on a long reflection on the nature of object-oriented programming and its application to Ada. The results of this reflection, presented in this paper, show how a fairly natural object-oriented style can indeed be developed even in Ada 83. The exercise of developing this style is useful for at least three reasons: (1) it provides a useful style for programming object-oriented applications in Ada 83 until new features become available with Ada 9X; (2) it demystifies many of the mechanisms that seem to be 'magic' in most object-oriented programming languages by making them explicit; and (3) it points out areas that are and are not in need of change in Ada 83 to make object-oriented programming more natural in Ada 9X. In the next four sections I will address in turn the issues of object-oriented classes, mixins, self-reference and supertyping. The presentation is through a sequence of examples. This results in some overlap with that paper, but all the examples in the present paper are written entirely in Ada 83. I will return to considerations for Ada 9X in the last section of the paper.

Ada--Programming Language of the Future.

Science.gov (United States)

Rudd, David

1983-01-01

Ada is a programing language developed for the Department of Defense, with a registered trademark. It was named for Ada Augusta, coworker of Charles Babbage and the world's first programer. The Department of Defense hopes to prevent variations and to establish Ada as a consistent, standardized language. (MNS)

An Embedded Rule-Based Diagnostic Expert System in Ada

Science.gov (United States)

Jones, Robert E.; Liberman, Eugene M.

1992-01-01

Ada is becoming an increasingly popular programming language for large Government-funded software projects. Ada with it portability, transportability, and maintainability lends itself well to today's complex programming environment. In addition, expert systems have also assumed a growing role in providing human-like reasoning capability expertise for computer systems. The integration is discussed of expert system technology with Ada programming language, especially a rule-based expert system using an ART-Ada (Automated Reasoning Tool for Ada) system shell. NASA Lewis was chosen as a beta test site for ART-Ada. The test was conducted by implementing the existing Autonomous Power EXpert System (APEX), a Lisp-based power expert system, in ART-Ada. Three components, the rule-based expert systems, a graphics user interface, and communications software make up SMART-Ada (Systems fault Management with ART-Ada). The rules were written in the ART-Ada development environment and converted to Ada source code. The graphics interface was developed with the Transportable Application Environment (TAE) Plus, which generates Ada source code to control graphics images. SMART-Ada communicates with a remote host to obtain either simulated or real data. The Ada source code generated with ART-Ada, TAE Plus, and communications code was incorporated into an Ada expert system that reads the data from a power distribution test bed, applies the rule to determine a fault, if one exists, and graphically displays it on the screen. The main objective, to conduct a beta test on the ART-Ada rule-based expert system shell, was achieved. The system is operational. New Ada tools will assist in future successful projects. ART-Ada is one such tool and is a viable alternative to the straight Ada code when an application requires a rule-based or knowledge-based approach.

Gamma ray observatory dynamics simulator in Ada (GRODY)

International Nuclear Information System (INIS)

1990-09-01

This experiment involved the parallel development of dynamics simulators for the Gamma Ray Observatory in both FORTRAN and Ada for the purpose of evaluating the applicability of Ada to the NASA/Goddard Space Flight Center's flight dynamics environment. The experiment successfully demonstrated that Ada is a viable, valuable technology for use in this environment. In addition to building a simulator, the Ada team evaluated training approaches, developed an Ada methodology appropriate to the flight dynamics environment, and established a baseline for evaluating future Ada projects

QUEST/Ada (Query Utility Environment for Software Testing of Ada): The development of a prgram analysis environment for Ada, task 1, phase 2

Science.gov (United States)

Brown, David B.

1990-01-01

The results of research and development efforts are described for Task one, Phase two of a general project entitled The Development of a Program Analysis Environment for Ada. The scope of this task includes the design and development of a prototype system for testing Ada software modules at the unit level. The system is called Query Utility Environment for Software Testing of Ada (QUEST/Ada). The prototype for condition coverage provides a platform that implements expert system interaction with program testing. The expert system can modify data in the instrument source code in order to achieve coverage goals. Given this initial prototype, it is possible to evaluate the rule base in order to develop improved rules for test case generation. The goals of Phase two are the following: (1) to continue to develop and improve the current user interface to support the other goals of this research effort (i.e., those related to improved testing efficiency and increased code reliable); (2) to develop and empirically evaluate a succession of alternative rule bases for the test case generator such that the expert system achieves coverage in a more efficient manner; and (3) to extend the concepts of the current test environment to address the issues of Ada concurrency.

The OPEN-ADAS Approach to Atomic Data Provision

Energy Technology Data Exchange (ETDEWEB)

O' Mullane, M [University of Strathclyde, Department of Physics, Glasgow (United Kingdom)

2011-11-15

Dr O'Mullane of University of Strathclyde presented an overview of the ADAS project (Atomic Data and Analysis Structure, http://www.adas.ac.uk/) and of OPEN-ADAS (http://open.adas.ac.uk/). ADAS is maintained as a self-funding consortium of fusion laboratories. The project provides an interconnected set of computer codes and data collections for modeling the radiating properties of ions and atoms in plasmas. The ADAS data fall into 3 broad classes: 1) Fundamental data such as A- values, cross-sections and effective collision strengths obtained from ADAS collaborators, the literature or data centres. 2) Derived data processed for modeling such as electron temperature and density dependent effective emission coefficients, effective ionization/recombination rates, radiated power and spectral emissivities. 3) Driver data which allow complete regeneration of all ADAS derived data in conjunction with the various ADAS codes. ADAS data uses high quality data as well as baseline data for fall-back when high quality data is not available. The data is mostly embedded in codes and the update without expert help is problematic. The ADAS data formats (adf) are precisely defined and Fortran codes are supplied to read the data sets for easy access. IDL can be used for interactive manipulation. The OPEN-ADAS project is a joint development between the ADAS Project and the IAEA to make the extensive fundamental and derived atomic data for fusion more widely available. It is designed to appeal to both plasma modelers and those interested in the detailed atomic physics. It has been searchable through the Google Scholar and appears in citations, which gives greater visibility and credits to the data producers. The OPEN-ADAS server was replaced due to a series of attacks since June 2011 and was off-line for 8 weeks. The new service removed the registration requirement and hence the user statistics is limited.

The OPEN-ADAS Approach to Atomic Data Provision

International Nuclear Information System (INIS)

O'Mullane, M.

2011-01-01

Dr O'Mullane of University of Strathclyde presented an overview of the ADAS project (Atomic Data and Analysis Structure, http://www.adas.ac.uk/) and of OPEN-ADAS (http://open.adas.ac.uk/). ADAS is maintained as a self-funding consortium of fusion laboratories. The project provides an interconnected set of computer codes and data collections for modeling the radiating properties of ions and atoms in plasmas. The ADAS data fall into 3 broad classes: 1) Fundamental data such as A- values, cross-sections and effective collision strengths obtained from ADAS collaborators, the literature or data centres. 2) Derived data processed for modeling such as electron temperature and density dependent effective emission coefficients, effective ionization/recombination rates, radiated power and spectral emissivities. 3) Driver data which allow complete regeneration of all ADAS derived data in conjunction with the various ADAS codes. ADAS data uses high quality data as well as baseline data for fall-back when high quality data is not available. The data is mostly embedded in codes and the update without expert help is problematic. The ADAS data formats (adf) are precisely defined and Fortran codes are supplied to read the data sets for easy access. IDL can be used for interactive manipulation. The OPEN-ADAS project is a joint development between the ADAS Project and the IAEA to make the extensive fundamental and derived atomic data for fusion more widely available. It is designed to appeal to both plasma modelers and those interested in the detailed atomic physics. It has been searchable through the Google Scholar and appears in citations, which gives greater visibility and credits to the data producers. The OPEN-ADAS server was replaced due to a series of attacks since June 2011 and was off-line for 8 weeks. The new service removed the registration requirement and hence the user statistics is limited.

Polyethylene glycols (PEG) and related structures

DEFF Research Database (Denmark)

Wenande, Emily; Kroigaard, Mogens; Mosbech, Holger

2015-01-01

We describe hypersensitivity to polyethylene glycols (PEGs), with cross-reactivity to a structural analog, polysorbate 80, in a 69-year-old patient with perioperative anaphylaxis and subsequent, severe anaphylactic reactions to unrelated medical products. PEGs and PEG analogs are prevalent in the...

Ada & the Analytical Engine.

Science.gov (United States)

Freeman, Elisabeth

1996-01-01

Presents a brief history of Ada Byron King, Countess of Lovelace, focusing on her primary role in the development of the Analytical Engine--the world's first computer. Describes the Ada Project (TAP), a centralized World Wide Web site that serves as a clearinghouse for information related to women in computing, and provides a Web address for…

Stereocomplex mediated gelation of PEG-(PLA)2 and PEG(PLA)8 block copolymers

NARCIS (Netherlands)

Hiemstra, C.; Zhong, Zhiyuan; Dijkstra, Pieter J.; Feijen, Jan

2005-01-01

Stereocomplex mediated hydrogels have been prepared by mixing solutions of polymers of opposite chirality of either PEG-(PLA)2 triblock copolymers or PEG-(PLA)8 star block copolymers. The critical gel concentrations of the mixed enantiomer solutions were considerably lower compared to polymer

Synthesis and bioactivity study of 30kda linear peg-interferon and its comparison with tri-branched peg-interferon

International Nuclear Information System (INIS)

Sabar, M.F.; Awan, F.I.

2013-01-01

Summary: Polyethylene glycol (PEG) is conjugated to the therapeutic proteins to enhance their circulating half life. PEGylation is a clinically proven strategy for increasing the therapeutic efficacy of protein-based medicines. PEG size and structure is very important in achieving specific properties in the conjugated protein. In this study we have compared the properties of newly synthesized linear PEG-IFN with a same sized (i.e., 30KDa) tri-branched PEG-IFN synthesized in the same lab earlier. For PEGylation reaction, interferon-alpha2 (IFNalpha2) concentration in sodium borate buffer pH 8.5 was optimized as 4.0mg/ml. The optimized molar ratio of PEG/IFN alpha2 was 3:1 instead of 5:1 in the case of tri-branched PEG published earlier. Other parameters of reaction were same as in our previous publication. Mono PEGylation degree reached to 21%. Cation exchange chromatography was used to separate and purify mono PEGylated IFN from the reaction mixture. The purity of mono PEGylated IFN was greater than 95%. It is noticed that PEGylation was more site specific in tribranched than the linear conjugate. The in vitro bioactivity of linear mPEG-IFN is 10-fold lesser than as reported of tri-branched mPEG3L2-IFN. Thermal stability of linear mPEG-IFN is also smaller than mPEG/sub 3/L/sub 2/-IFN at 4 degree C. (author)

Atomic Data and Modelling for Fusion: the ADAS Project

International Nuclear Information System (INIS)

Summers, H. P.; O'Mullane, M. G.

2011-01-01

The paper is an update on the Atomic Data and Analysis Structure, ADAS, since ICAM-DATA06 and a forward look to its evolution in the next five years. ADAS is an international project supporting principally magnetic confinement fusion research. It has participant laboratories throughout the world, including ITER and all its partner countries. In parallel with ADAS, the ADAS-EU Project provides enhanced support for fusion research at Associated Laboratories and Universities in Europe and ITER. OPEN-ADAS, sponsored jointly by the ADAS Project and IAEA, is the mechanism for open access to principal ADAS atomic data classes and facilitating software for their use. EXTENDED-ADAS comprises a variety of special, integrated application software, beyond the purely atomic bounds of ADAS, tuned closely to specific diagnostic analyses and plasma models.The current scientific content and scope of these various ADAS and ADAS related activities are briefly reviewed. These span a number of themes including heavy element spectroscopy and models, charge exchange spectroscopy, beam emission spectroscopy and special features which provide a broad baseline of atomic modelling and support. Emphasis will be placed on 'lifting the fundamental data baseline'--a principal ADAS task for the next few years. This will include discussion of ADAS and ADAS-EU coordinated and shared activities and some of the methods being exploited.

Enhanced EGFP Fluorescence Emission in Presence of PEG Aqueous Solutions and PIB1000-PEG6000-PIB1000 Copolymer Vesicles

Directory of Open Access Journals (Sweden)

Noor Muhammad

2013-01-01

Full Text Available An EGFP construct interacting with the PIB1000-PEG6000-PIB1000 vesicles surface reported a ~2-fold fluorescence emission enhancement. Because of the constructs nature with the amphiphilic peptide inserted into the PIB core, EGFP is expected to experience a “pure” PEG environment. To unravel this phenomenon PEG/water solutions at different molecular weights and concentrations were used. Already at ~1 : 10 protein/PEG molar ratio the increase in fluorescence emission is observed reaching a plateau correlating with the PEG molecular weight. Parallel experiments in presence of glycerol aqueous solutions did show a slight fluorescence enhancement however starting at much higher concentrations. Molecular dynamics simulations of EGFP in neat water, glycerol, and PEG aqueous solutions were performed showing that PEG molecules tend to “wrap” the protein creating a microenvironment where the local PEG concentration is higher compared to its bulk concentration. Because the fluorescent emission can be perturbed by the refractive index surrounding the protein, the clustering of PEG molecules induces an enhanced fluorescence emission already at extremely low concentrations. These findings can be important when related to the use of EGFP as reported in molecular biology experiments.

Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA:PEG ratios.

Science.gov (United States)

Phan, Quoc Thong; Le, Mai Huong; Le, Thi Thu Huong; Tran, Thi Hong Ha; Xuan, Phuc Nguyen; Ha, Phuong Thu

2016-06-30

Targeting delivery system use natural drugs for tumor cells is an appealing platform help to reduce the side effects and enhance the therapeutic effects of the drug. In this study, we synthesized curcumin (Cur) loaded (D, L Poly lactic - Poly ethylenglycol) micelle (Cur/PLA-PEG) with the ratio of PLA/PEG of 3:1 2:1 1:1 1:2 and 1:3 (w/w) and another micelle modified by folate (Cur/PLA-PEG-Fol) for targeting cancer therapy. The PLA-PEG copolymer was synthesized by ring opening polymerization method. After loading onto the micelle, solubility of Cur increased from 0.38 to 0.73mgml(-1). The average size of prepared Cur/PLA-PEG micelles was from 60 to 69nm (corresponding to the ratio difference of PLA/PEG) and the drug encapsulating efficiency was from 48.8 to 91.3%. Compared with the Cur/PLA-PEG micelles, the size of Cur/PLA-PEG-Fol micelles were from 80 to 86nm and showed better in vitro cellular uptake and cytotoxicity towards HepG2 cells. The cytotoxicity of the NPs however depends much on the PEG component. The results demonstrated that Folate-modified micelles could serve as a potential nano carrier to improve solubility, anti-cancer activity of Cur and targeting ability of the system. Copyright © 2016 Elsevier B.V. All rights reserved.

49 CFR 37.123 - ADA paratransit eligibility: Standards.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false ADA paratransit eligibility: Standards. 37.123... INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.123 ADA... complementary paratransit service shall provide the service to the ADA paratransit eligible individuals...

GRASP/Ada: Graphical Representations of Algorithms, Structures, and Processes for Ada. The development of a program analysis environment for Ada: Reverse engineering tools for Ada, task 2, phase 3

Science.gov (United States)

Cross, James H., II

1991-01-01

The main objective is the investigation, formulation, and generation of graphical representations of algorithms, structures, and processes for Ada (GRASP/Ada). The presented task, in which various graphical representations that can be extracted or generated from source code are described and categorized, is focused on reverse engineering. The following subject areas are covered: the system model; control structure diagram generator; object oriented design diagram generator; user interface; and the GRASP library.

Evolving impact of Ada on a production software environment

Science.gov (United States)

Mcgarry, F.; Esker, L.; Quimby, K.

1988-01-01

Many aspects of software development with Ada have evolved as our Ada development environment has matured and personnel have become more experienced in the use of Ada. The Software Engineering Laboratory (SEL) has seen differences in the areas of cost, reliability, reuse, size, and use of Ada features. A first Ada project can be expected to cost about 30 percent more than an equivalent FORTRAN project. However, the SEL has observed significant improvements over time as a development environment progresses to second and third uses of Ada. The reliability of Ada projects is initially similar to what is expected in a mature FORTRAN environment. However, with time, one can expect to gain improvements as experience with the language increases. Reuse is one of the most promising aspects of Ada. The proportion of reusable Ada software on our Ada projects exceeds the proportion of reusable FORTRAN software on our FORTRAN projects. This result was noted fairly early in our Ada projects, and experience shows an increasing trend over time.

49 CFR 37.125 - ADA paratransit eligibility: Process.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false ADA paratransit eligibility: Process. 37.125... INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.125 ADA... § 37.121 of this part shall establish a process for determining ADA paratransit eligibility. (a) The...

OLDER DRIVERS AND ADAS

Directory of Open Access Journals (Sweden)

Ragnhild J. DAVIDSE

2006-01-01

Next, based on the available literature, relevant ADAS are discussed in terms of their availability, their effects on safety and the willingness of older drivers to use and buy them. One of the conclusions is that only very few of the types of support that are thought to be most beneficial to the safety of older drivers are provided by the ADAS that are currently available.

AN ADA NAMELIST PACKAGE

Science.gov (United States)

Klumpp, A. R.

1994-01-01

The Ada Namelist Package, developed for the Ada programming language, enables a calling program to read and write FORTRAN-style namelist files. A namelist file consists of any number of assignment statements in any order. Features of the Ada Namelist Package are: the handling of any combination of user-defined types; the ability to read vectors, matrices, and slices of vectors and matrices; the handling of mismatches between variables in the namelist file and those in the programmed list of namelist variables; and the ability to avoid searching the entire input file for each variable. The principle user benefits of this software are the following: the ability to write namelist-readable files, the ability to detect most file errors in the initialization phase, a package organization that reduces the number of instantiated units to a few packages rather than to many subprograms, a reduced number of restrictions, and an increased execution speed. The Ada Namelist reads data from an input file into variables declared within a user program. It then writes data from the user program to an output file, printer, or display. The input file contains a sequence of assignment statements in arbitrary order. The output is in namelist-readable form. There is a one-to-one correspondence between namelist I/O statements executed in the user program and variables read or written. Nevertheless, in the input file, mismatches are allowed between assignment statements in the file and the namelist read procedure statements in the user program. The Ada Namelist Package itself is non-generic. However, it has a group of nested generic packages following the nongeneric opening portion. The opening portion declares a variety of useraccessible constants, variables and subprograms. The subprograms are procedures for initializing namelists for reading, reading and writing strings. The subprograms are also functions for analyzing the content of the current dataset and diagnosing errors. Two nested

Parallel Ada benchmarks for the SVMS

Science.gov (United States)

Collard, Philippe E.

1990-01-01

The use of parallel processing paradigm to design and develop faster and more reliable computers appear to clearly mark the future of information processing. NASA started the development of such an architecture: the Spaceborne VHSIC Multi-processor System (SVMS). Ada will be one of the languages used to program the SVMS. One of the unique characteristics of Ada is that it supports parallel processing at the language level through the tasking constructs. It is important for the SVMS project team to assess how efficiently the SVMS architecture will be implemented, as well as how efficiently Ada environment will be ported to the SVMS. AUTOCLASS II, a Bayesian classifier written in Common Lisp, was selected as one of the benchmarks for SVMS configurations. The purpose of the R and D effort was to provide the SVMS project team with the version of AUTOCLASS II, written in Ada, that would make use of Ada tasking constructs as much as possible so as to constitute a suitable benchmark. Additionally, a set of programs was developed that would measure Ada tasking efficiency on parallel architectures as well as determine the critical parameters influencing tasking efficiency. All this was designed to provide the SVMS project team with a set of suitable tools in the development of the SVMS architecture.

QUEST/Ada: Query utility environment for software testing of Ada

Science.gov (United States)

Brown, David B.

1989-01-01

Results of research and development efforts are presented for Task 1, Phase 2 of a general project entitled, The Development of a Program Analysis Environment for Ada. A prototype of the QUEST/Ada system was developed to collect data to determine the effectiveness of the rule-based testing paradigm. The prototype consists of five parts: the test data generator, the parser/scanner, the test coverage analyzer, a symbolic evaluator, and a data management facility, known as the Librarian. These components are discussed at length. Also presented is an experimental design for the evaluations, an overview of the project, and a schedule for its completion.

Comparison of Coatings from Reactive Star Shaped PEG-stat-PPG Prepolymers and Grafted Linear PEG for Biological and Medical Applications

DEFF Research Database (Denmark)

Groll, J.; Ademovic, Z.; Klee, D.

2005-01-01

). In an alternative approach, surfaces were modified with layers prepared from isocyanate terminated, star shaped poly(ethylene glycol-stat-propylene glycol) prepolymers (80% ethylene glycol, six arms, M. = 3000, 12 000, and 18 000; this compound will be referred to as "Star PEG" in the text). Due to the highly......Grafting of poly(ethylene glycol) (PEG) is a common strategy for reducing nonspecific interactions of surfaces with proteins. We have used grafting at "cloud point" solution conditions that ensures maximum grafting density of linear methoxy terminated PEG-aldehyde (mPEG-ald, M-W = 5000 and 30000....... Protein adsorption was monitored by surface MALDI-TOF MS and fluorescence microscopy. No protein adsorption could be detected on Star PEG coatings and on mPEG-ald 5000, whereas mPEG-ald 30 000 could only prevent adsorption of lysozyme but not of the smaller insulin....

Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles

Science.gov (United States)

Yamini, D.; Devanand Venkatasubbu, G.; Kumar, J.; Ramakrishnan, V.

2014-01-01

The pure hydroxyapatite (HAP) nanoparticles (NPs) have been synthesized by wet chemical precipitation method. Raman spectral measurements have been made for pure HAP, pure Polyethylene glycol (PEG) 6000 and PEG coated HAP in different mass ratios (sample 1, sample 2 and sample 3). The peaks observed in Raman spectrum of pure HAP and the XRD pattern have confirmed the formation of HAP NPs. Vibrational modes have been assigned for pure HAP and pure PEG 6000. The observed variation in peak position of Raman active vibrational modes of PEG in PEG coated HAP has been elucidated in this work, in terms of intermolecular interactions between PEG and HAP. Further these results suggest that the functionalization of nanoparticles may be independent of PEG mass.

Restoring balance to B cells in ADA deficiency.

Science.gov (United States)

Luning Prak, Eline T

2012-06-01

It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.

ADA members weigh in on critical issues.

Science.gov (United States)

Burgess, Karen; Ruesch, Jon D; Mikkelsen, Matthew C; Wagner, Karen Schaid

2003-01-01

Science, new technology, patient care, dental reimbursement and government regulations all affect today's dental practitioners. To find out more about how such challenges may affect current private practitioners, the American Dental Association conducted the 2000 Membership Needs and Opinions Survey. A questionnaire was sent to 6,310 ADA members in January 2000 with follow-up mailings in February, March and April 2000. Data collection was completed in July 2000. The survey included questions on critical professional issues, and on perceptions of the ADA and ADA priorities. A total of 3,558 completed surveys were received for an adjusted response rate of 59.5 percent. Members rated the identified issues' level of importance to them. The top three issues included "maintaining my ability to recommend the treatment option I feel is most appropriate for my patients," "receiving fair reimbursement for the dental services I provide," and "protecting myself, my staff and my patients from communicable diseases." New dentists found other items to be more significant to them compared with members overall. Although ADA members as a whole had similar views on critical issues facing dentistry and ADA priorities, there were significant differences regarding some issues. New dentists were far more concerned about securing funds for their practice and paying off debt than were all ADA members. Minority dentists expressed greater levels of concern about certain issues than did all ADA members. When planning and implementing ADA activities, the Association should continue to take into account members' relative rankings of professional issues and note issues of special interest to selected membership subgroups.

77 FR 29914 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

Science.gov (United States)

2012-05-21

... Spongiform Encephalopathy; Importation of Bovines and Bovine Products AGENCY: Animal and Plant Health... derived from bovines with regard to bovine spongiform encephalopathy. This action will allow interested... importation of live bovines and products derived from bovines with regard to bovine spongiform encephalopathy...

Investigation of PEG crystallization in frozen PEG-sucrose-water solutions. I. Characterization of the nonequilibrium behavior during freeze-thawing.

Science.gov (United States)

Bhatnagar, Bakul S; Martin, Susan M; Teagarden, Dirk L; Shalaev, Evgenyi Y; Suryanarayanan, Raj

2010-06-01

Our objective was to characterize the nonequilibrium thermal behavior of frozen aqueous solutions containing PEG and sucrose. Aqueous solutions of (i) sucrose (10%, w/v) with different concentrations of PEG (1-20%, w/v), and (ii) PEG (10%, w/v) with different concentrations of sucrose (2-20%, w/v), were cooled to -70 degrees C at 5 degrees C/min and heated to 25 degrees C at 2 degrees C/min in a differential scanning calorimeter. Annealing was performed at temperatures ranging from -50 to -20 degrees C for 2 or 6 h. Similar experiments were also performed in the low-temperature stage of a powder X-ray diffractometer. A limited number of additional DSC experiments were performed wherein the samples were cooled to -100 degrees C. In unannealed systems with a fixed sucrose concentration (10%, w/v), the T'g decreased from -35 to -48 degrees C when PEG concentration was increased from 1% to 20% (w/v). On annealing at -25 degrees C, PEG crystallized. This was evident from the increase in T'g and the appearance of a secondary melting endotherm in the DSC. Low-temperature XRD provided direct evidence of PEG crystallization. Annealing at temperatures PEG concentration (10%, w/v), the T'g increased from -50 to -40 degrees C when sucrose concentration was increased from 5% to 50%, w/v. As the annealing time increased (at -25 degrees C), the T'g approached that of a sucrose-water system, reflecting progressive PEG crystallization. A second glass transition at approximately -65 degrees C was evident in unannealed systems [10%, w/v sucrose and 10 (or 20%), w/v PEG] cooled to -100 degrees C. Investigation of the nonequilibrium behavior of frozen PEG-sucrose-water ternary system revealed phase separation in the freeze-concentrate. Annealing facilitated PEG crystallization. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Ada Namelist Package

Science.gov (United States)

Klumpp, Allan R.

1991-01-01

Ada Namelist Package, developed for Ada programming language, enables calling program to read and write FORTRAN-style namelist files. Features are: handling of any combination of types defined by user; ability to read vectors, matrices, and slices of vectors and matrices; handling of mismatches between variables in namelist file and those in programmed list of namelist variables; and ability to avoid searching entire input file for each variable. Principle benefits derived by user: ability to read and write namelist-readable files, ability to detect most file errors in initialization phase, and organization keeping number of instantiated units to few packages rather than to many subprograms.

Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions.

Science.gov (United States)

Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J; Harris, Michael T

2015-12-01

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.

Fine-Tuning ADAS Algorithm Parameters for Optimizing Traffic ...

Science.gov (United States)

With the development of the Connected Vehicle technology that facilitates wirelessly communication among vehicles and road-side infrastructure, the Advanced Driver Assistance Systems (ADAS) can be adopted as an effective tool for accelerating traffic safety and mobility optimization at various highway facilities. To this end, the traffic management centers identify the optimal ADAS algorithm parameter set that enables the maximum improvement of the traffic safety and mobility performance, and broadcast the optimal parameter set wirelessly to individual ADAS-equipped vehicles. After adopting the optimal parameter set, the ADAS-equipped drivers become active agents in the traffic stream that work collectively and consistently to prevent traffic conflicts, lower the intensity of traffic disturbances, and suppress the development of traffic oscillations into heavy traffic jams. Successful implementation of this objective requires the analysis capability of capturing the impact of the ADAS on driving behaviors, and measuring traffic safety and mobility performance under the influence of the ADAS. To address this challenge, this research proposes a synthetic methodology that incorporates the ADAS-affected driving behavior modeling and state-of-the-art microscopic traffic flow modeling into a virtually simulated environment. Building on such an environment, the optimal ADAS algorithm parameter set is identified through an optimization programming framework to enable th

The Katydid system for compiling KEE applications to Ada

Science.gov (United States)

Filman, Robert E.; Bock, Conrad; Feldman, Roy

1990-01-01

Components of a system known as Katydid are developed in an effort to compile knowledge-based systems developed in a multimechanism integrated environment (KEE) to Ada. The Katydid core is an Ada library supporting KEE object functionality, and the other elements include a rule compiler, a LISP-to-Ada translator, and a knowledge-base dumper. Katydid employs translation mechanisms that convert LISP knowledge structures and rules to Ada and utilizes basic prototypes of a run-time KEE object-structure library module for Ada. Preliminary results include the semiautomatic compilation of portions of a simple expert system to run in an Ada environment with the described algorithms. It is suggested that Ada can be employed for AI programming and implementation, and the Katydid system is being developed to include concurrency and synchronization mechanisms.

Ada (Trade Name) Bibliography. Volume 1.

Science.gov (United States)

1983-05-01

GLENN DOCUMENT NUMBER: 3268 TYPE: JOURNAL ARTICLE .5-., SCIENCE VOL 215 ISSUE 34 PP. 775-779S In this article, two principal themes are observed in...AINST LANAN RD NAY 83 ND9S-8-C-936 UNCLASSIFIED F/6 12/5 ML -4.4 ’-4-4----" ’°p..l i . d N N L. 131 t ’ll /II~ Ada Bibliography Volume I 95 𔃾- This...BUDAPEST,HUNGARY 4102 -01 ON THE TYPE CONCEPT OF ADA 6224 -03 UNORTHOGONALITIES IN THE IDENTIFICATION RULES IN ADA BACON, GLENN , IBM SANTA TERESA LABS

Toward the efficient implementation of expert systems in Ada

Science.gov (United States)

Lee, S. Daniel

1990-01-01

Here, the authors describe Ada language issues encountered during the development of ART-Ada, an expert system tool for Ada deployment. ART-Ada is being used to implement several expert system applications for the Space Station Freedom and the U.S. Air Force. Additional information is given on dynamic memory allocation.

Ada Run Time Support Environments and a common APSE Interface Set. [Ada Programming Support Environment

Science.gov (United States)

Mckay, C. W.; Bown, R. L.

1985-01-01

The paper discusses the importance of linking Ada Run Time Support Environments to the Common Ada Programming Support Environment (APSE) Interface Set (CAIS). A non-stop network operating systems scenario is presented to serve as a forum for identifying the important issues. The network operating system exemplifies the issues involved in the NASA Space Station data management system.

Evaluation of Clensia®, a new low-volume PEG bowel preparation in colonoscopy: Multicentre randomized controlled trial versus 4L PEG.

Science.gov (United States)

Spada, Cristiano; Cesaro, Paola; Bazzoli, Franco; Saracco, Giorgio Maria; Cipolletta, Livio; Buri, Luigi; Crosta, Cristiano; Petruzziello, Lucio; Ceroni, Liza; Fuccio, Lorenzo; Giordanino, Chiara; Elia, Chiara; Rotondano, Gianluca; Bianco, Maria A; Simeth, Catrin; Consalvo, Danilo; De Roberto, Giuseppe; Fiori, Giancarla; Campanale, Mariachiara; Costamagna, Guido

2017-06-01

Success of colonoscopy is linked to the adequacy of bowel cleansing. Polyethylene glycol 4L (PEG 4L) solutions are widely used for colonic cleansing but with limitations concerning tolerability and acceptability. To demonstrate the equivalence of a new low-volume PEG containing citrates and simeticone (Clensia) versus a standard PEG 4L. In this, multicentre, randomised, observer-blind trial, patients received either Clensia 2L or PEG 4L solution. Primary endpoint was the proportion of patients with colon cleansing evaluated as excellent or good. 422 patients received Clensia (n=213) or PEG 4L (n=209). Rate of excellent/good bowel cleansing was 73.6% and 72.3% in Clensia and PEG 4L group respectively. Clensia was demonstrated to be equivalent to PEG 4L. No SAEs were observed. Clensia showed better gastrointestinal tolerability (37.0% vs 25.4%). The acceptability was significantly better with Clensia in terms of proportion of subjects who felt no distress (Clensia 72.8% vs PEG 4L 63%, P=0.0314) and willingness-to-repeat (93.9% vs 82.2%, P=0.0002). The rate of optimal compliance was similar with both formulations (91.1% for Clensia vs 90.9% for PEG 4L, P=0.9388). The low-volume Clensia is equally effective and safe in bowel cleansing compared to the standard PEG 4L, with better gastrointestinal tolerability and acceptability. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Enteral alimentation at home: why PEG now?].

Science.gov (United States)

Suzuki, Y; Hanyu, N; Kashiwagi, H; Kubo, T; Aoki, T

1996-12-01

The history of percutaneous endoscopic gastrostomy (PEG) is relatively short. In 1980, a report entitled "Gastrostomy without laparotomy: A percutaneous endoscopic technique" by Ponsky and Gaudere was first published in the Journal of Pediatric Surgery. Thereafter, PEG soon saw widespread use in Western countries because of its clinical efficacy and economy. It has been performed in about 170,000 cases annually in the US. In contrast, its spread in Japan has been extremely slow: only about 10,000 cases have undergone this procedure annually, and this number accounted for less than 5% of patients receiving enteral alimentation. The reason why PEG has not spread may be the medical insurance system in Japan and the local distaste for operation scarring. However, in consideration of the unprecedented ageing of society that is surely coming in the near future, the role of PEG in Japan must be reexamined. In this report, we presented the methodology of enteral alimentation at home by means of PEG, giving special consideration to: (1) "What points are improved by using enteral alimentation at home by means of PEG in various diseases; (2) dysphagia due to cerebral angiopathy; (3) terminal cancer; (4) otolaryngological diseases; and (5) Crohn disease. We also discussed "Why PEG is important now?" in performing enteral alimentation at home.

PEMBUATAN DAN KARAKTERISASI MEMBRAN HIBRIDA KITOSAN-SILIKA- PEG

Directory of Open Access Journals (Sweden)

F Widhi Mahatmanti

2013-02-01

Full Text Available Membran kitosan mempunyai efektivitas pemisahan relatif tinggi tetapi kestabilan mekanik rendah. Untuk meningkatkan kestabilan perlu ditambahkan silika sehingga dihasilkan membran kitosan-silika. Sebagai bahan dasar silika digunakan natrium silikat yang diisolasi dari abu sekam padi. Dalam pembuatan membran kitosan-silika, plasticizer (polietilen glikol/PEG digunakan untuk meningkatkan kestabilan mekanik membran secara signifikan. Pembuatan membran kitosan-silika-PEG dilakukan dengan cara penguapan larutan dan pencetakan. Membran kitosan-silika-PEG dikarakterisasi sifat mekaniknya dengan menguji kekuatan tarik, persen perpanjangan dan Modulus Young, perubahan gugus fungsi, morfologi, sifat kristalinitas, kestabilan terhadap suhu, sifat hidrofilisitas, dan uji terhadap fluks air. Hasil penelitian menunjukkan bahwa membran kitosan-silika dengan komposisi kitosan/silika 1:0,8 mempunyai harga kuat tarik optimum. Penambahan PEG akan meningkatkan harga persen perpanjangan, tidak menunjukkan perubahan yang signifikan pada hasil uji FTIR dan XRD, tetapi meningkatkan sifat hidrofil seiring dengan meningkatnya konsentrasi PEG dan pH. Nilai Fluks air menurun dengan meningkatnya konsentrasi PEG, dimungkinkan PEG terjebak secara fisik dalam padatan komposit.

Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats

Directory of Open Access Journals (Sweden)

B. O. Chekh

2017-08-01

Full Text Available The aim of our work was to study biological properties of the polymer based on pseudo-polyamino acids GluLa-DPG-PEG600, its ability to bind albumin, as well as its localization in rat body and influence on physio­logical and functional state of rat kidneys and liver. We have found the ability of GluLa-DPG-PEG600 to bind bovine serum albumin (BSA using electrophoresis in 5% polyacrylamide gel. Structural and functional state of the liver and kidneys of rats after injections of polymer were investigated by histological analysis of organs and determination the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase and content of cholesterol and creatinine in blood. Our results showed little toxic effect of GluLa-DPG-PEG600 on rat body. Using fluorescent microscopy we have studied polymer in complex with BSA distribution in rat body: after intravenous injection polymer are localized in kidneys and spleen, and after intramuscular – in liver and brain. It has been shown that polymer passed through the blood-brain barrier and are localized in the immune organ – spleen, indicating GluLa-DPG-PEG600 as a potential drug transporter.

A Comparison of Ada 83 and C++

Science.gov (United States)

1991-06-01

developing large, complex, software systems with long lifetimes. Those interviewed for this study who are familiar with both Ada and C++ believe that Ada is...with those who are familiar with both languages, there was a clear preference for using Ada for large complex systems with long lifetimes. These...University, December 1990 Additions by Nelson H. Weiderman, June 1991. Chile Empresa Nacional de Aeronautica (ENAER), real-time avionics system, Data

The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study

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Sebastien Giraud

2018-02-01

Full Text Available University of Wisconsin (UW solution is not optimal for preservation of marginal organs. Polyethylene glycol (PEG could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on kidney endothelial cells, ex vivo on preserved kidneys, and in vivo in a pig kidney autograft model. In vitro, all PEGs provided superior preservation than UW in terms of cell survival, adenosine triphosphate (ATP production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L.

GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

Science.gov (United States)

Cross, James H., II

1990-01-01

The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

Multiprocessor performance modeling with ADAS

Science.gov (United States)

Hayes, Paul J.; Andrews, Asa M.

1989-01-01

A graph managing strategy referred to as the Algorithm to Architecture Mapping Model (ATAMM) appears useful for the time-optimized execution of application algorithm graphs in embedded multiprocessors and for the performance prediction of graph designs. This paper reports the modeling of ATAMM in the Architecture Design and Assessment System (ADAS) to make an independent verification of ATAMM's performance prediction capability and to provide a user framework for the evaluation of arbitrary algorithm graphs. Following an overview of ATAMM and its major functional rules are descriptions of the ADAS model of ATAMM, methods to enter an arbitrary graph into the model, and techniques to analyze the simulation results. The performance of a 7-node graph example is evaluated using the ADAS model and verifies the ATAMM concept by substantiating previously published performance results.

Ada and its impact on the scientific user

International Nuclear Information System (INIS)

Marty, R.

1982-01-01

The Ada programming language is the result of a collective effort to design a common language for programming real-time systems. The design of Ada was initiated by the United States Department of Defense (DoD) in 1975. Ada combines facilities found in most classical languages like Fortran, PL/I, Pascal, and Basic together with many features formerly found only in experimental languages. It is argued that these features make Ada a very decent tool not only for writing real-time programs but also for the development of software in the scientific sector. (orig.)

ADAS: Atomic data, modelling and analysis for fusion

International Nuclear Information System (INIS)

Summers, H. P.; O'Mullane, M. G.; Whiteford, A. D.; Badnell, N. R.; Loch, S. D.

2007-01-01

The Atomic Data and Analysis Structure, ADAS, comprises extensive fundamental and derived atomic data collections, interactive codes for the manipulation and generation of collisional-radiative data and models, off-line codes for large scale fundamental atomic data production and codes for diagnostic analysis in the fusion and astrophysical environments. ADAS data are organized according to precise specifications, tuned to application and are assigned to numbered ADAS data formats. Some of these formats contain very large quantities of data and some have achieved wide-scale adoption in the fusion community.The paper focuses on recent extensions of ADAS designed to orient ADAS to the needs of ITER. The issue of heavy atomic species, expected to be present as ITER wall and divertor materials, dopants or control species, will be addressed with a view to the economized handling of the emission and ionisation state data needed for diagnostic spectral analysis. Charge exchange and beam emission spectroscopic capabilities and developments in ADAS will be reviewed from an ITER perspective and in the context of a shared analysis between fusion laboratories. Finally an overview and summary of current large scale fundamental data production in the framework of the ADAS project will be given and its intended availability in both fusion and astrophysics noted

Safety of PEGylated recombinant human full-length coagulation factor VIII (BAX 855) in the overall context of PEG and PEG conjugates.

Science.gov (United States)

Stidl, R; Fuchs, S; Bossard, M; Siekmann, J; Turecek, P L; Putz, M

2016-01-01

BAX 855 is a PEGylated human full-length recombinant factor VIII (rFVIII) based on licensed rFVIII (ADVATE). The applied PEGylation technology has been optimized to retain functionality of the FVIII molecule, improve its pharmacokinetic properties and allow less frequent injections while maintaining efficacy. The aim of this study was to confirm that the excellent safety profile of ADVATE remains unchanged after PEGylation. Non-clinical safety studies with BAX 855 and its respective unbound polyethylene glycol (PEG) were conducted in several species. The distribution of a single dose of radiolabelled BAX 855 was further investigated in rats. Publically available safety data on PEG alone and PEGylated biomolecules were summarized and reviewed for specific safety findings attributable to PEG or PEGylated biopharmaceuticals. Safety pharmacology studies in rabbits and macaques and repeated dose toxicity studies in rats and macaques identified no safety issues. Results of a distribution study in rats administered radiolabelled BAX 855 showed that radioactivity was completely excreted; urine was the major elimination route. A 28-day study in rats dosed with the unbound PEG constituent (PEG2ru20KCOOH) of BAX 855 showed no adverse or non-adverse effects. Safety data for PEG and PEG-protein conjugates indicate no safety concerns associated with PEG at clinically relevant dose levels. Although vacuolation of certain cell types has been reported in mammals, no such vacuolation was observed with BAX 855 or with the unbound PEG constituent. Non-clinical safety evaluation of PEG and BAX 855 identified no safety signals; the compound is now in clinical development for the treatment of patients with haemophilia A. © 2015 Baxalta Innovations GmbH. Haemophilia Published by John Wiley & Sons Ltd.

Compiling knowledge-based systems from KEE to Ada

Science.gov (United States)

Filman, Robert E.; Bock, Conrad; Feldman, Roy

1990-01-01

The dominant technology for developing AI applications is to work in a multi-mechanism, integrated, knowledge-based system (KBS) development environment. Unfortunately, systems developed in such environments are inappropriate for delivering many applications - most importantly, they carry the baggage of the entire Lisp environment and are not written in conventional languages. One resolution of this problem would be to compile applications from complex environments to conventional languages. Here the first efforts to develop a system for compiling KBS developed in KEE to Ada (trademark). This system is called KATYDID, for KEE/Ada Translation Yields Development Into Delivery. KATYDID includes early prototypes of a run-time KEE core (object-structure) library module for Ada, and translation mechanisms for knowledge structures, rules, and Lisp code to Ada. Using these tools, part of a simple expert system was compiled (not quite automatically) to run in a purely Ada environment. This experience has given us various insights on Ada as an artificial intelligence programming language, potential solutions of some of the engineering difficulties encountered in early work, and inspiration on future system development.

The Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus): an expansion of the ADAS-Cog to improve responsiveness in MCI.

Science.gov (United States)

Skinner, Jeannine; Carvalho, Janessa O; Potter, Guy G; Thames, April; Zelinski, Elizabeth; Crane, Paul K; Gibbons, Laura E

2012-12-01

The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) is widely used in AD, but may be less responsive to change when used in people with mild cognitive impairment (MCI). Participants from the Alzheimer's Disease Neuroimaging Initiative were administered a neuropsychological battery and 1.5 T MRI scans over 2-3 years. Informants were queried regarding functional impairments. Some participants had lumbar punctures to obtain cerebrospinal fluid (CSF). We added executive functioning (EF) and functional ability (FA) items to the ADAS-Cog to generate candidate augmented measures. We calibrated these candidates using baseline data (n = 811) and selected the best candidate that added EF items alone and that added EF and FA items. We selected candidates based on their responsiveness over three years in a training sample of participants with MCI (n = 160). We compared traditional ADAS-Cog scores with the two candidates based on their responsiveness in a validation sample of participants with MCI (n = 234), ability to predict conversion to dementia (n = 394), strength of association with baseline MRI (n = 394) and CSF biomarkers (n = 193). The selected EF candidate added category fluency (ADAS Plus EF), and the selected EF and FA candidate added category fluency, Digit Symbol, Trail Making, and five items from the Functional Assessment Questionnaire (ADAS Plus EF&FA). The ADAS Plus EF& FA performed as well as or better than traditional ADAS-Cog scores. Adding EF and FA items to the ADAS-Cog may improve responsiveness among people with MCI without impairing validity.

Bovine plasma protein fractionation by ion exchange chromatography.

Science.gov (United States)

Moure, F; Rendueles, M; Díaz, M

2004-12-01

An ion exchange chromatography process was developed to separate the main protein fractions of bovine blood plasma using a composite material, Q-HyperD resin, and a gel material, DEAE-Sepharose. The experiments were carried out at semipreparative scale. It was necessary to establish analytical methods of electrophoresis and HPLC to identify the fractionated proteins. Results show that these materials are able to adequately fractionate different protein groups from the raw blood plasma. This method may be used to avoid chemical fractionation using agents such as ethanol or PEG and, thus, decrease protein denaturation of the different fractions to be used for research or pharmaceutical purposes. The Q-HyperD resin presents a better retention capacity for plasma protein than DEAE-Sepharose under the experimental conditions employed.

Experiences with Ada in an embedded system

Science.gov (United States)

Labaugh, Robert J.

1988-01-01

Recent experiences with using Ada in a real time environment are described. The application was the control system for an experimental robotic arm. The objectives of the effort were to experiment with developing embedded applications in Ada, evaluating the suitability of the language for the application, and determining the performance of the system. Additional objectives were to develop a control system based on the NASA/NBS Standard Reference Model for Telerobot Control System Architecture (NASREM) in Ada, and to experiment with the control laws and how to incorporate them into the NASREM architecture.

Techniques and implementation of the embedded rule-based expert system using Ada

Science.gov (United States)

Liberman, Eugene M.; Jones, Robert E.

1991-01-01

Ada is becoming an increasingly popular programming language for large Government-funded software projects. Ada with its portability, transportability, and maintainability lends itself well to today's complex programming environment. In addition, expert systems have also assured a growing role in providing human-like reasoning capability and expertise for computer systems. The integration of expert system technology with Ada programming language, specifically a rule-based expert system using an ART-Ada (Automated Reasoning Tool for Ada) system shell is discussed. The NASA Lewis Research Center was chosen as a beta test site for ART-Ada. The test was conducted by implementing the existing Autonomous Power EXpert System (APEX), a Lisp-base power expert system, in ART-Ada. Three components, the rule-based expert system, a graphics user interface, and communications software make up SMART-Ada (Systems fault Management with ART-Ada). The main objective, to conduct a beta test on the ART-Ada rule-based expert system shell, was achieved. The system is operational. New Ada tools will assist in future successful projects. ART-Ada is one such tool and is a viable alternative to the straight Ada code when an application requires a rule-based or knowledge-based approach.

Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

Directory of Open Access Journals (Sweden)

Salam Massadeh

2016-06-01

Full Text Available Background: PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic. In this study, methotrexate (MTX-loaded nanoparticles were prepared by the double emulsion method. Method: Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%. Results: Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion: The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

Science.gov (United States)

Massadeh, Salam; Alaamery, Manal; Al-Qatanani, Shatha; Alarifi, Saqer; Bawazeer, Shahad; Alyafee, Yusra

2016-01-01

Background PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic). In this study, methotrexate (MTX)-loaded nanoparticles were prepared by the double emulsion method. Method Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol) as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%). Results Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

Epitope characterization of the ADA response directed against a targeted immunocytokine.

Science.gov (United States)

Stubenrauch, Kay; Künzel, Christian; Vogel, Rudolf; Tuerck, Dietrich; Schick, Eginhard; Heinrich, Julia

2015-10-10

Targeted immunocytokines (TICs) display potent activity in selective tumor suppression. This class of multi domain biotherapeutics (MDBs) is composed of the three major domains Fab, Fc, and a cytokine which may induce a complex polyclonal anti-drug antibody (ADA) response. However, classical ADA assays usually are not suitable to specify ADAs and to identify the immunogenic domains of a TIC. The purpose of the present study was to establish epitope characterization of ADA responses in order to specify immunogenic responses against a TIC and their direct impact on the pharmacokinetic profile, safety, and efficacy. Based on standard ADA screening and confirmation assays, respectively, domain detection assays (DDAs) and domain competition assays (DCAs) were established and compared by the use of 12 ADA-positive samples obtained from a cynomolgus monkey study in early development. Both domain-specific assays were sensitive enough to preserve the positive screening assay result and revealed an overall accordance for the evaluation of domain-specific ADA responses. About half of the samples displayed one ADA specificity, either for the Fab or for the cytokine (Cy) domain, and the remaining samples showed a combination of Fab-specific and Cy-specific ADA fractions. Fc-specific ADAs occurred in only one sample. In-depth comparison of DCAs and DDAs showed that both assays appeared to be appropriate to assess multi-specific ADA responses as well as minor ADA fractions. An advantage of DCAs is typically a fast and easy assay establishment, whereas, DDAs in some cases may be superior to assess low abundant ADAs in multi-specific responses. Our results reveal that both approaches benefit from thorough reagent development as an essential precondition for reliable epitope characterization of ADA responses. Copyright © 2015 Elsevier B.V. All rights reserved.

Programming in a proposed 9X distributed Ada

Science.gov (United States)

Waldrop, Raymond S.; Volz, Richard A.; Goldsack, Stephen J.; Holzbach-Valero, A. A.

1991-01-01

The studies of the proposed Ada 9X constructs for distribution, now referred to as AdaPT are reported. The goals for this time period were to revise the chosen example scenario and to begin studying about how the proposed constructs might be implemented. The example scenario chosen is the Submarine Combat Information Center (CIC) developed by IBM for the Navy. The specification provided by IBM was preliminary and had several deficiencies. To address these problems, some changes to the scenario specification were made. Some of the more important changes include: (1) addition of a system database management function; (2) addition of a fourth processing unit to the standard resources; (3) addition of an operator console interface function; and (4) removal of the time synchronization function. To implement the CIC scenario in AdaPT, the decided strategy were publics, partitions, and nodes. The principle purpose for implementing the CIC scenario was to demonstrate how the AdaPT constructs interact with the program structure. While considering ways that the AdaPt constructs might be translated to Ada 83, it was observed that the partition construct could reasonably be modeled as an abstract data type. Although this gives a useful method of modeling partitions, it does not at all address the configuration aspects on the node construct.

Knowledge, programming, and programming cultures: LISP, C, and Ada

Science.gov (United States)

Rochowiak, Daniel

1990-01-01

The results of research 'Ada as an implementation language for knowledge based systems' are presented. The purpose of the research was to compare Ada to other programming languages. The report focuses on the programming languages Ada, C, and Lisp, the programming cultures that surround them, and the programming paradigms they support.

Development of the Korean version of Alzheimer's Disease Assessment Scale (ADAS-K).

Science.gov (United States)

Youn, J C; Lee, D Y; Kim, K W; Lee, J H; Jhoo, J H; Lee, K U; Ha, J; Woo, J I

2002-09-01

The purpose of this study was the development of the Korean Version of Alzheimer's Disease Assessment Scale (ADAS-K). ADAS-K was administrated to 84 AD patients as well as 105 non-demented control subjects. Three aspects of reliability were tested. To evaluate the validity of ADAS-K, discriminant validity and concurrent validity were tested. To evaluate the sensitivity of ADAS-K to disease severity, all subjects, AD patients and control subjects, were grouped by CDR scale and their mean scores on ADAS-K were compared. ADAS-K demonstrated high levels of reliability. Mean ADAS-K scores for AD patients were significantly different from the control group (p ADAS-K exhibited significant correlations with other tests and scales (range 0.45-0.85, p ADAS-K displayed high diagnostic efficacy and the optimal cut-off point was selected between 18/19. ADAS-K was able to discriminate the degree of AD severity according to CDR classification. Our results suggested that ADAS-K-cog was sensitive to very mild AD. We demonstrated that ADAS-K is a reliable and valid instrument not only for AD diagnosis but also for evaluation of its severity. Copyright 2002 John Wiley & Sons, Ltd.

Towards a formal semantics for Ada 9X

Science.gov (United States)

Guaspari, David; Mchugh, John; Wolfgang, Polak; Saaltink, Mark

1995-01-01

The Ada 9X language precision team was formed during the revisions of Ada 83, with the goal of analyzing the proposed design, identifying problems, and suggesting improvements, through the use of mathematical models. This report defines a framework for formally describing Ada 9X, based on Kahn's 'natural semantics', and applies the framework to portions of the language. The proposals for exceptions and optimization freedoms are also analyzed, using a different technique.

Ada (Trade Name) Bibliography. Volume 3.

Science.gov (United States)

1986-02-01

access to shared resources by concurrently callable procedures. Both rely on queues to achieve serialization, but calls on monitor procedures are...DOCUMENT CITATIONS ADA AS A PROGRAM DESCRIPTION LANGUAGE (PDL): A PROJECT SOFTW ARE MANAGEMENT PERSPECTIVE BOND , RODNEY M. DOCUMENT NUMBER: 6141 TYPE...HONEYWELL BULL-RESEARCH CTR,GRENOBLE,CEDEX,FRANCE 2548 -01 ADA, ABSTRACT DATA TYPES AND DISTRIBUTED DATABASES TRANSACTIONS BOND , RODNEYM., NONAFFILIATED 6141

Nondestructive evaluation of a new hydrolytically degradable and photo-clickable PEG hydrogel for cartilage tissue engineering.

Science.gov (United States)

Neumann, Alexander J; Quinn, Timothy; Bryant, Stephanie J

2016-07-15

Photopolymerizable and hydrolytically labile poly(ethylene glycol) (PEG) hydrogels formed from photo-clickable reactions were investigated as cell delivery platforms for cartilage tissue engineering (TE). PEG hydrogels were formed from thiol-norbornene PEG macromers whereby the crosslinks contained caprolactone segments with hydrolytically labile ester linkages. Juvenile bovine chondrocytes encapsulated in the hydrogels were cultured for up to four weeks and assessed biochemically and histologically, using standard destructive assays, and for mechanical and ultrasound properties, as nondestructive assays. Bulk degradation of acellular hydrogels was confirmed by a decrease in compressive modulus and an increase in mass swelling ratio over time. Chondrocytes deposited increasing amounts of sulfated glycosaminoglycans and collagens in the hydrogels with time. Spatially, collagen type II and aggrecan were present in the neotissue with formation of a territorial matrix beginning at day 21. Nondestructive measurements revealed an 8-fold increase in compressive modulus from days 7 to 28, which correlated with total collagen content. Ultrasound measurements revealed changes in the constructs over time, which differed from the mechanical properties, and appeared to correlate with ECM structure and organization shown by immunohistochemical analysis. Overall, non-destructive and destructive measurements show that this new hydrolytically degradable PEG hydrogel is promising for cartilage TE. Designing synthetic hydrogels whose degradation matches tissue growth is critical to maintaining mechanical integrity as the hydrogel degrades and new tissue forms, but is challenging due to the nature of the hydrogel crosslinks that inhibit diffusion of tissue matrix molecules. This study details a promising, new, photo-clickable and synthetic hydrogel whose degradation supports cartilaginous tissue matrix growth leading to the formation of a territorial matrix, concomitant with an

Subunits of ADA-two-A-containing (ATAC) or Spt-Ada-Gcn5-acetyltrasferase (SAGA) Coactivator Complexes Enhance the Acetyltransferase Activity of GCN5.

Science.gov (United States)

Riss, Anne; Scheer, Elisabeth; Joint, Mathilde; Trowitzsch, Simon; Berger, Imre; Tora, László

2015-11-27

Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus specific transcription. GCN5 (KAT2A) is a member of the GNAT (Gcn5-related N-acetyltransferase) family of HATs. In metazoans this enzyme is found in two functionally distinct coactivator complexes, SAGA (Spt Ada Gcn5 acetyltransferase) and ATAC (Ada Two A-containing). These two multiprotein complexes comprise complex-specific and shared subunits, which are organized in functional modules. The HAT module of ATAC is composed of GCN5, ADA2a, ADA3, and SGF29, whereas in the SAGA HAT module ADA2b is present instead of ADA2a. To better understand how the activity of human (h) hGCN5 is regulated in the two related, but different, HAT complexes we carried out in vitro HAT assays. We compared the activity of hGCN5 alone with its activity when it was part of purified recombinant hATAC or hSAGA HAT modules or endogenous hATAC or hSAGA complexes using histone tail peptides and full-length histones as substrates. We demonstrated that the subunit environment of the HAT complexes into which GCN5 incorporates determines the enhancement of GCN5 activity. On histone peptides we show that all the tested GCN5-containing complexes acetylate mainly histone H3K14. Our results suggest a stronger influence of ADA2b as compared with ADA2a on the activity of GCN5. However, the lysine acetylation specificity of GCN5 on histone tails or full-length histones was not changed when incorporated in the HAT modules of ATAC or SAGA complexes. Our results thus demonstrate that the catalytic activity of GCN5 is stimulated by subunits of the ADA2a- or ADA2b-containing HAT modules and is further increased by incorporation of the distinct HAT modules in the ATAC or SAGA holo-complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

PEG Grafted-Nanodiamonds for the Delivery of Gemcitabine.

Science.gov (United States)

Lu, Mingxia; Wang, Yu-Kai; Zhao, Jiacheng; Lu, Hongxu; Stenzel, Martina H; Xiao, Pu

2016-12-01

Carboxyl end-functionalized poly[poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)] and its block copolymer with gemcitabine substituted poly(N-hydroxysuccinimide methacrylate) [PGem-block-P(PEGMEMA)] are synthesized via reversible addition-fragmentation transfer (RAFT) polymerization. Then, two polymers are grafted onto the surface of amine-functionalized nanodiamonds to obtain [P(PEGMEMA)]-grafted nanodiamonds (ND-PEG) and [PGem-block-P(PEGMEMA)]-grafted nanodiamonds (ND-PF). Gemcitabine is physically absorbed to ND-PEG to produce ND-PEG (Gem). Two polymer-grafted nanodiamonds (i.e., with physically absorbed gemcitabine ND-PEG (Gem) and with chemically conjugated gemcitabine ND-PF) are characterized using attenuated total reflectance infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis. The drug release, cytotoxicity (to seed human pancreatic carcinoma AsPC-1 cells), and cellular uptake of ND-PEG (Gem) and ND-PF are also investigated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Examining the reliability of ADAS-Cog change scores.

Science.gov (United States)

Grochowalski, Joseph H; Liu, Ying; Siedlecki, Karen L

2016-09-01

The purpose of this study was to estimate and examine ways to improve the reliability of change scores on the Alzheimer's Disease Assessment Scale, Cognitive Subtest (ADAS-Cog). The sample, provided by the Alzheimer's Disease Neuroimaging Initiative, included individuals with Alzheimer's disease (AD) (n = 153) and individuals with mild cognitive impairment (MCI) (n = 352). All participants were administered the ADAS-Cog at baseline and 1 year, and change scores were calculated as the difference in scores over the 1-year period. Three types of change score reliabilities were estimated using multivariate generalizability. Two methods to increase change score reliability were evaluated: reweighting the subtests of the scale and adding more subtests. Reliability of ADAS-Cog change scores over 1 year was low for both the AD sample (ranging from .53 to .64) and the MCI sample (.39 to .61). Reweighting the change scores from the AD sample improved reliability (.68 to .76), but lengthening provided no useful improvement for either sample. The MCI change scores had low reliability, even with reweighting and adding additional subtests. The ADAS-Cog scores had low reliability for measuring change. Researchers using the ADAS-Cog should estimate and report reliability for their use of the change scores. The ADAS-Cog change scores are not recommended for assessment of meaningful clinical change.

Optimal Currency Basket Pegs for Developing and Emerging Economies

OpenAIRE

Joseph Daniels; Peter G. Toumanoff; Marc von der Ruhr

2001-01-01

The exchange rate arrangement represents an important policy choice for emerging and transitional economies as they strive to become stable and market-driven. A wide variety of arrangements have emerged, ranging from currency boards, basket-currency pegs and single-currency pegs to floating rates. Recently the IMF has recommended that, if the exchange value of a currency is to be pegged, it is better to peg to a basket of currencies rather than a single currency. Nonetheless, there has been l...

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle

Directory of Open Access Journals (Sweden)

Mullen Michael P

2010-10-01

Full Text Available Abstract Background Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. These SNPs are located proximal to, or within, the bovine orthologs of eight genes (CALCR, GRB10, PEG3, PHLDA2, RASGRF1, TSPAN32, ZIM2 and ZNF215 that have been shown to be imprinted in cattle or in at least one other mammalian species (i.e. human/mouse/pig/sheep. Results Heterozygosities for all SNPs analysed ranged from 0.09 to 0.46 and significant deviations from Hardy-Weinberg proportions (P ≤ 0.01 were observed at four loci. Phenotypic associations (P ≤ 0.05 were observed between nine SNPs proximal to, or within, six of the eight analysed genes and a number of performance traits evaluated, including milk protein percentage, somatic cell count, culled cow and progeny carcass weight, angularity, body conditioning score, progeny carcass conformation, body depth, rump angle, rump width, animal stature, calving difficulty, gestation length and calf perinatal mortality. Notably, SNPs within the imprinted paternally expressed gene 3 (PEG3 gene cluster were associated (P ≤ 0.05 with calving, calf performance and fertility traits, while a single SNP in the zinc finger protein 215 gene (ZNF215 was associated with milk protein percentage (P ≤ 0.05, progeny carcass weight (P ≤ 0.05, culled cow carcass weight (P ≤ 0

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle

Science.gov (United States)

2010-01-01

Background Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs) and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. These SNPs are located proximal to, or within, the bovine orthologs of eight genes (CALCR, GRB10, PEG3, PHLDA2, RASGRF1, TSPAN32, ZIM2 and ZNF215) that have been shown to be imprinted in cattle or in at least one other mammalian species (i.e. human/mouse/pig/sheep). Results Heterozygosities for all SNPs analysed ranged from 0.09 to 0.46 and significant deviations from Hardy-Weinberg proportions (P ≤ 0.01) were observed at four loci. Phenotypic associations (P ≤ 0.05) were observed between nine SNPs proximal to, or within, six of the eight analysed genes and a number of performance traits evaluated, including milk protein percentage, somatic cell count, culled cow and progeny carcass weight, angularity, body conditioning score, progeny carcass conformation, body depth, rump angle, rump width, animal stature, calving difficulty, gestation length and calf perinatal mortality. Notably, SNPs within the imprinted paternally expressed gene 3 (PEG3) gene cluster were associated (P ≤ 0.05) with calving, calf performance and fertility traits, while a single SNP in the zinc finger protein 215 gene (ZNF215) was associated with milk protein percentage (P ≤ 0.05), progeny carcass weight (P ≤ 0.05), culled cow carcass weight (P ≤ 0.01), angularity (P �

The ADAS-Cog revisited: novel composite scales based on ADAS-Cog to improve efficiency in MCI and early AD trials.

Science.gov (United States)

Raghavan, Nandini; Samtani, Mahesh N; Farnum, Michael; Yang, Eric; Novak, Gerald; Grundman, Michael; Narayan, Vaibhav; DiBernardo, Allitia

2013-02-01

The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) has been used widely as a cognitive end point in Alzheimer's Disease (AD) clinical trials. Efforts to treat AD pathology at earlier stages have also used ADAS-Cog, but failure in these trials can be difficult to interpret because the scale has well-known ceiling effects that limit its use in mild cognitive impairment (MCI) and early AD. A wealth of data exists in ADAS-Cog from both historical trials and contemporary longitudinal natural history studies that can provide insights about parts of the scale that may be better suited for MCI and early AD trials. Using Alzheimer's Disease Neuroimaging Initiative study data, we identified the most informative cognitive measures from the ADAS-Cog and other available scales. We used cross-sectional analyses to characterize trajectories of ADAS-Cog and its individual subscales, as well as other cognitive, functional, or global measures across disease stages. Informative measures were identified based on standardized mean of 2-year change from baseline and were combined into novel composite endpoints. We assessed performance of the novel endpoints based on sample size requirements for a 2-year clinical trial. A bootstrap validation procedure was also undertaken to assess the reproducibility of the standardized mean changes of the selected measures and the corresponding composites. All proposed novel endpoints have improved standardized mean changes and thus improved statistical power compared with the ADAS-Cog 11. Further improvements were achieved by using cognitive-functional composites. Combining the novel composites with an enrichment strategy based on cerebral spinal fluid beta-amyloid (Aβ(1-42)) in a 2-year trial yielded gains in power of 20% to 40% over ADAS-Cog 11, regardless of the novel measure considered. An empirical, data-driven approach with existing instruments was used to derive novel composite scales based on ADAS-Cog 11 with improved performance

On 'Money' in ISLM and AD/AS Models

OpenAIRE

Thomas K. Rymes; Colin Rogers

2000-01-01

Hicks's ISLM model interpretation of Keynes's theory is subject to much controversy. In this paper, we focus upon the 'real balance' effect and its role in ISLM and AD/AS analyses. We shall argue that ISLM and AD/AS require 'nominal anchors'. We live in a world where, increasingly, the 'money' in the ISLM and AD/AS model no longer exists (as Keynes imperfectly understood in his TREATISE ON MONEy). There are no longer any nominal anchors, rather they have been replaced by discretionary policy....

PEG minocycline-liposomes ameliorate CNS autoimmune disease.

Directory of Open Access Journals (Sweden)

Wei Hu

Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

PEG-based degradable networks for drug delivery applications

Science.gov (United States)

Ostroha, Jamie L.

The controlled delivery of therapeutic agents by biodegradable hydrogels has become a popular mechanism for drug administration in recent years. Hydrogels are three-dimensional networks of polymer chains held together by crosslinks. Although the changes which the hydrogel undergoes in solution are important to a wide range of experimental studies, they have not been investigated systematically and the factors which influence the degree of swelling have not been adequately described. Hydrogels made of poly(ethylene glycol) (PEG) will generally resist degradation in aqueous conditions, while a hydrogel made from a copolymer of poly(lactic acid) (PLA) and PEG will degrade via hydrolysis of the lactic acid group. This ability to degrade makes these hydrogels promising candidates for controlled release drug delivery systems. The goal of this research was to characterize the swelling and degradation of both degradable and non-degradable gels and to evaluate the release of different drugs from these hydrogels, where the key variable is the molecular weight of the PEG segment. These hydrogels were formed by the addition and subsequent chemically crosslinking of methacrylate end groups. During crosslinking, both PEG and LA-PEG-LA hydrogels of varied PEG molecular weight were loaded with Vitamin B12, Insulin, Haloperidol, and Dextran. It was shown that increasing PEG molecular weight produces a hydrogel with larger pores, thus increasing water uptake and degradation rate. While many environmental factors do not affect the swelling behavior, they do significantly impact the degradation of the hydrogel, and thus the release of incorporated therapeutic agents.

Software engineering and the role of Ada: Executive seminar

Science.gov (United States)

Freedman, Glenn B.

1987-01-01

The objective was to introduce the basic terminology and concepts of software engineering and Ada. The life cycle model is reviewed. The application of the goals and principles of software engineering is applied. An introductory understanding of the features of the Ada language is gained. Topics addressed include: the software crises; the mandate of the Space Station Program; software life cycle model; software engineering; and Ada under the software engineering umbrella.

ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.

Science.gov (United States)

Cagdas, Deniz; Gur Cetinkaya, Pınar; Karaatmaca, Betül; Esenboga, Saliha; Tan, Cagman; Yılmaz, Togay; Gümüş, Ersin; Barış, Safa; Kuşkonmaz, Barış; Ozgur, Tuba Turul; Bali, Pawan; Santisteban, Ines; Orhan, Diclehan; Yüce, Aysel; Cetinkaya, Duygu; Boztug, Kaan; Hershfield, Michael; Sanal, Ozden; Tezcan, İlhan

2018-05-09

Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9). All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T>C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning

Characterisation of Gliclazide-PEG 8000 Solid Dispersions

African Journals Online (AJOL)

Erah

Purpose: The aim of the present study was to characterise gliclazide solid dispersions (SDs) ... Results: The solubility of gliclazide increased with increasing amount of PEG 8000 in aqueous medium. ... FTIR analysis demonstrated the absence of well-defined gliclazide - PEG 8000 .... voltage of 35 kV and 20 mA current. The.

Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry

DEFF Research Database (Denmark)

Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus

2007-01-01

Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families......, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb...... upstream of the ADA transcription start site. All patients were homozygous for the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both...

An Ada-based preprocessor language for concurrent object oriented programming

International Nuclear Information System (INIS)

Almulla, M.; Al-Haddad, M.; Loeper, H.

2001-01-01

In this paper, implementation issues of concurrent-objected programming using Ada 95 are addressed. Ada is not a pure object-oriented language; in order to make it so, a uniform template for structuring object classes is proposed. The template constitutes a basis for an Ada-based preprocessor language that handles concurrent object-oriented programming. The preprocessor accepts Ada-like object-oriented programs (object classes, subclasses and main program) as input and produces Ada 95 concurrent object-oriented program units as output. The preprocessor language has the advantage of adding a new component to the class specification called the protocol, which specifies the order for requesting methods f an object. The preprocessor also touches on the extensibility of object classes issue. It supports defining class hierarchies by inheritance and aggregation. In addition, the preprocessor language supports the re-use of Ada packages, which are not necessarily written according to the object-oriented approach. The paper also investigates the definition of circular dependent object classes and proposes a solution for introducing a collection of classes. (author)

Final report on the safety assessment of Triethylene Glycol and PEG-4.

Science.gov (United States)

2006-01-01

Triethylene Glycol and PEG-4 (polyethylene glycol) are polymers of ethylene oxide alcohol. Triethylene Glycol is a specific three-unit chain, whereas PEG-4 is a polymer with an average of four units, but may contain polymers ranging from two to eight ethylene oxide units. In the same manner, other PEG compounds, e.g., PEG-6, are mixtures and likely contain some Triethylene Glycol and PEG-4. Triethylene Glycol is a fragrance ingredient and viscosity decreasing agent in cosmetic formulations, with a maximum concentration of use of 0.08% in skin-cleansing products. Following oral doses, Triethylene Glycol and its metabolites are excreted primarily in urine, with small amounts released in feces and expired air. With oral LD50 values in rodents from 15 to 22 g/kg, this compound has little acute toxicity. Rats given short term oral doses of 3% in water showed no signs of toxicity, whereas all rats given 10% died by the 12th day of exposure. At levels up to 1 g/m3, rats exposed to aerosolized Triethylene Glycol for 6 h per day for 9 days showed no signs of toxicity. Rats fed a diet containing 4% Triethylene Glycol for 2 years showed no signs of toxicity. There were no treatment-related effects on rats exposed to supersaturated Triethylene Glycol vapor for 13 months nor in rats that consumed 0.533 cc Triethylene Glycol per day in drinking water for 13 months. Triethylene Glycol was not irritating to the skin of rabbits and produced only minimal injury to the eye. In reproductive and developmental toxicity studies in rats and mice, Triethylene Glycol did not produce biologically significant embryotoxicity or teratogenicity. However, some maternal toxicity was seen in dams given 10 ml/kg/day during gestation. Triethylene Glycol was not mutagenic or genotoxic in Ames-type assays, the Chinese hamster ovary mutation assay, and the sister chromatid exchange assays. PEG-4 is a humectant and solvent in cosmetic products, with a maximum concentration of use of 20% in the "other

Characterization of bovine serum albumin partitioning behaviors in polymer-salt aqueous two-phase systems.

Science.gov (United States)

Chow, Yin Hui; Yap, Yee Jiun; Tan, Chin Ping; Anuar, Mohd Shamsul; Tejo, Bimo Ario; Show, Pau Loke; Ariff, Arbakariya Bin; Ng, Eng-Poh; Ling, Tau Chuan

2015-07-01

In this paper, a linear relationship is proposed relating the natural logarithm of partition coefficient, ln K for protein partitioning in poly (ethylene glycol) (PEG)-phosphate aqueous two-phase system (ATPS) to the square of tie-line length (TLL(2)). This relationship provides good fits (r(2) > 0.98) to the partition of bovine serum albumin (BSA) in PEG (1450 g/mol, 2000 g/mol, 3350 g/mol, and 4000 g/mol)-phosphate ATPS with TLL of 25.0-50.0% (w/w) at pH 7.0. Results also showed that the plot of ln K against pH for BSA partitioning in the ATPS containing 33.0% (w/w) PEG1450 and 8.0% (w/w) phosphate with varied working pH between 6.0 and 9.0 exhibited a linear relationship which is in good agreement (r(2) = 0.94) with the proposed relationship, ln K = α' pH + β'. These results suggested that both the relationships proposed could be applied to correlate and elucidate the partition behavior of biomolecules in the polymer-salt ATPS. The influence of other system parameters on the partition behavior of BSA was also investigated. An optimum BSA yield of 90.80% in the top phase and K of 2.40 was achieved in an ATPS constituted with 33.0% (w/w) PEG 1450 and 8.0% (w/w) phosphate in the presence of 8.5% (w/w) sodium chloride (NaCl) at pH 9.0 for 0.3% (w/w) BSA load. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Further observations on associations between the ADA gene and past malaria morbidity in Sardinia.

Science.gov (United States)

Gloria-Bottini, Fulvia; Saccucci, Patrizia; Meloni, Gianfranco; Bottini, Egidio

2014-01-01

Adenosine Deaminase (ADA) contributes to the regulation of adenosine concentration and in turn to T cell activation. Genetic variability of ADA activity may have, therefore, an important role in resistance to malaria. Indeed, previous studies in Sardinia have shown a lower frequency of ADA1 *2 allele (associated with low ADA activity) in areas, where malaria was heavily endemic compared to areas where malaria was not endemic. We have now studied the ADA2 locus, another polymorphic site with two alleles ADA2 *1 and ADA2 *2 within the ADA gene. In the area of Oristano (where malaria was endemic in the past) 51 consecutive newborns and in the area of Nuoro (where malaria was not as endemic) 48 consecutive newborns were examined. ADA1 and ADA2 genotypes were determined by DNA analysis. The low frequency of the ADA1 *2 allele in the area where malaria was endemic is confirmed. The frequency of the ADA2 *2 allele is higher in Oristano than in Nuoro resulting in a higher frequency of the ADA1 *1/ADA2 *2 haplotype in Oristano as compared to Nuoro. This suggests a selective advantage of this haplotype in a malarial environment. The ADA gene shows other polymorphic sites further studies on their role in human adaptation to malaria could be rewarding. © 2014 Wiley Periodicals, Inc.

SEL Ada reuse analysis and representations

Science.gov (United States)

Kester, Rush

1990-01-01

Overall, it was revealed that the pattern of Ada reuse has evolved from initial reuse of utility components into reuse of generalized application architectures. Utility components were both domain-independent utilities, such as queues and stacks, and domain-specific utilities, such as those that implement spacecraft orbit and attitude mathematical functions and physics or astronomical models. The level of reuse was significantly increased with the development of a generalized telemetry simulator architecture. The use of Ada generics significantly increased the level of verbatum reuse, which is due to the ability, using Ada generics, to parameterize the aspects of design that are configurable during reuse. A key factor in implementing generalized architectures was the ability to use generic subprogram parameters to tailor parts of the algorithm embedded within the architecture. The use of object oriented design (in which objects model real world entities) significantly improved the modularity for reuse. Encapsulating into packages the data and operations associated with common real world entities creates natural building blocks for reuse.

What is the clinically relevant change on the ADAS-Cog?

Science.gov (United States)

Schrag, Anette; Schott, Jonathan M

2012-02-01

To establish the minimal clinically relevant change (MCRC) on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) for patients with mild Alzheimer's disease (AD). Cohort study. 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative. Outpatients with AD in the Alzheimer's Disease Neuroimaging Initiative. The authors applied anchor-based MCRC methodology comparing ADAS-Cog change against clinicians' judgement of clinically relevant worsening between baseline and 6 months in four domains: memory and non-memory cognitive performance; Clinical Dementia Rating Scale; and Functional Assessment Questionnaire. The analysis was repeated for the 6-12-month interval. To support these findings, the authors calculated distribution-based measures including half-baseline SD (1/2 SD) and SEM. 181 patients (baseline ADAS-Cog score 18.5±6.4) had ADAS-Cog data at 0 and 6 months. Those undergoing clinically significant worsening on any of the four anchor questions (n=41-47) had an average ADAS-Cog change of 3.1-3.8 points. Similar results were found for the 177 patients with 6-12-month data. The average 1/2 SD for the baseline ADAS-Cog score was 3.2, and the SEM was 3.7. 3 points decline on the ADAS-Cog may be an appropriate MCRC for clinical trials of patients with early AD. However, further studies assessing the MCRC for improvement on the ADAS-Cog, using patient-based judgement as an anchor, and determining the minimal clinically relevant difference between change on two treatments are required. http://clinicalTrials.gov Identifier: NCT00106899.

Ballistic energy transport in PEG oligomers

Directory of Open Access Journals (Sweden)

Kireev Victor V.

2013-03-01

Full Text Available Energy transport between the terminal groups of the azido-PEG-succinimide ester compounds with a number of repeating PEG units of 0, 4, 8, and 12 was studied using relaxation-assisted two-dimensional infrared spectroscopy. The through-bond energy transport time, evaluated as the waiting time at which the cross peak maximum is reached, Tmax, was found to be linearly dependent on the chain length for chain lengths up to 60 Å suggesting a ballistic energy transport regime. The through-bond energy transport speed is found to be ca. 500 m/s. The cross-peak amplitude at the maximum decays exponentially with the chain length with a characteristic decay distance of 15.7 ± 1 Å. Substantial mode delocalization across the PEG bridge is found, which can support the energy propagation as a wavepacket.

Ada Linear-Algebra Program

Science.gov (United States)

Klumpp, A. R.; Lawson, C. L.

1988-01-01

Routines provided for common scalar, vector, matrix, and quaternion operations. Computer program extends Ada programming language to include linear-algebra capabilities similar to HAS/S programming language. Designed for such avionics applications as software for Space Station.

PREVALENCE OF BOVINE HERPESVIRUS-1,PARAINFLUENZA-3,BOVINE ROTAVIRUS, BOVINE VIRAL DIARRHEA, BOVINE ADENOVIRUS-7,BOVINE LEUKEMIA VIRUS AND BLUETONGUE VIRUS ANTIBODIES IN CATTLE IN MEXICO

OpenAIRE

SUZAN, Victor M.; ONUMA, Misao; AGUILAR, Romero E.; MURAKAMI, Yosuke

1983-01-01

Sera were collected from dairy and beef cattle in 19 different states of Mexico. These sera were tested for bovine herpesvirus-1 (BHV-1), parainfluenza-3 virus (PIV-3), bovine rotavirus (BRV), bovine leukemia virus (BLV), bovine adenovirus-7 (BAV-7), bluetongue virus (BTV) and bovine viral diarrhea virus (BVDV). Seropositive rates for each virus for dairy cattle tested were 158/277(57.0%) for BHV-1,217/286(75.0%) for PIV-3,541/1498(36.1%) for BLV, 134/144(93.1%) for BRV, 39/90(43.3%) for BTV,...

Initial Ada components evaluation

Science.gov (United States)

Moebes, Travis

1989-01-01

The SAIC has the responsibility for independent test and validation of the SSE. They have been using a mathematical functions library package implemented in Ada to test the SSE IV and V process. The library package consists of elementary mathematical functions and is both machine and accuracy independent. The SSE Ada components evaluation includes code complexity metrics based on Halstead's software science metrics and McCabe's measure of cyclomatic complexity. Halstead's metrics are based on the number of operators and operands on a logical unit of code and are compiled from the number of distinct operators, distinct operands, and total number of occurrences of operators and operands. These metrics give an indication of the physical size of a program in terms of operators and operands and are used diagnostically to point to potential problems. McCabe's Cyclomatic Complexity Metrics (CCM) are compiled from flow charts transformed to equivalent directed graphs. The CCM is a measure of the total number of linearly independent paths through the code's control structure. These metrics were computed for the Ada mathematical functions library using Software Automated Verification and Validation (SAVVAS), the SSE IV and V tool. A table with selected results was shown, indicating that most of these routines are of good quality. Thresholds for the Halstead measures indicate poor quality if the length metric exceeds 260 or difficulty is greater than 190. The McCabe CCM indicated a high quality of software products.

Integrity and security in an Ada runtime environment

Science.gov (United States)

Bown, Rodney L.

1991-01-01

A review is provided of the Formal Methods group discussions. It was stated that integrity is not a pure mathematical dual of security. The input data is part of the integrity domain. The group provided a roadmap for research. One item of the roadmap and the final position statement are closely related to the space shuttle and space station. The group's position is to use a safe subset of Ada. Examples of safe sets include the Army Secure Operating System and the Penelope Ada verification tool. It is recommended that a conservative attitude is required when writing Ada code for life and property critical systems.

Formal methods in the design of Ada 1995

Science.gov (United States)

Guaspari, David

1995-01-01

Formal, mathematical methods are most useful when applied early in the design and implementation of a software system--that, at least, is the familiar refrain. I will report on a modest effort to apply formal methods at the earliest possible stage, namely, in the design of the Ada 95 programming language itself. This talk is an 'experience report' that provides brief case studies illustrating the kinds of problems we worked on, how we approached them, and the extent (if any) to which the results proved useful. It also derives some lessons and suggestions for those undertaking future projects of this kind. Ada 95 is the first revision of the standard for the Ada programming language. The revision began in 1988, when the Ada Joint Programming Office first asked the Ada Board to recommend a plan for revising the Ada standard. The first step in the revision was to solicit criticisms of Ada 83. A set of requirements for the new language standard, based on those criticisms, was published in 1990. A small design team, the Mapping Revision Team (MRT), became exclusively responsible for revising the language standard to satisfy those requirements. The MRT, from Intermetrics, is led by S. Tucker Taft. The work of the MRT was regularly subject to independent review and criticism by a committee of distinguished Reviewers and by several advisory teams--for example, the two User/Implementor teams, each consisting of an industrial user (attempting to make significant use of the new language on a realistic application) and a compiler vendor (undertaking, experimentally, to modify its current implementation in order to provide the necessary new features). One novel decision established the Language Precision Team (LPT), which investigated language proposals from a mathematical point of view. The LPT applied formal mathematical analysis to help improve the design of Ada 95 (e.g., by clarifying the language proposals) and to help promote its acceptance (e.g., by identifying a

Issues Involved in Developing Ada Real-Time Systems

Science.gov (United States)

1989-02-15

expensive modifications to the compiler or Ada runtime system to fit a particular application. Whether we can solve the problems of programming real - time systems in...lock in solutions to problems that are not yet well understood in standards as rigorous as the Ada language. Moreover, real - time systems typically have

Ada Lovelace Poster

OpenAIRE

Charman-Anderson, Suw

2016-01-01

Who was Ada Lovelace? What were her greatest achievements? This ‘infoposter’ describes Lovelace’s achievements and describes why she’s thought of as the world’s first computer programmer.Available to buy from RedBubble as a poster, photographic print, art print, framed print, canvas print, metal print, greetings card, spiral bound notebook or hardback journal. 

Ada in Introductory Computer Science Courses

Science.gov (United States)

1993-01-01

M2 111418111 1111111 I s%1 tems to des elop soaftware Systems for IM5. ONhalt oIf dt ufl’wae mownev b f "bs" arn .exti to k ,ulift la Ada. COMPUT...beftjobamdsodeckldthesespienicngamnug them. A celula 101110011ui systm Service in Ada& using an rmniticdawau dipay shows *I tatus. The systm objweaniiimd...liftt aftr of Fucal Nikkao Wirh. Some say Software i - , I, ced a pse-validaed ver. origina soitweim is coded. The idWa is to that Ads is the las gpat

KYTC sidewalk and curb ramp inventory for ADA compliance.

Science.gov (United States)

2017-09-01

The Americans with Disabilities Act of 1990 (ADA) requires that all public and private organizations providing services to the public ensure their facilities and infrastructure comply with regulations set forth therein. The ADA requires that a transi...

Ada Compiler Validation Summary Report: Certificate Number 890711W1. 10109 Concurrent Computer Corporation C(3) Ada, Version R02-02.00 Concurrent Computer Corporation 3280 MPS

Science.gov (United States)

1989-07-11

Wright-Patterson ATB Dayton, OH, USA Ada Joint Prograr Office United States De artment of Defense " * ’ , Washington, DC 2 301-3061 i4. I 10 k A$ -h-Y...dependent but is permitted by the Ada Standard. Six classes of tests are used. These tests are designed to perform checks at compile time, at link time...the direction of the AVF according to procedures establizhed by the Ada Joia ,, Program Office and administered by the Ada Validation Organization (AVO

Applications of an architecture design and assessment system (ADAS)

Science.gov (United States)

Gray, F. Gail; Debrunner, Linda S.; White, Tennis S.

1988-01-01

A new Architecture Design and Assessment System (ADAS) tool package is introduced, and a range of possible applications is illustrated. ADAS was used to evaluate the performance of an advanced fault-tolerant computer architecture in a modern flight control application. Bottlenecks were identified and possible solutions suggested. The tool was also used to inject faults into the architecture and evaluate the synchronization algorithm, and improvements are suggested. Finally, ADAS was used as a front end research tool to aid in the design of reconfiguration algorithms in a distributed array architecture.

Ada developers' supplement to the recommended approach

Science.gov (United States)

Kester, Rush; Landis, Linda

1993-01-01

This document is a collection of guidelines for programmers and managers who are responsible for the development of flight dynamics applications in Ada. It is intended to be used in conjunction with the Recommended Approach to Software Development (SEL-81-305), which describes the software development life cycle, its products, reviews, methods, tools, and measures. The Ada Developers' Supplement provides additional detail on such topics as reuse, object-oriented analysis, and object-oriented design.

Gender-specific association of ADA genetic polymorphism with human longevity.

Science.gov (United States)

Napolioni, Valerio; Lucarini, Nazzareno

2010-08-01

Aim of this study was to investigate whether the polymorphic ADA (Adenosine Deaminase, EC 3.5.4.4) gene, which determines the cellular level of adenosine and plays a crucial role in the regulation of the immune system and in the control of metabolic rates, is involved in longevity. 884 unrelated healthy individuals (age range 10-106 years, 400 males and 484 females) from central Italy were studied. ADA genotyping was performed by RFLP-PCR. Frequency distributions were compared using the chi-square test and a three-way contingency table analysis by a log linear model was applied to test independence between the variables. We found that ADA influences human life-span in a sex and age specific way. An increased frequency of ADA*2 carriers was found in males aged 80-85, and a decreased frequency in males over 85 (chi(2) = 13.93; df = 3; P = 0.003); significant differences among the age groups was not found in females. A strong interaction among age groups, ADA genotype and sex (G = 15.086; df = 3; P = 0.0017) was found. Males aged 80-85 could be protected from ischemic stroke by higher levels of adenosine (determined by the ADA*2 allele). The decrease of ADA*2 carriers in males over 85 may depend essentially on immunological factors; reduced levels of adenosine protect from asthma and other pulmonary diseases and lead to a reduced activation of inflammatory cells and pro-inflammatory cytokines production. Moreover, the low level of adenosine may potentiate the activity of NK and other cellular effectors against tumor cells. The negligible effect of ADA genetic polymorphism in females suggest a marginal influence of genetic factors in determining longevity in this sex, confirming previous reports.

PEG tubes: dealing with complications.

Science.gov (United States)

Malhi, Hardip; Thompson, Rosie

A percutaneous endoscopic gastronomy tube can be used to deliver nutrition, hydration and medicines directly into the patient's stomach. Patients will require a tube if they are unable to swallow safely, putting them at risk of aspiration of food, drink and medicines into their lungs. It is vital that nurses are aware of the complications that may arise when caring for a patient with a PEG tube. It is equally important that nurses know how to deal with these complications or from where tc seek advice. This article provides a quick troubleshooting guide to help nurses deal with complications that can arise with PEG feeding.

Electrospinning synthesis and characterization of PLA-PEG-MNPs composite fibrous membranes

Science.gov (United States)

Kumar, M.; Klimke, S.; Preiss, A.; Unruh, D.; Wengerowsky, D.; Lehmann, R.; Sindelar, R.; Klingelhöfer, G.; Boča, R.; Renz, F.

2017-11-01

An electrospinning technique was used to fabricate PLA, PLA-PEG and PLA-PEG-MNPs composite fibrous membranes. The morphology of electrospun composite membranes were characterized by scanning electron microscope. To test the potential availability of MNPs in PLA-PEG composite membranes, TG, Raman, Mössbauer, VSM and ICP-OES analysis were used. The PLA-PEG composite fibrous membranes showed the presence of MNPs, hence offers the possibility for magnetically triggered on-demand drug delivery.

Catching the PEG-induced attractive interaction between proteins.

Science.gov (United States)

Vivarès, D; Belloni, L; Tardieu, A; Bonneté, F

2002-09-01

We present the experimental and theoretical background of a method to characterize the protein-protein attractive potential induced by one of the mostly used crystallizing agents in the protein-field, the poly(ethylene glycol) (PEG). This attractive interaction is commonly called, in colloid physics, the depletion interaction. Small-Angle X-ray Scattering experiments and numerical treatments based on liquid-state theories were performed on urate oxidase-PEG mixtures with two different PEGs (3350 Da and 8000 Da). A "two-component" approach was used in which the polymer-polymer, the protein-polymer and the protein-protein pair potentials were determined. The resulting effective protein-protein potential was characterized. This potential is the sum of the free-polymer protein-protein potential and of the PEG-induced depletion potential. The depletion potential was found to be hardly dependent upon the protein concentration but strongly function of the polymer size and concentration. Our results were also compared with two models, which give an analytic expression for the depletion potential.

Assessment of percutaneous endoscopic gastrostomy (PEG) in head and neck cancer patients

International Nuclear Information System (INIS)

Kakuta, Risako; Matsuura, Kazuto; Noguchi, Tetsuya; Katagiri, Katsunori; Imai, Takayuki; Ishida, Eichi; Saijyo, Shigeru; Kato, Kengo

2011-01-01

As nutrition support for head and neck cancer patients who receive chemoradiotherapy (CRT) and whose oral cavity or pharynx is exposed to radiation, we perform percutaneous endoscopic gastrostomy (PEG) tube placement. We examined 235 patients who underwent PEG in our division between January 2003 and December 2009. For 64% of them, the purpose of performing PEG was nutrition support for CRT, of whom 74% actually used the tube. However, the situation varied according to the primary sites of patients. Forty-four percent of laryngeal cancer patients who underwent PEG actually used the tube, which was a significantly lower rate than others. Also, 81% of them removed the PEG tube within one year. These findings suggest that PEG-tube placement for nutrition support is not indispensable for all CRT cases. Therefore, we recommend performing PEG for oral, oropharyngeal, and hypopharyngeal cancer patients. (author)

Efficacy of polyethylene glycol-conjugated bovine granulocyte colony-stimulating factor for reducing the incidence of naturally occurring clinical mastitis in periparturient dairy cows and heifers.

Science.gov (United States)

Hassfurther, Renee L; TerHune, Terry N; Canning, Peter C

2015-03-01

To evaluate effects of various doses of polyethylene glycol (PEG)-conjugated bovine granulocyte colony-stimulating factor (bG-CSF) on the incidence of naturally occurring clinical mastitis in periparturient dairy cattle. 211 periparturient Holstein cows and heifers. Approximately 7 days before the anticipated date of parturition (day of parturition = day 0), healthy cattle received SC injections of sterile saline (0.9% NaCl) solution (control treatment) or PEG-bG-CSF at 5, 10, or 20 μg/kg. Cattle were commingled and housed in a pen with dirt flooring, which was kept wet to maximize the incidence of naturally occurring clinical mastitis. Within 24 hours after parturition, each animal again received the assigned treatment. Mammary glands and milk were visually scored for abnormalities twice daily for 28 days after parturition. Milk samples were aseptically collected from mammary glands with an abnormal appearance or abnormal milk and submitted for microbial culture. Daily milk production was recorded, and milk composition was assessed on days 3, 5, 7, and 10. Cattle treated with PEG-bG-CSF at 10 and 20 μg/kg had significantly fewer cases of clinical mastitis (9/54 and 5/53, respectively), compared with control cattle (18/53). Administration of PEG -bG-CSF did not significantly affect daily milk production or milk composition. Results suggested that PEG-bG-CSF was effective for reducing the incidence of naturally occurring clinical mastitis in periparturient dairy cattle. Further investigations of the use of PEG-bG-CSF as a potential preventative intervention should be conducted.

Electro-spun PLA-PEG-yarns for tissue engineering applications.

Science.gov (United States)

Kruse, Magnus; Greuel, Marc; Kreimendahl, Franziska; Schneiders, Thomas; Bauer, Benedict; Gries, Thomas; Jockenhoevel, Stefan

2018-06-27

Electro-spinning is widely used in tissue-engineered applications mostly in form of non-woven structures. The development of e-spun yarn opens the door for textile fabrics which combine the micro to nanoscale dimension of electro-spun filaments with three-dimensional (3D) drapable textile fabrics. Therefore, the aim of the study was the implementation of a process for electro-spun yarns. Polylactic acid (PLA) and polyethylene glycol (PEG) were spun from chloroform solutions with varying PLA/PEG ratios (100:0, 90:10, 75:25 and 50:50). The yarn samples produced were analyzed regarding their morphology, tensile strength, water uptake and cytocompatibility. It was found that the yarn diameter decreased when the funnel collector rotation was increasd, however, the fiber diameter was not influenced. The tensile strength was also found to be dependent on the PEG content. While samples composed of 100% PLA showed a tensile strength of 2.5±0.7 cN/tex, the tensile strength increased with a decreasing PLA content (PLA 75%/PEG 25%) to 6.2±0.5 cN/tex. The variation of the PEG content also influenced the viscosity of the spinning solutions. The investigation of the cytocompatibility with endothelial cells was conducted for PLA/PEG 90:10 and 75:25 and indicated that the samples are cytocompatible.

Synthesis, characterization, and cytotoxicity of glutathione-PEG-iron oxide magnetic nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Haddad, Paula S.; Santos, Marconi C. [Universidade Federal de São Paulo, UNIFESP, Exact and Earth Sciences Department (Brazil); Guzzi Cassago, Carolina Aparecida de [Universidade Estadual de Campinas, UNICAMP, Department of Biochemistry and Tissue Biology, Institute of Biology (Brazil); Bernardes, Juliana S. [National Nanotechnology Laboratory (LNNano), National Center for Energy and Materials (CNPEM) (Brazil); Jesus, Marcelo Bispo de [Universidade Estadual de Campinas, UNICAMP, Department of Biochemistry and Tissue Biology, Institute of Biology (Brazil); Seabra, Amedea B., E-mail: amedea.seabra@ufabc.edu.br [Universidade Federal de São Paulo, UNIFESP, Exact and Earth Sciences Department (Brazil)

2016-12-15

Recently, increasing interest is spent on the synthesis of superparamagnetic iron oxide nanoparticles, followed by their characterization and evaluation of cytotoxicity towards tumorigenic cell lines. In this work, magnetite (Fe{sub 3}O{sub 4}) nanoparticles were synthesized by the polyol method and coated with polyethylene glycol (PEG) and glutathione (GSH), leading to the formation of PEG-Fe{sub 3}O{sub 4} and GSH-PEG-Fe{sub 3}O{sub 4} nanoparticles. The nanoparticles were characterized by state-of-the-art techniques: dynamic light scattering (DLS), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and superconducting quantum interference device (SQUID) magnetic measurements. PEG-Fe{sub 3}O{sub 4} and GSH-PEG-Fe{sub 3}O{sub 4} nanoparticles have crystallite sizes of 10 and 5 nm, respectively, indicating compression in crystalline lattice upon addition of GSH on the nanoparticle surface. Both nanoparticles presented superparamagnetic behavior at room temperature, and AFM images revealed the regular spherical shape of the nanomaterials and the absence of particle aggregation. The average hydrodynamic sizes of PEG-Fe{sub 3}O{sub 4} and GSH-PEG-Fe{sub 3}O{sub 4} nanoparticles were 69 ± 37 and 124 nm ± 75 nm, respectively. The cytotoxicity of both nanoparticles was screened towards human prostatic carcinoma cells (PC-3). The results demonstrated a decrease in PC-3 viability upon treatment with PEG-Fe{sub 3}O{sub 4} or GSH-PEG-Fe{sub 3}O{sub 4} nanoparticles in a concentration-dependent manner. However, the cytotoxicity was not time-dependent. Due to the superparamagnetic behavior of PEG-Fe{sub 3}O{sub 4} or GSH-PEG-Fe{sub 3}O{sub 4} nanoparticles, upon the application of an external magnetic field, those nanoparticles can be guided to the target site yielding local toxic effects to tumor cells with minimal side effects to normal tissues, highlighting the promising uses of iron oxide nanoparticles in

PEGYLATION OF αα-Hb USING SUCCINIMIDYL PROPIONIC ACID PEG 5K

Science.gov (United States)

Meng, Fantao; Tsai, Amy G.; Intaglietta, Marcos; Acharya, Seetharama A.

2014-01-01

PEGylation of intramolecularly crosslinked Hb has been studied here to overcome the limitation of dissociation of Hb tetramers. New hexa and deca PEGylated low oxygen affi nity PEG-αα-Hbs have been generated. Infl uence of PEG conjugation chemistry and the PEG shell structure on the functional properties as well as PEGylation induced plasma expander like properties of the protein has been delineated. The results have established that in the design of PEG-Hbs as oxygen therapeutics, the infl uence of conjugation chemistry and the PEG shell structure on the oxygen affi nity of Hb needs to be optimized independently besides optimizing the PEG shell structure for inducing resuscitation fluid like properties. PMID:24597567

A report on NASA software engineering and Ada training requirements

Science.gov (United States)

Legrand, Sue; Freedman, Glenn B.; Svabek, L.

1987-01-01

NASA's software engineering and Ada skill base are assessed and information that may result in new models for software engineering, Ada training plans, and curricula are provided. A quantitative assessment which reflects the requirements for software engineering and Ada training across NASA is provided. A recommended implementation plan including a suggested curriculum with associated duration per course and suggested means of delivery is also provided. The distinction between education and training is made. Although it was directed to focus on NASA's need for the latter, the key relationships to software engineering education are also identified. A rationale and strategy for implementing a life cycle education and training program are detailed in support of improved software engineering practices and the transition to Ada.

Ada Lovelace : a primeira programadora da história

OpenAIRE

Martins, Maria do Carmo

2016-01-01

Ada Augusta King, Condessa de Lovelace, sendo conhecida como Ada Lovelace nasceu a 10 de dezembro de 1815 em Londres. Foi uma matemática e escritora inglesa, autora do primeiro algoritmo para ser processado por uma máquina, a máquina analítica de Charles Babbage, um computador proposto em 1837. Aquando da sua participação no projeto de Babbage, Ada desenvolveu os algoritmos que permitiriam à máquina computar os valores de funções matemáticas. Além disso, publicou uma coleção de notas sobre a ...

Development of Software Tools for ADA Compliance Data Collection, Management, and Inquiry

Science.gov (United States)

2014-07-01

In this NUTC research project, the UNR research team developed an iOS application (named NDOT ADA Data) to efficiently and intuitively collect ADA inventory data with iPhones or iPads. This tool was developed to facilitate NDOT ADA data collect...

78 FR 10263 - Proposed Collection; Comment Request for ADA Accommodations Request Packet

Science.gov (United States)

2013-02-13

... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for ADA... the ADA Accommodations Packet. DATES: Written comments should be received on or before April 15, 2013...: ADA Accommodations Request Packet. OMB Number: 1545-2027. Abstract: Information is collected so that...

Artificial Intelligence in ADA: Pattern-Directed Processing. Final Report.

Science.gov (United States)

Reeker, Larry H.; And Others

To demonstrate to computer programmers that the programming language Ada provides superior facilities for use in artificial intelligence applications, the three papers included in this report investigate the capabilities that exist within Ada for "pattern-directed" programming. The first paper (Larry H. Reeker, Tulane University) is…

[Tolerance, safety and efficacy of the one-day preparation of PEG3350 + bisacodyl compared to 2 days of PEG3350 + bisacodyl in pediatric patients].

Science.gov (United States)

Portillo Canizalez, Ligia Marcela; Blanco Rodriguez, Gerardo; Teyssier Morales, Gustavo; Penchyna Grub, Jaime; Trauernicht Mendieta, Sean; Zurita-Cruz, Jessie Nallely

Multiple intestinal preparations have been used in children undergoing colonoscopy, with variable limitation due to acceptance, tolerance, and proper cleaning. The objective of this study was to compare the tolerability, safety and efficacy of the colonoscopy preparation with 1 day with PEG 3350 (poliethylenglycol) (4g/kg/day) + bisacodyl compared to 2 days of preparation with PEG 3350 (2g/kg/day) + bisacodyl in pediatric patients. A clinical, randomized, and blind trial was performed. Patients aged 2 to 18 years scheduled for colonoscopy were included. Patients were randomized into two groups: 1 day of preparation with PEG 3350 4g/kg/day + bisacodyl and 2 days of preparation with PEG 3350 2g/kg/day + bisacodyl. Through a questionnaire, physical examination and endoscopic evaluation (Boston scale), the tolerance, safety and efficacy of the 2 preparations to be evaluated were determined. Student's t test was performed for quantitative variables and χ 2 for qualitative variables. There were no significant differences in compliance rates, adverse effects, and extent of colonoscopic evaluation. Tolerance and safety between the intestinal preparation for 1-day colonoscopy with PEG 3350 (4g/kg/day) + bisacodyl and the 2-day preparation with PEG 3350 (2g/kg/day) + bisacodyl were similar. The quality of cleanliness was good in both groups, being partially more effective in the 1-day group with PEG 3350 (4g/kg/day). Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Overcoming the PEG-addiction: well-defined alternatives to PEG, from structure–property relationships to better defined therapeutics

KAUST Repository

Barz, Matthias

2011-01-01

Synthetic methods in polymer chemistry have evolved tremendously during the last decade. Nowadays more and more attention is devoted to the application of those tools in the development of the next generation of nanomedicines. Nevertheless, poly(ethylene glycol) (PEG) remains the most frequently used polymer for biomedical applications. In this review, we try to summarize recent efforts and developments in controlled polymerisation techniques that may allow alternatives to PEG based systems and can be used to improve the properties of future polymer therapeutics. © 2011 The Royal Society of Chemistry.

State of the art Advanced Driver Assistance Systems (ADAS).

NARCIS (Netherlands)

OEI, H.-L.

2017-01-01

An overview of state-of-the-art ADA Advanced Driver Assistance systems is given. First a main structuring system for the ADA systems is presented, needed for purposes of relevancy, and consistency : the three phases in the accident process, i.e. pre-crash, crash and post-crash; the driving task at

Diagnostic Value of Serum Adenosine Deaminase (ADA) Level for Pulmonary Tuberculosis.

Science.gov (United States)

Salmanzadeh, Shokrollah; Tavakkol, Heshmatollah; Bavieh, Khalid; Alavi, Seyed Mohammad

2015-03-01

Diagnosis of tuberculosis (TB) is not always easy, thus employing methods with a short duration and acceptable sensitivity and specificity is necessary to diagnose TB. The aim of this study was to investigate the diagnostic value of serum adenosine deaminase (ADA) level for diagnosis of pulmonary tuberculosis. A total of 160 sex and age-matched subjects were included in this study, and were divided to four groups; forty patients with pulmonary tuberculosis (PTB) diagnosed based on the national TB program (NTP), forty patients with non-tuberculosis bacterial pneumonia, forty patients with lung cancer and forty people who were healthy in every respect. Serum adenosine deaminase activity in patients of each group was measured by the Giusti and Galanti calorimetry method using a commercial kit (Diazyme, USA). The ANOVA analysis was used to compare groups for quantitative variables. Mean serum ADA level in the PTB group was clearly higher than the mean serum ADA in the other three groups. Mean serum ADA was 26 IU/L in PTB patients, 19.48 IU/L in patients with pneumonia, 15.8 IU/L in patients with lung cancer, and 10.7 IU/L in the control group (P ADA in patients with PTB sensitivity and specificity was defined as 35% and 91%, respectively. Serum ADA activity with high specificity percentage may be a useful alternative test in restricted resource areas to rule out diagnosis of PTB. However, serum ADA activity is not a useful tool for TB diagnosis.

PEG Enhancement for EM1 and EM2+ Missions

Science.gov (United States)

Von der Porten, Paul; Ahmad, Naeem; Hawkins, Matt

2018-01-01

NASA is currently building the Space Launch System (SLS) Block-1 launch vehicle for the Exploration Mission 1 (EM-1) test flight. The next evolution of SLS, the Block-1B Exploration Mission 2 (EM-2), is currently being designed. The Block-1 and Block-1B vehicles will use the Powered Explicit Guidance (PEG) algorithm. Due to the relatively low thrust-to-weight ratio of the Exploration Upper Stage (EUS), certain enhancements to the Block-1 PEG algorithm are needed to perform Block-1B missions. In order to accommodate mission design for EM-2 and beyond, PEG has been significantly improved since its use on the Space Shuttle program. The current version of PEG has the ability to switch to different targets during Core Stage (CS) or EUS flight, and can automatically reconfigure for a single Engine Out (EO) scenario, loss of communication with the Launch Abort System (LAS), and Inertial Navigation System (INS) failure. The Thrust Factor (TF) algorithm uses measured state information in addition to a priori parameters, providing PEG with an improved estimate of propulsion information. This provides robustness against unknown or undetected engine failures. A loft parameter input allows LAS jettison while maximizing payload mass. The current PEG algorithm is now able to handle various classes of missions with burn arcs much longer than were seen in the shuttle program. These missions include targeting a circular LEO orbit with a low-thrust, long-burn-duration upper stage, targeting a highly eccentric Trans-Lunar Injection (TLI) orbit, targeting a disposal orbit using the low-thrust Reaction Control System (RCS), and targeting a hyperbolic orbit. This paper will describe the design and implementation of the TF algorithm, the strategy to handle EO in various flight regimes, algorithms to cover off-nominal conditions, and other enhancements to the Block-1 PEG algorithm. This paper illustrates challenges posed by the Block-1B vehicle, and results show that the improved PEG

An Ada environment for relativistic cross section calculations

International Nuclear Information System (INIS)

Nilsson, E.

1990-01-01

We have developed an Ada environment adapted to relativistic cross section calculations. Objects such as four-vectors, γ- matrices and propagators are defined as well as operations between these objects. In this environment matrix elements can be expressed in a compact and readable way as Ada code. Unpolarized cross sections are calculated numerically by explicitly summing and averaging over spins and polarizations. A short presentation of the technique is given

Paternally expressed Peg3 controls maternally expressed Zim1 as a trans factor.

Directory of Open Access Journals (Sweden)

An Ye

Full Text Available The expression of two adjacent imprinted genes, Peg3 and Zim1, is inversely correlated: down-regulation of Peg3 coinciding with up-regulation of Zim1. The current study characterized this inverse correlation using a mutant allele targeting Peg3. According to the results, the mutation on the paternal allele of Peg3 resulted in a dramatic increase in the transcription levels of the maternal allele of Zim1, suggesting the involvement of unknown trans factors in this trans-allelic event. Subsequent ChIP experiments revealed that the protein encoded by Peg3 itself binds to the zinc finger exon of Zim1, which is modified with the repression mark H3K9me3. Interestingly, the levels of H3K9me3 on Zim1 are also reduced in the mutant cells lacking the protein PEG3, suggesting potential roles for PEG3 in establishing H3K9me3 on Zim1. Reintroducing PEG3 into the mutant cell restored down-regulation of Zim1, confirming the predicted repressor role for Peg3 on Zim1. Overall, these results demonstrated that paternally expressed Peg3 controls maternally expressed Zim1 as a trans factor. The current study also provides the first case for the trans-allelic interaction of two oppositely imprinted genes through their gene products.

Nanobody-functionalized PEG-b-PCL polymersomes and their targeting study.

Science.gov (United States)

Zou, Tao; Dembele, Fatimata; Beugnet, Anne; Sengmanivong, Lucie; Trepout, Sylvain; Marco, Sergio; de Marco, Ario; Li, Min-Hui

2015-11-20

We prepared and characterized polymersomes functionalized with nanobodies (VHHs) on the basis of biocompatible, biodegradable and FDA-approved poly(ethylene glycol)-block-poly(ϵ-caprolactone) (PEG-b-PCL). Fluorescein isothiocyanate (FITC) and N-beta-maleimidopropyl-oxysuccinimide ester were allowed reacting with H2N-PEG-b-PCL to produce FITC and maleimide (Mal) functionalized copolymers, Mal-PEG-b-PCL and FITC-PEG-b-PCL. A mixture of MeO-PEG-b-PCL, Mal-PEG-b-PCL and FITC-PEG-b-PCL was used to prepare polymersomes by thin film hydration and nanoprecipitation methods. Morphological studies by cryogenic transmission electron microscopy (Cryo-TEM) showed that the nanoparticles exhibited predominantly vesicular structures (polymersomes). Their mean diameters measured by dynamic light scattering were around 150 nm and the zeta-potentials around -1 mV at pH 7.4. The nanoparticles were functionalized with either anti-HER2 (VHH1) or anti-GFP (VHH2) nanobodies using maleimide-cysteine chemistry. Their particle size and zeta-potential increased slightly after nanobody-functionalization. The specific binding of VHH-functionalized polymersomes and control nanoparticles towards HER2 positive breast cancer cells was analyzed by flow cytometry and confocal microscopy. The collected results represent the first report which experimentally demonstrates that VHH1-functionalized PEO-b-PCL polymersomes can target specifically breast cancer cells expressing HER2 receptors. The detailed morphological and cell-binding studies described herein pave the way for future in vivo studies to evaluate the feasibility to use such nanoparticles for targeted drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimizing the Esthetics of peg-shaped teeth

OpenAIRE

Fabia Danielle Sales da Cunha Medeiros e Silva; Rosângela Marques Duarte; Ana Karina Maciel Andrade; Ricardo Jorge Alves Figueiredo

2008-01-01

In modern esthetic dentistry, recontouring peg-shaped teeth present the option of a technique for obtaining a harmonious smile. In thiscontext, the advancement of direct dental materials, such as resin composites and adhesive systems, allows this procedure to be performedsimply and efficiently, when compared with other available techniques. Thus, the aim of this report is to present a clinical case with an esthetic solution in peg-shaped lateral incisors (12 and 22). Initially, it was opted f...

Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and Semiquantitation

Science.gov (United States)

2016-01-01

Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing “fit-for-purpose” bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma. PMID:27034966

Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and Semiquantitation.

Science.gov (United States)

Chen, Lin-Zhi; Roos, David; Philip, Elsy

2016-01-01

Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing "fit-for-purpose" bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma.

ICAM-1 targeted catalase encapsulated PLGA-b-PEG nanoparticles against vascular oxidative stress.

Science.gov (United States)

Sari, Ece; Tunc-Sarisozen, Yeliz; Mutlu, Hulya; Shahbazi, Reza; Ucar, Gulberk; Ulubayram, Kezban

2015-01-01

Targeted delivery of therapeutics is the favourable idea, whereas it is possible to distribute the therapeutically active drug molecule only to the site of action. For this purpose, in this study, catalase encapsulated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles were developed and an endothelial target molecule (anti-ICAM-1) was conjugated to this carrier system in order to decrease the oxidative stress level in the target site. According to the enzymatic activity results, initial catalase activity of nanoparticles was increased from 27.39 U/mg to up to 45.66 U/mg by adding 5 mg/mL bovine serum albumin (BSA). After 4 h, initial catalase activity was preserved up to 46.98% while free catalase retained less than 4% of its activity in proteolytic environment. Furthermore, FITC labelled anti-ICAM-1 targeted catalase encapsulated nanoparticles (anti-ICAM-1/CatNPs) were rapidly taken up by cultured endothelial cells and concomitantly endothelial cells were resistant to H2O2 induced oxidative impairment.

Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products

International Nuclear Information System (INIS)

Fruijtier-Poelloth, Claudia

2005-01-01

This assessment focusses on polyethylene glycols (PEGs) and on anionic or nonionic PEG derivatives, which are currently used in cosmetics in Europe. These compounds are used in a great variety of cosmetic applications because of their solubility and viscosity properties, and because of their low toxicity. The PEGs, their ethers, and their fatty acid esters produce little or no ocular or dermal irritation and have extremely low acute and chronic toxicities. They do not readily penetrate intact skin, and in view of the wide use of preparations containing PEG and PEG derivatives, only few case reports on sensitisation reactions have been published, mainly involving patients with exposure to PEGs in medicines or following exposure to injured or chronically inflamed skin. On healthy skin, the sensitising potential of these compounds appears to be negligible. For some representative substances of this class, information was available on reproductive and developmental toxicity, on genotoxicty and carcinogenic properties. Taking into consideration all available information from related compounds, as well as the mode and mechanism of action, no safety concern with regard to these endpoints could be identified. Based on the available data it is therefore concluded that PEGs of a wide molecular weight range (200 to over 10,000), their ethers (laureths. ceteths, ceteareths, steareths, and oleths), and fatty acid esters (laurates, dilaurates, stearates, distearates) are safe for use in cosmetics. Limited data were available for PEG sorbitan/sorbitol fatty acid esters, PEG sorbitan beeswax and PEG soy sterols. Taking into account all the information available for closely related compounds, it can be assumed that these compounds as presently used in cosmetic preparations will not present a risk for human health. PEG castor oils and PEG hydrogenated castor oils have caused anaphylactic reactions when used in intravenous medicinal products. Their topical use in cosmetics is

Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

Science.gov (United States)

Sampogna-Mireles, Diana; Araya-Durán, Ingrid D; Márquez-Miranda, Valeria; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

2017-03-01

Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-α. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ‡

Science.gov (United States)

Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

2016-01-01

Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1–20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8–14 days post-immunization, shortly before EAU expression, but ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses and this effect was γδ T cell-dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help improve the design of ADA- and AR-targeted therapies. PMID:26856700

ADAS Update and Maintainability

Science.gov (United States)

Watson, Leela R.

2010-01-01

Since 2000, both the National Weather Service Melbourne (NWS MLB) and the Spaceflight Meteorology Group (SMG) have used a local data integration system (LOIS) as part of their forecast and warning operations. The original LOIS was developed by the Applied Meteorology Unit (AMU) in 1998 (Manobianco and Case 1998) and has undergone subsequent improvements. Each has benefited from three-dimensional (3-D) analyses that are delivered to forecasters every 15 minutes across the peninsula of Florida. The intent is to generate products that enhance short-range weather forecasts issued in support of NWS MLB and SMG operational requirements within East Central Florida. The current LDIS uses the Advanced Regional Prediction System (ARPS) Data Analysis System (AD AS) package as its core, which integrates a wide variety of national, regional, and local observational data sets. It assimilates all available real-time data within its domain and is run at a finer spatial and temporal resolution than current national or regional-scale analysis packages. As such, it provides local forecasters with a more comprehensive understanding of evolving fine-scale weather features. Over the years, the LDIS has become problematic to maintain since it depends on AMU-developed shell scripts that were written for an earlier version of the ADAS software. The goals of this task were to update the NWS MLB/SMG LDIS with the latest version of ADAS, incorporate new sources of observational data, and upgrade and modify the AMU-developed shell scripts written to govern the system. In addition, the previously developed ADAS graphical user interface (GUI) was updated. Operationally, these upgrades will result in more accurate depictions of the current local environment to help with short-range weather forecasting applications, while also offering an improved initialization for local versions of the Weather Research and Forecasting (WRF) model used by both groups.

PEG/CaFe2O4 nanocomposite: Structural, morphological, magnetic and thermal analyses

International Nuclear Information System (INIS)

Khanna, Lavanya; Verma, Narendra K.

2013-01-01

The coating of Polyethylene Glycol (PEG) on calcium ferrite (CaFe 2 O 4 ) nanoparticles has been reported in the present study. The X-ray diffraction pattern revealed the formation of orthorhombic structure of bare CaFe 2 O 4 nanoparticles, which was also retained after the PEG coating, along with additional characteristic peaks of PEG at 19° and 23°. The rings of CaFe 2 O 4 nanoparticles were identified by the selected area electron diffraction pattern. The characteristic bands of PEG as observed in its Fourier transform infrared spectrum were also present in PEG coated CaFe 2 O 4 nanoparticles, hence confirming its presence. In the thermal gravimetric studies, the complete thermal decomposition of PEG occurred in a one step process, but in case of PEG coated CaFe 2 O 4 nanoparticles, the decomposition took place at a higher temperature owing to the formation of covalent bonds of PEG with CaFe 2 O 4 nanoparticles. The presence of PEG on CaFe 2 O 4 nanoparticles, spherical formation of PEG coated CaFe 2 O 4 nanoparticles and reduced agglomeration in the CaFe 2 O 4 nanoparticles were revealed by high resolution transmission electron microscope, transmission electron microscope and scanning electron microscope studies, respectively. In vibrating sample magnetometer analysis, both bare as well as coated CaFe 2 O 4 nanoparticles exhibited superparamagnetic behavior. However, a drop in the magnetic saturation value was observed from 36.76 emu/g for CaFe 2 O 4 nanoparticles to 6.74 emu/g for PEG coated CaFe 2 O 4 nanoparticles, due to the formation of magnetically dead layer of PEG. In ZFC and FC analyses, superparamagnetic behavior with blocking temperature for bare and coated nanoparticles has been observed at ∼40 K and ∼60 K, respectively. The increase in the blocking temperature is attributed to the increase in the particle size after PEG coating

PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

Science.gov (United States)

Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

2015-04-01

PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

Development practices and lessons learned in developing SimPEG

Science.gov (United States)

Cockett, R.; Heagy, L. J.; Kang, S.; Rosenkjaer, G. K.

2015-12-01

Inverse modelling provides a mathematical framework for constructing a model of physical property distributions in the subsurface that are consistent with the data collected in geophysical surveys. The geosciences are increasingly moving towards the integration of geological, geophysical, and hydrological information to better characterize the subsurface. This integration must span disciplines and is not only challenging scientifically, but additionally the inconsistencies between conventions often makes implementations complicated, non­ reproducible, or inefficient. SimPEG is an open-source, multi-university effort aimed at providing a generalized framework for solving forward and inverse problems. SimPEG includes finite volume discretizations on structured and unstructured meshes, interfaces to standard numerical solver packages, convex optimization algorithms, model parameterizations, and visualization routines. The SimPEG package (http://simpeg.xyz) supports an ecosystem of forward and inverse modelling applications, including electromagnetics, vadose zone flow, seismic, and potential­ fields, that are all written with a common interface and toolbox. The goal of SimPEG is to support a community of researchers with well-tested, extensible tools, and encourage transparency and reproducibility both of the SimPEG software and the geoscientific research it is applied to. In this presentation, we will share some of the lessons we have learned in designing the modular infrastructure, testing and development practices of SimPEG. We will discuss our use of version control, extensive unit-testing, continuous integration, documentation, issue tracking, and resources that facilitate communication between existing team members and allows new researchers to get involved. These practices have enabled the use of SimPEG in research, industry, and education as well as the ability to support a growing number of dependent repositories and applications. We hope that sharing our

Debinding behaviour of a water soluble PEG/PMMA binder for Ti metal injection moulding

Energy Technology Data Exchange (ETDEWEB)

Chen, Gang [Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Cao, Peng, E-mail: p.cao@auckland.ac.nz [Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Wen, Guian [Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Edmonds, Neil [School of Chemical Science, The University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand)

2013-05-15

Polyethylene glycol (PEG) has been becoming a common component in the design of water soluble binder systems for metal injection moulding. Similar to solvent debinding, PEG can be leached out by water and the mechanism of debinding was proposed in the literature with somehow misleading information about the debinding mechanism, particularly about the formation of PEG gel. This work investigates the debinding behaviours of a PEG-based binder in titanium compacts. Titanium powder is formulated with PEG, poly(methyl methacrylate) (PMMA) and stearic acid (SA) to formulate titanium feedstock. To determine the debinding kinetics, the PEG removal percentages are measured at three different temperatures and for various specimen thicknesses. A mathematic model based on diffusion-controlled debinding process is established. The evolution of porous microstructure during the water debinding process is observed using scanning electron microscopy. Based on these observations, a water debinding mechanism for titanium alloy compacts formulated with PEG-based binders is proposed. - Highlights: ► The water-debinding behaviours of the PEG binder system were investigated. ► PEG dissolution and transportation, and the pore structure development. ► A water debinding mechanism of PEG-based binders is proposed. ► Incorrect explanation of PEG gelling in the literature is corrected. ► Correction/modification made as per the reviewers' comments and suggestions.

Debinding behaviour of a water soluble PEG/PMMA binder for Ti metal injection moulding

International Nuclear Information System (INIS)

Chen, Gang; Cao, Peng; Wen, Guian; Edmonds, Neil

2013-01-01

Polyethylene glycol (PEG) has been becoming a common component in the design of water soluble binder systems for metal injection moulding. Similar to solvent debinding, PEG can be leached out by water and the mechanism of debinding was proposed in the literature with somehow misleading information about the debinding mechanism, particularly about the formation of PEG gel. This work investigates the debinding behaviours of a PEG-based binder in titanium compacts. Titanium powder is formulated with PEG, poly(methyl methacrylate) (PMMA) and stearic acid (SA) to formulate titanium feedstock. To determine the debinding kinetics, the PEG removal percentages are measured at three different temperatures and for various specimen thicknesses. A mathematic model based on diffusion-controlled debinding process is established. The evolution of porous microstructure during the water debinding process is observed using scanning electron microscopy. Based on these observations, a water debinding mechanism for titanium alloy compacts formulated with PEG-based binders is proposed. - Highlights: ► The water-debinding behaviours of the PEG binder system were investigated. ► PEG dissolution and transportation, and the pore structure development. ► A water debinding mechanism of PEG-based binders is proposed. ► Incorrect explanation of PEG gelling in the literature is corrected. ► Correction/modification made as per the reviewers' comments and suggestions

Optimizing the Esthetics of peg-shaped teeth

Directory of Open Access Journals (Sweden)

Fabia Danielle Sales da Cunha Medeiros e Silva

2008-01-01

Full Text Available In modern esthetic dentistry, recontouring peg-shaped teeth present the option of a technique for obtaining a harmonious smile. In thiscontext, the advancement of direct dental materials, such as resin composites and adhesive systems, allows this procedure to be performedsimply and efficiently, when compared with other available techniques. Thus, the aim of this report is to present a clinical case with an esthetic solution in peg-shaped lateral incisors (12 and 22. Initially, it was opted first to perform dental bleaching with a home bleaching gel (16% carbamide peroxide associated with an acetate mold duly made for this purpose. The peg-shaped teeth were recontoured with a microhybrid resin composite (shade EA1 and DA1 with the aid of a platinum guide in silicone, obtained after diagnostic waxing on the plaster model. It was concluded that the association of esthetic procedures is of the utmost importance for obtaining good looking, aligned and harmonious teeth.

Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations.

Science.gov (United States)

Bradford, Kathryn L; Moretti, Federico A; Carbonaro-Sarracino, Denise A; Gaspar, Hubert B; Kohn, Donald B

2017-10-01

Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme of purine metabolism encoded by the Ada gene, is a cause of human severe combined immune deficiency (SCID). Numerous deleterious mutations occurring in the ADA gene have been found in patients with profound lymphopenia (T - B - NK - ), thus underscoring the importance of functional purine metabolism for the development of the immune defense. While untreated ADA SCID is a fatal disorder, there are multiple life-saving therapeutic modalities to restore ADA activity and reconstitute protective immunity, including enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) with autologous gene-corrected hematopoietic stem cells (HSC). We review the pathogenic mechanisms and clinical manifestations of ADA SCID.

Ada Lovelace, a encantadora de números

OpenAIRE

Ibaldo, Adriana; Schwantes, Cíntia

2017-01-01

Ada Lovelace foi a única filha legítima de seu famoso pai, o poeta George Gordon, Lord Byron. Seus pais se divorciaram quando Ada tinha apenas meses de idade, e ela nunca o conheceu. Mais do que isso, ela foi educada para evitar que a hereditariedade de loucura, que sua mãe acreditava que ela estaria em risco de desenvolver, se manifestasse. Assim, ela teve uma extensa educação matemática. Sua vida se desenrolou dentro do esperável para uma mulher de sua classe social em sua época, com um dif...

Ada response - a strategy for repair of alkylated DNA in bacteria.

Science.gov (United States)

Mielecki, Damian; Grzesiuk, Elżbieta

2014-06-01

Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N(3)-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N(1)-methyladenine (1meA) and N(3)-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O(6)-methylguanine (O(6) meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA. © 2014 The Authors. FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

78 FR 34095 - Adequacy Status of the Idaho, Northern Ada County PM10

Science.gov (United States)

2013-06-06

..., Northern Ada County PM 10 State Implementation Plan for Transportation Conformity Purposes AGENCY...), and volatile organic compounds (VOC) for the years 2008, 2015 and 2023 in the Northern Ada County PM... Northern Ada County. The EPA's finding was made pursuant to the adequacy review process for implementation...

Intercellular coupling mediated by potassium accumulation in peg-and-socket junctions

DEFF Research Database (Denmark)

Vigmond, Edward J.; Bardakjian, Berj L.; Thuneberg, Lars

2000-01-01

Physiology, peg-and-socket junctions, smooth muscle, boundary element method, coupling, morphology......Physiology, peg-and-socket junctions, smooth muscle, boundary element method, coupling, morphology...

Psychometric evaluation of ADAS-Cog and NTB for measuring drug response.

Science.gov (United States)

Karin, A; Hannesdottir, K; Jaeger, J; Annas, P; Segerdahl, M; Karlsson, P; Sjögren, N; von Rosen, T; Miller, F

2014-02-01

To conduct a psychometric analysis to determine the adequacy of instruments that measure cognition in Alzheimer's disease trials. Both the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and the Neuropsychological Test Battery (NTB) are validated outcome measures for clinical trials in Alzheimer's disease and are approved also for regulatory purposes. However, it is not clear how comparable they are in measuring cognitive function. In fact, many recent trials in Alzheimer's disease patients have failed and it has been questioned if ADAS-Cog still is a sensitive measure. The present paper examines the psychometric properties of ADAS-Cog and NTB, based on a post hoc analysis of data from a clinical trial (NCT01024660), which was conducted by AstraZeneca, in mild-to-moderate Alzheimer's disease (AD) patients, with a Mini Mental State Examination (MMSE) Total score 16-24. Acceptability, reliability, different types of validity and ability to detect change were assessed using relevant statistical methods. Total scores of both tests, as well as separate domains of both tests, including the Wechsler Memory Scale (WMS), Rey Auditory Verbal Learning Test (RAVLT) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Condition, were analyzed. Overall, NTB performed well, with acceptable reliability and ability to detect change, while ADAS-Cog had insufficient psychometric properties, including ceiling effects in 8 out of a total of 11 ADAS-Cog items in mild AD patients, as well as low test-retest reliability in some of the items. Based on a direct comparison on the same patient sample, we see advantages of the NTB compared with the ADAS-Cog for the evaluation of cognitive function in the population of mild-to-moderate AD patients. The results suggest that not all of ADAS-Cog items are relevant for both mild and moderate AD population. This validation study demonstrates satisfactory psychometric properties of the NTB, while ADAS-Cog was found to be

The ada operon of Mycobacterium tuberculosis encodes two DNA methyltransferases for inducible repair of DNA alkylation damage.

Science.gov (United States)

Yang, Mingyi; Aamodt, Randi M; Dalhus, Bjørn; Balasingham, Seetha; Helle, Ina; Andersen, Pernille; Tønjum, Tone; Alseth, Ingrun; Rognes, Torbjørn; Bjørås, Magnar

2011-06-10

The ada operon of Mycobacterium tuberculosis, which encodes a composite protein of AdaA and AlkA and a separate AdaB/Ogt protein, was characterized. M. tuberculosis treated with N-methyl-N'-nitro-N-nitrosoguanidine induced transcription of the adaA-alkA and adaB genes, suggesting that M. tuberculosis mount an inducible response to methylating agents. Survival assays of the methyltransferase defective Escherichia coli mutant KT233 (ada ogt), showed that expression of the adaB gene rescued the alkylation sensitivity. Further, adaB but not adaA-alkA complemented the hypermutator phenotype of KT233. Purified AdaA-AlkA and AdaB possessed methyltransferase activity. These data suggested that AdaB counteract the cytotoxic and mutagenic effect of O(6)-methylguanine, while AdaA-AlkA most likely transfers methyl groups from innocuous methylphosphotriesters. AdaA-AlkA did not possess alkylbase DNA glycosylase activity nor rescue the alkylation sensitivity of the E. coli mutant BK2118 (tag alkA). We propose that AdaA-AlkA is a positive regulator of the adaptive response in M. tuberculosis. It thus appears that the ada operon of M. tuberculosis suppresses the mutagenic effect of alkylation but not the cytotoxic effect of lesions such as 3-methylpurines. Collectively, these data indicate that M. tuberculosis hypermutator strains with defective adaptive response genes might sustain robustness to cytotoxic alkylation DNA damage and confer a selective advantage contributing to host adaptation. Copyright © 2011 Elsevier B.V. All rights reserved.

Pore structure modified diatomite-supported PEG composites for thermal energy storage

Science.gov (United States)

Qian, Tingting; Li, Jinhong; Deng, Yong

2016-09-01

A series of novel composite phase change materials (PCMs) were tailored by blending PEG and five kinds of diatomite via a vacuum impregnation method. To enlarge its pore size and specific surface area, different modification approaches including calcination, acid treatment, alkali leaching and nano-silica decoration on the microstructure of diatomite were outlined. Among them, 8 min of 5 wt% NaOH dissolution at 70 °C has been proven to be the most effective and facile. While PEG melted during phase transformation, the maximum load of PEG could reach 70 wt.%, which was 46% higher than that of the raw diatomite. The apparent activation energy of PEG in the composite was 1031.85 kJ·mol-1, which was twice higher than that of the pristine PEG. Moreover, using the nano-silica decorated diatomite as carrier, the maximum PEG load was 66 wt%. The composite PCM was stable in terms of thermal and chemical manners even after 200 cycles of melting and freezing. All results indicated that the obtained composite PCMs were promising candidate materials for building applications due to its large latent heat, suitable phase change temperature, excellent chemical compatibility, improved supercooling extent, high thermal stability and long-term reliability.

Pore structure modified diatomite-supported PEG composites for thermal energy storage.

Science.gov (United States)

Qian, Tingting; Li, Jinhong; Deng, Yong

2016-09-01

A series of novel composite phase change materials (PCMs) were tailored by blending PEG and five kinds of diatomite via a vacuum impregnation method. To enlarge its pore size and specific surface area, different modification approaches including calcination, acid treatment, alkali leaching and nano-silica decoration on the microstructure of diatomite were outlined. Among them, 8 min of 5 wt% NaOH dissolution at 70 °C has been proven to be the most effective and facile. While PEG melted during phase transformation, the maximum load of PEG could reach 70 wt.%, which was 46% higher than that of the raw diatomite. The apparent activation energy of PEG in the composite was 1031.85 kJ·mol(-1), which was twice higher than that of the pristine PEG. Moreover, using the nano-silica decorated diatomite as carrier, the maximum PEG load was 66 wt%. The composite PCM was stable in terms of thermal and chemical manners even after 200 cycles of melting and freezing. All results indicated that the obtained composite PCMs were promising candidate materials for building applications due to its large latent heat, suitable phase change temperature, excellent chemical compatibility, improved supercooling extent, high thermal stability and long-term reliability.

Adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals to improve its dispersity.

Science.gov (United States)

Cheng, Dong; Wen, Yangbing; Wang, Lijuan; An, Xingye; Zhu, Xuhai; Ni, Yonghao

2015-06-05

In this work, the adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals (CNC) was investigated for preparing re-dispersible dried CNC. Results showed that the re-dispersity of CNC in water can be significantly enhanced using a PEG1000 dosage of 5wt% (based on the dry weight of CNC). The elemental analysis confirmed the adsorption of PEG onto the CNC surface. Transmission electron microscopy (TEM) was used to characterize the dry powder and indicated that the irreversible agglomeration of CNC after drying was essentially eliminated based on the PEG adsorption concept. Thermo-gravimetric analysis (TGA) and X-ray diffraction (XRD) suggested that CNC crystallinity and thermal stability were not affected by the adsorption of PEG. Thus, the adsorption of PEG has great potential for producing re-dispersible powder CNC. Copyright © 2015 Elsevier Ltd. All rights reserved.

PEG-stearate coated solid lipid nanoparticles as levothyroxine carriers for oral administration

Science.gov (United States)

Kashanian, Soheila; Rostami, Elham

2014-03-01

In this study, poly ethylene glycol 100 stearate (PEG 100-S) was used to prepare coated solid lipid nanoparticles with loading levothyroxine sodium (levo-loaded PEG 100-S-coated SLNs) by microemulsification technique. Evaluation of the release kinetic of prepared colloidal carriers was conducted. The particle size and zeta potential of levo-loaded PEG 100-S-coated SLNs have been measured to be 187.5 nm and -23.0 mV, respectively, using photon correlation spectroscopy (PCS). Drug entrapment efficiency (EE) was calculated to be 99 %. Differential scanning calorimetry indicated that the majority of drug loaded in PEG 100-S-coated SLNs were in amorphous state which could be considered desirable for drug delivery. The purpose of this study was to develop a new nanoparticle system, consisting lipid nanoparticles coated with PEG 100-S. The modification procedure led to a reduction in the zeta potential values, varying from -40.0 to -23.0 mV for the uncoated and PEG-coated SLNs, respectively. Stability results of the nanoparticles in gastric and intestinal media show that the low pH of the gastric medium is responsible for the critical aggregation and degradation of the uncoated lipid nanoparticles. PEG 100-S-coated SLNs were more stable due to their polymer coating layer which prevented aggregation of SLNs. Consequently, it is possible that the PEG surrounds the particles reducing the attachment of enzymes and further degradation of the triglyceride cores. Shape and surface morphology of particles were determined by transition electron microscopy and scanning electron microscopy that revealed spherical shape of nanoparticles. In vitro drug release of PEG 100-S-coated SLNs was characterized using diffusion cell which showed a controlled release for drug.

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

Science.gov (United States)

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

Errors in ADAS-cog administration and scoring may undermine clinical trials results.

Science.gov (United States)

Schafer, K; De Santi, S; Schneider, L S

2011-06-01

The Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) is the most widely used cognitive outcome measure in AD trials. Although errors in administration and scoring have been suggested as factors masking accurate estimates and potential effects of treatments, there have been few formal examinations of errors with the ADAS-cog. We provided ADAS-cog administration training using standard methods to raters who were designated as experienced, potential raters by sponsors or contract research organizations for two clinical trials. Training included 1 hour sessions on test administration, scoring, question periods, and required that raters individually view and score a model ADAS-cog administration. Raters scores were compared to the criterion scores established for the model administration. A total of 108 errors were made by 80.6% of the 72 raters; 37.5% made 1 error, 25.0% made 2 errors and 18.0% made 3 or more. Errors were made in all ADAS-cog subsections. The most common were in word finding difficulty (67% of the raters), word recognition (22%), and orientation (22%). For the raters who made 1, 2, or ≥ 3 errors the ADAS-cog score was 17.5 (95% CI, 17.3 - 17.8), 17.8 (17.0 - 18.5), and 18.8 (17.6 - 20.0), respectively, and compared to the criterion score, 18.3. ADAS-cog means differed significantly and the variances were more than twice as large between those who made errors on word finding and those who did not, 17.6 (SD=1.4) vs. 18.8 (SD=0.9), respectively (χ(2) = 37.2, P ADAS-cog scores and clinical trials outcomes. These errors may undermine detection of medication effects by contributing both to a biased point estimate and increased variance of the outcome.

Graphene oxide stabilized by PLA-PEG copolymers for the controlled delivery of paclitaxel.

Science.gov (United States)

Angelopoulou, A; Voulgari, E; Diamanti, E K; Gournis, D; Avgoustakis, K

2015-06-01

To investigate the application of water-dispersible poly(lactide)-poly(ethylene glycol) (PLA-PEG) copolymers for the stabilization of graphene oxide (GO) aqueous dispersions and the feasibility of using the PLA-PEG stabilized GO as a delivery system for the potent anticancer agent paclitaxel. A modified Staudenmaier method was applied to synthesize graphene oxide (GO). Diblock PLA-PEG copolymers were synthesized by ring-opening polymerization of dl-lactide in the presence of monomethoxy-poly(ethylene glycol) (mPEG). Probe sonication in the presence of PLA-PEG copolymers was applied in order to reduce the hydrodynamic diameter of GO to the nano-size range according to dynamic light scattering (DLS) and obtain nano-graphene oxide (NGO) composites with PLA-PEG. The composites were characterized by atomic force microscopy (AFM), thermogravimetric analysis (TGA), and DLS. The colloidal stability of the composites was evaluated by recording the size of the composite particles with time and the resistance of composites to aggregation induced by increasing concentrations of NaCl. The composites were loaded with paclitaxel and the in vitro release profile was determined. The cytotoxicity of composites against A549 human lung cancer cells in culture was evaluated by flow cytometry. The uptake of FITC-labeled NGO/PLA-PEG by A549 cells was also estimated with flow cytometry and visualized with fluorescence microscopy. The average hydrodynamic diameter of NGO/PLA-PEG according to DLS ranged between 455 and 534 nm, depending on the molecular weight and proportion of PLA-PEG in the composites. NGO/PLA-PEG exhibited high colloidal stability on storage and in the presence of high concentrations of NaCl (far exceeding physiological concentrations). Paclitaxel was effectively loaded in the composites and released by a highly sustained fashion. Drug release could be regulated by the molecular weight of the PLA-PEG copolymer and its proportion in the composite. The paclitaxel

In vitro studies of PEG thin films with different molecular weights deposited by MAPLE

DEFF Research Database (Denmark)

Paun, Irina Alexandra; Ion, Valentin; Luculescu, Catalin-Romeo

2012-01-01

and their behavior in vitro. Thus, immersion in PBS induced swelling of the PEG films, which was more pronounced for PEG polymers of higher molecular weight. Prior to immersion in PBS, the PEG films of higher molecular weight were more hydrophilic, the water contact angles decreasing from ∼66 grd for PEG400 to ∼41...

The ADA and IDEA Basics: Inclusion of Children with Disabilities

Science.gov (United States)

Motwani, Mona

2007-01-01

This article discusses the American with Disabilities Act (ADA) and the Individuals with Disabilities Education Act (IDEA). The ADA is a federal civil rights law that was passed in 1990 with the aim of securing equal rights for persons with disabilities in the employment, housing, government, transportation, and public accommodation contexts. It…

Application of microchip CGE for the analysis of PEG-modified recombinant human granulocyte-colony stimulating factors.

Science.gov (United States)

Park, Eun Ji; Lee, Kyung Soo; Lee, Kang Choon; Na, Dong Hee

2010-11-01

The purpose of this study was to evaluate the microchip CGE (MCGE) for the analysis of PEG-modified granulocyte-colony stimulating factor (PEG-G-CSF) prepared with PEG-aldehydes. The unmodified and PEG-modified G-CSFs were analyzed by Protein 80 and 230 Labchips on the Agilent 2100 Bioanalyzer. The MCGE allowed size-based separation and quantitation of PEG-G-CSF. The Protein 80 Labchip was useful for PEG-5K-G-CSF, while the Protein 230 Labchip was more suitable for PEG-20K-G-CSF. The MCGE was also used to monitor a search for optimal PEG-modification (PEGylation) conditions to produce mono-PEG-G-CSF. This study demonstrates the usefulness of MCGE for monitoring and optimizing the PEGylation of G-CSF with the advantages of speed, minimal sample consumption, and automatic quantitation.

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Science.gov (United States)

Su, Yu-Cheng; Burnouf, Pierre-Alain; Chuang, Kuo-Hsiang; Chen, Bing-Mae; Cheng, Tian-Lu; Roffler, Steve R.

2017-06-01

Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

Ada response – a strategy for repair of alkylated DNA in bacteria

Science.gov (United States)

Mielecki, Damian; Grzesiuk, Elżbieta

2014-01-01

Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N3-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N1-methyladenine (1meA) and N3-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O6-methylguanine (O6meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA. PMID:24810496

A high proportion of ADA point mutations associated with a specific alanine-to-valine substitution.

OpenAIRE

Markert, M L; Norby-Slycord, C; Ward, F E

1989-01-01

In 15%-20% of children with severe combined immunodeficiency (SCID), the underlying defect is adenosine deaminase (ADA) deficiency. The overall goal of our research has been to identify the precise molecular defects in patients with ADA-deficient SCID. In this study, we focused on a patient whom we found to have normal sized ADA mRNA by Northern analysis and an intact ADA structural gene by Southern analysis. By cloning and sequencing this patient's ADA cDNA, we found a C-to-T point mutation ...

Ada 9X Project Revision Request Report. Supplement 1

Science.gov (United States)

1990-01-01

SYNCHRONIZATION POINTS OF A TASK DATE: August 8, 1989 NAME: Patrick de Bondeli ADDRESS: CR2A, 19 Avenue Dubonnet 92411 - COURBEVOIE - CEDEX, FRANCE TELEPHONE...to the parent task. Evaluating the attributes TERMINATED or CALLABLE - Giovini and Zucca (1986) consider them as synchronization points, but we do not...Elena. An Analysis of Ada Tasking December 1986. Companion paper of the Ada Formal Definition Sponsored by the European Commission. De Bondeli , Patrick

Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

International Nuclear Information System (INIS)

Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu; Abu Lila, Amr S.; Ishida, Tatsuhiro; Kiwada, Hiroshi

2014-01-01

PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG 2000 conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH 2 CH 2 ) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal anti-PEG Ig

Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Abu Lila, Amr S. [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Sharqia Governorate, Zagazig 44519 (Egypt); Ishida, Tatsuhiro, E-mail: ishida@tokushima-u.ac.jp [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Kiwada, Hiroshi [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan)

2014-05-15

PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal

ARE: Ada Rendering Engine

Directory of Open Access Journals (Sweden)

Stefano Penge

2009-10-01

Full Text Available E' ormai pratica diffusa, nello sviluppo di applicazioni web, l'utilizzo di template e di potenti template engine per automatizzare la generazione dei contenuti da presentare all'utente. Tuttavia a volte la potenza di tali engine è€ ottenuta mescolando logica e interfaccia, introducendo linguaggi diversi da quelli di descrizione della pagina, o addirittura inventando nuovi linguaggi dedicati.ARE (ADA Rendering Engine è€ pensato per gestire l'intero flusso di creazione del contenuto HTML/XHTML dinamico, la selezione del corretto template, CSS, JavaScript e la produzione dell'output separando completamente logica e interfaccia. I templates utilizzati sono puro HTML senza parti in altri linguaggi, e possono quindi essere gestiti e visualizzati autonomamente. Il codice HTML generato è€ uniforme e parametrizzato.E' composto da due moduli, CORE (Common Output Rendering Engine e ALE (ADA Layout Engine.Il primo (CORE viene utilizzato per la generazione OO degli elementi del DOM ed è pensato per aiutare lo sviluppatore nella produzione di codice valido rispetto al DTD utilizzato. CORE genera automaticamente gli elementi del DOM in base al DTD impostato nella configurazioneIl secondo (ALE viene utilizzato come template engine per selezionare automaticamente in base ad alcuni parametri (modulo, profilo utente, tipologia del nodo, del corso, preferenze di installazione il template HTML, i CSS e i file JavaScript appropriati. ALE permette di usare templates di default e microtemplates ricorsivi per semplificare il lavoro del grafico.I due moduli possono in ogni caso essere utilizzati indipendentemente l'uno dall'altro. E' possibile generare e renderizzare una pagina HTML utilizzando solo CORE oppure inviare gli oggetti CORE al template engine ALE che provvede a renderizzare la pagina HTML. Viceversa è possibile generare HTML senza utilizzare CORE ed inviarlo al template engine ALECORE è alla prima release ed è€ già utilizzato all

Development and in vivo evaluation of an oral insulin-PEG delivery system.

Science.gov (United States)

Calceti, P; Salmaso, S; Walker, G; Bernkop-Schnürch, A

2004-07-01

Insulin-monomethoxypoly(ethylene glycol) derivatives were obtained by preparation of mono- and di-terbutyl carbonate insulin derivatives, reaction of available protein amino groups with activated 750 Da PEG and, finally, amino group de-protection. This procedure allowed for obtaining high yield of insulin-1PEG and insulin-2PEG. In vivo studies carried out by subcutaneous injection into diabetic mice demonstrated that the two bioconjugates maintained the native biological activity. In vitro, PEGylation was found to enhance the hormone stability towards proteases. After 1 h incubation with elastase, native insulin, insulin-1PEG and insulin-2PEG undergo about 70, 30 and 10% degradation, respectively, while in the presence of pepsin protein degradation was 100, 70 and 50%, respectively. The attachment of low molecular weight PEG did not significantly (P >0.05) alter insulin permeation behavior across the intestinal mucosa. Insulin-1PEG was formulated into mucoadhesive tablets constituted by the thiolated polymer poly(acrylic acid)-cysteine. The therapeutic agent was sustained released from these tablets within 5 h. In vivo, by oral administration to diabetic mice, the glucose levels were found to decrease of about 40% since the third hour from administration and the biological activity was maintained up to 30 h. According to these results, the combination of PEGylated insulin with a thiolated polymer used as drug carrier matrix might be a promising strategy for oral insulin administration.

The Effect of Tannins and Additional Peg on In Vitro Gas Production

International Nuclear Information System (INIS)

Irawan Sugoro

2004-01-01

Agro-wastes such as sugar cane straw are potential sources as feed. Sugar cane straw contains tannins, an anti-nutrient, which could effect feed quality. The effect of tannins by in vitro gas production was compared to maize straw which has low tannins. Tannin concentration was measured by using PEG which is labelled by 14 C. The result showed that the tannins concentration of sugar cane straw is 10.88 % dry matter. The others are digestibility of dry matter and organic matter, VFA, ammonia and pH. The gas production is 48.83 ml/500 mg after 24 h incubation. It is lower than the control i.e. 100.64 ml/500 mg. Additional PEG increase the gas production i.e. 30.5 %, because tannins is bounded by it. The concentration of ammonia, VFA, dry matter and organic matter digestibility on sugar cane straw with additional PEG is higher than without PEG, i.e 28.29 mg/100 ml, 15.56 nmol/100 ml, 52.18 % and 47.54 %. pH of sugar cane without PEG i.e. 6.62 is higher than additional PEG, i.e. 6.54. It could be concluded, tannins decrease of gas production, ammonia, VFA, dry matter, and organic matter digestibility and additional PEG increase gas production of sugar cane. (author)

Long-term stability of PEG-based antifouling surfaces in seawater

DEFF Research Database (Denmark)

Noguer, Albert Camós; Olsen, Stefan Møller; Hvilsted, Søren

2016-01-01

Poly(ethylene glycol) (PEG) is a hydrophilic polymer that has been extensively used in the biomedical and marine environment due to its antifouling properties. In the biomedical field, PEG has been successfully used to functionalize surfaces due to its resistance to cell and nonspecific protein...

77 FR 36231 - Americans With Disabilities Act (ADA) and Architectural Barriers Act (ABA) Accessibility...

Science.gov (United States)

2012-06-18

...-0004] RIN 3014-AA39 Americans With Disabilities Act (ADA) and Architectural Barriers Act (ABA... (ADA) and Architectural Barriers Act (ABA) Accessibility Guidelines to specifically address emergency... ensure that newly constructed and altered emergency transportable housing units covered by the ADA or ABA...

Stabilization of sputtered gold and silver nanoparticles in PEG colloid solutions

International Nuclear Information System (INIS)

Slepička, P.; Elashnikov, R.; Ulbrich, P.; Staszek, M.; Kolská, Z.; Švorčík, V.

2015-01-01

In this study, a simple technique for preparation of colloid solution of metal nanoparticles in polyethylene glycol (PEG)/H 2 O is described. By this technique, stable colloidal metal solutions can be prepared ready for use without application of chemical reactions, stabilizers, or reducing agents. The nanoparticles are created by direct sputtering of metal into PEG. The influence of sputter conditions and the concentration of PEG/H 2 O on the properties of nanoparticles was studied. The nanoparticles were characterized by transmission electron microscopy, atomic absorption spectrometry, dynamic light scattering, and UV–Vis spectroscopy. UV–Vis spectra of gold nanoparticle solution exhibit localized surface plasmon resonance characteristic peaks located in the region 513–560 nm (PEG/H 2 O—1/1), 509–535 nm (PEG/H 2 O—1/9), and for silver nanoparticles in the region from 401 to 421 nm. Silver nanoparticles have a broader size distribution compared with gold ones. An appropriate choice of concentration, mixing, and deposition conditions allows preparing the stable solution of gold or silver nanoparticles

Stabilization of sputtered gold and silver nanoparticles in PEG colloid solutions

Energy Technology Data Exchange (ETDEWEB)

Slepička, P., E-mail: petr.slepicka@vscht.cz; Elashnikov, R. [University of Chemistry and Technology Prague, Department of Solid State Engineering (Czech Republic); Ulbrich, P. [University of Chemistry and Technology Prague, Department of Biochemistry and Microbiology (Czech Republic); Staszek, M. [University of Chemistry and Technology Prague, Department of Solid State Engineering (Czech Republic); Kolská, Z. [University of J. E. Purkyně, Faculty of Science (Czech Republic); Švorčík, V. [University of Chemistry and Technology Prague, Department of Solid State Engineering (Czech Republic)

2015-01-15

In this study, a simple technique for preparation of colloid solution of metal nanoparticles in polyethylene glycol (PEG)/H{sub 2}O is described. By this technique, stable colloidal metal solutions can be prepared ready for use without application of chemical reactions, stabilizers, or reducing agents. The nanoparticles are created by direct sputtering of metal into PEG. The influence of sputter conditions and the concentration of PEG/H{sub 2}O on the properties of nanoparticles was studied. The nanoparticles were characterized by transmission electron microscopy, atomic absorption spectrometry, dynamic light scattering, and UV–Vis spectroscopy. UV–Vis spectra of gold nanoparticle solution exhibit localized surface plasmon resonance characteristic peaks located in the region 513–560 nm (PEG/H{sub 2}O—1/1), 509–535 nm (PEG/H{sub 2}O—1/9), and for silver nanoparticles in the region from 401 to 421 nm. Silver nanoparticles have a broader size distribution compared with gold ones. An appropriate choice of concentration, mixing, and deposition conditions allows preparing the stable solution of gold or silver nanoparticles.

Analytical performances of the Diazyme ADA assay on the Cobas® 6000 system.

Science.gov (United States)

Delacour, Hervé; Sauvanet, Christophe; Ceppa, Franck; Burnat, Pascal

2010-12-01

To evaluate the analytical performance of the Diazyme ADA assay on the Cobas® 6000 system for pleural fluid samples analysis. Imprecision, linearity, calibration curve stability, interference, and correlation studies were completed. The Diazyme ADA assay demonstrated excellent precision (CVADA assay correlated well with the Giusti method (r(2)=0.93) but exhibited a negative bias (~ -30%). The Diazyme ADA assay on the Cobas® 6000 system represents a rapid, accurate, precise and reliable method for determination of ADA activity in pleural fluid samples. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

PEG-related polymer resins as synthetic supports

Institute of Scientific and Technical Information of China (English)

无

2010-01-01

Combinatorial chemistry has become a significant part of the discovery and optimization process for novel drugs,affinity ligands,and catalysts.The polymeric supports play a key role in combinatory chemistry.Therefore,various kinds of functional polymer resins have been exploited as supports,reagents,and catalysts in organic synthesis.In comparison to the conventional Merrifield resins,the poly(ethylene glycol)(PEG)-related polymer resins have advantages including good compatibilities with polar solvents,good solvent absorbency and swelling properties.This review focuses primarily on the more recent work in the field of developing PEG-related polymer resins as supports for organic synthesis.

Effects of PEG4000 template on sol-gel synthesis of porous cerium titanate photocatalyst

Science.gov (United States)

Zhang, Wenjie; Tao, Yingjie; Li, Chuanguo

2018-04-01

Porous cerium titanate was synthesized by sol-gel method, using polyethylene glycol (PEG4000) as template agent. Brannerite structured CeTi2O6 in monoclinic system is the major substance formed in the materials. Formation of CeO2 and rutile TiO2 depends on the amount of PEG4000. The addition of PEG4000 leads to production of fine particles in the samples, but it does not apparently affect the band gap energy. Pore volume of the cerium titanate sample continuously increases with rising PEG4000 amount. The sample obtained using 3.5 g PEG4000 has BET surface area of 16.2 m2/g and pore volume of 0.0232 cm3/g. The addition of PEG4000 can obviously promote photocatalytic activity of cerium titanate, which can be proven by both enhanced production of hydroxyl radical and ofloxacin degradation efficiency. As much as 95.2% of the initial ofloxacin molecules are removed from the solution after 50 min of photocatalytic degradation on the cerium titanate obtained using 3.5 g PEG4000, while only 48.4% ofloxacin is removed on cerium titanate obtained without PEG4000.

PEG 3350 Administration Is Not Associated with Sustained Elevation of Glycol Levels.

Science.gov (United States)

Williams, Kent C; Rogers, Lynette K; Hill, Ivor; Barnard, John; Di Lorenzo, Carlo

2018-04-01

To determine whether trace amounts of ethylene glycol (EG), diethylene glycol (DEG), or triethylene glycol (TEG) in PEG 3350 are associated with increased blood levels of EG, DEG, or TEG in children receiving daily PEG 3350 therapy. Blood samples were drawn from 9 children who were being treated for constipation with PEG 3350 (6-12 years old) before and every 30 minutes for 3 hours after receiving 17 g of PEG 3350. PEG 3350, tap water, and blood samples from 18 age- and sex-matched controls also were analyzed. Baseline blood levels of EG and TEG did not differ between control and treated groups. DEG levels (median [IQR]) were lower in the PEG 3350 group (40.13 ng/mL [36.69, 63.94] vs 92.83 ng/mL [51.06, 128.93], P = .008). After PEG 3350 dose, levels of EG (390.51 ng/mL [326.06, 624.55]) and TEG (2.21 ng/mL [0, 4.5]) peaked at 90 minutes at 1032.81 ng/mL (826.84, 1486.13) (P = .009) and 35.17 ng/mL (15.81, 45.13) (P = .0005), respectively. DEG levels did not significantly change. Standard 17-g doses of PEG 3350 in 8 oz (237 mL) of water resulted in concentrations (mean ± SD) of EG, DEG, and TEG of 1.32 ± 0.23 µg/mL, 0.18 ± 0.03 µg/mL, and 0.12 ± 0.01 µg/mL, respectively. EG, DEG, and TEG levels in public water supply were 0.07 µg/mL, 0.21 µg/mL, and 0.02 µg/mL, respectively. Daily PEG 3350 therapy in children was not associated with sustained elevation of EG, DEG, or TEG blood levels over levels in matched controls. Although EG and TEG levels increased after a standard dose of PEG 3350, their peak values remained well below toxic levels. Copyright © 2017 Elsevier Inc. All rights reserved.

A PEG Construction of LDPC Codes Based on the Betweenness Centrality Metric

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BHURTAH-SEEWOOSUNGKUR, I.

2016-05-01

Full Text Available Progressive Edge Growth (PEG constructions are usually based on optimizing the distance metric by using various methods. In this work however, the distance metric is replaced by a different one, namely the betweenness centrality metric, which was shown to enhance routing performance in wireless mesh networks. A new type of PEG construction for Low-Density Parity-Check (LDPC codes is introduced based on the betweenness centrality metric borrowed from social networks terminology given that the bipartite graph describing the LDPC is analogous to a network of nodes. The algorithm is very efficient in filling edges on the bipartite graph by adding its connections in an edge-by-edge manner. The smallest graph size the new code could construct surpasses those obtained from a modified PEG algorithm - the RandPEG algorithm. To the best of the authors' knowledge, this paper produces the best regular LDPC column-weight two graphs. In addition, the technique proves to be competitive in terms of error-correcting performance. When compared to MacKay, PEG and other recent modified-PEG codes, the algorithm gives better performance over high SNR due to its particular edge and local graph properties.

Germination Behaviour of Lawsonia inermis L. as Influenced by Polyethylene Glycol (PEG

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Enneb Hanen

2016-11-01

Full Text Available Tunisian Flora is well known for its richness and diversity of medicinal plants such as henna plant (Lawsonia inermis L. a flowering plant belongs to the family of Lyteraceae, distributed in dry tropical and subtropical zones including North Africa. This plant pertains to continental oases where water shortage, constitute the essential limiting factor of agricultural production. The present study was carried out to evaluate the impact of water stress on the germination of the henna plant (Lawsonia inermis L.. Seeds were germinated under stress of aqueous Polyethylene Glycol (PEG solutions blended to create water potentials of 0, -0.2, -0.4, -0.6, - 0.8 and -1 MPa. Results showed that seeds germinated in PEG solutions exhibited significantly lower cumulative germination rate (CGR than control especially when water potential fell below -0.6 MPa. Mean germination time (MGT was delayed by increasing PEG concentrations, while germination stress tolerance index (GSTI was decreased with the increase in PEG concentrations. The highest percentage of GSTI in stressed condition was 84.13% for PEG (-0.2MPa whereas, the lowest value was 8.37% for PEG (-1MPa.

Diagnostic value of sputum adenosine deaminase (ADA) level in pulmonary tuberculosis.

Science.gov (United States)

Binesh, Fariba; Jalali, Hadi; Zare, Mohammad Reza; Behravan, Farhad; Tafti, Arefeh Dehghani; Behnaz, Fatemah; Tabatabaee, Mohammad; Shahcheraghi, Seyed Hossein

2016-06-01

Tuberculosis is still a considerable health problem in many countries. Rapid diagnosis of this disease is important, and adenosine deaminase (ADA) has been used as a diagnostic test. The aim of this study was to assess the diagnostic value of ADA in the sputum of patients with pulmonary tuberculosis. The current study included 40 patients with pulmonary tuberculosis (culture positive, smear ±) and 42 patients with non tuberculosis pulmonary diseases (culture negative). ADA was measured on all of the samples. The median value of ADA in non-tuberculosis patients was 2.94 (4.2) U/L and 4.01 (6.54) U/L in tuberculosis patients, but this difference was not statistically significant (p=0.100). The cut-off point of 3.1 U/L had a sensitivity of 61% and a specificity of 53%, the cut-off point of 2.81 U/L had a sensitivity of 64% and a specificity of 50% and the cut-off point of 2.78 U/L had a sensitivity of 65% and a specificity of 48%. The positive predictive values for cut-off points of 3.1, 2.81 and 2.78 U/L were 55.7%, 57.44% and 69.23%, respectively. The negative predictive values for the abovementioned cut-off points were 56.75%, 57.14% and 55.88%, respectively. Our results showed that sputum ADA test is neither specific nor sensitive. Because of its low sensitivity and specificity, determination of sputum ADA for the diagnosis of pulmonary tuberculosis is not recommended.

Antibiofouling hybrid dendritic Boltorn/star PEG thiol-ene cross-linked networks.

Science.gov (United States)

Bartels, Jeremy W; Imbesi, Philip M; Finlay, John A; Fidge, Christopher; Ma, Jun; Seppala, Jonathan E; Nystrom, Andreas M; Mackay, Michael E; Callow, James A; Callow, Maureen E; Wooley, Karen L

2011-06-01

A series of thiol-ene generated amphiphilic cross-linked networks was prepared by reaction of alkene-modified Boltorn polyesters (Boltorn-ene) with varying weight percent of 4-armed poly(ethylene glycol) (PEG) tetrathiol (0-25 wt%) and varying equivalents of pentaerythritol tetrakis(3-mercaptopropionate) (PETMP) (0-64 wt%). These materials were designed to present complex surface topographies and morphologies, with heterogeneity of surface composition and properties and robust mechanical properties, to serve as nontoxic antibiofouling coatings that are amenable to large-scale production for application in the marine environment. Therefore, a two-dimensional matrix of materials compositions was prepared to study the physical and mechanical properties, over which the compositions spanned from 0 to 25 wt% PEG tetrathiol and 0-64 wt% PETMP (the overall thiol/alkene (SH/ene) ratios ranged from 0.00 to 1.00 equiv), with both cross-linker weight percentages calculated with respect to the weight of Boltorn-ene. The Boltorn-ene components were prepared through the esterification of commercially available Boltorn H30 with 3-butenoic acid. The subsequent cross-linking of the Boltorn-PEG-PETMP films was monitored using IR spectroscopy, where it was found that near-complete consumption of both thiol and alkene groups occurred when the stoichiometry was ca. 48 wt% PETMP (0.75 equiv SH/ene, independent of PEG amount). The thermal properties of the films showed an increase in T(g) with an increase in 4-armed PEG-tetrathiol wt%, regardless of the PETMP concentration. Investigation of the bulk mechanical properties in dry and wet states found that the Young's modulus was the greatest at 48 wt% PETMP (0.75 equiv of SH/ene). The ultimate tensile strength increased when PETMP was constant and the PEG concentration was increased. The Young's modulus was slightly lower for wet films at constant PEG or constant PETMP amounts, than for the dry samples. The nanoscopic surface features were

Optimizing ADAS-Cog Worksheets: A Survey of Clinical Trial Rater s' Perceptions.

Science.gov (United States)

Meyer, Stephen M; Bertzos, Kristina A; Perez, Magdalena; Connor, Donald J; Schafer, Kimberly; Walter, Sarah

2017-01-01

The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADASCog) remains the most widely used test of longitudinal cognitive functioning in Alzheimer's disease (AD) clinical trials. Unlike most neuropsychological tests, the ADAS-Cog source documentation worksheets are not uniform across clinical trials, and vary by document layout, inclusion of administration and/or scoring instructions, and documentation of subtest scoring (e.g., recording correct versus incorrect scores), among other differences. Many ADAS-Cog test administrators (raters) participate in multiple AD trials and switching between different ADAS-Cog worksheets may increase the likelihood of administration and/or scoring mistakes that lessen the reliability of the instrument. An anonymous online survey sought raters' experiences with ADAS-Cog worksheets and their opinions on the design and content of the worksheets. Results of the survey indicated preference for structure and standardization of the ADASCog worksheets, which has been considered in the development of a standard ADAS-Cog source document by the Alzheimer's Disease Cooperative Study (ADCS) Working Group. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sensitive and rapid detection of anti-PEG in blood using surface plasmon resonance sensor (Conference Presentation)

Science.gov (United States)

Sun, Fang; Jiang, Shaoyi; Yu, Qiuming

2016-03-01

Polyethylene glycol (PEG) is widely used to modify many therapeutic proteins and nanoparticles to reduce their immunogenicity and to improve their pharmacokinetic and therapeutic properties. It is generally accepted that PEG is non-immunogenic and non-antigenic. However, an emerging of literature and studies shows that the immune system can generate specific antibodies binding PEG. These anti-PEG antibodies not only correlate with adverse reactions appeared after patient infusions, but are also found to be the reason for therapeutic efficacy loss during chronical administrations. In addition, because of constant exposure to PEG in daily consumer products including detergents, processed food and cosmetics, a substantial proportion of the population has likely developed anti-PEG immunity. Thus a method to quickly and accurately measure the anti-PEG antibody level is desired. Nevertheless, the gold standard to detect anti-PEG antibodies is ELISA, which is costly and time-consuming especially for quantification. Herein, we demonstrated the anti-PEG measurement in blood serum using surface plasmon resonance (SPR) sensor. Several PEG-based surface functionalization on SPR sensor chip were studied in terms of protein resistance and the limit of detection (LOD) of anti-PEG. The quantitative detection can be achieved in less than 30 min with LOD comparable to ELISA. Furthermore, the IgG and IgM of anti-PEG can be differentiated by following the secondary antibody.

Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles

Directory of Open Access Journals (Sweden)

Tianmu Hu

2018-03-01

Full Text Available In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine (PEG-modified alginate microparticles (ALG-PEG MPs were developed then two different mechanisms were employed to load doxorubicin (Dox: 1 forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2 forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT, a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant (p > 0.05. In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.

[Diagnostic value and functional correlations of the ADAS-Cog scale in Alzheimer's disease: data on NORMACODEM project].

Science.gov (United States)

Monllau, A; Pena-Casanova, J; Blesa, R; Aguilar, M; Bohm, P; Sol, J M; Hernandez, G

2007-10-01

The aims of this study were to assess the criterion validity of Alzheimer's Disease Assessment Scale (ADAS) and its cognitive subscale (ADAS-Cog) for the diagnosis of Alzheimer's disease (AD), and to determine their different cut-off scores and sensitivity and specificity values. In addition, we also attempted to study the possible correlations between cognitive scores (ADAS) and functional measures. 451 subjects were studied (254 controls, 86 subjects with mild cognitive impairment and 111 patients with AD). ADAS total score was obtained by adding the cognitive (ADAS-Cog) and non-cognitive (ADAS-Nocog) scales. Scores were adjusted for age and formal education. For assessing the possible correlation between cognitive and functional measures, the following instruments were administered: Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale (BDRS) and the Interview for the Deterioration of Daily Living in Dementia (IDDD). ROC curves and Pearson correlation coefficient. ADAS best cut-off score for dementia was > or = 17 providing sensitivity and specificity values of 90.09% and 85.88 % respectively, while for the ADAS-Cog best cut-off score was > or = 12 with sensitivity and specificity values of 89.19 % and 88.53 % respectively. In both cases scores were adjusted for age and formal education. The area under the ROC curve was 0.95 and 0.94 respectively. Highly significant correlations were found for ADAS and 19 ADAS-Cog with the functional scales studied. Both, ADAS and ADAS-Cog report good validity in terms of sensitivity, specificity and as predictive value for AD. Moreover, significant correlations were found between the functional impairment observed in patients with AD and the overall scores achieved in the ADAS and ADAS-Cog.

Incorporation of fluconazole in copolymer PMMA-g-PEG derivatives; Incorporacao de fluconazol em ineditos derivados do copolimero PMMA-g-PEG

Energy Technology Data Exchange (ETDEWEB)

Silveira, B.M.; Santos, V.M.R. dos; Novack, K.M.; Lopes, S.A., E-mail: vmrebello@yahoo.com.br [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

2014-07-01

The graft copolymer PMMA-g-PEG went through chemical transformations in its chain through acetylation, halogenation, methylation and esterification followed by hydrolysis reactions. Subsequently, the copolymer PMMA-g-PEG derivatives passed through the process of emulsification and incorporation of the drug fluconazole. Derivatives copolymers were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) after incorporation in order to evaluate their effectiveness. The efficiency of incorporation was observed and it was also verified that the complexity of polymer chain influence in the incorporated fluconazole content. (author)

SDI satellite autonomy using AI and Ada

Science.gov (United States)

Fiala, Harvey E.

1990-01-01

The use of Artificial Intelligence (AI) and the programming language Ada to help a satellite recover from selected failures that could lead to mission failure are described. An unmanned satellite will have a separate AI subsystem running in parallel with the normal satellite subsystems. A satellite monitoring subsystem (SMS), under the control of a blackboard system, will continuously monitor selected satellite subsystems to become alert to any actual or potential problems. In the case of loss of communications with the earth or the home base, the satellite will go into a survival mode to reestablish communications with the earth. The use of an AI subsystem in this manner would have avoided the tragic loss of the two recent Soviet probes that were sent to investigate the planet Mars and its moons. The blackboard system works in conjunction with an SMS and a reconfiguration control subsystem (RCS). It can be shown to be an effective way for one central control subsystem to monitor and coordinate the activities and loads of many interacting subsystems that may or may not contain redundant and/or fault-tolerant elements. The blackboard system will be coded in Ada using tools such as the ABLE development system and the Ada Production system.

Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles

International Nuclear Information System (INIS)

Cho, Wan-Seob; Cho, Minjung; Jeong, Jinyoung; Choi, Mina; Cho, Hea-Young; Han, Beom Seok; Kim, Sheen Hee; Kim, Hyoung Ook; Lim, Yong Taik; Chung, Bong Hyun; Jeong, Jayoung

2009-01-01

In general, gold nanoparticles are recognized as being as nontoxic. Still, there have been some reports on their toxicity, which has been shown to depend on the physical dimension, surface chemistry, and shape of the nanoparticles. In this study, we carry out an in vivo toxicity study using 13 nm-sized gold nanoparticles coated with PEG (MW 5000). In our findings the 13 nm sized PEG-coated gold nanoparticles were seen to induce acute inflammation and apoptosis in the liver. These nanoparticles were found to accumulate in the liver and spleen for up to 7 days after injection and to have long blood circulation times. In addition, transmission electron microscopy showed that numerous cytoplasmic vesicles and lysosomes of liver Kupffer cells and spleen macrophages contained the PEG-coated gold nanoparticles. These findings of toxicity and kinetics of PEG-coated gold nanoparticles may have important clinical implications regarding the safety issue as PEG-coated gold nanoparticles are widely used in biomedical applications

76 FR 31892 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

Science.gov (United States)

2011-06-02

... Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION: Notice... Civil Rights Act of 1964 (Title VII) and the Americans with Disabilities Act (ADA) to entities covered... the same record retention requirements under GINA that are imposed under Title VII and the ADA, i.e...

76 FR 38124 - Applications for New Awards; Americans With Disabilities Act (ADA) National Network Regional...

Science.gov (United States)

2011-06-29

... DEPARTMENT OF EDUCATION Applications for New Awards; Americans With Disabilities Act (ADA) National Network Regional Centers and ADA National Network Collaborative Research Projects AGENCY: Office... Rehabilitation Research Projects and Centers Program--Disability Rehabilitation Research Projects (DRRP)--ADA...

76 FR 38129 - Applications for New Awards; Americans With Disabilities Act (ADA) National Network Knowledge...

Science.gov (United States)

2011-06-29

... DEPARTMENT OF EDUCATION Applications for New Awards; Americans With Disabilities Act (ADA) National Network Knowledge Translation Center (ADA KT Center) AGENCY: Office of Special Education and... Program--Disability Rehabilitation Research Projects (DRRP)--The ADA National Network Knowledge...

Coaxial electro-spun PEG/PA6 composite fibers: Fabrication and characterization

International Nuclear Information System (INIS)

Babapoor, Aziz; Karimi, Gholamreza; Golestaneh, Seyyed Iman; Mezjin, Mehdi Ahmadi

2017-01-01

Highlights: • Core-shell PCM nanofibers are fabricated by coaxial electrospinning. • PEG1000 (core) and PA6 (shell) are used to fabricate nanofibers. • The peak temperature is increased by raising the PEG concentration. • The shell structure can prevent PEG leakage at high temperatures. - Abstract: Energy storage systems have been recognized as one of the most important technologies for conservation and utilization of renewable energy sources. In this study, core-shell phase change material (PCM) nanofibers were fabricated by using coaxial electrospinning of polyethylene glycol (PEG1000) as the core material (i.e., PCM) and polyamide 6 (PA6) as the shell (supporting) material. The effects of inner core solution flow rate and PEG content on the morphology, structure, and phase change behavior of the produced composite fibers were studied thoroughly by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The experimental results indicated that by increasing the flow rate of the core solution, slightly thicker fibers can be produced, and the onset temperature of melting is reduced. Also, as the PEG concentration rises, the peak temperature increases and higher amounts of latent heat enthalpy are achieved. The results indicate that the fabricated core-shell structure has almost resolved the leakage instability normally associated with other types of PCM fibers and hence, has the potential to improve thermal storage capacity.

Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

Science.gov (United States)

Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

2016-06-01

7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. Copyright © 2016 Elsevier B.V. All rights reserved.

Ada Dual-Use Summary: Ada Dual-Use Workshop Held in Vienna, Virginia on October 19-20, 1993. Ada Dual-Use Committee Briefing, November 8, 1993

Science.gov (United States)

1993-11-29

Systems Agency C- 19 Novemtiber 8., 1993 Promoting the Use of Ada in Computer Science Curricula Timothy J. Long Ohio State University ®I To L4 ease...framework, distributed file systems, a high-performance fiber-optic connection and multi-processor modules to work with the OSF’s Mach 3 microkernel (again

Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Cuong, Nguyen-Van [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Department of Chemical Engineering, Ho Chi Minh City University of Industry, 12 Nguyen Van Bao St, Ho Chi Minh (Viet Nam); Jiang, Jian-Lin; Li, Yu-Lun [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Chen, Jim-Ray [Department of Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Jwo, Shyh-Chuan [Division of General Surgery, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Hsieh, Ming-Fa, E-mail: mfhsieh@cycu.edu.tw [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China)

2010-12-28

The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

International Nuclear Information System (INIS)

Cuong, Nguyen-Van; Jiang, Jian-Lin; Li, Yu-Lun; Chen, Jim-Ray; Jwo, Shyh-Chuan; Hsieh, Ming-Fa

2010-01-01

The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX

First International Conference on Ada (R) Programming Language Applications for the NASA Space Station, volume 1

Science.gov (United States)

Bown, Rodney L. (Editor)

1986-01-01

Topics discussed include: test and verification; environment issues; distributed Ada issues; life cycle issues; Ada in Europe; management/training issues; common Ada interface set; and run time issues.

Revising the ADAS-cog for a more accurate assessment of cognitive impairment.

Science.gov (United States)

Wouters, Hans; van Gool, Willem A; Schmand, Ben; Lindeboom, Robert

2008-01-01

To examine whether it is appropriate to sum the cognitive part of the Alzheimer Disease Assessment Scale (ADAS-cog) items to assess cognitive impairment. This assumes items to have (1) equal measurement precision and (2) hierarchically ordered categories. Rasch analysis on the basis of pooled data from 3 Randomized Controlled Trials was used to examine these assumptions and to estimate each patient's level of impairment. Analyses were replicated in an independent sample. The original ADAS-cog scoring did not fit the Rasch Model and did not reliably distinguish between impairment levels. Patients with equal test scores had different impairment levels. Similarly, patients with different test scores could have the same impairment level. Revising the ADAS-cog by (1) weighting the items by their measurement precision and (2) collapsing nonhierarchical item categories resulted in good fit and a valid one to one correspondence between sum scores and estimated impairment levels. This revealed that equal differences in ADAS-cog scores did not reflect equal differences in impairment level along the test's score range. It is appropriate to summate the ADAS-cog items provided that the items are weighted and have their categories hierarchically ordered.

Transcriptional Adaptor ADA3 of Drosophila melanogaster Is Required for Histone Modification, Position Effect Variegation, and Transcription▿ †

OpenAIRE

Grau, Benjamin; Popescu, Cristina; Torroja, Laura; Ortuño-Sahagún, Daniel; Boros, Imre; Ferrús, Alberto

2007-01-01

The Drosophila melanogaster gene diskette (also known as dik or dAda3) encodes a protein 29% identical to human ADA3, a subunit of GCN5-containing histone acetyltransferase (HAT) complexes. The fly dADA3 is a major contributor to oogenesis, and it is also required for somatic cell viability. dADA3 localizes to chromosomes, and it is significantly reduced in dGcn5 and dAda2a, but not in dAda2b, mutant backgrounds. In dAda3 mutants, acetylation at histone H3 K9 and K14, but not K18, and at hist...

Preplacement evaluation: thriving within the ADA guidelines.

Science.gov (United States)

Pruitt, R H

1995-03-01

1. The intent of the Americans With Disabilities Act (ADA) is to remove barriers against those with known disabilities and to require reasonable accommodation to enable qualified employees to perform a job. The ADA is not meant to facilitate those with covert preexisting conditions in setting up workers' compensation and disability claims. 2. Essential job functions are physical and mental requirements for a job that are developed by the supervisor and the occupational health department. These functions should be included with the posting of any position. 3. Preplacement evaluation requirements: essential job functions that are used to determine what is included in the assessment; employee capability statement (with reasonable accommodation); and conditional offer of employment pending a satisfactory post-offer evaluation prior to beginning the job.

76 FR 79065 - Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA

Science.gov (United States)

2011-12-21

... Reporting Requirements Under Title VII, the ADA and GINA CFR Correction In Title 29 of the Code of Federal... title VII or section 107 of the ADA'' and add in their place the words ``section 709(c) of title VII, section 107 of the ADA, or section 207(a) of GINA'' wherever they appear in the following sections...

ADA genetic polymorphism and the effect of smoking on neonatal bilirubinemia and developmental parameters.

Science.gov (United States)

Gloria-Bottini, F; Magrini, A; Cozzoli, E; Bergamaschi, A; Bottini, E

2008-11-01

Genetic variability of metabolic enzymes may influence the effect of cigarette smoking on intrauterine development and on early neonatal events. To investigate the role of adenosine deaminase genetic polymorphism on the effect of smoking on neonatal bilirubinemia and developmental parameters. Analysis of association between adenosine deaminase phenotypes and neonatal developmental parameters. Prospective study of serum bilirubin level in relation to adenosine deaminase phenotype. We have studied 360 consecutive newborn infants from the Caucasian population of Rome. Serum bilirubin concentration was determined at birth and every 24 h for the first five days. Overall maternal smoking is associated with a slight decrease in the incidence of phototherapy (13.4% in non smoking vs 11.7% in smoking mothers) and with a reduction of birth weight (3374 g in non smoking mothers vs 3133 g in smoking mothers). There is a significant interaction between smoke and adenosine deaminase. While in non smoking mothers the incidence of phototherapy in carriers of ADA 2 allele is higher than in ADA 1 phenotype, in infants from smoking mothers the pattern is reversed and the incidence of phototherapy in carriers of ADA 2 allele is lower than in infants with ADA 1 phenotype. Other neonatal bilirubin parameters follow a similar pattern of interaction between smoking and ADA. The negative effect of smoke on birth weight is much more evident in infant with ADA 1 phenotype than in those carrying the ADA 2 allele. The data suggest that ADA phenotype modifies the effect of smoking on developmental and bilirubin parameters.

Automated real time peg and tool detection for the FLS trainer box.

Science.gov (United States)

Nemani, Arun; Sankaranarayanan, Ganesh

2012-01-01

This study proposes a method that effectively tracks trocar tool and peg positions in real time to allow real time assessment of the peg transfer task of the Fundamentals of Laparoscopic Surgery (FLS). By utilizing custom code along with OpenCV libraries, tool and peg positions can be accurately tracked without altering the original setup conditions of the FLS trainer box. This is achieved via a series of image filtration sequences, thresholding functions, and Haar training methods.

The effect of pH on bromelain partition from Ananas comosus by PEG4000/phosphate ATPS

Directory of Open Access Journals (Sweden)

Juliana Ferrari Ferreira

2011-02-01

Full Text Available In this work, the thermodynamic equilibrium and applying of PEG4000/Phosphate ATPS on the purification of bromelain extracted from pineapple was studied. A rigorous study of the equilibrium curves and tie-line length from PEG4000/phosphate ATPS were done for the pH 6-11 at 25ºC. Results showed that there was augment in the PEG and salt contents with the high pH value from PEG4000/Phosphate ATPS and two-phase formation needed only increasing the PEG content. Two tie-line length at pH 11 from PEG4000/Phosphate ATPS were optimal condition for bromelain purification, one on composition of 14% PEG and 13% salt and other at 12.6% PEG and 12.2% salt, while a 25-62 folds of enzyme was found. SDS-PAGE electrophoreses had one band only, which showed that bromelain was purified. Optimum conditions of bromelain use were found at pH 7 and between 30-40ºC.

DNA repair by the Ada protein of E. coli

International Nuclear Information System (INIS)

Karran, P.; Hall, J.

1988-01-01

This paper discusses the Ada protein of E. coli which exemplifies the highly specialized nature of the enzymes which have evolved to repair DNA. According to the authors, this protein exhibits not only novel mechanistic features but also provides an apparently unique example of a strategy for controlling gene expression in E. coli. They report that knowledge of the properties and mode of action of the Ada protein has afforded insight into how human cells are affected by alkylating agents, including those used in chemotherapy

Cytoplasmic localization of alteration/deficiency in activation 3 (ADA3) predicts poor clinical outcome in breast cancer patients.

Science.gov (United States)

Mirza, Sameer; Rakha, Emad A; Alshareeda, Alaa; Mohibi, Shakur; Zhao, Xiangshan; Katafiasz, Bryan J; Wang, Jun; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Ellis, Ian O; Green, Andrew R; Band, Hamid; Band, Vimla

2013-02-01

Transcriptional activation by estrogen receptor (ER) is a key step to breast oncogenesis. Given previous findings that ADA3 is a critical component of HAT complexes that regulate ER function and evidence that overexpression of other ER coactivators such as SRC-3 is associated with clinical outcomes in breast cancer, the current study was designed to assess the potential significance of ADA3 expression/localization in human breast cancer patients. In this study, we analyzed ADA3 expression in breast cancer tissue specimens and assessed the correlation of ADA3 staining with cancer progression and patient outcome. Tissue microarrays prepared from large series of breast cancer patients with long-term follow-ups were stained with anti-ADA3 monoclonal antibody using immunohistochemistry. Samples were analyzed for ADA3 expression followed by correlation with various clinicopathological parameters and patients' outcomes. We report that breast cancer specimens show predominant nuclear, cytoplasmic, or mixed nuclear + cytoplasmic ADA3 staining patterns. Predominant nuclear ADA3 staining correlated with ER+ status. While predominant cytoplasmic ADA3 staining negatively correlated with ER+ status, but positively correlated with ErbB2, EGFR, and Ki67. Furthermore, a positive correlation of cytoplasmic ADA3 was observed with higher histological grade, mitotic counts, Nottingham Prognostic Index, and positive vascular invasion. Patients with nuclear ADA3 and ER positivity have better breast cancer specific survival and distant metastasis free survival. Significantly, cytoplasmic expression of ADA3 showed a strong positive association with reduced BCSS and DMFS in ErbB2+/EGFR+ patients. Although in multivariate analyses ADA3 expression was not an independent marker of survival, predominant nuclear ADA3 staining in breast cancer tissues correlates with ER+ expression and together serves as a marker of good prognosis, whereas predominant cytoplasmic ADA3 expression correlates with

Synthesis and characterisation of PEG modified chitosan nanocapsules loaded with thymoquinone.

Science.gov (United States)

Vignesh Kumar, Suresh Kumar; Renuka Devi, Ponnuswamy; Harish, Saru; Hemananthan, Eswaran

2017-02-01

Thymoquinone (TQ), a major bioactive compound of Nigella sativa seeds has several therapeutic properties. The main drawback in bringing TQ to therapeutic application is that it has poor stability and bioavailability. Hence a suitable carrier is essential for TQ delivery. Recent studies indicate biodegradable polymers are potentially good carriers of bioactive compounds. In this study, polyethylene glycol (PEG) modified chitosan (Cs) nanocapsules were developed as a carrier for TQ. Aqueous soluble low molecular weight Cs and PEG was selected among different biodegradable polymers based on their biocompatibility and efficacy as a carrier. Optimisation of synthesis of nanocapsules was done based on particle size, PDI, encapsulation efficiency and process yield. A positive zeta potential value of +48 mV, indicating good stability was observed. Scanning electron microscope and atomic-force microscopy analysis revealed spherical shaped and smooth surfaced nanocapsules with size between 100 to 300 nm. The molecular dispersion of the TQ in Cs PEG nanocapsules was studied using X-ray powder diffraction. The Fourier transform infrared spectrum of optimised nanocapsule exhibited functional groups of both polymer and drug, confirming the presence of Cs, PEG and TQ. In vitro drug release studies showed that PEG modified Cs nanocapsules loaded with TQ had a slow and sustained release.

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

Science.gov (United States)

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

PEG/CaFe{sub 2}O{sub 4} nanocomposite: Structural, morphological, magnetic and thermal analyses

Energy Technology Data Exchange (ETDEWEB)

Khanna, Lavanya, E-mail: lavanshya@yahoo.co.in; Verma, Narendra K., E-mail: nkverma@thapar.edu

2013-10-15

The coating of Polyethylene Glycol (PEG) on calcium ferrite (CaFe{sub 2}O{sub 4}) nanoparticles has been reported in the present study. The X-ray diffraction pattern revealed the formation of orthorhombic structure of bare CaFe{sub 2}O{sub 4} nanoparticles, which was also retained after the PEG coating, along with additional characteristic peaks of PEG at 19° and 23°. The rings of CaFe{sub 2}O{sub 4} nanoparticles were identified by the selected area electron diffraction pattern. The characteristic bands of PEG as observed in its Fourier transform infrared spectrum were also present in PEG coated CaFe{sub 2}O{sub 4} nanoparticles, hence confirming its presence. In the thermal gravimetric studies, the complete thermal decomposition of PEG occurred in a one step process, but in case of PEG coated CaFe{sub 2}O{sub 4} nanoparticles, the decomposition took place at a higher temperature owing to the formation of covalent bonds of PEG with CaFe{sub 2}O{sub 4} nanoparticles. The presence of PEG on CaFe{sub 2}O{sub 4} nanoparticles, spherical formation of PEG coated CaFe{sub 2}O{sub 4} nanoparticles and reduced agglomeration in the CaFe{sub 2}O{sub 4} nanoparticles were revealed by high resolution transmission electron microscope, transmission electron microscope and scanning electron microscope studies, respectively. In vibrating sample magnetometer analysis, both bare as well as coated CaFe{sub 2}O{sub 4} nanoparticles exhibited superparamagnetic behavior. However, a drop in the magnetic saturation value was observed from 36.76 emu/g for CaFe{sub 2}O{sub 4} nanoparticles to 6.74 emu/g for PEG coated CaFe{sub 2}O{sub 4} nanoparticles, due to the formation of magnetically dead layer of PEG. In ZFC and FC analyses, superparamagnetic behavior with blocking temperature for bare and coated nanoparticles has been observed at ∼40 K and ∼60 K, respectively. The increase in the blocking temperature is attributed to the increase in the particle size after PEG coating.

Effect of PEG-6000 Imposed Water Deficit on Chlorophyll Metabolism in Maize Leaves

Directory of Open Access Journals (Sweden)

Rekha Gadre

2013-08-01

Full Text Available Drought stress is one of the major abiotic constraint limiting plant growth and productivity world wide. The current study was undertaken with the aim to investigate the effect of water deficit imposed by PEG-6000, on chlorophyll metabolism in maize leaves to work out the mechanistic details. Leaf segments prepared from primary leaves of etiolated maize seedlings were treated with varying concentrations of polyethylene glycol-6000 (PEG-6000; w/v- 5%, 10%, 20%, 30% in continuous light of intensity 40 Wm-2 at 26±2 °C for 24 h in light chamber. The results demonstrate a concentration dependent decline in chlorophyll content with increasing concentration of polyethylene glycol-6000 (PEG-6000. Reduction in chlorophyll ‘a’ level was to a greater extent than the chlorophyll ‘b’. The RNA content decreased in a concentration dependent manner with PEG, however, proline content increased significantly. Relative water content decreased significantly with the supply of 30% PEG only. A substantial decrease in chlorophyll synthesis due to significant reduction in ALA content and ALAD activity, with no change in chlorophyllase activity with the supply of PEG suggests that water deficit affects chlorophyll formation rather than its degradation.

Constructing a working taxonomy of functional Ada software components for real-time embedded system applications

Science.gov (United States)

Wallace, Robert

1986-01-01

A major impediment to a systematic attack on Ada software reusability is the lack of an effective taxonomy for software component functions. The scope of all possible applications of Ada software is considered too great to allow the practical development of a working taxonomy. Instead, for the purposes herein, the scope of Ada software application is limited to device and subsystem control in real-time embedded systems. A functional approach is taken in constructing the taxonomy tree for identified Ada domain. The use of modular software functions as a starting point fits well with the object oriented programming philosophy of Ada. Examples of the types of functions represented within the working taxonomy are real time kernels, interrupt service routines, synchronization and message passing, data conversion, digital filtering and signal conditioning, and device control. The constructed taxonomy is proposed as a framework from which a need analysis can be performed to reveal voids in current Ada real-time embedded programming efforts for Space Station.

Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

Science.gov (United States)

Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

2011-03-01

Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA. © Georg Thieme Verlag KG Stuttgart · New York.

A fundamental research on T3 radioimmunoassay by polyethylene glycol (PEG) method

International Nuclear Information System (INIS)

Takahashi, Tadashige; Hayakawa, Susumu; Takagi, Atsushi; Sugisawa, Yoshihiko; Kurata, Kunio

1976-01-01

Since Chopra, et al. produced an antibody of triiodothyronine (T 3 ), measurement of serum T 3 by radioimmunoassay has been widely used as a clinical test. However, the dextran coated charcoal (DCC) method which is most commonly used for B/F separation requires strict control of incubation temperature and time. The authors reduced this disadvantage by using polyethylene glycol (PEG) instead of DCC for B/F separation. Crossreactivities of the antibody used with thyroxine, monoiodothyrosine and diiodotyrosine are less than 0.06% which is considered to be satisfactory in comparison with those previously reported. The recovery ratios of added T 3 were between 92.4 - 105.9% and that reflected T 3 concentration well. The dilution test showed good linearity. Correlation of T 3 values measured by DCC method and PEG method in 26 sera was good (r=0.99), and linear regression function was y=0.89x + 0.30 (y: PEG method and x: DCC method). No significant differences were observed in the results obtained by 2 hr incubation at 20 - 35 0 C and 24 hr incubation at 4 0 C. As for the volume of PEG solution, 1.0 ml was most suitable. Samples should be kept at 4 0 C when centrifugation is impossible within 30 min after addition of PEG. Also in various conditions of centrifugation, the authors obtained almost same results. As described above, the authors conquered the problem involved in the DCC method, and also simplified the assay procedure by using the PEG method for B/F separation. PEG method is considered to be the methods of choice for clinical routine test for serum T 3 levels (Evans, J.)

New control system: IMAGIN supervision in ADA

International Nuclear Information System (INIS)

Maugeais, C.

1991-01-01

The structure, the initialization, the operating cycle, the different messages and the errors treatment of the new user oriented packages written in ADA language for IMAGIN software are presented. (A.B.). 2 figs

A mixed ruthenium polypyridyl complex containing a PEG-bipyridine macroligand

Energy Technology Data Exchange (ETDEWEB)

Marin, Veronica; Holder, Elisabeth; Meier, Michael A.R.; Hoogenboom, Richard; Schubert, Ulrich S. [Laboratory of Macromolecular Chemistry and Nanoscience, Eindhoven University of Technology and Dutch Polymer Institute (DPI), P. O. Box 513, 5600 MB Eindhoven (Netherlands)

2004-04-06

An amino-functionalized bipyridine ligand was prepared in order to serve as a bridging unit to an activated low-molecular-weight monomethyl ether of poly(ethylene glycol) (PEG). Coordination of a ruthenium(II) phenantroline precursor onto the formed PEG-containing bipyridine ligand yielded a metal-containing polymer which shows interesting properties for solar cell applications. (Abstract Copyright [2004], Wiley Periodicals, Inc.)

ADA Compliance and Accessibility of Fitness Facilities in Western Wisconsin.

Science.gov (United States)

Johnson, Marquell J; Stoelzle, Hannah Y; Finco, Kristi L; Foss, Sadie E; Carstens, Katie

2012-01-01

The study expands the research on fitness facility accessibility by determining how compliant fitness facilities in rural western Wisconsin were with Title III of the Americans with Disabilities Act (ADA). Comparisons were made with 4 other studies that were conducted in different geographical regions. The study also examined fitness professionals' disability knowledge and awareness. An ADA fitness facility compliance instrument and a fitness professional disability awareness survey were used. Direct observation and physical measurements were taken during on-site visits to 16 of 36 eligible fitness facilities in rural western Wisconsin. Ten fitness professionals from participating facilities completed an online survey. Frequencies were used to analyze the results. None of the participating facilities were in 100% compliance with ADA. Customer service desk (84%) and path of travel throughout the facility (72%) were the highest compliance areas. Telephone (6%) and locker rooms (32%) were the lowest compliance areas. No fitness professional was trained in wheelchair transfers and very few had received training in providing services to individuals with disabilities. Fitness facility accessibility remains a concern nationally. Continued efforts need to be made to raise the awareness of ADA compliance among fitness professionals across the United States, especially in rural areas where fitness facility availability is limited.

Vector-matrix-quaternion, array and arithmetic packages: All HAL/S functions implemented in Ada

Science.gov (United States)

Klumpp, Allan R.; Kwong, David D.

1986-01-01

The HAL/S avionics programmers have enjoyed a variety of tools built into a language tailored to their special requirements. Ada is designed for a broader group of applications. Rather than providing built-in tools, Ada provides the elements with which users can build their own. Standard avionic packages remain to be developed. These must enable programmers to code in Ada as they have coded in HAL/S. The packages under development at JPL will provide all of the vector-matrix, array, and arithmetic functions described in the HAL/S manuals. In addition, the linear algebra package will provide all of the quaternion functions used in Shuttle steering and Galileo attitude control. Furthermore, using Ada's extensibility, many quaternion functions are being implemented as infix operations; equivalent capabilities were never implemented in HAL/S because doing so would entail modifying the compiler and expanding the language. With these packages, many HAL/S expressions will compile and execute in Ada, unchanged. Others can be converted simply by replacing the implicit HAL/S multiply operator with the Ada *. Errors will be trapped and identified. Input/output will be convenient and readable.

Improving dielectric permittivity by incorporating PDMS-PEG block copolymer into PDMS network

DEFF Research Database (Denmark)

A Razak, Aliff Hisyam; Szabo, Peter; Skov, Anne Ladegaard

Polydimethylsiloxane (PDMS) based elastomers are well-known to actuate with large strain mainly due to their low modulus and their non-conducting nature. On the other hand, polyethyleneglycols(PEG) are not stretchable but they have high permittivity and are conductive. Combination of the two...... polymers as a block copolymer depicts a possibility for substantial improvement of properties such as high permittivity and non-conductivity – if carefully designed. The objective is to synthesize PDMS-PEG multiblock copolymer assembling into different morphologies1 such as lamellar,cylinder, gyroid...... and spheres based on variation of volume fractions of PDMS and PEG. The synthesisis amended from Klasner et al.2 and Jukarainen et al.3 Variation in the ratio between the two constituents introduces distinctive properties in terms of dielectric permittivity and rheological behaviour. PDMS-PEG multiblock...

Ada Integrated Environment III Computer Program Development Specification. Volume III. Ada Optimizing Compiler.

Science.gov (United States)

1981-12-01

file.library-unit{.subunit).SYMAP Statement Map: library-file. library-unit.subunit).SMAP Type Map: 1 ibrary.fi le. 1 ibrary-unit{.subunit). TMAP The library...generator SYMAP Symbol Map code generator SMAP Updated Statement Map code generator TMAP Type Map code generator A.3.5 The PUNIT Command The P UNIT...Core.Stmtmap) NAME Tmap (Core.Typemap) END Example A-3 Compiler Command Stream for the Code Generator Texas Instruments A-5 Ada Optimizing Compiler

Current status of percutaneous endoscopic gastrostomy (PEG) in a general hospital in Japan: a cross-sectional study

Science.gov (United States)

Kusano, Chika; Yamada, Nobuo; Kikuchi, Kenji; Hashimoto, Masaji; Gotoda, Takuji

2016-01-01

Background: There has been debate over the indications for percutaneous endoscopic gastrostomy (PEG) in recent years in Japan. In addition, the level of satisfaction of patients and patient’s family after PEG remains unclear. The aim of this study was to investigate the current status of PEG and the level of satisfaction of patients and patients’ families after PEG in Japan. Methods: We reviewed the existing data of all patients who underwent PEG tube insertion at Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We examined the following points: underlying diseases requiring PEG, levels of consciousness, and performance status. We also sent a questionnaire to the patients and patient’s families to ask about their satisfaction with and thoughts about PEG. Results: The data of 545 patients who underwent PEG were reviewed. There were 295 men and 250 women, with a mean age of 77.2 ± 11.4 years. PEG was indicated most frequently for cerebrovascular disorders (48.2%, 239/545). There were 515 (94.4%, 515/545) patients showing consciousness disturbance and 444 (81.5%, 444/545) bedridden patients. The questionnaire was answered by one patient himself and 316 patients’ families. When asked, “Was performing PEG a good decision?”, 57.5% (182/316) of the patients’ families answered yes. Meanwhile, when patients’ family members were asked if they would wish to undergo PEG if they were in the same condition as the patient, 28.4% (90/316) answered yes, whereas 55.3% (175/316) answered no. Conclusions: Few patients were able to make their own decision about PEG tube placement because of consciousness disturbance. As a result, many family members of the patients did not want to experience PEG for themselves. Future studies should be performed to clarify the quality of life and ethical aspects associated with PEG. PMID:27313796

ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK.

Science.gov (United States)

Gao, Ge; Zhang, Tianshun; Wang, Qiushi; Reddy, Kanamata; Chen, Hanyong; Yao, Ke; Wang, Keke; Roh, Eunmiri; Zykova, Tatyana; Ma, Weiya; Ryu, Joohyun; Curiel-Lewandrowski, Clara; Alberts, David; Dickinson, Sally E; Bode, Ann M; Xing, Ying; Dong, Zigang

2017-09-01

Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell-originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843-54. ©2017 AACR . ©2017 American Association for Cancer Research.

Co-electrospun blends of PU and PEG as potential biocompatible scaffolds for small-diameter vascular tissue engineering

International Nuclear Information System (INIS)

Wang, Heyun; Feng, Yakai; Fang, Zichen; Yuan, Wenjie; Khan, Musammir

2012-01-01

A small-diameter vascular graft (inner diameter 4 mm) was fabricated from polyurethane (PU) and poly(ethylene glycol) (PEG) solutions by blend electrospinning technology. The fiber diameter decreased from 1023 ± 185 nm to 394 ± 106 nm with the increasing content of PEG in electrospinning solutions. The hybrid PU/PEG scaffolds showed randomly nanofibrous morphology, high porosity and well-interconnected porous structure. The hydrophilicity of these scaffolds had been improved significantly with the increasing contents of PEG. The mechanical properties of electrospun hybrid PU/PEG scaffolds were obviously different from that of PU scaffold, which was caused by plasticizing or hardening effect imparted by PEG composition. Under hydrated state, the hybrid PU/PEG scaffolds demonstrated low mechanical performance due to the hydrophilic property of materials. Compared with dry PU/PEG scaffolds with the same content of PEG, the tensile strength and elastic modulus of hydrated PU/PEG scaffolds decreased significantly, while the elongation at break increased. The hybrid PU/PEG scaffolds demonstrated a lower possibility of thrombi formation than blank PU scaffold in platelet adhesion test. The hemolysis assay illustrated that all scaffolds could act as blood contacting materials. To investigate further in vitro cytocompatibility, HUVECs were seeded on the scaffolds and cultured over 14 days. The cells could attach and proliferate well on the hybrid scaffolds than blank PU scaffold, and form a cell monolayer fully covering on the PU/PEG (80/20) hybrid scaffold surface. The results demonstrated that the electrospun hybrid PU/PEG tubular scaffolds possessed the special capacity with excellent hemocompatibility while simultaneously supporting extensive endothelialization with the 20 and 30% content of PEG in hybrid scaffolds. - Highlights: ► We develop small-diameter vascular grafts made of PU and PEG by electrospinning. ► The hybrid scaffolds could suppress the platelet

Clicked bis-PEG-peptide conjugates for studying calmodulin-Kv7.2 channel binding.

Science.gov (United States)

Bonache, M Angeles; Alaimo, Alessandro; Malo, Covadonga; Millet, Oscar; Villarroel, Alvaro; González-Muñiz, Rosario

2014-11-28

The recombinant Kv7.2 calmodulin (CaM) binding site (Q2AB CaMBD) shows a high tendency to aggregate, thus complicating biochemical and structural studies. To facilitate these studies we have conceived bis-PEG-peptide CaMBD-mimetics linking helices A and B in single, easy to handle molecules. Short PEG chains were selected as spacers between the two peptide molecules, and a Cu(i)-catalyzed cycloaddition (CuAAC) protocol was used to assemble the final bis-PEG-peptide conjugate, by the convenient functionalization of PEG arms with azide and alkyne groups. The resulting conjugates, with a certain helical character in TFE solutions (CD), showed nanomolar affinity in a fluorescence CaM binding in vitro assay, higher than just the sum of the precursor PEG-peptide affinities, thus validating our design. The approach to these first described examples of Kv7.2 CaMBD-mimetics could pave the way to chimeric conjugates merging helices A and B from different Kv7 subunits.

Stabilization of Resveratrol in Blood Circulation by Conjugation to mPEG and mPEG-PLA Polymers: Investigation of Conjugate Linker and Polymer Composition on Stability, Metabolism, Antioxidant Activity and Pharmacokinetic Profile

Science.gov (United States)

Siddalingappa, Basavaraj; Benson, Heather A. E.; Brown, David H.; Batty, Kevin T.; Chen, Yan

2015-01-01

Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing different chemical linkers and polymer compositions was investigated for enhanced pharmacokinetic profile of resveratrol. Ester conjugates such as α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol (MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol (MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were synthesized by alkali-mediated etherification. All polymer conjugates were fully characterized in vitro and the pharmacokinetic profile of selected conjugates was characterized in rats. Buffer and plasma stability of conjugates was dependent on polymer hydrophobicity, aggregation behavior and PEG corona, with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in vitro. Polymer conjugates irrespective of linker chemistry protected resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa), Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles with significantly higher plasma area under curve (AUC), slower clearance and smaller volume of distribution, compared to resveratrol. PMID:25799413

Surfactant-assisted carbon doping in ZnO nanowires using Poly Ethylene Glycol (PEG)

Energy Technology Data Exchange (ETDEWEB)

Amanullah, Malik; Javed, Qurat-ul-Ain, E-mail: Quratulain@sns.nust.edu.pk; Rizwan, Syed

2016-09-01

Zinc Oxide (ZnO) provides unique properties owing to its wide bandgap, large resistivity range and possibility to tune the physical properties. The surfactant assisted carbon doping was made possible due to the lowering of surface energy. The ZnO and carbon doped ZnO (C-ZnO) nanowires fabricated by hydrothermal process, Poly Ethylene Glycol (PEG) is used as surfactant in hydrothermal synthesis followed by post growth annealing treatment at 600 °C–700 °C. At 5%–10% of diluted PEG carbon is doped in ZnO. The crystallinity, structural morphology and elemental composition analysis for ZnO and C-ZnO nanowires were carried out using X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy techniques respectively. Carbon doping in ZnO nanowires in the presence of different percentage of surfactant is explained by calculating the change in surface energy with respect to change in PEG molecule concentration. It was found that the surface energy per molecule modulates from 3.92 × 10{sup −8} J/m{sup 2} to 8.16 × 10{sup −7} J/m{sup 2} in the PEG concentration range between 5% and 10%. Our results provides a new theoretical calculations, implemented on real system, to observe the details of PEG-assisted Carbon doping in II-VI semiconductor nanowires. - Highlights: • ZnO and C-ZnO was synthesized by PEG assisted post growth annealing process. • At 5% and 10% of PEG successful synthesis of C-ZnO was found. • XRD, SEM and EDX characterizations confirm the successful synthesis of ZnO and C-ZnO. • Change in surface energy with respect to PEG molecule concentration was calculated.

Preparation of flexible PLA/PEG-POSS nanocomposites by melt blending and radiation crosslinking

International Nuclear Information System (INIS)

Jung, Chang-Hee; Hwang, In-Tae; Jung, Chan-Hee; Choi, Jae-Hak

2014-01-01

In this study, poly(lactic acid) (PLA)/poly(ethylene glycol)-functionalized polyhedral oligomeric silsesquioxane (PEG-POSS) nanocomposites with or without triallyl isocyanurate (TAIC) were investigated by melt blending and electron beam irradiation to enhance the flexibility of PLA. Based on the results of the crosslinking degree measurements, the PLA/PEG-POSS nanocomposites were crosslinked by electron beam irradiation in the presence of triallyl isocyanurate (TAIC) and their crosslinking degree reached up to 80% based on the absorbed dose and their compositions. From the results of the FE-SEM and EDX Si-mapping, the crosslinked PLA/PEG-POSS nanocomposites were homogenous without a micro-phase separation or radiation-induced morphological change. Based on the results of the tensile test, the PLA/PEG-POSS nanocomposites containing 15 wt% PEG-POSS exhibited the highest flexibility, and their tensile strength showed a maximum value of 44.5 MPa after electron beam irradiation at an absorbed dose of 100 kGy in the presence of TAIC, which is comparable to non-biodegradable polypropylene. The results of the dynamic mechanical analysis revealed that the crosslinked PLA/PEG-POSS nanocomposites exhibited a higher thermal resistance above their melting temperature in comparison to that of the neat PLA, although their glass transition temperature was lower than that of the neat PLA. The enzymatic biodegradation test revealed that the PLA/PEG-POSS nanocomposites were biodegradable even though their biodegradability was deteriorated in comparison to that of the neat PLA. - Highlights: • PLA/PEG-POSS nanocomposites were prepared by melt blending. • The nanocomposites containing TAIC were crosslinked by electron beam irradiation. • The mechanical properties of the nanocomposites were comparable to polypropylene. • The crosslinked nanocomposites can be biodegradable

Solid-state NMR study of stereocomplexes formed by enantiomeric star-shaped PEG-PLA copolymers in water

NARCIS (Netherlands)

Calucci, Lucia; Forte, Claudia; Buwalda, S.J.; Dijkstra, Pieter J.

2011-01-01

Solid-state NMR was applied to samples obtained by freeze-drying hydrogels of 1:1 (PEG65-NHCO-PLLA13)8/(PEG65-NHCO-PDLA13)8 or (PEG65-NHCO-PDLA13)8 only star block copolymers (where PEG, PLLA, and PDLA stand for poly(ethylene glycol), poly(l-lactide), and poly(d-lactide), respectively) in order to

How Do Scores on the ADAS-Cog, MMSE, and CDR-SOB Correspond?

Science.gov (United States)

Balsis, Steve; Benge, Jared F; Lowe, Deborah A; Geraci, Lisa; Doody, Rachelle S

2015-01-01

Clinicians and researchers who measure cognitive dysfunction often use the Alzheimer's Disease Assessment Scale--Cognitive Subscale (ADAS-Cog), the Mini-Mental State Examination (MMSE), or the Clinical Dementia Rating scale (CDR-SOB). But, the use of different measures can make it difficult to compare data across patients or studies. What is needed is a simple chart that shows how scores on these three important measures correspond to each other. Using data from 1709 participants from the Alzheimer's Disease Neuroimaging Initiative and item response theory-based statistics, we analyzed how scores on each measure, the ADAS-Cog, the MMSE, and the CDR-SOB, correspond. Results indicated multiple inflections in CDR-SOB and ADAS-Cog scores within a given MMSE score, suggesting that the CDR-SOB and ADAS-Cog are more precise in measuring the severity of cognitive dysfunction than the MMSE. This study shows how scores on these three popular measures of cognitive dysfunction correspond to each other, which is very useful information for both researchers and clinicians.

Alteration of lysine 178 in the hinge region of the Escherichia coli ada protein interferes with activation of ada, but not alkA, transcription.

OpenAIRE

Saget, B M; Shevell, D E; Walker, G C

1995-01-01

The ada gene of Escherichia coli K-12 encodes the 39-kDa Ada protein, which consists of two domains joined by a hinge region that is sensitive to proteolytic cleavage in vitro. The amino-terminal domain has a DNA methyltransferase activity that repairs the S-diastereoisomer of methylphosphotriesters while the carboxyl-terminal domain has a DNA methyltransferase activity that repairs O6-methylguanine and O4-methylthymine lesions. Transfer of a methyl group to Cys-69 by repair of a methylphosph...

The effect of combined Moringa oleifera and demineralized freeze-dried bovine bone xenograft on the amount of osteoblast and osteoclast in the healing of tooth extraction socket of Cavia cobaya

Directory of Open Access Journals (Sweden)

Rostiny Rostiny

2016-12-01

Full Text Available Background: Alveolar bone has an important role in providing support to teeth and dentures. Loss of support caused by alveolar resorption will cause functional and aesthetic problems. Preservation socket using bone graft is one way to maintain the dimensions of the alveolar bone. Moringa oleifera leaf can increase the activity of bone graft in the formation of new bone. Purpose: This study was aimed to evaluate the effect of combined Moringa oleivera leaf extract and demineralized freeze-dried bovine bone xenograft (DFDBBX towards the formation of osteoblasts and osteoclasts in the tooth extraction sockets of cavia cobaya. Method: This study used 28 cavia cobayas divided into four groups. The combination of Moringa oleifera leaf extract and DFDBBX was inducted into the sockets of lower incisor tooth with certain dose in each group, ointment 1 containing PEG (a mixture of PEG 400 and PEG 4000 for control group, ointment 2 containing Moringa oleifera leaf extract and DFDBBX and PEG (at active subtance consentration of 0.5% for group 1, ointment 3 containing Moringa oleifera leaf extract and DFDBBX and PEG (at active substance concentration of 1% for group 2, and Ointment 4 containing Moringa oleifera leaf extract and DFDBBX and PEG (at active substance consentration of 2% for group 3. paraffin block preparations were made for histopathology examination using hematoxylin eosin staining. Result: The results showed that there were significant differences of the number of osteoblasts and osteoclasts in each treatment group (p <0.05. Conclusion: It can be concluded that the combination of Moringa oleifera leaf extract and DFDBBX at 2% cocentration can increase the number of osteoblasts and decrease osteoclasts in the healing of tooth extraction sockets of cavia cobaya.

PEG and Thickeners: A Critical Interaction Between Polyethylene Glycol Laxative and Starch-Based Thickeners.

Science.gov (United States)

Carlisle, Brian J; Craft, Garrett; Harmon, Julie P; Ilkevitch, Alina; Nicoghosian, Jenik; Sheyner, Inna; Stewart, Jonathan T

2016-09-01

Clinicians commonly encounter dysphagia and constipation in a skilled nursing population. Increasing the viscosity of liquids, usually with a starch- or xanthan gum-based thickener, serves as a key intervention for patients with dysphagia. We report a newly identified and potentially dangerous interaction between polyethylene glycol 3350 laxative (PEG) and starch-thickened liquids. A patient requiring nectar-thickened liquids became constipated, and medical staff prescribed PEG for constipation. His nurse observed that the thickened apple juice immediately thinned to near-water consistency when PEG was added. She obtained the same results with thickened water and coffee. We quantified this phenomenon by isothermal rotational rheology. Results confirmed a precipitous loss of thickening when PEG was added to starch-based thickeners but not with xanthan gum-based thickeners. Clinicians and front-line staff should be aware of this potentially critical interaction between PEG- and starch-based thickeners. Although confirmatory studies are needed, our preliminary data suggest that PEG may be compatible with xanthan gum-- based thickeners. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.

mPEG-PLA Micelle for Delivery of Effective Parts of Andrographis Paniculata.

Science.gov (United States)

Yao, Hailu; Song, Shiyong; Miao, Xiaolu; Liu, Xiao; Zhao, Junli; Wang, Zhen; Shao, Xiaoting; Zhang, Yu; Han, Guang

2018-01-01

Many studies have shown that Andrographis paniculata (Burm. f.) Nees has a good anti-tumor effect, but poor solubility in water and poor bioavailability hinder the modernization of it. To formulate the effective parts (mainly diterpene lactones) of Andrographis paniculata (AEP) into targeting drug delivery system, a series of poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) with different ratio of hydrophilic and hydrophobic segment was synthetized to encapsulate AEP. AEP micelles were prepared by a simple solvent-evaporation method. According to the loading capacity, the best polymer was chosen. mPEG-PLA micelles were characterized in terms of drug entrapping efficiency, loading capacity, size, the crystalline state of AEP, stability and release profile. Meanwhile, the cytotoxicity of micelles on mouse breast cancer 4T-1 was investigated. These micelle (mPEG-PLA-AEP) particles had a size of (92.84±5.63) nm and a high entrapping efficiency and loading capacity of (91.00±11.53)% and (32.14±3.02)%(w/w), respectively. The powder DSC showed that drugs were well encapsulated in the core of micelles. mPEG-PLA-AEP had a good stability against salt dissociation, protein adsorption and anion substitution and the solubility of andrographolide (AG) and 14-deoxy-11,12-didehydroandrographolide(DDAG) in AEP increased 4.51 times and 2.12 times in water, and the solubility of DAG showed no difference. mPEG-PLA-AEP had the same release profile in different dissolution medium. Cytotoxicity testing in vitro demonstrated that mPEG-PLA-AEP exhibited higher cell viability inhibition in mouse breast cancer 4T-1 than free AEP. mPEG-PLA micelles offer a promising alternative for TCM therapy with higher solubility and improved antitumor effect. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel

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Kim Bokyung

2010-05-01

Full Text Available Abstract Background We have studied the in vitro and in vivo utility of polyethylene glycol (PEG-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU delivery system. Methods A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group/or a 5-FU-loaded PEG-hydrogel (treated group at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC cell line, A549 was inoculated to male nude mice with a cell density of 3 × 106. Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR over the duration of the study. Results In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p Conclusion We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.

Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

Science.gov (United States)

Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

2011-09-01

A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

An enhanced Ada run-time system for real-time embedded processors

Science.gov (United States)

Sims, J. T.

1991-01-01

An enhanced Ada run-time system has been developed to support real-time embedded processor applications. The primary focus of this development effort has been on the tasking system and the memory management facilities of the run-time system. The tasking system has been extended to support efficient and precise periodic task execution as required for control applications. Event-driven task execution providing a means of task-asynchronous control and communication among Ada tasks is supported in this system. Inter-task control is even provided among tasks distributed on separate physical processors. The memory management system has been enhanced to provide object allocation and protected access support for memory shared between disjoint processors, each of which is executing a distinct Ada program.

The testability of Ada programs

Science.gov (United States)

Auty, David; Cohen, Norman H.

1986-01-01

Software development for NASA's Space Station poses a significant problem; considered the most difficult by some. The difficulty is the magnitude and complexity of the required software. The concerns raised by consideration of the requirements for testing and checkout procedures for the Space Station software are addressed. In particular, it addresses the use of Ada in the development of widely distributed yet closely coordinated processing.

[Synthesis of a supermolecular nanoparticle γ-hy-PC/Ada-Dox and its antitumor activity].

Science.gov (United States)

Li, Yong-bin; Wang, Kai; Hu, Tian-nan; Wang, Qi-wen; Hu, Qi-da; Zhou, Jun; Hu, Xiu-rong; Tang, Gu-ping

2012-11-01

To synthesize a (2-Hydroxypropyl)-γ-cyclodextrin-polyethylenimine/adamantane-conjugated doxorubicin (γ-hy-PC/Ada-Dox) based supramolecular nanoparticle with host-guest interaction and to identify its physicochemical characterizations and antitumor effect. A novel non-viral gene delivery vector γ-hy-PC/Ada-Dox was synthesized based on host-guest interaction. 1H-NMR, NOESY, UV-Vis, XRD and TGA were used to confirm the structure of the vector. The DNA condensing ability of complexes was investigated by particle size, zeta potential and gel retardation assay. Cytotoxicity of complexes was determined by MTT assay in BEL-7402 and SMMC-7721 cells. Cell wound healing assay was performed in HEK293 and BEL-7404 cells. The transfection efficiency was investigated in HEK293 cells. H/E staining and cell uptake assay was performed in BEL-7402 cells. The structure of γ-hy-PC/Ada-Dox was characterized by 1H-NMR, NOESY, UV-Vis, XRD, TGA. The drug loading was 0.5% and 5.5%. Gel retardation assay showed that γ-hy-PC was able to completely condense DNA at N/P ratio of 2; 0.5% and 5.5% γ-hy-PC/Ada-Dox was able to completely condense DNA at N/P ratio of 3 and 4,respectively. The cytotoxicity of polymers was lower than that of PEI25KDa. The transfection efficiency of γ-hy-PC was higher than that of γ-hy-PC/Ada-Dox at N/P ratio of 30 in HEK293 cells; and the transfection efficiency was decreasing when Ada-Dox loading was increasing. Cell uptake assay showed that γ-hy-PC/Ada-Dox was able to carry drug and FAM-siRNA into cells. The novel vector γ-hy-PC/Ada-Dox has been developed successfully, which has certain transfection efficiency and antitumor activity.

Alteration of the carboxyl-terminal domain of Ada protein influences its inducibility, specificity, and strength as a transcriptional activator.

OpenAIRE

Shevell, D E; LeMotte, P K; Walker, G C

1988-01-01

The ada gene of Escherichia coli K-12 encodes the regulatory protein for the adaptive response to alkylating agents. A set of plasmids carrying ordered deletions from the 3' end of the ada gene were isolated and characterized. These ada deletions encode fusion proteins that derive their amino termini from ada and their carboxyl termini from the downstream vector sequence that occurs before an in-frame stop codon. Several of these ada deletions encode Ada derivatives that constitutively activa...

Chagas Parasite Detection in Blood Images Using AdaBoost

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Víctor Uc-Cetina

2015-01-01

Full Text Available The Chagas disease is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi. Visual detection of such parasite through microscopic inspection is a tedious and time-consuming task. In this paper, we provide an AdaBoost learning solution to the task of Chagas parasite detection in blood images. We give details of the algorithm and our experimental setup. With this method, we get 100% and 93.25% of sensitivity and specificity, respectively. A ROC comparison with the method most commonly used for the detection of malaria parasites based on support vector machines (SVM is also provided. Our experimental work shows mainly two things: (1 Chagas parasites can be detected automatically using machine learning methods with high accuracy and (2 AdaBoost + SVM provides better overall detection performance than AdaBoost or SVMs alone. Such results are the best ones known so far for the problem of automatic detection of Chagas parasites through the use of machine learning, computer vision, and image processing methods.

Overfitting Reduction of Text Classification Based on AdaBELM

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Xiaoyue Feng

2017-07-01

Full Text Available Overfitting is an important problem in machine learning. Several algorithms, such as the extreme learning machine (ELM, suffer from this issue when facing high-dimensional sparse data, e.g., in text classification. One common issue is that the extent of overfitting is not well quantified. In this paper, we propose a quantitative measure of overfitting referred to as the rate of overfitting (RO and a novel model, named AdaBELM, to reduce the overfitting. With RO, the overfitting problem can be quantitatively measured and identified. The newly proposed model can achieve high performance on multi-class text classification. To evaluate the generalizability of the new model, we designed experiments based on three datasets, i.e., the 20 Newsgroups, Reuters-21578, and BioMed corpora, which represent balanced, unbalanced, and real application data, respectively. Experiment results demonstrate that AdaBELM can reduce overfitting and outperform classical ELM, decision tree, random forests, and AdaBoost on all three text-classification datasets; for example, it can achieve 62.2% higher accuracy than ELM. Therefore, the proposed model has a good generalizability.

Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections.

Science.gov (United States)

Abdi, Mohammad; Rahbari, Rizgar; Khatooni, Zahed; Naseri, Nima; Najafi, Adel; Khodadadi, Iraj

2016-05-01

CD4(+) cell count, the common HIV infection screening test, is costly and unable to differentiate HIV monoinfection from its concurrent infection with hepatitis B or C virus. We aimed to ascertain diagnostic value of serum adenosine deaminase (ADA) activity as a useful tool to differentiate HIV mono- and co-infection. Blood samples were collected from 30 HIV-HBV and 30 HIV-HCV coinfected patients, 33 HIV positive subjects, and 72 controls. CD4(+) cell count, serum total ADA (tADA), and ADA1, and ADA2 isoenzyme activities were determined and their sensitivity and specificity were computed. tADA and ADA2 activities were significantly higher and CD4(+) counts were markedly lower in all patients compared with controls. Strong inverse agreements between CD4(+) cell counts and both tADA and ADA2 activities were observed. Serum tADA and ADA1 activities showed the highest specificity and the highest sensitivity, respectively, for differentiating HIV monoinfection from HIV-HBV and HIV-HCV coinfections. We showed strong agreement and correlation between CD4(+) cell count and ADA enzyme activity. Based on high ADA sensitivity and specificity, it is concluded that determination of ADA activity might be a novel diagnostic tool to distinguish of HIV monoinfection from its coinfection with HBV or HCV. © 2015 Wiley Periodicals, Inc.

Crutch art painting in the Middle Ages as orthopaedic heritage (part II: the peg leg, the bent-knee peg and the beggar).

Science.gov (United States)

Hernigou, Philippe

2014-07-01

Little of historical value about crutches can be ascertained before the Middle Ages. In contrast, the Middle Ages offer many examples for the study of crutches. Even if no medical report can be found, the immense patronage of the Church, encouraging artists to portray the saints and their miracles, has left great masterpieces that drew people with crutches. Pictures and the history of medieval conceptions of disability appear to provide an interesting chronicle of surgery of the peg leg and the bent-knee peg among the representations of cripples and beggars.

New control system: ADA softwares organization

International Nuclear Information System (INIS)

David, L.

1992-01-01

On VAX/VMS, ADA compiler is integrated in a workshop of ACS software engineering which allows a coherent development by control of source and executable programs, by separation of applications in various levels of visibility and by management of existing links between different modules of a same application. (A.B.)

Administration and scoring variance on the ADAS-Cog.

Science.gov (United States)

Connor, Donald J; Sabbagh, Marwan N

2008-11-01

The Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) is the most commonly used primary outcome instrument in clinical trials for treatments of dementia. Variations in forms, administration procedures and scoring rules, along with rater turnover and intra-rater drift may decrease the reliability of the instrument. A survey of possible variations in the ADAS-Cog was administered to 26 volunteer raters at a clinical trials meeting. Results indicate notable protocol variations in the forms used, administration procedures, and scoring rules. Since change over time is used to determine treatment effect in clinical trials, standardizing the instrument's ambiguities and addressing common problems will greatly increase the instrument's reliability and thereby enhance its sensitivity to treatment effects.

Geophysical analysis for the Ada Tepe region (Bulgaria) - case study

Science.gov (United States)

Trifonova, Petya; Metodiev, Metodi; Solakov, Dimcho; Simeonova, Stela; Vatseva, Rumiana

2013-04-01

According to the current archeological investigations Ada Tepe is the oldest gold mine in Europe with Late Bronze and Early Iron age. It is a typical low-sulfidation epithermal gold deposit and is hosted in Maastrichtian-Paleocene sedimentary rocks above a detachment fault contact with underlying Paleozoic metamorphic rocks. Ada Tepe (25o.39'E; 41o.25'N) is located in the Eastern Rhodope unit. The region is highly segmented despite the low altitude (470-750 m) due to widespread volcanic and sediment rocks susceptible to torrential erosion during the cold season. Besides the thorough geological exploration focused on identifying cost-effective stocks of mineral resources, a detailed geophysical analysis concernig diferent stages of the gold extraction project was accomplished. We present the main results from the geophysical investigation aimed to clarify the complex seismotectonic setting of the Ada Tepe site region. The overall study methodology consists of collecting, reviewing and estimating geophysical and seismological information to constrain the model used for seismic hazard assessment of the area. Geophysical information used in the present work consists of gravity, geomagnetic and seismological data. Interpretation of gravity data is applied to outline the axes of steep gravity transitions marked as potential axes of faults, flexures and other structures of dislocation. Direct inverse techniques are also utilized to estimate the form and depth of anomalous sources. For the purposes of seismological investigation of the Ada Tepe site region an earthquake catalogue is compiled for the time period 510BC - 2011AD. Statistical parameters of seismicity - annual seismic rate parameter, ?, and the b-value of the Gutenberg-Richter exponential relation for Ada Tepe site region, are estimated. All geophysical datasets and derived results are integrated using GIS techniques ensuring interoperability of data when combining, processing and visualizing obtained

Clinical significance of determination of serum HA, PCIII and ADA levels in patients with chronic hepatitis C

International Nuclear Information System (INIS)

Zhang Jing; Yu Fan; Zhao Changxin

2006-01-01

Objective: To explore the changes of serum HA, PCIII and ADA levels in patients with chronic hepatitis C. Methods: Serum HA, PCIII and ADA levels were detected with RIA in 42 cases with chronic hepatitis C and 35 controls. Results: The levels of serum HA, PC III and ADA in the patients were significantly higher than those in controls (P<0.01). Serum HA, PC m and ADA levels were positive correlated (r=0.6178, 0.6211, P<0.01). Conclusion: The results suggested the serum HA, PC m and ADA levels can reflect the degree of hepatic injury in the patients with cirrhosis, detection of serum HA, PC m and ADA levels is helpful in estimating the status of the disease. (authors)

Preparation and Characterization of Cationic PLA-PEG Nanoparticles for Delivery of Plasmid DNA

Directory of Open Access Journals (Sweden)

Zou Weiwei

2009-01-01

Full Text Available Abstract The purpose of the present work was to formulate and evaluate cationic poly(lactic acid-poly(ethylene glycol (PLA-PEG nanoparticles as novel non-viral gene delivery nano-device. Cationic PLA-PEG nanoparticles were prepared by nanoprecipitation method. The gene loaded nanoparticles were obtained by incubating the report gene pEGFP with cationic PLA-PEG nanoparticles. The physicochemical properties (e.g., morphology, particle size, surface charge, DNA binding efficiency and biological properties (e.g., integrity of the released DNA, protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in Hela cells of the gene loaded PLA-PEG nanoparticles were evaluated, respectively. The obtained cationic PLA-PEG nanoparticles and gene loaded nanoparticles were both spherical in shape with average particle size of 89.7 and 128.9 nm, polydispersity index of 0.185 and 0.161, zeta potentials of +28.9 and +16.8 mV, respectively. The obtained cationic PLA-PEG nanoparticles with high binding efficiency (>95% could protect the loaded DNA from the degradation by nuclease and plasma. The nanoparticles displayed sustained-release properties in vitro and the released DNA maintained its structural and functional integrity. It also showed lower cytotoxicity than Lipofectamine 2000 and could successfully transfect gene into Hela cells even in presence of serum. It could be concluded that the established gene loaded cationic PLA-PEG nanoparticles with excellent properties were promising non-viral nano-device, which had potential to make cancer gene therapy achievable.

Improved utilization of ADAS-cog assessment data through item response theory based pharmacometric modeling.

Science.gov (United States)

Ueckert, Sebastian; Plan, Elodie L; Ito, Kaori; Karlsson, Mats O; Corrigan, Brian; Hooker, Andrew C

2014-08-01

This work investigates improved utilization of ADAS-cog data (the primary outcome in Alzheimer's disease (AD) trials of mild and moderate AD) by combining pharmacometric modeling and item response theory (IRT). A baseline IRT model characterizing the ADAS-cog was built based on data from 2,744 individuals. Pharmacometric methods were used to extend the baseline IRT model to describe longitudinal ADAS-cog scores from an 18-month clinical study with 322 patients. Sensitivity of the ADAS-cog items in different patient populations as well as the power to detect a drug effect in relation to total score based methods were assessed with the IRT based model. IRT analysis was able to describe both total and item level baseline ADAS-cog data. Longitudinal data were also well described. Differences in the information content of the item level components could be quantitatively characterized and ranked for mild cognitively impairment and mild AD populations. Based on clinical trial simulations with a theoretical drug effect, the IRT method demonstrated a significantly higher power to detect drug effect compared to the traditional method of analysis. A combined framework of IRT and pharmacometric modeling permits a more effective and precise analysis than total score based methods and therefore increases the value of ADAS-cog data.

A study of three polymorphic sites of ADA gene in colon cancer.

Science.gov (United States)

Spina, C; Saccucci, P; Cozzoli, E; Bottini, E; Gloria-Bottini, F

2010-12-01

Adenosine inhibits the immune response in tumors. Adenosine deaminase (ADA) controls adenosine level and as ecto-enzyme acts as costimulatory molecule of adenosine receptors and/or CD26. We examined ADA₁, ADA₂, ADA₆ polymorphic sites of ADA gene in 109 subjects with colon cancer from Rome's population and in 246 blood donors as controls from the same population. In colon cancer ADA₁*2/ADA₂*1 haplotype is more represented, while ADA₁*2/ADA₂*2 is less represented than in controls. ADA₂*2/ADA₆*2 is less represented in patients than in controls. Polymorphic sites of ADA might influence cell-mediated anti-tumor immune responses controlling adenosine level and extraenzymatic protein functions.

A Retrospective Study of Association between Peg-shaped Maxillary Lateral Incisors and Dental Anomalies.

Science.gov (United States)

Kim, Jae-Hwan; Choi, Nam-Ki; Kim, Seon-Mi

The purpose of this study was to investigate the prevalence of peg-shaped maxillary lateral incisors and the incidence of associated dental anomalies in children. We investigated the prevalence of peg-laterals and incidence of associated dental anomalies in 3,834 children aged 7-15 who visited the Department of Pediatric Dentistry from January 2010 to December 2015 and underwent panoramic radiographs. The prevalence of peg-laterals was 1.69% in boys, 1.75% in girls, and 1.72% overall. Among children with peg-laterals, the frequencies of associated dental anomalies were as follows: congenitally missing teeth, 31.8%; dens invaginatus, 19.7%; palatally displaced canines, 12.1%; supernumerary teeth, 7.6%; and transposition, 7.6%. As children with peg-laterals have a higher incidence of other dental anomalies, careful consideration is needed when planning diagnosis and treatment.

Latvian PR people are world class / Ada Parr

Index Scriptorium Estoniae

Parr, Ada

2004-01-01

Suhtekorraldusfirma Porter Novelli rahvusvahelise partnerluse juht suhtekorralduse osatähtsuse kasvust ettevõtete äritegevuses, suhtekorraldusturu olukorrast ja teenuste kvaliteedi tasemest Baltimaades. Vt. samas: Ada Parr recommends

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

Science.gov (United States)

la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

2014-01-01

Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program. Copyright © 2013 Elsevier B.V. All rights reserved.

77 FR 46008 - Approval and Promulgation of State Implementation Plans: Idaho; Boise-Northern Ada County Air...

Science.gov (United States)

2012-08-02

... Promulgation of State Implementation Plans: Idaho; Boise-Northern Ada County Air Quality Maintenance Area... the Northern Ada County Air Quality Maintenance Area Second 10-year Carbon Monoxide Maintenance Plan...-Northern Ada County Air Quality Maintenance Area will maintain air quality standards for carbon monoxide...

77 FR 45962 - Approval and Promulgation of State Implementation Plans: Idaho; Boise-Northern Ada County Air...

Science.gov (United States)

2012-08-02

... Promulgation of State Implementation Plans: Idaho; Boise-Northern Ada County Air Quality Maintenance Area... (IDEQ) submitted the Northern Ada County Air Quality Maintenance Area Second 10-year Carbon Monoxide... Ada County Air Quality Maintenance Area will maintain air quality standards for carbon monoxide (CO...

Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation.

Science.gov (United States)

Mohibi, Shakur; Srivastava, Shashank; Bele, Aditya; Mirza, Sameer; Band, Hamid; Band, Vimla

2016-10-01

Alteration/deficiency in activation 3 (ADA3) is an essential component of specific histone acetyltransferase (HAT) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression (S. Mohibi et al., J Biol Chem 287:29442-29456, 2012, http://dx.doi.org/10.1074/jbc.M112.378901). Here, we report that these functional roles of ADA3 require its acetylation. We show that ADA3 acetylation, which is dynamically regulated in a cell cycle-dependent manner, reflects a balance of coordinated actions of its associated HATs, GCN5, PCAF, and p300, and a new partner that we define, the deacetylase SIRT1. We use mass spectrometry and site-directed mutagenesis to identify major sites of ADA3 acetylated by GCN5 and p300. Acetylation-defective mutants are capable of interacting with HATs and other components of HAT complexes but are deficient in their ability to restore ADA3-dependent global or locus-specific histone acetylation marks and cell proliferation in Ada3-deleted murine embryonic fibroblasts (MEFs). Given the key importance of ADA3-containing HAT complexes in the regulation of various biological processes, including the cell cycle, our study presents a novel mechanism to regulate the function of these complexes through dynamic ADA3 acetylation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease.

Science.gov (United States)

McCoy, Melissa K; Martinez, Terina N; Ruhn, Kelly A; Wrage, Philip C; Keefer, Edward W; Botterman, Barry R; Tansey, Keith E; Tansey, Malú G

2008-03-01

Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned dopaminergic pathway. In vitro-expanded naïve or differentiated ADAS cells were autologously transplanted into substantia nigra 1 week after an intrastriatal 6-hydroxydopamine injection. Neurochemical and behavioral measures demonstrated neuroprotective effects of both ADAS grafts against 6-hydroxydopamine-induced dopaminergic neuron death, suggesting that pre-transplantation differentiation of the cells does not determine their ability to survive or neuroprotect in vivo. Therefore, we investigated whether equivalent protection by naïve and neurally-induced ADAS grafts resulted from robust in situ differentiation of both graft types into dopaminergic fates. Immunohistological analyses revealed that ADAS cells did not adopt dopaminergic cell fates in situ, consistent with the limited ability of these cells to undergo terminal differentiation into electrically active neurons in vitro. Moreover, re-exposure of neurally-differentiated ADAS cells to serum-containing medium in vitro confirmed ADAS cell phenotypic instability (plasticity). Lastly, given that gene expression analyses of in vitro-expanded ADAS cells revealed that both naïve and differentiated ADAS cells express potent dopaminergic survival factors, ADAS transplants may have exerted neuroprotective effects by production of trophic factors at the lesion site. ADAS cells may be ideal for ex vivo gene transfer therapies in Parkinson's disease treatment.

PNA-PEG modified silicon platforms as functional bio-interfaces for applications in DNA microarrays and biosensors.

Science.gov (United States)

Cattani-Scholz, Anna; Pedone, Daniel; Blobner, Florian; Abstreiter, Gerhard; Schwartz, Jeffrey; Tornow, Marc; Andruzzi, Luisa

2009-03-09

The synthesis and characterization of two types of silicon-based biofunctional interfaces are reported; each interface bonds a dense layer of poly(ethylene glycol) (PEG(n)) and peptide nucleic acid (PNA) probes. Phosphonate self-assembled monolayers were derivatized with PNA using a maleimido-terminated PEG(45). Similarly, siloxane monolayers were functionalized with PNA using a maleimido-terminated PEG(45) spacer and were subsequently modified with a shorter methoxy-terminated PEG(12) ("back-filling"). The long PEG(45) spacer was used to distance the PNA probe from the surface and to minimize undesirable nonspecific adsorption of DNA analyte. The short PEG(12) "back-filler" was used to provide additional passivation of the surface against nonspecific DNA adsorption. X-ray photoelectron spectroscopic (XPS) analysis near the C 1s and N 1s ionization edges was done to characterize chemical groups formed in the near-surface region, which confirmed binding of PEG and PNA to the phosphonate and silane films. XPS also indicated that additional PEG chains were tethered to the surface during the back-filling process. Fluorescence hybridization experiments were carried out with complementary and noncDNA strands; both phosphonate and siloxane biofunctional surfaces were effective for hybridization of cDNA strands and significantly reduced nonspecific adsorption of the analyte. Spatial patterns were prepared by polydimethylsiloxane (PDMS) micromolding on the PNA-functionalized surfaces; selective hybridization of fluorescently labeled DNA was shown at the PNA functionalized regions, and physisorption at the probe-less PEG-functionalized regions was dramatically reduced. These results show that PNA-PEG derivatized phosphonate monolayers hold promise for the smooth integration of device surface chemistry with semiconductor technology for the fabrication of DNA biosensors. In addition, our results confirm that PNA-PEG derivatized self-assembled carboxyalkylsiloxane films are

Application of 10BSH entrapped transferrin-PEG-liposome to boron neutron-capture therapy (BNCT) for solid tumor

International Nuclear Information System (INIS)

Maruyama, K.; Ishida, O.; Iwatsuru, M.; Yanagie, H.; Eriguchi, M.; Kobayashi, H.

2000-01-01

The successful treatment of cancer by BNCT requires the selective concentration of 10 B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of 10 B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vivo, and were internalized by receptor-mediated endocytosis. 10 B-PEG-liposomes and 10 B-TF-PEG-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of 10 B content in tumor. After thermal neutron irradiation of mice injected with 10 B-PEG-liposomes or 10 B-TF-PEG-liposome, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of 10 B TF-PEG-liposome can increase the intracellular retention of 10 B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility.

Science.gov (United States)

Muhammad, Zarmina; Raza, Abida; Ghafoor, Sana; Naeem, Ayesha; Naz, Syeda Sohaila; Riaz, Sundus; Ahmed, Wajiha; Rana, Nosheen Fatima

2016-08-25

Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail. Copyright © 2016 Elsevier B.V. All rights reserved.

CREASE 6.0 Catalog of Resources for Education in Ada and Software Engineering

Science.gov (United States)

1992-02-01

Programming Software Engineering Strong Typing Tasking Audene . Computer Scientists Terbook(s): Barnes, J. Programming in Ada, 3rd ed. Addison-Wesley...Ada. Concept: Abstract Data Types Management Overview Package Real-Time Programming Tasking Audene Computer Scientists Textbook(s): Barnes, J

Synthesis and preliminary biodistribution studies of [131I]SIB-PEG4-CHC in tumor-bearing mice

International Nuclear Information System (INIS)

Xiaobei Zheng; Jing Yang; Xiaojiang Duan; Tingting Niu; Wangsuo Wu; Jianjun Wang; Feng Dong

2011-01-01

This work reports the synthesis and preliminary biodistribution results of [ 131 I]SIB-PEG 4 -CHC in tumor-bearing mice. The tributylstannyl precursor ATE-PEG 4 -CHC was synthesized by conjugation of ATE to amino pegylated colchicine NH 2 -PEG 4 -CHC. [ 131 I]SIB-PEG 4 -CHC was radiosynthesized by electrophilic destannylation of the precursor with a yield of ∼44%. The radiochemical purity (RCP) appeared to be >95% by a Sep-Pak cartridge purification. [ 131 I]SIB-PEG 4 -CHC was lipophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that [ 131 I]SIB-PEG 4 -CHC cleared from background rapidly, and didn't deiodinate in vivo. However, the poor tumor localization excluded it from further investigations as a tumor-targeted radiopharmaceuticals. (author)

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression.

Science.gov (United States)

Trinh, Alice T; Ball, Bret G; Weber, Erin; Gallaher, Timothy K; Gluzman-Poltorak, Zoya; Anderson, French; Basile, Lena A

2009-12-30

Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression

Science.gov (United States)

2009-01-01

Background Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. Methods A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Results Vectors that contained the ADA LCR were preferentially expressed in T

Formal Semanol Specification of Ada.

Science.gov (United States)

1980-09-01

concurrent task modeling involved very little change to the SEMANOL metalanguage. A primitive capable of initiating concurrent SEMANOL task processors...i.e., #CO-COMPUTE) and two primitivc-; corresponding to integer semaphores (i.c., #P and #V) were all that were required. In addition, these changes... synchronization techniques and choice of correct unblocking alternatives. We should note that it had been our original intention to use the Ada Translator program

Synthesis and in vitro cytotoxicity of mPEG-SH modified gold nanorods

Science.gov (United States)

Didychuk, Candice L.; Ephrat, Pinhas; Belton, Michelle; Carson, Jeffrey J. L.

2008-02-01

Plasmon-resonant gold nanorods show great potential as an agent for contrast-enhanced biomedical imaging or for phototherapeutics. This is primarily due to the high molar extinction coefficient at the absorption maximum and the dependence of the wavelength of the absorption maximum on the aspect ratio, which is tunable in the near-infrared (NIR) during synthesis. Although gold nanorods can be produced in high-yield through the seed-mediated growth technique, the presence of residual cetyltrimethylammonium bromide (CTAB), a stabilizing surfactant required for nanorod growth, interferes with cell function and causes cytotoxicity. To overcome this potential obstacle to in vivo use, we synthesized gold nanorods and conjugated them to a methoxy (polyethylene glycol)-thiol (mPEG (5000)-SH). This approach yielded mPEG-SH modified gold nanorods with optical and morphometric properties that were similar to raw (CTAB) nanorods. Both the CTAB and mPEG-SH nanorods were tested for cytotoxicity against the HL-60 human leukemia cell line by trypan blue exclusion, and the mPEG-SH modified gold nanorods were also tested against a rat insulinoma (RIN-38) and squamous cell carcinoma (SCCVII) cell line. Cells incubated for 24 h with the mPEG-SH modified nanorods had little change in cell viability compared to cells incubated with vehicle alone. This was in contrast to cytotoxicity of CTAB nanorods on HL-60 cells. These results suggest that mPEG-SH modified gold nanorods are better suited for cell loading protocols and injection into animals and facilitate their use for imaging and phototherapeutic purposes.

Sustainable and Low Viscous 1-Allyl-3-methylimidazolium Acetate + PEG Solvent for Cellulose Processing

Directory of Open Access Journals (Sweden)

Airong Xu

2017-02-01

Full Text Available Developing sustainable, low viscous and efficient solvents are always advantageous to the processing/fabricating of cellulose materials in practical applications. To this end, in this work novel solvents were developed; ([Amim][CH3COO]/PEG by dissolving polyethylene glycol 200 (PEG-200 in 1-allyl-3-methylimidazolium acetate ([Amim][CH3COO]. The solubilities of cellulose in [Amim][CH3COO]/PEG solvents were determined as a function of temperature, and the possible dissolution mechanism of cellulose in [Amim][CH3COO]/PEG solvent was investigated. The novel solvent exhibits outstanding advantages for good dissolution capacity of cellulose, such as low viscosity, negligible vapor pressure, and recycling capability. The [CH3COO]− anion and the [Amim]+ cation of [Amim][CH3COO] in [Amim][CH3COO]/PEG-10 are the driving force for cellulose dissolution verified by the 13C NMR spectra. In addition, the regenerated cellulose films from [Amim][CH3COO]/PEG solvent were characterized by scanning electron microscopy (SEM, X-ray diffraction (XRD, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR, and thermogravimetric analysis (TGA to estimate their morphologies and structures.

AdaFF: Adaptive Failure-Handling Framework for Composite Web Services

Science.gov (United States)

Kim, Yuna; Lee, Wan Yeon; Kim, Kyong Hoon; Kim, Jong

In this paper, we propose a novel Web service composition framework which dynamically accommodates various failure recovery requirements. In the proposed framework called Adaptive Failure-handling Framework (AdaFF), failure-handling submodules are prepared during the design of a composite service, and some of them are systematically selected and automatically combined with the composite Web service at service instantiation in accordance with the requirement of individual users. In contrast, existing frameworks cannot adapt the failure-handling behaviors to user's requirements. AdaFF rapidly delivers a composite service supporting the requirement-matched failure handling without manual development, and contributes to a flexible composite Web service design in that service architects never care about failure handling or variable requirements of users. For proof of concept, we implement a prototype system of the AdaFF, which automatically generates a composite service instance with Web Services Business Process Execution Language (WS-BPEL) according to the users' requirement specified in XML format and executes the generated instance on the ActiveBPEL engine.

Ada Compiler Validation Summary Report: Certificate Number: 901112W1. 11116 Cray Research, Inc., Cray Ada Compiler, Release 2.0, Cray X-MP/EA (Host & Target)

Science.gov (United States)

1990-11-12

semaphores : 0.00 44858 Waiting on shared registers : 0.00 0 Waiting on A-registers/funct.units : 19.69 5551338711 Waiting on S-registers/funct.units...dependent bodies that implement the fundamental low-level primitives on which SR-3082 2.0 Cray Research, Inc. 73 Ada Program Runtime Model Cray Ada...operations provided by the runtime library are performed synchronously , with program execution suspended until the 1/O operation is complete. The

Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats.

Science.gov (United States)

Alalaiwe, Ahmed; Roberts, Georgia; Carpinone, Paul; Munson, John; Roberts, Stephen

2017-11-01

Metallic nanoparticles can be produced in a variety of shapes, sizes, and surface chemistries, making them promising potential tools for drug delivery. Most studies to date have evaluated uptake of metallic nanoparticles from the GI tract with methods that are at best semi-quantitative. This study used the classical method of comparing blood concentration area under the curve (AUC) following intravenous and oral doses to determine the oral bioavailability of 1, 2 and 5 kDa PEG-coated 5 nm gold nanoparticles (AuNPs). Male rats were given a single intravenous dose (0.8 mg/kg) or oral (gavage) dose (8 mg/kg) of a PEG-coated AuNP, and the concentration of gold was measured in blood over time and in tissues (liver, spleen and kidney) at sacrifice. Blood concentrations following oral administration were inversely related to PEG size, and the AUC in blood was significantly greater for the 1 kDa PEG-coated AuNPs than particles coated with 2 or 5 kDa PEG. However, bioavailabilities of all of the particles were very low (bioavailability of AuNPs coated with PEG in the 1-5 kDa range, this study demonstrates the utility of applying the blood AUC approach to assess the quantitative oral bioavailability of metallic nanoparticles.

Improving dielectric permittivity by incorporating PDMS-PEG block copolymer into PDMS network

DEFF Research Database (Denmark)

A Razak, Aliff Hisyam; Szabo, Peter; Skov, Anne Ladegaard

introduces different properties in terms of contact angles, dielectric permittivity and rheological behaviour. All morphologies of PDMS-PEG block copolymer in this study exhibit high storage permittivity; at the same time the loss permittivity is even higher which implies that the synthesized PDMS-PEG block...

``Sheddable'' PEG-lipid to balance the contradiction of PEGylation between long circulation and poor uptake

Science.gov (United States)

Zhao, Caiyan; Deng, Hongzhang; Xu, Jing; Li, Shuyi; Zhong, Lin; Shao, Leihou; Wu, Yan; Liang, Xing-Jie

2016-05-01

PEGylated lipids confer longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. In order to balance the contradiction between the advantages of long circulation and the disadvantages of poor uptake of PEGylated lipids, we prepared a ``sheddable'' PEG-lipid micelle system based on the conjugation of PEG and phosphatidyl ethanolamine (DSPE) with a pH sensitive benzoic imine bond. In a physiological environment, the PEG-protected micelles were not readily taken up by the reticuloendothelial system (RES) and could be successfully delivered to tumor tissue by the EPR effect. In a tumor acidic microenvironment, the PEG chains detached from the surfaces of the micelles while the degree of linker cleavage could not cause a significant particle size change, which facilitated the carrier binding to tumor cells and improved the cellular uptake. Subsequently, the ``sheddable'' PEG-lipid micelles easily internalized into cells and the increased acidity in the lysosomes further promoted drug release. Thus, this ``sheddable'' PEG-lipid nanocarrier could be a good candidate for effective intracellular drug delivery in cancer chemotherapy.PEGylated lipids confer longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. In order to balance the contradiction between the advantages of long circulation and the disadvantages of poor uptake of PEGylated lipids, we prepared a ``sheddable'' PEG-lipid micelle system based on the conjugation of PEG and phosphatidyl ethanolamine (DSPE) with a pH sensitive benzoic imine bond. In a physiological environment, the PEG-protected micelles were not readily taken up by the reticuloendothelial system (RES) and could be successfully delivered to tumor tissue by the EPR effect. In a tumor acidic

Incorporation of fluconazole in copolymer PMMA-g-PEG derivatives

International Nuclear Information System (INIS)

Silveira, B.M.; Santos, V.M.R. dos; Novack, K.M.; Lopes, S.A.

2014-01-01

The graft copolymer PMMA-g-PEG went through chemical transformations in its chain through acetylation, halogenation, methylation and esterification followed by hydrolysis reactions. Subsequently, the copolymer PMMA-g-PEG derivatives passed through the process of emulsification and incorporation of the drug fluconazole. Derivatives copolymers were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) after incorporation in order to evaluate their effectiveness. The efficiency of incorporation was observed and it was also verified that the complexity of polymer chain influence in the incorporated fluconazole content. (author)

Assessment of adenosine deaminase (ADA) activity and oxidative stress in patients with chronic tonsillitis.

Science.gov (United States)

Garca, Mehmet Fatih; Demir, Halit; Turan, Mahfuz; Bozan, Nazım; Kozan, Ahmet; Belli, Şeyda Bayel; Arslan, Ayşe; Cankaya, Hakan

2014-06-01

To emphasize the effectiveness of adenosine deaminase (ADA) enzyme, which has important roles in the differentiation of lymphoid cells, and oxidative stress in patients with chronic tonsillitis. Serum and tissue samples were obtained from 25 patients who underwent tonsillectomy due to recurrent episodes of acute tonsillitis. In the control group, which also had 25 subjects, only serum samples were taken as obtaining tissue samples would not have been ethically appropriate. ADA enzyme activity, catalase (CAT), carbonic anhydrase (CA), nitric oxide (NO) and malondialdehyde (MDA) were measured in the serum and tissue samples of patients and control group subjects. The serum values of both groups were compared. In addition, the tissue and serum values of patients were compared. Serum ADA activity and the oxidant enzymes MDA and NO values of the patient group were significantly higher than those of the control group (p ADA activity (p > 0.05). Elevated ADA activity may be effective in the pathogenesis of chronic tonsillitis both by impairing tissue structure and contributing to SOR formation.

Reliability of the Alzheimer's disease assessment scale (ADAS-Cog) in longitudinal studies.

Science.gov (United States)

Khan, Anzalee; Yavorsky, Christian; DiClemente, Guillermo; Opler, Mark; Liechti, Stacy; Rothman, Brian; Jovic, Sofija

2013-11-01

Considering the scarcity of longitudinal assessments of reliability, there is need for a more precise understanding of cognitive decline in Alzheimer's Disease (AD). The primary goal was to assess longitudinal changes in inter-rater reliability, test retest reliability and internal consistency of scores of the ADAS-Cog. 2,618 AD subjects were enrolled in seven randomized, double-blind, placebo-controlled, multicenter-trials from 1986 to 2009. Reliability, internal-consistency and cross-sectional analysis of ADAS-Cog and MMSE across seven visits were examined. Intra-class correlation (ICC) for ADAS-Cog was moderate to high supporting their reliability. Absolute Agreement ICCs 0.392 (Visit-7) to 0.806 (Visit-2) showed a progressive decrease in correlations across time. Item analysis revealed a decrease in item correlations, with the lowest correlations for Visit 7 for Commands (ICC=0.148), Comprehension (ICC=0.092), Spoken Language (ICC=0.044). Suitable assessment of AD treatments is maintained through accurate measurement of clinically significant outcomes. Targeted rater education ADAS-Cog items over-time can improve ability to administer and score the scale.

How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID).

Science.gov (United States)

Kohn, Donald B; Gaspar, H Bobby

2017-05-01

Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

E-ADA activity in serum of lambs experimentally infected with Haemonchus contortus.

Science.gov (United States)

Da Silva, Aleksandro S; Fausto, Guilherme C; Grando, Thirssa H; Cadore, Carlos A; Pimentel, Victor C; Jaques, Jeandre A; Schetinger, Maria R C; Monteiro, Silvia G; Leal, Marta L R

2013-08-01

The aim of this study was to evaluate adenosine deaminase (E-ADA) activity in sera of lambs experimentally infected with Haemonchus contortus. We used 12 lambs divided into 2 groups; Group A had 5 healthy, non-infected animals (control) and Group B had 7 healthy animals infected with H. contortus . Lambs were infected orally with 500 larvae (L3) per animal every 2 days, for a period of 20 days, and later the infection was confirmed by examination of feces (eggs per gram [EPG] via fecal egg count). Blood collection was performed at days 0, 20, 40, 60, and 80 post-infection (PI) for analysis of E-ADA activity. Animals in Group A showed negative EPG throughout the experiment unlike those from Group B that had elevated EPG counts. E-ADA activity was reduced in the serum of animals infected with H. contortus when compared to non-infected controls at days 20, 40, 60, and 80 PI. Therefore, it is concluded that infection with H. contortus influences the E-ADA activity in lambs.

The exploration of endocytic mechanisms of PLA-PEG nanoparticles prepared by coaxialtri-capillary electrospray-template removal method.

Science.gov (United States)

Chen, Jiaming; Cao, Lihua; Cui, Yuecheng; Tu, Kehua; Wang, Hongjun; Wang, Li-Qun

2018-01-01

The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with core-shell structure were efficiently prepared by using coaxial tri-capillary electrospray-template removal method. The cellular uptake mechanism, intracellular distribution and exocytosis in A549 cell model of electrosprayed PLA-PEG nanoparticles were systemically studied. The drug release behavior of electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells. The cellular uptake of PLA-PEG nanoparticles was an energy dependent endocytosis process. Caveolae-mediated endocytosis was only one of endocytosis pathways in A549 cells for PLA-PEG nanoparticles, while clathrin mediated endocytosis was not involved in the endocytosis process. The endocytosed PLA-PEG nanoparticles enriched in the head of A549 cells and only a small amount of them was transported into lysosome after 24h incubation. These findings provided insights into the application of electrosprayed PLA-PEG nanoparticles in nano drug delivery field. Copyright © 2017 Elsevier B.V. All rights reserved.

Ada and the rapid development lifecycle

Science.gov (United States)

Deforrest, Lloyd; Gref, Lynn

1991-01-01

JPL is under contract, through NASA, with the US Army to develop a state-of-the-art Command Center System for the US European Command (USEUCOM). The Command Center System will receive, process, and integrate force status information from various sources and provide this integrated information to staff officers and decision makers in a format designed to enhance user comprehension and utility. The system is based on distributed workstation class microcomputers, VAX- and SUN-based data servers, and interfaces to existing military mainframe systems and communication networks. JPL is developing the Command Center System utilizing an incremental delivery methodology called the Rapid Development Methodology with adherence to government and industry standards including the UNIX operating system, X Windows, OSF/Motif, and the Ada programming language. Through a combination of software engineering techniques specific to the Ada programming language and the Rapid Development Approach, JPL was able to deliver capability to the military user incrementally, with comparable quality and improved economies of projects developed under more traditional software intensive system implementation methodologies.

Facile synthesis, spectral properties and formation mechanism of sulfur nanorods in PEG-200

International Nuclear Information System (INIS)

Xie, Xin-yuan; Li, Li-yun; Zheng, Pu-sheng; Zheng, Wen-jie; Bai, Yan; Cheng, Tian-feng; Liu, Jie

2012-01-01

Graphical abstract: Homogeneous rod-like structure of sulfur with a typical diameter of about 80 nm and an average aspect ratio of about 6–8 was obtained. The sulfur nanoparticles could self-assemble from spherical particles to nanorods in PEG-200. During the self-assembling process, the absorption band showed a red shift which was due to the production of nanorods. Highlights: ► A novel, facile and greener method to synthesize sulfur nanorods by the solubilizing and templating effect of PEG-200 was reported. ► S 0 nanoparticles could self assemble in PEG-200 and finally form monodisperse and homogeneous rod-like structure with an average diameter of about 80 nm, the length ca. 600 nm. ► The absorption band showed a red shift and the RRS intensity enhanced continuously during the self-assembling process. ► PEG-200 induced the oriented attachment of sulfur nanoparticles by the terminal hydroxyl groups. -- Abstract: The synthesis of nano-sulfur sol by dissolving sublimed sulfur in a green solvent-PEG-200 was studied. Homogeneous rod-like structure of sulfur with a typical diameter of about 80 nm and an average aspect ratio of 6–8 was obtained. The structure, morphology, size, and stability of the products were investigated by transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) measurements. The spectral properties of the products were investigated by ultraviolet-visible (UV–vis) absorption and resonance Rayleigh scattering spectroscopy (RRS). The results showed that the spherical sulfur nanoparticles could self-assemble into nanorods in PEG-200. During the self-assembling process, the absorption band showed a red shift and the RRS intensity enhanced continuously. There was physical cross-linking between PEG and sulfur nanoparticles. PEG-200 induced the oriented attachment of sulfur nanoparticles by the

Enhancement of light absorption by blood to Nd:YAG laser using PEG-modified gold nanorods.

Science.gov (United States)

Xing, Linzhuang; Li, Dong; Chen, Bin; Dai, Yuze; Wu, Wenjuan; Wang, Guoxiang

2016-10-01

On the basis of the principle of selective photothermolysis, laser therapy has been the most effective treatment strategy for Port-wine stains (PWSs) caused by the expansion of dermal capillaries. Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser at 1064 nm wavelength has great potential for deeply buried PWS, although its application is limited because of its weak absorption by blood. The purpose of this study is to investigate the effect of PEG-modified gold nanorods (NRs) on the blood absorption enhancement for Nd:YAG laser. PEG-modified gold nanorods (NRs) were synthesized via the seeded growth method. Then, the effect of PEG-modified gold NRs on blood light absorbance was investigated through adding different concentration of PEG-modified gold NRs to 1 ml of blood at room temperature. Finally, the optical properties of whole mice blood with or without PEG-modified gold NRs under slow heating were investigated. The average length and width of PEG-modified gold NRs are 79.5 ± 10.5 and 13.5 ± 0.9 nm, respectively, with the aspect ratio of 5.89, and a strong absorption peak exists at ∼1050 nm in the near-infrared range. A linear correlation between the blood absorbance at 1064 nm and the amount of PEG-modified gold NRs was obtained. The absorbance at 1064 nm increased 17.6, 33.0, 48.3, and 65.4 times when 0.4, 0.8, 1.2, and 1.6 mg of PEG-modified gold NRs was added to 1 ml of blood at room temperature, respectively. After adding 0.8 mg of PEG-modified gold NRs to 1 ml of blood, blood absorbance at 1064 nm at different temperatures increased by an average of 24.0 times. After intravenously injecting PEG-modified gold NRs (0.87 mg/ml) into Sprague-Dawley mice, the blood absorbance at 1064 nm increased from 0.014 to 0.5. Our findings suggest that PEG-modified gold NRs injection is an efficient way to enhance light absorption by blood to Nd:YAG laser. Lasers Surg. Med. 48:790-803, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley

76 FR 66034 - Proposed Foreign-Trade Zone-Ada and Canyon Counties, ID, Under Alternative Site Framework...

Science.gov (United States)

2011-10-25

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [Docket 65-2011] Proposed Foreign-Trade Zone--Ada... establish a general-purpose foreign-trade zone at sites in Ada and Canyon Counties, Idaho, adjacent to the... proposed service area under the ASF would be Ada and Canyon Counties, Idaho. If approved, the applicant...

X-ray studies of recombinant anti-testosterone Fab fragments: the use of PEG 3350 in crystallization.

Science.gov (United States)

Valjakka, J; Hemminki, A; Teerinen, T; Takkinen, K; Rouvinen, J

2000-02-01

Recombinant anti-testosterone wild-type Fab fragment and mutant Fab fragments with high binding selectivity developed by protein engineering have been crystallized with and without ligands. Crystals of these Fab fragments were obtained by the vapour-diffusion technique at room temperature using solutions of PEG 3350 with various biological buffers and with a wide pH range. So far, five data sets have been collected from crystals of three Fab-antigen complexes and from two uncomplexed Fab fragments, with resolutions ranging from 2.10 to 3.1 A. Crystallization conditions for Fab fragments were found by using modifications of the low ionic strength PEG 3350 series. Suitable concentrations of PEG 400, MPD and glycerol solutions for use as cryoprotectants in PEG 3350 solutions have been determined. One useful observation was that PEG 3350 is able to work alone as a cryoprotectant. The screening protocol used requires a smaller amount of protein material to achieve auspicious pre-crystals than previously. Results support the claim that PEG 3350 is more suitable for the crystallization of Fab fragments than higher molecular weight PEGs.

18F-PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, 18F-labelling and an in-vitro assessment of its binding with NeutravidinTM-trastuzumab pre-treated cells

International Nuclear Information System (INIS)

Smith, Tim A.D.; Simpson, Michael; Cheyne, Richard; Trembleau, Laurent

2011-01-01

In terms of nuclear decay 18 F is the most ideal PET nuclide but its short t 1/2 precludes its use for directly labelling whole antibodies due to their long blood residence times. Pre-targeted imaging using affinity systems such as Neutravidin TM -biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin TM -conjugated antibodies. Methods: Boroaryl functionalised biotin was prepared with a PEG linker and radiolabelled by incubation with 18 F in acidified aqueous solution. Cells expressing high (SKBr3), medium (MDA-MB-453) and low (MDA-MB-468) levels of HER-2 were pre-incubated with Neutravidin TM -conjugated trastuzumab, washed, and then incubated with 18 F-PEG-biotin. Results: The 18 F-fluorination of boroaryl-PEG-biotin was much more efficient than reported for other versions of boroaryl-biotin. The novel 18 F-PEG-biotin was demonstrated to bind to HER-2-expressing cells in-vitro pre-incubated with Neutravidin TM -conjugated trastuzumab. Conclusion: Biotin can be functionalised with boroaryl and readily 18 F-radiolabelled in aqueous solution and will bind to cells pre-incubated with Neutravidin TM -antibody conjugates. - Highlights: → Boroaryl-biotin precursor is prepared. → Rapid 18 F-fluorination is demonstrated. → HER-2 expressing breast cancer cells pre-treated with trastuzumab-Neutravidin TM . → 18 F-PEG-biotin binding to pre-treated cells corresponds with HER-2 expression.

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

Science.gov (United States)

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

School Issues Under [Section] 504 and the ADA: The Latest and Greatest.

Science.gov (United States)

Aleman, Steven R.

This paper highlights recent guidance and rulings from the Office of Civil Rights (OCR) of interest to administrators, advocates, and attorneys. It is a companion piece to Student Issues on SectionNB504/ADA: The Latest and Greatest. Compliance with SectionNB504 and the Americans with Disabilities Act (ADA) continues to involve debate and dialog on…

CITY GROUND DESIGN AND THE IMAGE OF THE CITY: THE PORTUGUESE CALÇADA

Directory of Open Access Journals (Sweden)

Antoni Remesar

2014-10-01

The pavement-form - including the "calçada-form"-is at the root of some of the flagship operations creating the image of the city (Havana, 1928; Alicante, 1957; the Ramblas in Barcelona, 1969; reform of the Avenida Atlantica in Rio by Burle Marx, 1970. However, these same operations show that the "form-calçada" does not meet many of the requirements of economy, security or universal accessibility required by the contemporary city. In the paper was to analyze the causes and reasons that hover over the announced death of calçada á Portugueza.

Enhancing relative permittivity by incorporating PDMS-PEG multi block copolymers in binary polymer blends

DEFF Research Database (Denmark)

A Razak, Aliff Hisyam; Szabo, Peter; Skov, Anne Ladegaard

Polydimethylsiloxanes (PDMS) are well-known to actuate with relatively large strains due to low modulus, but they possess lowpermittivity. Contrary, polyethyleneglycols (PEG) are not stretchable but possess high permittivity. Combination of the two polymers in a block copolymer depicts a possibil......Polydimethylsiloxanes (PDMS) are well-known to actuate with relatively large strains due to low modulus, but they possess lowpermittivity. Contrary, polyethyleneglycols (PEG) are not stretchable but possess high permittivity. Combination of the two polymers in a block copolymer depicts...... a possibility for substantial improvement of properties such as high permittivity, stretchability and non-conductivity – if carefully designed. The objective is to synthesize PDMS-PEG multiblock copolymer assembling into discontinuous morphologies in PEG based on variation of volume fractions of PDMS....... The utilized synthesis of PDMS-PEG multiblock copolymer is based on hydrosilylation reaction, which is amended from Klasner et al.1 and Jukarainen etal.2 Variation in the ratio between the two constituents introduces distinctive properties in terms of dielectric permittivity and rheological behaviour. PDMS...

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment

Science.gov (United States)

Rajan, Sujata Sundara; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

2014-01-01

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV. PMID:25223229

PEG IS 40!: place, community, identity, memory and myth in the Dandenong Ranges

OpenAIRE

Dyson, Brydie Shae

2017-01-01

PEG IS 40! investigates memory, myth and storytelling as well as personal and communal identity with a sense of place, focusing on a particular site, that of the PEG IS 40! inscription on the train bridge in Upper Femtree Gully above Burwood Highway. The text there has not been weathered away, further graffiti has not overwritten it, and it has not been removed by council. In this time of rapid cultural transformation and global pressures, Peg is still and has always been 40. There is a certa...

Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

Directory of Open Access Journals (Sweden)

Tomohiro Okagawa

2017-06-01

Full Text Available Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1/PD-ligand 1 (PD-L1, is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat–bovine chimeric monoclonal antibody 5D2 (Boch5D2 was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV. Purified Boch5D2 was capable of detecting bovine PD-1 molecules expressed on cell membranes in flow cytometric analysis. In particular, Biacore analysis determined that the binding affinity of Boch5D2 to bovine PD-1 protein was similar to that of the original anti-bovine PD-1 rat monoclonal antibody 5D2. Boch5D2 was also capable of blocking PD-1/PD-L1 binding at the same level as 5D2. The immunomodulatory and therapeutic effects of Boch5D2 were evaluated by in vivo administration of the antibody to a BLV-infected calf. Inoculated Boch5D2 was sustained in the serum for a longer period. Boch5D2 inoculation resulted in activation of the proliferation of BLV-specific CD4+ T cells and decrease in the proviral load of BLV in the peripheral blood. This study demonstrates that Boch5D2 retains an equivalent biochemical function to that of the original antibody 5D2 and is a candidate therapeutic agent for regulating antiviral immune response in vivo. Clinical efficacy of PD-1/PD-L1 blockade awaits further experimentation with a large number of animals.

Buried bumper syndrome revisited: a rare but potentially fatal complication of PEG tube placement.

Science.gov (United States)

Biswas, Saptarshi; Dontukurthy, Sujana; Rosenzweig, Mathew G; Kothuru, Ravi; Abrol, Sunil

2014-01-01

Percutaneous endoscopic gastrostomy (PEG) has been used for providing enteral access to patients who require long-term enteral nutrition for years. Although generally considered safe, PEG tube placement can be associated with many immediate and delayed complications. Buried bumper syndrome (BBS) is one of the uncommon and late complications of percutaneous endoscopic gastrostomy (PEG) placement. It occurs when the internal bumper of the PEG tube erodes into the gastric wall and lodges itself between the gastric wall and skin. This can lead to a variety of additional complications such as wound infection, peritonitis, and necrotizing fasciitis. We present here a case of buried bumper syndrome which caused extensive necrosis of the anterior abdominal wall.

Mechanically compliant electrodes and dielectric elastomers from PEG-PDMS copolymers

DEFF Research Database (Denmark)

A Razak, Aliff Hisyam; Madsen, Frederikke Bahrt; Skov, Anne Ladegaard

2016-01-01

Soft conducting elastomers have been prepared from polydimethylsiloxane-polyethyleneglycol (PDMS-PEG) copolymer and surfactant-stabilized multi-walled carbon nanotubes (MWCNTs). The copolymer was chain-extended with PDMS of molecular weight 17.2 kg mol-1 in order to obtain a crosslinkable PDMS...... showed high conductivity combined with inherent softness. The high conductivity and softness, PDMS-PEG copolymers with incorporated MWCNTs hold great promises as compliant and highly stretchable electrodes for stretchable devices such as electro-mechanical transducers....

ADA perceived disability claims: a decision-tree analysis.

Science.gov (United States)

Draper, William R; Hawley, Carolyn E; McMahon, Brian T; Reid, Christine A; Barbir, Lara A

2014-06-01

The purpose of this study is to examine the possible interactions of predictor variables pertaining to perceived disability claims contained in a large governmental database. Specifically, it is a retrospective analysis of US Equal Employment Opportunity Commission (EEOC) data for the entire population of workplace discrimination claims based on the "regarded as disabled" prong of the Americans with Disabilities Act (ADA) definition of disability. The study utilized records extracted from a "master database" of over two million charges of workplace discrimination in the Integrated Mission System of the EEOC. This database includes all ADA-related discrimination allegations filed from July 26, 1992 through December 31, 2008. Chi squared automatic interaction detection (CHAID) was employed to analyze interaction effects of relevant variables, such as issue (grievance) and industry type. The research question addressed by CHAID is: What combination of factors are associated with merit outcomes for people making ADA EEOC allegations who are "regarded as" having disabilities? The CHAID analysis shows how merit outcome is predicted by the interaction of relevant variables. Issue was found to be the most prominent variable in determining merit outcome, followed by industry type, but the picture is made more complex by qualifications regarding age and race data. Although discharge was the most frequent grievance among charging parties in the perceived disability group, its merit outcome was significantly less than that for the leading factor of hiring.

Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes.

Science.gov (United States)

Lee, Kenneth K; Sardiu, Mihaela E; Swanson, Selene K; Gilmore, Joshua M; Torok, Michael; Grant, Patrick A; Florens, Laurence; Workman, Jerry L; Washburn, Michael P

2011-07-05

Despite the availability of several large-scale proteomics studies aiming to identify protein interactions on a global scale, little is known about how proteins interact and are organized within macromolecular complexes. Here, we describe a technique that consists of a combination of biochemistry approaches, quantitative proteomics and computational methods using wild-type and deletion strains to investigate the organization of proteins within macromolecular protein complexes. We applied this technique to determine the organization of two well-studied complexes, Spt-Ada-Gcn5 histone acetyltransferase (SAGA) and ADA, for which no comprehensive high-resolution structures exist. This approach revealed that SAGA/ADA is composed of five distinct functional modules, which can persist separately. Furthermore, we identified a novel subunit of the ADA complex, termed Ahc2, and characterized Sgf29 as an ADA family protein present in all Gcn5 histone acetyltransferase complexes. Finally, we propose a model for the architecture of the SAGA and ADA complexes, which predicts novel functional associations within the SAGA complex and provides mechanistic insights into phenotypical observations in SAGA mutants.

CSF ADA Determination in Early Diagnosis of Tuberculous Meningitis in HIV-Infected Patients.

Science.gov (United States)

Ghosh, Gopal Chandra; Sharma, Brijesh; Gupta, B B

2016-01-01

Tuberculous and Cryptococcal meningitis are common in HIV patients. A highly specific and sensitive rapid test for diagnosis of Tuberculous meningitis especially in setting of HIV is not available in developing countries where the burden of disease is high. We measured ADA (adenosine deaminase) levels using spectrophotometric method in the CSF of HIV patients with meningitis to differentiate Tuberculous meningitis from meningitis due to other causes. Kruskal-Wallis test was used to compare ADA values between tuberculous meningitis (TBM) and nontuberculous (non-TB) meningitis patients and a receiver-operating characteristic (ROC) analysis curve was drawn from these values. Levels of ADA in the CSF of patients with TBM were significantly higher than those in patients with meningitis due to other causes. CSF ADA level determination with a cut-off value of 6 IU/L was found to be highly specific and fairly sensitive test for the diagnosis of TBM in HIV positive patients.

The ADAS-cog and clinically meaningful change in the VISTA clinical trial of galantamine for Alzheimer's disease.

Science.gov (United States)

Rockwood, Kenneth; Fay, Sherri; Gorman, Mary

2010-02-01

A minimum 4-point change at 6 months on the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) is deemed clinically important, but this cut-point has been little studied in relation to clinical meaningfulness. In an investigator-initiated, clinical trial of galantamine, we investigated the extent to which a 4-point change classifies goal attainment by individual patients. Secondary analysis of the video imaging synthesis of treating Alzheimer's disease (VISTA) study: a 4-month, multi-centre, parallel-group, double-blind, placebo-controlled, trial of galantamine in 130 mild-moderate Alzheimer's disease patients (4-month open-label follow-up). ADAS-cog responses at 6 months were compared with outcomes on three clinical measures: clinician's interview based impression of change-plus caregiver input (CIBIC+), patient/carer-goal attainment scaling (PGAS) and clinician-GAS (CGAS). Thirty-seven of 99 patients improved by > or = 4 points on the ADAS-cog at 6 months, and 16/99 showed > or = 4-point worsening. ADAS-cog change scores correlated notionally to modestly with changes on the CGAS (r = -0.31), the PGAS (r = -0.29) and the CIBIC+ (r = 0.31). As a group, patients with ADAS-cog improvement were significantly more likely to improve on the clinical measures; those who worsened showed non-significant clinical decline. Individually, about half were misclassified in relation to each clinical measure; often when the ADAS-Cog detected 'no change', clinically meaningful effects could be detected. Even so, no ADAS-Cog cut-point optimally classified patients' clinical responses. A 4-point ADAS-cog change at 6 months is clinically meaningful for groups. Substantial individual misclassification between the ADAS-cog and clinical measures suggests no inherent meaning to a 4-point ADAS-cog change for a given patient.

Time-Resolved SAXS/WAXS Study of the Phase Behavior and Microstructural Evolution of Drug/PEG Solid Dispersions

International Nuclear Information System (INIS)

Zhu, Qing; Harris, Michael T.; Taylor, Lynne S.

2011-01-01

Simultaneous small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS) was employed to elucidate the physical state and location of various small molecule drugs blended with polyethylene glycol (PEG), as well as the time dependent microstructural evolution of the systems. Samples were prepared by comelting physical mixtures of the drug and PEG, followed by solidification at 25 C. The model drugs selected encompassed a wide variety of physicochemical properties in terms of crystallization tendency and potential for interaction with PEG. It was observed that compounds which crystallized rapidly and had weak interactions with PEG tended to be excluded from the interlamellar region of the PEG matrix. In contrast, drugs which had favorable interactions with PEG were incorporated into the interlamellar regions of the polymer up until the point at which the drug crystallized whereby phase separation occurred. These factors are likely to impact the effectiveness of drug/PEG systems as drug delivery systems.

Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles.

Science.gov (United States)

Kheiri Manjili, Hamidreza; Ghasemi, Parisa; Malvandi, Hojjat; Mousavi, Mir Sajjad; Attari, Elahe; Danafar, Hossein

2017-07-01

Curcumin (CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability. To progress the bioavailability and water solubility of CUR, we synthesized five series of mono methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by H NMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxicity of void CUR, mPEG-PCL and CUR/mPEG-PCL micelles was compared to each other by performing MTT assay of the treated MCF-7 and 4T1 cell line. Study of the in vivo pharmacokinetics of the CUR-loaded micelles was also carried out on selected copolymers in comparison with CUR solution formulations. The results showed that the zeta potential of CUR-loaded micelles was about -11.5mV and the average size was 81.0nm. CUR was encapsulated into mPEG-PCL micelles with loading capacity of 20.65±0.015% and entrapment efficiency of 89.32±0.34%. The plasma AUC (0-t), t 1/2 and C max of CUR micelles were increased by 52.8, 4.63 and 7.51-fold compared to the CUR solution, respectively. In vivo results showed that multiple injections of CUR-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of CUR. These results suggested that mPEG-PCL micelles would be a potential carrier for CUR. Copyright © 2016 Elsevier B.V. All rights reserved.

State prisons are covered by ADA, 7th Circuit rules.

Science.gov (United States)

1997-07-25

Prison inmate [name removed] sued the Indiana Department of Corrections, claiming it violated the Americans with Disabilities Act (ADA) by denying him access to education programs, the library, and the dining hall because he is blind. The 7th U.S. Circuit Court of Appeals rejected the district court's decision to dismiss the case based on the grounds that the ADA does not apply to prison inmates. The court held that the Department of Corrections cannot exclude an inmate with a disability from prison programs unless the accommodation caused an undue burden on the system.

Request for Observations of V405 Peg

Science.gov (United States)

Templeton, Matthew R.

2009-12-01

Dr. Axel Schwope (Astrophysikalisches Institut Potsdam) requests time-series monitoring of the magnetic cataclysmic variable V405 Pegasi from 2009 December 28 through 2009 December 30. These observations are requested in support of a planned XMM-Newton observation of V405 Peg on 2009 December 29 beginning at 18:51 UT (JD 2455195.2854) and continuing for 12.5 hours. Observers are asked to provide intensive coverage during the three day window centered on the XMM-Newton observation to provide information on the activity state of V405 Peg, to improve the orbital ephemeris, and to provide optical data that will help constrain the spectral energy distribution of this poorly understood cataclysmic variable. The primary filters for this observation are Johnson B and Cousins I, but all observations will be useful for determining the orbital ephemeris. V405 Peg may show both orbital modulation as well as changes in its activity level. The orbital period is approximately four hours, and observers are asked to obtain at least ten and preferably more data points per cycle in each filter. Please use exposure times that provide S/N of at least 20 in both the comparison and target stars but short exposure times are preferred to detect flickering and other short-timescale variations. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

Polyethylene Glycol (PEG-Treated Hydroponic Culture Reduces Length and Diameter of Root Hairs of Wheat Varieties

Directory of Open Access Journals (Sweden)

Arif Hasan Khan Robin

2015-10-01

Full Text Available Wheat is an important cereal crop worldwide that often suffers from moisture deficits at the reproductive stage. Polyethylene glycol (PEG-treated hydroponic conditions create negative osmotic potential which is compared with moisture deficit stress. An experiment was conducted in a growth chamber to study the effects of PEG on root hair morphology and associated traits of wheat varieties. Plants of 13 wheat varieties were grown hydroponically and three different doses of PEG 6000 (w/v: 0% (control, 0.3% and 0.6% (less than −1 bar were imposed on 60 days after sowing for 20 days’ duration. A low PEG concentration was imposed to observe how initial low moisture stress might affect root hair development. PEG-treated hydroponic culture significantly decreased root hair diameter and length. Estimated surface area reduction of root hairs at the main axes of wheat plants was around nine times at the 0.6% PEG level compared to the control plants. Decrease in root hair diameter and length under PEG-induced culture decreased “potential” root surface area per unit length of main root axis. A negative association between panicle traits, length and dry weight and the main axis length of young roots indicated competition for carbon during their development. Data provides insight into how a low PEG level might alter root hair development.

Difficulties with percutaneous endoscopic gastrostomy (PEG): a practical guide for the endoscopist.

LENUS (Irish Health Repository)

O'Mahony, S

2013-03-01

Percutaneous endoscopic gastrostomy (PEG) is a widely used and effective means of providing long-term nutrition in patients with inadequate oral intake. The demand for this intervention has risen steadily since the early 1990s. Endoscopists who perform PEG insertion have become increasingly concerned about inappropriate use of this intervention.

The Long-Term Fate and Toxicity of PEG-Modified Single-Walled Carbon Nanotube Isoliquiritigenin Delivery Vehicles in Rats

Directory of Open Access Journals (Sweden)

Bo Han

2014-01-01

Full Text Available Oxidized single-walled carbon nanotubes (o-SWNTs was modified by covalently and noncovalently linking PEG to the o-SWNTs. The influence of oxidation time, PEG molecular weight, and type of PEG linkage on the blood clearance time of PEG-modified single-walled carbon nanotubes (SWNTs was investigated. The toxicity profile of SWNTs covalently linked to PEG (c-PEG-o-SWNTs in rats has also been determined. The pharmacokinetics of c-PEG-o-SWNTs in rats and their distribution in vital organs were monitored by Raman spectroscopy, and the blood clearance of homogenate isoliquiritigenin (ISL was determined by HPLC. Photos of tissue and tissue sections were taken to evaluate the toxicity of c-PEG-o-SWNTs. We found that SWNTs which were covalently modified with PEG and have a molecular weight of 3500 had the longest blood clearance half-lives. However, SWNTs were toxic to the kidneys and the hearts. The high renal clearance of long-term fate SWNTs may occur because of impaired kidney filtration function. Therefore, we assume that while researchers study the long-term fate of SWNTs, the toxicity of SWNTs also needs to be taken into account.

Predictive value of 6-month decline in ADAS-cog for survival without severe Alzheimer's disease.

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Helmer, Catherine; Andrieu, Sandrine; Pérès, Karine; Orgogozo, Jean-Marc; Vellas, Bruno; Dartigues, Jean-François

2007-01-01

To determine the predictive value of the 6-month evolution of the ADAS-cog score in initially mild to moderate Alzheimer's disease (AD) patients on the risk of death or severe dementia (MMSE ADAS-cog scale in the Real.fr study, a cohort of AD patients. Six classes of ADAS-cog evolution were distinguished, from the severest deterioration (decline >or=7 points) to the greatest cognitive improvement (gain >or=4 points). Among 536 AD patients, 53 (9.9%) had a 6-month decline of 7 points or more. This group with the severest deterioration was significantly associated with the risk of severe dementia or death at 2 years (relative risk, RR = 3.8, 95% confidence interval, CI = 2.1-6.8), even after adjustment for baseline MMSE, disability and ADAS-cog score (RR = 2.6, 95% CI = 1.4-5.0). In addition, subjects with a decline by at least 4 points were also at greater risk of severe dementia. These results confirm the value of the ADAS-cog scale as a judgement criterion in clinical trials since it is a good surrogate marker of long-term prognosis. The proportion of fast decliners on the ADAS-cog could be a helpful judgement criterion for future trials in AD.

PEG conjugates in clinical development or use as anticancer agents: an overview.

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Pasut, Gianfranco; Veronese, Francesco M

2009-11-12

During the almost forty years of PEGylation, several antitumour agents, either proteins, peptides or low molecular weight drugs, have been considered for polymer conjugation but only few entered clinical phase studies. The results from the first clinical trials have shared and improved the knowledge on biodistribution, clearance, mechanism of action and stability of a polymer conjugate in vivo. This has helped to design conjugates with improved features. So far, most of the PEG conjugates comprise of a protein, which in the native form has serious shortcomings that limit the full exploitation of its therapeutic action. The main issues can be short in vivo half-life, instability towards degrading enzymes or immunogenicity. PEGylation proved to be effective in shielding sensitive sites at the protein surface, such as antigenic epitopes and enzymatic degradable sequences, as well as in prolonging the drug half-life by decreasing the kidney clearance. In this review PEG conjugates of proteins or low molecular weight drugs, in clinical development or use as anticancer agents, will be taken into consideration. In the case of PEG-protein derivatives the most represented are depleting enzymes, which act by degrading amino acids essential for cancer cells. Interestingly, PEGylated conjugates have been also considered as adjuvant therapy in many standard anticancer protocols, in this regard the case of PEG-G-CSF and PEG-interferons will be presented.

PEG-b-PCL polymeric nano-micelle inhibits vascular angiogenesis by activating p53-dependent apoptosis in zebrafish.

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Zhou, Tian; Dong, Qinglei; Shen, Yang; Wu, Wei; Wu, Haide; Luo, Xianglin; Liao, Xiaoling; Wang, Guixue

Micro/nanoparticles could cause adverse effects on cardiovascular system and increase the risk for cardiovascular disease-related events. Nanoparticles prepared from poly(ethylene glycol) (PEG)- b -poly( ε -caprolactone) (PCL), namely PEG- b -PCL, a widely studied biodegradable copolymer, are promising carriers for the drug delivery systems. However, it is unknown whether polymeric PEG- b -PCL nano-micelles give rise to potential complications of the cardiovascular system. Zebrafish were used as an in vivo model to evaluate the effects of PEG- b -PCL nano-micelle on cardiovascular development. The results showed that PEG- b -PCL nano-micelle caused embryo mortality as well as embryonic and larval malformations in a dose-dependent manner. To determine PEG- b -PCL nano-micelle effects on embryonic angiogenesis, a critical process in zebrafish cardiovascular development, growth of intersegmental vessels (ISVs) and caudal vessels (CVs) in flk1-GFP transgenic zebrafish embryos using fluorescent stereomicroscopy were examined. The expression of fetal liver kinase 1 (flk1), an angiogenic factor, by real-time quantitative polymerase chain reaction (qPCR) and in situ whole-mount hybridization were also analyzed. PEG- b -PCL nano-micelle decreased growth of ISVs and CVs, as well as reduced flk1 expression in a concentration-dependent manner. Parallel to the inhibitory effects on angiogenesis, PEG- b -PCL nano-micelle exposure upregulated p53 pro-apoptotic pathway and induced cellular apoptosis in angiogenic regions by qPCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay. This study further showed that inhibiting p53 activity, either by pharmacological inhibitor or RNA interference, could abrogate the apoptosis and angiogenic defects caused by PEG- b -PCL nano-micelles, indicating that PEG- b -PCL nano-micelle inhibits angiogenesis by activating p53-mediated apoptosis. This study indicates that polymeric PEG- b -PCL nano-micelle could

Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice.

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Bhirde, Ashwin A; Patel, Sachin; Sousa, Alioscka A; Patel, Vyomesh; Molinolo, Alfredo A; Ji, Youngmi; Leapman, Richard D; Gutkind, J Silvio; Rusling, James F

2010-12-01

To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice. PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT-cisplatin for tumor growth inhibition was studied in mice. PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT-cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice. PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.

Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio).

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Verma, Akash; Abisheganaden, John; Light, R W

2016-02-01

We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

Mitochondria-targeting cyclometalated iridium(III)-PEG complexes with tunable photodynamic activity.

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Li, Steve Po-Yam; Lau, Chris Tsan-Shing; Louie, Man-Wai; Lam, Yun-Wah; Cheng, Shuk Han; Lo, Kenneth Kam-Wing

2013-10-01

We present a new class of phosphorescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N(^)C)2(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG = 4-(N-(2-(ω-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, number average molecular weight (Mn) = 5272.23, weight average molecular weight (Mw) = 5317.38, polydispersity index (PDI) = 1.009; HN(^)C = 2-phenylpyridine, Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine, Hpppy (2a), 2-phenylquinoline, Hpq (3a), 2-phenylbenzothiazole, Hbt (4a), 2-(1-naphthyl)benzothiazole, Hbsn (5a)). The photophysical, photochemical, and biological properties of these complexes have been compared with those of their PEG-free counterparts [Ir(N(^)C)2(bpy-CONH-Et)](PF6) (bpy-CONH-Et = 4-(N-ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine; HN(^)C = Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)). Upon irradiation, all the complexes exhibited intense and long-lived green to orange-red emission under ambient conditions. The emission was phosphorescence in nature and can be quenched by O2 with the generation of singlet oxygen ((1)O2). The quantum yields for (1)O2 production of the complexes in aerated DMSO (0.24-0.83) were found to be dependent on the excited-state lifetimes of the complexes, which can be altered using different cyclometalating ligands (N(^)C). Cell-based assays indicated that the PEG complexes were noncytotoxic in the dark (IC50 > 300 μM); however, most of them became significantly cytotoxic upon irradiation (IC50 = 3.4 - 23.2 μM). Laser-scanning confocal microscopy images revealed localization of complex 3a in the mitochondrial region of HeLa cells and the induction of rapid necrotic cell death upon light activation. Additionally, the lack of dark toxicity and potential application of the PEG complexes as a visualizing reagent have been demonstrated using zebrafish (Danio rerio) as an animal model. Copyright © 2013 Elsevier Ltd. All rights reserved.

Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation

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Sanyuan Hu

2010-11-01

Full Text Available Sanyuan Hu1, Yangde Zhang21Xiangya School of Medicine and 2National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Changsha, Hunan Province, People’s Republic of ChinaAbstract: Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol modified poly (DL-lactide-co-glycolide (PEG-PLGA by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM, photon correlation spectroscopy (PCS, and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak

A study of the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) in an Icelandic elderly population.

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Hannesdóttir, Kristin; Snaedal, Jón

2002-01-01

The Alzheimer's Disease Assessment Scale (ADAS) is designed for screening of cognitive and non-cognitive dysfunctions characteristic of persons with probable Alzheimer's disease (AD). The cognitive part of the scale (ADAS-Cog) is both convenient for screening of probable AD and as a measure of cognitive functioning during drug intervention. The aim of this study was to translate the ADAS-Cognitive sub-test (ADAS-Cog) into Icelandic and to study its application in an elderly Icelandic population. The Mini-Mental State Examination (MMSE) and the ADAS-Cog were administered to 20 AD patients and 20 controls. Each patient was also rated on the Global Deterioration Scale (GDS). The probable AD patients were divided into two groups based on their GDS: 3-4 and 5-6 points. The patients were also divided into two groups based on their MMSE score: very mild to mild (23-30 points) and mild to moderate (15-22 points). Furthermore, the subjects were divided into two age groups: 65-76 and 77-92 years. Results revealed a highly significant difference on MMSE (22.3 +/- 3.4; 26.8 +/- 1.6; P ADAS-Cog (18.4 +/- 7.7; 7.3 +/- 3.5; P ADAS-Cog plays an important role in the diagnostic makeup of AD along with other detailed investigations, such as neuropsychological assessment.

Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

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Ming-Fa Hsieh

2010-12-01

Full Text Available The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol (mPEG and one hydrophobic segment poly(ε‑caprolactone (PCL; which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14 of DOX-loaded micelles as compared to multiple administrations of free DOX.

Anemia nos pacientes com insuficiência cardíaca avançada

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Juliano Cardoso

2010-10-01

Full Text Available FUNDAMENTO: Anemia está associada à pior evolução nos pacientes com insuficiência cardíaca (IC. Entretanto, há poucos estudos sobre a anemia nos pacientes com IC avançada. OBJETIVO: Avaliar as características da anemia na IC em fase avançada. MÉTODOS: Foram incluídos 99 pacientes hospitalizados para compensação de IC (CF IV/NYHA, com idade > 18 anos e FEVE 12 g/dl. A anemia foi marcador independente de mau prognóstico na análise multivariada (mortalidade 47% vs 24,6%, p = 0,016, risco relativo 2,54. CONCLUSÃO: Anemia acomete, aproximadamente, 1/3 dos pacientes com IC avançada, e a deficiência de ferro é uma importante etiologia. Pacientes anêmicos são mais idosos e apresentaram função renal mais deteriorada. A melhora da congestão não foi suficiente para melhorar a anemia na maioria dos casos. Nos pacientes com IC avançada, a anemia é marcador independente de mau prognóstico.

Bovine TLR2 and TLR4 mediate Cryptosporidium parvum recognition in bovine intestinal epithelial cells.

Science.gov (United States)

Yang, Zhengtao; Fu, Yunhe; Gong, Pengtao; Zheng, Jingtong; Liu, Li; Yu, Yuqiang; Li, Jianhua; Li, He; Yang, Ju; Zhang, Xichen

2015-08-01

Cryptosporidium parvum (C. parvum) is an intestinal parasite that causes diarrhea in neonatal calves. It results in significant morbidity of neonatal calves and economic losses for producers worldwide. Innate resistance against C. parvum is thought to depend on engagement of pattern recognition receptors. However, the role of innate responses to C. parvum has not been elucidated in bovine. The aim of this study was to evaluate the role of TLRs in host-cell responses during C. parvum infection of cultured bovine intestinal epithelial cells. The expressions of TLRs in bovine intestinal epithelial cells were detected by qRT-PCR. To determine which, if any, TLRs may play a role in the response of bovine intestinal epithelial cells to C. parvum, the cells were stimulated with C. parvum and the expression of TLRs were tested by qRT-PCR. The expression of NF-κB was detected by western blotting. Further analyses were carried out in bovine TLRs transfected HEK293 cells and by TLRs-DN transfected bovine intestinal epithelial cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs. The expression of TLR2 and TLR4 were up-regulated when bovine intestinal epithelial cells were treated with C. parvum. Meanwhile, C. parvum induced IL-8 production in TLR2 or TLR4/MD-2 transfected HEK293 cells. Moreover, C. parvum induced NF-κB activation and cytokine expression in bovine intestinal epithelial cells. The induction of NF-κB activation and cytokine expression by C. parvum were reduced in TLR2-DN and TLR4-DN transfected cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs, and bovine intestinal epithelial cells recognized and responded to C. parvum via TLR2 and TLR4. Copyright © 2015 Elsevier Ltd. All rights reserved.

AN ADA LINEAR ALGEBRA PACKAGE MODELED AFTER HAL/S

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Klumpp, A. R.

1994-01-01

This package extends the Ada programming language to include linear algebra capabilities similar to those of the HAL/S programming language. The package is designed for avionics applications such as Space Station flight software. In addition to the HAL/S built-in functions, the package incorporates the quaternion functions used in the Shuttle and Galileo projects, and routines from LINPAK that solve systems of equations involving general square matrices. Language conventions in this package follow those of HAL/S to the maximum extent practical and minimize the effort required for writing new avionics software and translating existent software into Ada. Valid numeric types in this package include scalar, vector, matrix, and quaternion declarations. (Quaternions are fourcomponent vectors used in representing motion between two coordinate frames). Single precision and double precision floating point arithmetic is available in addition to the standard double precision integer manipulation. Infix operators are used instead of function calls to define dot products, cross products, quaternion products, and mixed scalar-vector, scalar-matrix, and vector-matrix products. The package contains two generic programs: one for floating point, and one for integer. The actual component type is passed as a formal parameter to the generic linear algebra package. The procedures for solving systems of linear equations defined by general matrices include GEFA, GECO, GESL, and GIDI. The HAL/S functions include ABVAL, UNIT, TRACE, DET, INVERSE, TRANSPOSE, GET, PUT, FETCH, PLACE, and IDENTITY. This package is written in Ada (Version 1.2) for batch execution and is machine independent. The linear algebra software depends on nothing outside the Ada language except for a call to a square root function for floating point scalars (such as SQRT in the DEC VAX MATHLIB library). This program was developed in 1989, and is a copyrighted work with all copyright vested in NASA.

Upper estimates of complexity of algorithms for multi-peg Tower of Hanoi problem

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Sergey Novikov

2007-06-01

Full Text Available There are proved upper explicit estimates of complexity of lgorithms: for multi-peg Tower of Hanoi problem with the limited number of disks, for Reve's puzzle and for $5$-peg Tower of Hanoi problem with the free number of disks.

Detecting treatment effects with combinations of the ADAS-cog items in patients with mild and moderate Alzheimer's disease.

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Ihl, Ralf; Ferris, Steven; Robert, Philippe; Winblad, Bengt; Gauthier, Serge; Tennigkeit, Frank

2012-01-01

When complex cognitive functions are measured with multi-item scales like the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), it seems valuable information can be lost due to combination of the ADAS-cog items results into a total score. We hypothesized, that an analysis of the results of different ADAS-cog item combinations may reveal drug treatment effects in distinct cognitive domains and/or enhance the sensitivity to detect such treatment effects. Here, we present a novel approach called 'subsetting analysis' for assessment of drug treatment effects with multi-item scales, like the ADAS-cog. The subsetting approach is a mathematical algorithm designed to select and group scale items in a subset detecting drug treatment effects in a particular study population. The approach was applied in a post-hoc analysis of ADAS-cog results from two randomized, placebo-controlled and double-blind clinical trials with memantine in mild to moderate Alzheimer's disease (AD). The subsetting analysis of the ADAS-cog combined database aimed at selecting the scale items showing no worsening at study end compared to baseline due to memantine treatment in mild AD (Mini-Mental State Examination (MMSE >19)) patients. Two ADAS-cog subsets were finally revealed by the analysis: a subset of five ADAS-cog items, identified as most sensitive to memantine effects in mild AD patients, and a subset of six ADAS-cog items shown to detect significant memantine effects in moderate AD patients. The subsetting approach of analyzing ADAS-cog data is a powerful alternative for gaining information about drug effects on cognitive performance in mild and moderate AD patients. Copyright © 2011 John Wiley & Sons, Ltd.

Using ADA Tasks to Simulate Operating Equipment

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DeAcetis, Louis A.; Schmidt, Oron; Krishen, Kumar

1990-01-01

A method of simulating equipment using ADA tasks is discussed. Individual units of equipment are coded as concurrently running tasks that monitor and respond to input signals. This technique has been used in a simulation of the space-to-ground Communications and Tracking subsystem of Space Station Freedom.

Cholesterol-PEG comodified poly (N-butyl) cyanoacrylate nanoparticles for brain delivery: in vitro and in vivo evaluations.

Science.gov (United States)

Hu, Xiao; Yang, Feifei; Liao, Yonghong; Li, Lin; Zhang, Lan

2017-11-01

This study investigated cholesterol-polyethylene glycol (PEG) comodified poly (ethyleneglycol)-poly (lactide) nanoparticles (CLS-PEG NPs) as a novel, biodegradable brain drug delivery system and included an evaluation of its in vitro and in vivo properties. To this end, coumarin-6 (C6), a fluorescent probe, was encapsulated into CLS-PEG NPs by an emulsion polymerization method. We reported that the use of CLS-PEG NPs led to a sustained drug release in vitro. Additionally, cell viability experiments confirmed their safety. The uptake and transport of CLS-PEG NPs, by bEnd.3 cells (an immortalized mouse brain endothelial cell line), was significantly higher than that of a control C6 solution. An investigation of the uptake mechanisms of different NP formulations demonstrated that cholesterol modifications may be the primary way to improve the efficiency of cellular uptake, wherein macropinocytosis may be the most important endocytic pathway in this process. An investigation of the transport mechanisms of CLS-PEG NPs also implicated macropinocytosis, energy and cholesterol in bEnd.3 cells lines. Following an intravenous (IV) administration to rats, pharmacokinetic experiments indicated that C6-loaded CLS-PEG NPs achieved sustained release for up to 12 h. In addition, IV delivery of CLS-PEG NPs appeared to significantly improve the ability of C6 to pass through the blood-brain barrier: the concentration of C6 found in the brain increased nearly 14.2-fold when C6 CLS-PEG NPs were used rather than a C6 solution. These in vitro and in vivo results strongly suggest that CLS-PEG NPs are a promising drug delivery system for targeting the brain, with low toxicity.

Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro

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Xiang GH

2013-12-01

Full Text Available Guang-Hua Xiang,1,2,* Guo-Bin Hong,2,3,* Yong Wang,2 Du Cheng,2 Jing-Xing Zhou,1 Xin-Tao Shuai21Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Department of Radiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, People's Republic of China*These two authors contributed equally to this workObjective: To evaluate the cytotoxicity of poly(ethylene glycol-block-poly(D,L-lactic acid (PEG-PDLLA nanovesicles loaded with doxorubicin (DOX and the photosensitizer hematoporphyrin monomethyl ether (HMME on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms.Methods: PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME, and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX, HMME (PEG-PDLLA-HMME, or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined.Results: Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

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Malhotra M

2013-05-01

Full Text Available Meenakshi Malhotra,1 Catherine Tomaro-Duchesneau,1 Shyamali Saha,2 Imen Kahouli,3 Satya Prakash11Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, 2Faculty of Dentistry, 3Department of Experimental Medicine, McGill University, Montreal, QC, CanadaAbstract: Recently, cell-penetrating peptides have been proposed to translocate antibodies, proteins, and other molecules in targeted drug delivery. The proposed study presents the synthesis and characterization of a peptide-based chitosan nanoparticle for small interfering RNA (siRNA delivery, in-vitro. Specifically, the synthesis included polyethylene glycol (PEG, a hydrophilic polymer, and trans-activated transcription (TAT peptide, which were chemically conjugated on the chitosan polymer. The conjugation was achieved using N-Hydroxysuccinimide-PEG-maleimide (heterobifunctional PEG as a cross-linker, with the bifunctional PEG facilitating the amidation reaction through its N-Hydroxysuccinimide group and reacting with the amines on chitosan. At the other end of PEG, the maleimide group was chemically conjugated with the cysteine-modified TAT peptide. The degree of substitution on chitosan with PEG and on PEG with TAT was confirmed using colorimetric assays. The resultant polymer was used to form nanoparticles complexing siRNA, which were then characterized for particle size, morphology, cellular uptake, and cytotoxicity. The nanoparticles were tested in-vitro on mouse neuroblastoma cells (Neuro2a. Particle size and surface charge were characterized and an optimal pH condition and PEG molecular weight were determined to form sterically stable nanoparticles. Results indicate 7.5% of the amines in chitosan polymer were conjugated to the PEG and complete conjugation of TAT peptide was observed on the synthesized PEGylated chitosan polymer. Compared with unmodified chitosan nanoparticles, the nanoparticles formed at pH 6 were

Cartalk 2000: development of a co-operative ADAS based on vehicle-to-vehicle communication

NARCIS (Netherlands)

Morsink, P.L.J.; Hallouzi, R.; Dagli, I.; Cseh, C.; Schäfers, L.; Nelisse, M.W.; Bruin, D. de

2003-01-01

Advanced Driver Assistance Systems (ADAS) benefit from using vehicle-to-vehicle communication. In the 5th framework EC project CarTALK2000 co-operative ADAS are designed, tested and evaluated with respect to increasing traffic safety, efficiency and driving comfort. Communication based longitudinal

Software tools to aid Pascal and Ada program design

Energy Technology Data Exchange (ETDEWEB)

Jankowitz, H.T.

1987-01-01

This thesis describes a software tool which analyses the style and structure of Pascal and Ada programs by ensuring that some minimum design requirements are fulfilled. The tool is used in much the same way as a compiler is used to teach students the syntax of a language, only in this case issues related to the design and structure of the program are of paramount importance. The tool operates by analyzing the design and structure of a syntactically correct program, automatically generating a report detailing changes that need to be made in order to ensure that the program is structurally sound. The author discusses how the model gradually evolved from a plagiarism detection system which extracted several measurable characteristics in a program to a model that analyzed the style of Pascal programs. In order to incorporate more-sophistical concepts like data abstraction, information hiding and data protection, this model was then extended to analyze the composition of Ada programs. The Ada model takes full advantage of facilities offered in the language and by using this tool the standard and quality of written programs is raised whilst the fundamental principles of program design are grasped through a process of self-tuition.

Use of read-across and computer-based predictive analysis for the safety assessment of PEG cocamines.

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Skare, Julie A; Blackburn, Karen; Wu, Shengde; Re, Thomas A; Duche, Daniel; Ringeissen, Stephanie; Bjerke, Donald L; Srinivasan, Viny; Eisenmann, Carol

2015-04-01

In the European Union animal testing has been eliminated for cosmetic ingredients while the US Cosmetic Ingredient Review Expert Panel may request data from animal studies. The use of read-across and predictive toxicology provides a path for filling data gaps without additional animal testing. The PEG cocamines are tertiary amines with an alkyl group derived from coconut fatty acids and two PEG chains of varying length. Toxicology data gaps for the PEG cocamines can be addressed by read-across based on structure-activity relationship using the framework described by Wu et al. (2010) for identifying suitable structural analogs. Data for structural analogs supports the conclusion that the PEG cocamines are non-genotoxic and not expected to exhibit systemic or developmental/reproductive toxicity with use in cosmetics. Due to lack of reliable dermal sensitization data for suitable analogs, this endpoint was addressed using predictive software (TIMES SS) as a first step (Laboratory of Mathematical Chemistry). The prediction for PEG cocamines was the same as that for PEGs, which have been concluded to not present a significant concern for dermal sensitization. This evaluation for PEG cocamines demonstrates the utility of read-across and predictive toxicology tools to assess the safety of cosmetic ingredients. Copyright © 2015 Elsevier Inc. All rights reserved.

A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent.

Science.gov (United States)

Xiong, Fei; Hu, Ke; Yu, Haoli; Zhou, Lijun; Song, Lina; Zhang, Yu; Shan, Xiuhong; Liu, Jianping; Gu, Ning

2017-08-01

Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe 3 O 4 @OA NPs. The stability and anti phagocytosis of Fe 3 O 4 @OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo. These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose. The DG can validly enhance the tumor-targetting effect of Fe 3 O 4 @OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

The implications of the ADA Amendments Act of 2008 for residency training program administration.

Science.gov (United States)

Regenbogen, Alexandra; Recupero, Patricia R

2012-01-01

The Americans with Disabilities Act (ADA) is rarely invoked by medical residents in training. Dr. Martin Jakubowski, a family medicine resident with Asperger's disorder, was dismissed for communicating poorly with patients, peers, and supervisors and for issuing dangerous medical orders. In an attempt to become reinstated, he sued under the ADA (Jakubowski v. The Christ Hospital), arguing that the program had failed to make reasonable accommodation for his disability. The Sixth Circuit Court of Appeals ruled in favor of the hospital, finding that although the doctor was disabled under the ADA, he had failed to demonstrate that he was otherwise qualified for the position. This article comments on the ADA Amendments Act of 2008, the Equal Employment Opportunity Commission (EEOC) guidelines from 2011 and their application to medical residency training, and the Accreditation Council for Graduate Medical Education (ACGME) core competencies as essential job functions.

Characterization and tribology of PEG-like coatings on UHMWPE for total hip replacements.

Science.gov (United States)

Kane, Sheryl R; Ashby, Paul D; Pruitt, Lisa A

2010-03-15

A crosslinked hydrogel coating similar to poly(ethylene glycol) (PEG) was covalently bonded to the surface of ultrahigh molecular weight polyethylene (UHMWPE) to improve the lubricity and wear resistance of the UHWMPE for use in total joint replacements. The chemistry, hydrophilicity, and protein adsorption resistance of the coatings were determined, and the wear behavior of the PEG-like coating was examined by two methods: pin-on-disk tribometry to evaluate macroscale behavior, and atomic force microscopy (AFM) to simulate asperity wear. As expected, the coating was found to be highly PEG-like, with approximately 83% ether content by x-ray photoelectron spectroscopy and more hydrophilic and resistant to protein adsorption than uncoated UHMWPE. Pin-on-disk testing showed that the PEG-like coating could survive 3 MPa of contact pressure, comparable to that experienced by total hip replacements. AFM nanoscratching experiments uncovered three damage mechanisms for the coatings: adhesion/microfracture, pure adhesion, and delamination. The latter two mechanisms appear to correlate well with wear patterns induced by pin-on-disk testing and evaluated by attenuated total reflection Fourier transform infrared spectroscopy mapping. Understanding the mechanisms by which the PEG-like coatings wear is critical for improving the behavior of subsequent generations of wear-resistant hydrogel coatings. (c) 2009 Wiley Periodicals, Inc.

[Is it pseudo-dementia? The validation of the Adas-Cog questionnaire in Hungary].

Science.gov (United States)

Drótos, Gergely; Pákáski, Magdolna; Papp, Edina; Kálmán, János

2012-01-01

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) has been established internationally as an instrument for the assessment of treatment efficacy and cognitive performance in clinical trials. There is no data about the validity and characteristics of ADAS-Cog in Hungarian sample. This study is a part of the Hungarian standardization process of ADAS-Cog. It is crucial to examine the cognitive performance of patients with pseudodementia caused by depression (D) because of its' similarities with Alzheimer's disease (AK). The objective of the study was to analyze the characteristics of the cognitive subscale for further validation purposes. The study aimed at analyzing the ADAS-Cog performance of patients with D and AK in a Hungarian sample to make future studies more accurate through more exact differentiation between the two diseases. Fourty-seven normal elderly control (KNT) subjects, 66 AK patients and 39 patients with D participated in the study. The mental state and the severity of depressive symptoms of the participants were assessed by the means of ADAS-Cog, Mini Mental State Examination (MMSE) and Beck Depression Inventory. The ADAS-Cog is sensitive to the cognitive decline of the depressed group (sensitivity=69.2%, specificity=89.4%, AUC=0.868, p>0.001). While the performance of the two patient groups differed from the KNT, the groups are overlapping and the characteristic of the ROC curve and the optimal cut-off point (D:11.8; AK:12.1) indicates that the differentiation is mediocre. The results suggest that pseudodementia should be considered during the design of studies using ADASCog. Because the cognitive subscale can't accurately differentiate between AK and pseudodementia additional measures like BDI should be administered.

Lack of lasting effectiveness of PEG 3350 laxative treatment of constipation.

Science.gov (United States)

Tran, Lily C; Di Palma, Jack A

2005-08-01

PEG 3350 (MiraLax, Braintree Laboratories Inc., Braintree, MA) 17 g daily has been shown to be safe and effective in a 14-day trial for constipation. This present investigation was designed to extend the treatment and safety experience with PEG 3350 and to evaluate any lasting effectiveness during a 30-day post-treatment observation period. Study subjects met Rome II criteria for constipation and reported PEG 3350 17 g daily for 14 days. Treatment efficacy was defined by resolution of constipation symptoms as determined by the Rome II and stool frequency definitions during the treatment period. Fifty healthy constipated subjects formed the study group. There were 42 females and 8 males. Mean age was 52 +/- 15.5 years (+/-SD). Symptom duration was 22.6 +/- 16.7 months (+/-SD). At baseline, all had 3 stools in the last week and no longer met Rome criteria. Thirty-two of 45 (71.1%) reported satisfaction with the first bowel movement after initiating treatment. Thirty days after active treatment, 29 of 47 (61.7%) responded that they needed laxative treatment. PEG 3350 relieved constipation in most treated study subjects. During a 30-day post-treatment observation period, 29 of 47 (61.7%) had additional constipation treatment interventions.

Diagnosis of tuberculosis pleurisy with adenosine deaminase (ADA): a systematic review and meta-analysis.

Science.gov (United States)

Gui, Xuwei; Xiao, Heping

2014-01-01

This systematic review and meta-analysis was performed to determine accuracy and usefulness of adenosine deaminase (ADA) in diagnosis of tuberculosis pleurisy. Medline, Google scholar and Web of Science databases were searched to identify related studies until 2014. Two reviewers independently assessed quality of studies included according to standard Quality Assessment of Diagnosis Accuracy Studies (QUADAS) criteria. The sensitivity, specificity, diagnostic odds ratio and other parameters of ADA in diagnosis of tuberculosis pleurisy were analyzed with Meta-DiSC1.4 software, and pooled using the random effects model. Twelve studies including 865 tuberculosis pleurisy patients and 1379 non-tuberculosis pleurisy subjects were identified from 110 studies for this meta-analysis. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnosis odds ratio (DOR) of ADA in the diagnosis of tuberculosis pleurisy were 45.25 (95% CI 27.63-74.08), 0.86 (95% CI 0.84-0.88), 0.88 (95% CI 0.86-0.90), 6.32 (95% CI 4.83-8.26) and 0.15 (95% 0.11-0.22), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.9340. Our results demonstrate that the sensitivity and specificity of ADA are high in the diagnosis of tuberculosis pleurisy especially when ADA≥50 (U/L). Thus, ADA is a relatively sensitive and specific marker for tuberculosis pleurisy diagnosis. However, it is cautious to apply these results due to the heterogeneity in study design of these studies. Further studies are required to confirm the optimal cut-off value of ADA.

Adult Autism Subthreshold Spectrum (AdAS Spectrum): Validation of a questionnaire investigating subthreshold autism spectrum.

Science.gov (United States)

Dell'Osso, L; Gesi, C; Massimetti, E; Cremone, I M; Barbuti, M; Maccariello, G; Moroni, I; Barlati, S; Castellini, G; Luciano, M; Bossini, L; Rocchetti, M; Signorelli, M; Aguglia, E; Fagiolini, A; Politi, P; Ricca, V; Vita, A; Carmassi, C; Maj, M

2017-02-01

Increasing literature has shown the usefulness of a dimensional approach to autism. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of autism spectrum disorder (ASD) in adulthood. 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with a feeding and eating disorder (FED), and 160 subjects with no mental disorders (CTL), were recruited from 7 Italian University Departments of Psychiatry and administered the following: SCID-5, Autism-Spectrum Quotient (AQ), Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14), and AdAS Spectrum. The AdAS Spectrum demonstrated excellent internal consistency for the total score (Kuder-Richardson's coefficient=.964) as well as for five out of seven domains (all coefficients>.80) and sound test-retest reliability (ICC=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (pcriteria (FED 0 ) and those with one ASD symptom criterion (FED 1 ) , a gradient of severity in AdAS Spectrum scores from CTL subjects to ASD patients, across FED 0 , ASD 1 , FED 1 was shown. The AdAS Spectrum showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of ASD. The questionnaire performed differently among the three diagnostic groups and enlightened some significant effects of gender in the expression of autistic traits. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term changes in ADAS-cog: what is clinically relevant for disease modifying trials in Alzheimer?

Science.gov (United States)

Vellas, B; Andrieu, S; Cantet, C; Dartigues, J F; Gauthier, S

2007-01-01

With the development of long-term disease modifying trials, changes in ADAS-Cog at 18 months will rise certainly many questions. We decided to look in the Real.fr study at the links between changes in cognition, ADAS-Cog and function. A total of 346 Alzheimer's patients with ADAS-cog at entry and at 18 months. were eligible for this analysis. These patients were on average 77.44 years old and 254 (72.36%) were women. The great majority lived at home and about 93% were treated with a cholinesterase inhibitor at baseline. Thirty three patients (9%) had a gain of more than 2 points at the ADAS-cog at 18 months (Group I, improvement); 130 (38%) were considered as stable, the reference group (Group II ) characterized by a stability at the ADAS-cog: decline of 2 points to gain of 2 points, 112 subjects (32%) had a moderate decline between 2 and 7 at the ADAScog (Group III) and finally 71 subjects (21%) had a severe impairment more than seven points at the ADAS-cog. A loss of one Basic ADL is certainly highly relevant, and such a change was found at 18 months in more than half of the subjects, which is not surprising for a long-term evolution in mild to moderate AD. An impairment of more than 7 points at the ADAS-cog was found in 21% of the subjects at 18 months and was associated with loss.

A New Method of Cloud Detection Based on Cascaded AdaBoost

International Nuclear Information System (INIS)

Ma, C; Chen, F; Liu, J; Duan, J

2014-01-01

Cloud detection of remote sensing image is a critical step in the processing of the remote sensing images. How to quickly, accurately and effectively detect cloud on remote sensing images, is still a challenging issue in this area. In order to avoid disadvantages of the current algorithms, the cascaded AdaBoost classifier algorithm is successfully applied to the cloud detection. A new algorithm combined cascaded AdaBoost classifier and multi-features, is proposed in this paper. First, multi-features based on the color, texture and spectral features are extracted from the remote sensing image. Second, the automatic cloud detection model is obtained based on the cascaded AdaBoost algorithm. In this paper, the results show that the new algorithm can determine cloud detection model and threshold values adaptively for different resolution remote sensing training data. The accuracy of cloud detection is improved. So it is a new effective algorithm for the cloud detection of remote sensing images

The effect of polymer size and charge of molecules on permeation through synovial membrane and accumulation in hyaline articular cartilage.

Science.gov (United States)

Sterner, B; Harms, M; Wöll, S; Weigandt, M; Windbergs, M; Lehr, C M

2016-04-01

The treatment of joint related diseases often involves direct intra-articular injections. For rational development of novel delivery systems with extended residence time in the joint, detailed understanding of transport and retention phenomena within the joint is mandatory. This work presents a systematic study on the in vitro permeation, penetration and accumulation of model polymers with differing charges and molecular weights in bovine joint tissue. Permeation experiments with bovine synovial membrane were performed with PEG polymers (6-200 kDa) and methylene blue in customized diffusion chambers. For polyethylene glycol, 2-fold (PEG 6 kDa), 3-fold (PEG 10 kDa) and 13-fold (PEG 35 kDa) retention by the synovial membrane in reference to the small molecule methylene blue was demonstrated. No PEG 200 kDa was found in the acceptor in detectable amounts after 48 h. This showed the potential for a distinct extension of joint residence times by increasing molecular weights. In addition, experiments with bovine cartilage tissue were conducted. The ability for positively charged, high molecular weight chitosans and HEMA-Co-TMAP (HCT) polymers (up to 233 kDa) to distribute throughout the entire cartilage matrix was demonstrated. In contrast, a distribution into cartilage was not observed for neutral PEG polymers (6-200 kDa). Furthermore, the positive charge density of different compounds (chitosan, HEMA-Co-TMAP, methylene blue, MSC C1 (neutral NCE) and MSC D1 (positively charged NCE) was found to correlate with their accumulation in bovine cartilage tissue. In summary, the results offer pre-clinical in vitro data, indicating that the modification of molecular size and charge of a substance has the potential to decelerate its clearance through the synovial membrane and to promote accumulation inside the cartilage matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ?

OpenAIRE

Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

2016-01-01

Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoim...

Bahan pemutih gigi dengan sertifikat ADA/ISO (Tooth bleaching material with ADA/ISO certificate

Directory of Open Access Journals (Sweden)

Asti Meizarini

2005-06-01

Full Text Available Bleaching of teeth for cosmetic reasons is a popular aspect of cosmetic dentistry because patients realize the aesthetical benefits of these products. The dentist as a clinician's practitioner must be knowledgeable of the products and their application techniques. Bleaching materials which are safe and effective are the ADA accepted or manufactured by those which have already haved ISO certificate. Dentist must have enough knowledge about in-office bleaching prescribed for home-use bleaching including their contra indication and side effects, to advise the patients and provide effective bleaching services.

Biomedical applications of SPION@APTES@PEG-folic acid@carboxylated quercetin nanodrug on various cancer cells

International Nuclear Information System (INIS)

Akal, Z.Ü.; Alpsoy, L.; Baykal, A.

2016-01-01

Highlights: • SPION has been synthesized via Reflux synthesis route. • SPION@APTES@FA-PEG@CQ nanodrug has super paramagnetic property. • SPION@APTES@FA-PEG@CQ nanodrug has cytotoxic, apoptotic and necrotic effects on HeLa and MCF-7 cells. • SPION@APTES@FA-PEG@CQ nanodrug can be potentially used for the delivery of quercetin to cervical and breast cancer cells. - Abstract: In this study, carboxylated quercetin (CQ) was conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) which were modified by (3-aminopropyl) triethoxysilane (APTES), Folic acid (FA) and carboxylated Polyethylene glycol (PEG); (SPION@APTES@FA-PEG@CQ), nanodrug has been synthesized via polyol and accompanying by various chemical synthesis routes. The characterization of the final product was done via X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Thermal gravimetric analysis (TGA), Transmission electron spectroscopy (TEM) and Vibrating sample magnetometer (VSM). Its cytotoxic and apoptotic activities on over expressed folic acid receptor (FR + ) (MCF-7, HeLa) and none expressed folic acid receptor (FR-) (A549) cancer cell lines were determined by using MTT assay, Real-Time Cell Analysis, TUNEL assay, Annexin assay and RT-PCR analysis for Caspase3/7 respectively. SPION@APTES@FA-PEG@CQ nanodrug showed higher cytotoxicity against HeLa and MCF-7 cell lines as compared with A549 cell line. Moreover, SPION@APTES@FA-PEG@CQ nanodrug also caused higher apoptotic and necrotic effects in 100 μg/mL HeLa and MCF-7 cells than A549 cells. The findings showed that SPION@APTES@FA-PEG@CQ nanodrug has cytotoxic, apoptotic and necrotic effects on HeLa and MCF-7 which are FR over expressed cell lines and can be potentially used for the delivery of quercetin to cervical and breast cancer cells.

Biomedical applications of SPION@APTES@PEG-folic acid@carboxylated quercetin nanodrug on various cancer cells

Energy Technology Data Exchange (ETDEWEB)

Akal, Z.Ü., E-mail: zulker@fatih.edu.tr [Department of Biology, 34500 Büyükçekmece, Istanbul (Turkey); Alpsoy, L. [Department of Biology, 34500 Büyükçekmece, Istanbul (Turkey); Department of Medical Biology, 34500 Büyükçekmece, Istanbul (Turkey); Baykal, A. [Department of Chemistry, Fatih University, 34500 Büyükçekmece, Istanbul (Turkey)

2016-08-15

Highlights: • SPION has been synthesized via Reflux synthesis route. • SPION@APTES@FA-PEG@CQ nanodrug has super paramagnetic property. • SPION@APTES@FA-PEG@CQ nanodrug has cytotoxic, apoptotic and necrotic effects on HeLa and MCF-7 cells. • SPION@APTES@FA-PEG@CQ nanodrug can be potentially used for the delivery of quercetin to cervical and breast cancer cells. - Abstract: In this study, carboxylated quercetin (CQ) was conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) which were modified by (3-aminopropyl) triethoxysilane (APTES), Folic acid (FA) and carboxylated Polyethylene glycol (PEG); (SPION@APTES@FA-PEG@CQ), nanodrug has been synthesized via polyol and accompanying by various chemical synthesis routes. The characterization of the final product was done via X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Thermal gravimetric analysis (TGA), Transmission electron spectroscopy (TEM) and Vibrating sample magnetometer (VSM). Its cytotoxic and apoptotic activities on over expressed folic acid receptor (FR + ) (MCF-7, HeLa) and none expressed folic acid receptor (FR-) (A549) cancer cell lines were determined by using MTT assay, Real-Time Cell Analysis, TUNEL assay, Annexin assay and RT-PCR analysis for Caspase3/7 respectively. SPION@APTES@FA-PEG@CQ nanodrug showed higher cytotoxicity against HeLa and MCF-7 cell lines as compared with A549 cell line. Moreover, SPION@APTES@FA-PEG@CQ nanodrug also caused higher apoptotic and necrotic effects in 100 μg/mL HeLa and MCF-7 cells than A549 cells. The findings showed that SPION@APTES@FA-PEG@CQ nanodrug has cytotoxic, apoptotic and necrotic effects on HeLa and MCF-7 which are FR over expressed cell lines and can be potentially used for the delivery of quercetin to cervical and breast cancer cells.

Twenty-Five Years of Gene Therapy for ADA-SCID: From Bubble Babies to an Approved Drug.

Science.gov (United States)

Ferrua, Francesca; Aiuti, Alessandro

2017-11-01

Twenty-five years have passed since first attempts of gene therapy (GT) in children affected by severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) defect, also known by the general public as bubble babies. ADA-SCID is fatal early in life if untreated. Unconditioned hematopoietic stem cell (HSC) transplant from matched sibling donor represents a curative treatment but is available for few patients. Enzyme replacement therapy can be life-saving, but its chronic use has many drawbacks. This review summarizes the history of ADA-SCID GT over the last 25 years, starting from first pioneering studies in the early 1990s using gamma-retroviral vectors, based on multiple infusions of genetically corrected autologous peripheral blood lymphocytes. HSC represented the ideal target for gene correction to guarantee production of engineered multi-lineage progeny, but it required a decade to achieve therapeutic benefit with this approach. Introduction of low-intensity conditioning represented a crucial step in achieving stable gene-corrected HSC engraftment and therapeutic levels of ADA-expressing cells. Recent clinical trials demonstrated that gamma-retroviral GT for ADA-SCID has a favorable safety profile and is effective in restoring normal purine metabolism and immune functions in patients >13 years after treatment. No abnormal clonal proliferation or leukemia development have been observed in >40 patients treated experimentally in five different centers worldwide. In 2016, the medicinal product Strimvelis™ received marketing approval in Europe for patients affected by ADA-SCID without a suitable human leukocyte antigen-matched related donor. Positive safety and efficacy results have been obtained in GT clinical trials using lentiviral vectors encoding ADA. The results obtained in last 25 years in ADA-SCID GT development fundamentally contributed to improve patients' prognosis, together with earlier diagnosis thanks to newborn screening. These advances

The effectiveness of polyethylene glycol (PEG) and polyvinyl ...

African Journals Online (AJOL)

mahlos

2012-05-29

May 29, 2012 ... Key words: Acetone, tannin, polyethylene glycol (PEG), polyvinyl polypyrrolidone (PVPP). ... hydrolysable tannins may occur in the same plant. ..... Rev. Food Sci. Nutr., 38: 421-464. Cornell. (2000). Tannins: Chemical analysis.

DNA psi-condensation and reentrant decondensation: Effect of the PEG degree of polymerization

NARCIS (Netherlands)

Ramos, J.E.B.; Vries, de R.J.; Neto, J.R.

2005-01-01

¿-Condensation of DNA fragments of about 4 kbp was induced by poly(ethylene glycol) (PEG), with degrees of polymerization ranging from 45 to 182, and univalent salt (NaCl). Using circular dichroism spectroscopy, we were able to accurately determine the critical amount of PEG needed to induce

Functional reconstitution of prostaglandin E receptor from bovine adrenal medulla with guanine nucleotide binding proteins

International Nuclear Information System (INIS)

Negishi, M.; Ito, S.; Yokohama, H.; Hayashi, H.; Katada, T.; Ui, M.; Hayaishi, O.

1988-01-01

Prostaglandin E 2 (PEG 2 ) was found to bind specifically to a 100,000 x g pellet prepared from bovine adrenal medulla. The PGE receptor was associated with a GTP-binding protein (G-protein) and could be covalently cross-linked with this G-protein by dithiobis(succinimidyl propionate) in the 100,000 x g pellet. In order to characterize the G-protein associated with the PGE receptor and reconstitute these proteins in phospholipid vesicles, the authors purified the G-protein to apparent homogeneity from the 100,000 x g pellet. The G-protein served as a substrate of pertussis toxin but differed in its α subunit from two known pertussis toxin substrate G-proteins (G/sub i/ and G 0 ) purified from bovine brain. The molecular weight of the α subunit was 40,000, which is between those of G/sub i/ and G 0 . The purified protein was also distinguished immunologically from G/sub i/ and G 0 and was referred to as G/sub am/. Reconstitution of the PGE receptor with pure C/sub am/, G/sub i/, or G 0 in phospholipid vesicles resulted in a remarkable restoration of [ 3 H]PGE 2 binding activity in a GTP-dependent manner. The efficiency of these three G-proteins in this capacity was roughly equal. When pertussis toxin- or N-ethylmaleimide-treated G-proteins, instead of the native ones, were reconstituted into vesicles, the restoration of binding activity was no longer observed. These results indicate that the PGE receptor can couple functionally with G/sub am/, G/sub i/, or G 0 in phospholipid vesicles and suggest that G/sub am/ may be involved in signal transduction of the PGE receptor in bovine adrenal medulla

The optimal currency-peg for an oil exporting country: The case of Saudi Arabia

International Nuclear Information System (INIS)

Almasbahi, M.S.

1990-01-01

In a world of generalized floating exchange rates, it is not enough to solve the problem of exchange rate policy by determining whether to peg or float the currency under consideration. It is also necessary to choose to what major currency to peg. The main purpose of this study is to investigate and determine empirically the optimum currency peg for the Saudi riyal. To accomplish this goal, a simple conventional trade model, that includes variables found in many other studies of import and export demand, was used. In addition, an exchange rate term was added as a separate independent variable in the import and export demand equations in order to assess the effect of exchange rate on the trade flows. The criteria for the optimal currency peg in this study were based on two factors. First, the error statistics for projected imports and exports using alternative exchange rate regimes. Second, variances of projected imports, exports and trade balance using alternative exchange rate regimes. The exchange rate has a significant impact on the Saudia Arabian trade flows which implies that changes in the riyals value affect the Saudi trade deficit. Moreover, the exchange rate has a more powerful effect on its aggregate imports than on the world demand for its exports. There is also a strong support for the hypothesis that the exchange rate affects the value of the Saudi bilateral trade with its five major trade partners. On the aggregate level, the SDR peg seems to be the best currency peg for the Saudi riyal since it provides the best prediction errors and the lowest variance for the trade balance. Finally, on the disaggregate level, the US dollar provides the best performance and yields the best results among all the six currency pegs considered in this study

The Influence of PEG400 and Acetone on Polysulfone Membrane Morphology and Fouling Behaviour

Directory of Open Access Journals (Sweden)

P.T.P. Aryanti

2016-05-01

Full Text Available Modification of polysulfone ultrafiltration membrane was conducted by blending polysulfone with PEG400 and acetone as additives. The influence of each additive on the resulted membrane morphology and fouling characteristics were investigated. The experimental results showed that the hydrophilicity of the polysulfone membrane was improved by the increase of PEG400 in the polysulfone membrane. The water contact angle of the membrane was decreased from 76.1° to 38.31° when 35 %wt of PEG400 was added into the polysulfone solution, while the water content of the membrane was increased by around 38%. The high concentration of PEG400 in the polysulfone solution led to the formation of longer finger-like cavities in the membrane structure and resulted in a thicker membrane skin layer. The high concentration of PEG400 also contributed to the increase in hydraulic resistance of the membrane due to organic matter fouling. This problem could be minimized by the addition of acetone into the polysulfone solution, which resulted in a lower fouling resistance of organic matter during up to five hours of peat water filtration.

Enhancing relative permittivity by incorporating PDMS-PEG multiblock copolymers in binary polymer blends

DEFF Research Database (Denmark)

A Razak, Aliff Hisyam; Szabo, Peter; Skov, Anne Ladegaard

Polydimethylsiloxane (PDMS) elastomers are well-known to be soft and highly stretchable, yet they never achieve maximum elongation when utilised as dielectric elastomers, simply because their dielectric permittivity remains rather low. Conversely, polyethyleneglycols (PEG) are not stretchable......, but they do possess high permittivity. Combining two such polymers in a block copolymer allows for further crosslinking and presents the possibility of substantial improvements in the actuation response of the resulting dielectric elastomer – if carefully designed. The objective is to synthesise a PDMS......, the discontinuity in PEG can be acquired and the relative permittivity (ε’) is significantly enhanced (60%) with 5wt% of PDMS-PEG block copolymer incorporated into the silicone elastomer....

76 FR 57013 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

Science.gov (United States)

2011-09-15

... EQUAL EMPLOYMENT OPPORTUNITY COMMISSION 29 CFR Part 1602 RIN 3046-AA89 Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION... under title VII, the ADA, and GINA. (76 FR 31892, June 2, 2011). No requests to present oral testimony...

IDA and the Technical Cooperation Program Real-Time Systems and Ada Workshop, 21-23 June 1988

Science.gov (United States)

1988-06-01

IDA Memorandum Report M-540, IDA and the Technical Cooperation Program Real - Time Systems and Ada Workshop, 21-23 June 1988, documents the results of... time systems , (2) identify and clarify known Ada real-time issues, (3) identify near-term and long-term solutions, and (4) provide assessment and...Technology (ODUSD R&AT). Funding was provided by the STARS Joint Program Office. The objectives were to (1) define requirements for using Ada in real

The clinical meaningfulness of ADAS-Cog changes in Alzheimer's disease patients treated with donepezil in an open-label trial.

Science.gov (United States)

Rockwood, Kenneth; Fay, Sherri; Gorman, Mary; Carver, Daniel; Graham, Janice E

2007-08-30

In 6-month anti-dementia drug trials, a 4-point change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is held to be clinically important. We examined how this change compared with measures of clinical meaningfulness. This is a secondary analysis of a 12 month open-label study of 100 patients (71 women) diagnosed with mild to moderate AD treated with 5-10 mg of donepezil daily. We studied the observed case, 6-month change from baseline on the ADAS-Cog, the Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-Plus), patient-Goal Attainment Scaling (PGAS) and clinician-GAS (CGAS). At 6 months, donepezil-treated patients (n = 95) were more likely to show no change (+/- 3 points) on the ADAS-Cog (56%) than to improve (20%) or decline (24%) by 4-points. ADAS-Cog change scores were little correlated with other measures: from -0.09 for PGAS to 0.27 for the CIBIC-Plus. While patients who improved on the ADAS-Cog were less likely to decline on the clinical measures (26%), 43% of patients who declined on the ADAS-Cog improved on at least two of the clinical measures. The ADAS-Cog did not capture all clinically important effects. In general, ADAS-Cog improvement indicates clinical improvement, whereas many people with ADAS-Cog decline do not show clinical decline. The open-label design of this study does not allow us to know whether this is a treatment effect, which requires further investigation.

Polyethylene Glycol (PEG-3350, Colyte Poisoning due to Intra-Peritoneal Leakage in an Elderly Patient

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Jae Hee Chung

Full Text Available Polyethylene glycol (PEG-3350 is the most frequently used lavage solution for bowel cleansing prior to colonoscopy or elective surgery because its large molecular weight means that it is poorly absorbed. However, if it leaks into the peritoneal cavity, complications may arise. Few published studies have assessed the absorption, distribution, metabolism and excretion of PEG. Moreover, no published clinical data regarding complications due to the intra-peritoneal leakage of PEG-3350 could be found. We report on an elderly patient who developed the poisoning caused by leaking of PEG-3350 during bowel preparation. It resulted in severe metabolic acidosis, hypernatremia, hyperosmolality and a high anion gap, but it was effectively treated with early continuous renal replacement therapy after surgery.

Adenosine-deaminase (ADA activity in Psoriasis (A Preliminary Study

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S D Chaudhry

1988-01-01

Full Text Available Study of adenosine-deaminase activity ′in 23 patients hav-mg psoriasis compared with an equal number of healthy controls revealed significantly high ADA-activity in the psotiatic patients.

Targeted PEG-based bioconjugates enhance the cellular uptake and transport of a HIV-1 TAT nonapeptide.

Science.gov (United States)

Ramanathan, S; Qiu, B; Pooyan, S; Zhang, G; Stein, S; Leibowitz, M J; Sinko, P J

2001-12-13

We previously described the enhanced cell uptake and transport of R.I-K(biotin)-Tat9, a large ( approximately 1500 Da) peptidic inhibitor of HIV-1 Tat protein, via SMVT, the intestinal biotin transporter. The aim of the present study was to investigate the feasibility of targeting biotinylated PEG-based conjugates to SMVT in order to enhance cell uptake and transport of Tat9. The 29 kDa peptide-loaded bioconjugate (PEG:(R.I-Cys-K(biotin)-Tat9)8) used in these studies contained eight copies of R.I-K(biotin)-Tat9 appended to PEG by means of a cysteine linkage. The absorptive transport of biotin-PEG-3400 (0.6-100 microM) and the bioconjugate (0.1-30 microM) was studied using Caco-2 cell monolayers. Inhibition of biotin-PEG-3400 by positive controls (biotin, biocytin, and desthiobiotin) was also determined. Uptake of these two compounds was also determined in CHO cells transfected with human SMVT (CHO/hSMVT) and control cells (CHO/pSPORT) over the concentration ranges of 0.05-12.5 microM and 0.003-30 microM, respectively. Nonbiotinylated forms of these two compounds, PEG-3350 and PEG:(R.I-Cys-K-Tat9)8, were used in the control studies. Biotin-PEG-3400 transport was found to be concentration-dependent and saturable in Caco-2 cells (K(m)=6.61 microM) and CHO/hSMVT cells (K(m)=1.26 microM). Transport/uptake was significantly inhibited by positive control substrates of SMVT. PEG:(R.I-Cys-K(biotin)Tat9)8 also showed saturable transport kinetics in Caco-2 cells (K(m)=6.13 microM) and CHO/hSMVT cells (K(m)=8.19 microM). Maximal uptake in molar equivalents of R.I-Cys-K(biotin)Tat9 was 5.7 times greater using the conjugate versus the biotinylated peptide alone. Transport of the nonbiotinylated forms was significantly lower (PPEG-3400 and PEG:(R.I-Cys-K(biotin)Tat9)8 interact with human SMVT to enhance the cellular uptake and transport of these larger molecules and that targeted bioconjugates may have potential for enhancing the cellular uptake and transport of small peptide

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

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Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; Duross, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-08-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1-/-) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1-/- cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

Science.gov (United States)

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; DuRoss, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-01-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1−/−) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1−/− cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders. PMID:27572704

Biochemical detection of E-ADA on Neospora caninum tachyzoites and the effects of a specific enzymatic inhibitor

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Alexandre A. Tonin

2015-01-01

Full Text Available Objective. This study aimed to investigate the presence and activity of the ecto adenosine deaminase (E-ADA enzyme in tachyzoites of Neospora caninum (Nc-1 strain, as well as to assess the activity of a well-known E-ADA inhibitor, the deoxycoformycin. Materials and methods. The parasites were grown in cell culture, being subsequently separated in a pellet of tachyzoites, on which the E-ADA activity was tested using the concentrations 0 (control, 0.2, 0.4 and 0.8 mg mL-1. Results. The E-ADA showed high activity, progressively increasing its activity according to the enhancement of the protein concentration. The test was carried out with different concentrations of deoxycoformycin, showing that it was able to inhibit the E-ADA present on the free form of the parasite. Conclusions. Based on these results we conclude that the E-ADA is present on tachyzoites of N. caninum, and deoxycoformycin is able to inhibit this enzyme. In this sense, knowing the negative impact of N. caninum on reproductive issue in cattle (mainly abortion, might it is an alternative in order to deal with this parasitic infection.

Concomitant infection of Neospora caninum and Bovine Herpesvirus type 5 in spontaneous bovine abortions

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Maia S. Marin

2013-11-01

Full Text Available Bovine Herpesvirus type 5 (BoHV-5 has not been conclusively demonstrated to cause bovine abortion. Brain lesions produced by Neospora caninum and Bovine Herpesvirus type 1 (BoHV-1 exhibit common features. Therefore, careful microscopic evaluation and additional diagnostic procedures are required to achieve an accurate final etiological diagnosis. The aim of the present work was to investigate the occurrence of infections due to BoHV-1, BoHV-5 and N. caninum in 68 cases of spontaneous bovine abortions which showed microscopic lesions in the fetal central nervous system. This study allowed the identification of 4 (5.9% fetuses with dual infection by BoHV-5 and N. caninum and 33 (48.5% cases in which N. caninum was the sole pathogen identified. All cases were negative to BoHV-1. The results of this study provide evidence that dual infection by BoHV-5 and N. caninum occur during pregnancy in cattle; however, the role of BoHV-5 as a primary cause of bovine abortion needs further research. Molecular diagnosis of BoHV-5 and N. caninum confirmed the importance of applying complementary assays to improve the sensitivity of diagnosing bovine abortion.

Detection and identification of the atypical bovine pestiviruses in commercial foetal bovine serum batches.

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Hongyan Xia

Full Text Available The recently emerging atypical bovine pestiviruses have been detected in commercial foetal bovine serum (FBS of mainly South American origin so far. It is unclear how widely the viruses are presented in commercial FBS of different geographic origins. To further investigate the possible pestivirus contamination of commercially available FBS batches, 33 batches of FBS were obtained from ten suppliers and analysed in this study for the presence of both the recognised and the atypical bovine pestiviruses. All 33 batches of FBS were positive by real-time RT-PCR assays for at least one species of bovine pestiviruses. According to the certificate of analysis that the suppliers claimed for each batch of FBS, BVDV-1 was detected in all 11 countries and BVDV-2 was detected exclusively in the America Continent. The atypical pestiviruses were detected in 13 batches claimed to originate from five countries. Analysis of partial 5'UTR sequences showed a high similarity among these atypical bovine pestiviruses. This study has demonstrated, for the first time that commercial FBS batches of different geographic origins are contaminated not only with the recognised species BVDV-1 and BVDV-2, but also with the emerging atypical bovine pestiviruses.

A Versatile Star PEG Grafting Method for the Generation of Nonfouling and Nonthrombogenic Surfaces

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Pradeep Kumar Thalla

2013-01-01

Full Text Available Polyethylene glycol (PEG grafting has a great potential to create nonfouling and nonthrombogenic surfaces, but present techniques lack versatility and stability. The present work aimed to develop a versatile PEG grafting method applicable to most biomaterial surfaces, by taking advantage of novel primary amine-rich plasma-polymerized coatings. Star-shaped PEG covalent binding was studied using static contact angle, X-ray photoelectron spectroscopy (XPS, and quartz crystal microbalance with dissipation monitoring (QCM-D. Fluorescence and QCM-D both confirmed strong reduction of protein adsorption when compared to plasma-polymerized coatings and pristine poly(ethyleneterephthalate (PET. Moreover, almost no platelet adhesion was observed after 15 min perfusion in whole blood. Altogether, our results suggest that primary amine-rich plasma-polymerized coatings offer a promising stable and versatile method for PEG grafting in order to create nonfouling and nonthrombogenic surfaces and micropatterns.

Optimization of PEG-based extraction of polysaccharides from Dendrobium nobile Lindl. and bioactivity study.

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Zhang, Yi; Wang, Hongxin; Wang, Peng; Ma, ChaoYang; He, GuoHua; Rahman, Md Ramim Tanver

2016-11-01

Polyethylene glycol (PEG) as a green solvent was employed to extract polysaccharide. The optimal conditions for PEG-based ultrasonic extraction of Dendrobium nobile Lindl. polysaccharide (JCP) were determined by response surface methodology. Under the optimal conditions: extraction temperature of 58.5°C; ultrasound power of 193W, and the concentration of polyethylene glycol-200 (PEG-200) solution of 45%, the highest JCP yield was obtained as 15.23±0.57%, which was close to the predicted yield, 15.57%. UV and FT-IR analysis revealed the general characteristic absorption peaks of both JCP with water extraction (JCP w ) and PEG-200 solvent extraction (JCP p ). Thermal analysis of both JCPs was performed with Thermal Gravimetric Analyzer (TGA) and Differential Scanning Calorimeter (DSC). Antioxidant activities of two polysaccharides were also compared and no significant difference in vitro was obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

Can pleural adenosine deaminase (ADA) levels in pleural tuberculosis predict the presence of pulmonary tuberculosis? A CT analysis.

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Koh, Myung Je; Lee, In Jae; Kim, Joo-Hee

2016-06-01

To assess the relationship between imaging features of pulmonary tuberculosis at computed tomography (CT) and adenosine deaminase (ADA) values via pleural fluid analysis in patients with pleural tuberculosis. This retrospective study enrolled 60 patients who underwent fluid analysis for ADA and chest CT and were diagnosed with tuberculosis by culture or polymerase chain reaction of pleural fluid and sputum. The presence of centrilobular nodules, consolidation, cavitation, and mediastinal lymphadenopathy at CT were evaluated. The relationship between ADA values and the pattern of pulmonary involvement of tuberculosis was analysed. Pulmonary involvement was seen in 42 of the 60 patients. A centrilobular nodular pattern was seen in 37 and consolidation in 22. In 17 patients, both findings were identified. A centrilobular nodular pattern was more common than consolidation or cavitary lesions. When ADA values were high, pulmonary involvement was more frequent (p=0.002). Comparing low and high ADA groups using an obtained cut-off value of 80 IU/l, the high group had more frequent pulmonary involvement (pADA values had a higher probability of manifesting pulmonary tuberculosis. High ADA values may help predict contagious pleuroparenchymal tuberculosis. The most common pulmonary involvement of tuberculous pleurisy showed a centrilobular nodular pattern. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

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Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Insulin radioimmunoassay kit (125I) using polyethyleneglycol (PEG) and a double antibody separation method

International Nuclear Information System (INIS)

Borza, Virginia; Chariton, Delfina; Neacsu, Elena

1997-01-01

Insulin is a polypeptide hormone formed from proinsulin in the b-cells of the islets of Langerhans in the pancreas. It has a widespread effect on carbohydrate, lipid and protein metabolism. Diabetes mellitus is the result of an insulin deficiency brought about either by insufficient insulin secretion or by rapid insulin catabolism. The determination of the insulin level is important for differential etiologic diagnosis and subsequent therapy and prognosis. Insulin radioimmunoassay kit provides a sensitive, precise and specific assay for insulin concentration in serum. Standard and insulin in the patient sample compete with tracer for binding sites on an insulin antibody. The antigen-antibody combination, which forms during incubation time, will be separated from free insulin by different methods. The separation technique using the double antibody technique combined with Polyethyleneglycol (PEG) is presented. The results are compared with the separation method using PEG alone and with double antibody technique. Antiserum to insulin was produced in rats immunized with porcine insulin, while rabbits immunized with rat-g globulin were used as a source for the second antibody.The tested PEG was PEG 6000. The best results were obtained using the double antibody at a 1/50 dilution combined with 7.5 PEG solutions. The time for precipitating the antibody bound fraction by this technique was established to be 30 minutes. The results obtained using this method as separation technique for insulin - antibody complex were better than those obtained using the double antibody techniques or PEG as precipitating agent alone. (authors)

Vexatious Litigants and the ADA: Strategies to Fairly Address the Need to Improve Access for Individuals with Disabilities.

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Hull, Helia Garrido

2016-01-01

This Article addresses the need to reform the ADA to prevent vexatious litigation and to promote the underlying goals of the Act. Part I of this Article introduces the topic of vexatious litigation and the importance of remedying the effects of exploitation of the ADA. Part II provides an overview of the ADA and its efforts to increase accessibility to individuals with disabilities, emphasizing the provisions of the Act that create incentives to engage in vexatious litigation. Part III examines and analyzes the judiciary's response to vexatious litigation under the ADA, and sanctions that have been issued to limit exploitation. Finally, Part IV provides recommendations to reform the ADA and state disability law counterparts, suggests corrective actions to address vexatious litigation, and identifies methods to promote equality for individuals with disabilities.

ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency.

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Sauer, Aisha V; Mrak, Emanuela; Hernandez, Raisa Jofra; Zacchi, Elena; Cavani, Francesco; Casiraghi, Miriam; Grunebaum, Eyal; Roifman, Chaim M; Cervi, Maria C; Ambrosi, Alessandro; Carlucci, Filippo; Roncarolo, Maria Grazia; Villa, Anna; Rubinacci, Alessandro; Aiuti, Alessandro

2009-10-08

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children's growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling.

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

Science.gov (United States)

Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

2012-11-01

Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

Preparation of 99mTc-HYNIC-PEG-liposomes for imaging of the focal sites infection

International Nuclear Information System (INIS)

Hong, Jun Pyo; Awh, Ok Doo; Kim, Hyun Suk; Lee, Eun Sook; Lee, Tae Sup; Choi, Tae Hyun; Choi, Chang Woon; Lim, Sang Moo

2002-01-01

A new linker, hydrazino nicotinamide (HYNIC), was recently introduced for labelling of liposome with 99m Tc. In this study we synthesized HYNIC derivatized PEG (polyethylene glycol)-liposomes radiolabeled with 99m Tc. In order to synthesize HYNIC-DSPE (distearoyl phosphatidyl ethanolamine) which is a crucial component for 99m Tc chelation, first of all succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized from 6-chloronicotinic acid by three sequential reactions. A DSPE derivative of succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was transformed into HYNIC-DSPE by HCI/dioxane. HYNIC-PEG-liposomes were prepared by hydration of the dried lipid mixture of EPC (egg phosphatidyl choline): PEG-DSPE : HYNIC-DSPE: cholesterol (1.85:0.15:0.07:1, molar ratio). The HYNIC-PEG-liposomes were labeled with 99m Tc in the presence of SnCl 2 ·2H 2 O (a reducing agent) and tricine (a colignad). To investigate the level of in vivo transchelation of 99m Tc in the liposomes, the 99m Tc-HYNIC-PEG-liposomes were incubated with a molar excess of DTPA, cysteine or glutathione solutions at 37 .deg. C for 24 hours. 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized with 77.3% overall yield. The HYNIC concentration in the PEG-coated liposome dispersion was 1.08 mM. In condition of considering the measured liposome size of 106 nm, the phospholipid concentration of 77.5 μmol/ ml and the liposomal particle number of 5.2x10 14 liposomes/ml, it is corresponded to approximate 1,250 nicotinyl hydrazine group per liposome in HYNIC-PEG-liposome. The removal of free 99m Tc was not necessary because the labeling efficiency were above 99%. The radiolabeled liposomes maintained 98%, 96% and 99%, respectively, of radioactivity after incubation with transchelators. The radiolabeled liposomes possessed above 90% of the radioactivity in serum. These results suggest that the HYNIC can be synthesized easily and applied in labelling of PEG-liposomes with 99m Tc

Microelectrode Arrays and the Use of PEG-Functionalized Diblock Copolymer Coatings

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Sakshi Uppal

2014-09-01

Full Text Available PEG-modified diblock copolymer surfaces have been examined for their compatibility with microelectrode array based analytical methods. The use of PEG-modified polymer surfaces on the arrays was initially problematic because the redox couples used in the experiments were adsorbed by the polymer. This led the current measured by cyclic voltammetry for the redox couple to be unstable and increase with time. However, two key findings allow the experiments to be successful. First, after multiple cyclic voltammograms the current associated with the redox couple does stabilize so that a good baseline current can be established. Second, the rate at which the current stabilizes is consistent every time a particular coated array is used. Hence, multiple analytical experiments can be conducted on an array coated with a PEG-modified diblock copolymer and the data obtained is comparable as long as the data for each experiment is collected at a consistent time point.

Ultrasensitive probing of the protein resistance of PEG surfaces by secondary ion mass spectrometry

DEFF Research Database (Denmark)

Kingshott, P.; McArthur, S.; Thissen, H.

2002-01-01

The highly sensitive surface analytical techniques X-ray photoelectron spectroscopy (XPS) and time-of-flight static secondary ion mass spectrometry (ToF-SIMS) were used to test the resistance of poly(ethylene glycol) (PEG) coatings towards adsorption of lysozyme (LYS) and fibronectin (FN). PEG co...

Software/hardware distributed processing network supporting the Ada environment

Science.gov (United States)

Wood, Richard J.; Pryk, Zen

1993-09-01

A high-performance, fault-tolerant, distributed network has been developed, tested, and demonstrated. The network is based on the MIPS Computer Systems, Inc. R3000 Risc for processing, VHSIC ASICs for high speed, reliable, inter-node communications and compatible commercial memory and I/O boards. The network is an evolution of the Advanced Onboard Signal Processor (AOSP) architecture. It supports Ada application software with an Ada- implemented operating system. A six-node implementation (capable of expansion up to 256 nodes) of the RISC multiprocessor architecture provides 120 MIPS of scalar throughput, 96 Mbytes of RAM and 24 Mbytes of non-volatile memory. The network provides for all ground processing applications, has merit for space-qualified RISC-based network, and interfaces to advanced Computer Aided Software Engineering (CASE) tools for application software development.

Proteomic Analysis of Bovine Nucleolus

Institute of Scientific and Technical Information of China (English)

Amrutlal K.Patel; Doug Olson; Suresh K. Tikoo

2010-01-01

Nucleolus is the most prominent subnuclear structure, which performs a wide variety of functions in the eu-karyotic cellular processes. In order to understand the structural and functional role of the nucleoli in bovine cells,we analyzed the proteomie composition of the bovine nueleoli. The nucleoli were isolated from Madin Darby bo-vine kidney cells and subjected to proteomie analysis by LC-MS/MS after fractionation by SDS-PAGE and strongcation exchange chromatography. Analysis of the data using the Mascot database search and the GPM databasesearch identified 311 proteins in the bovine nucleoli, which contained 22 proteins previously not identified in theproteomic analysis of human nucleoli. Analysis of the identified proteins using the GoMiner software suggestedthat the bovine nueleoli contained proteins involved in ribosomal biogenesis, cell cycle control, transcriptional,translational and post-translational regulation, transport, and structural organization.

New scoring methodology improves the sensitivity of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials.

Science.gov (United States)

Verma, Nishant; Beretvas, S Natasha; Pascual, Belen; Masdeu, Joseph C; Markey, Mia K

2015-11-12

As currently used, the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) has low sensitivity for measuring Alzheimer's disease progression in clinical trials. A major reason behind the low sensitivity is its sub-optimal scoring methodology, which can be improved to obtain better sensitivity. Using item response theory, we developed a new scoring methodology (ADAS-CogIRT) for the ADAS-Cog, which addresses several major limitations of the current scoring methodology. The sensitivity of the ADAS-CogIRT methodology was evaluated using clinical trial simulations as well as a negative clinical trial, which had shown an evidence of a treatment effect. The ADAS-Cog was found to measure impairment in three cognitive domains of memory, language, and praxis. The ADAS-CogIRT methodology required significantly fewer patients and shorter trial durations as compared to the current scoring methodology when both were evaluated in simulated clinical trials. When validated on data from a real clinical trial, the ADAS-CogIRT methodology had higher sensitivity than the current scoring methodology in detecting the treatment effect. The proposed scoring methodology significantly improves the sensitivity of the ADAS-Cog in measuring progression of cognitive impairment in clinical trials focused in the mild-to-moderate Alzheimer's disease stage. This provides a boost to the efficiency of clinical trials requiring fewer patients and shorter durations for investigating disease-modifying treatments.

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

Science.gov (United States)

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-11-01

Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. After faecal disimpaction, patients PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

Longer-term effects of ADAS use on speed and headway control in drivers diagnosed with Parkinson's disease.

Science.gov (United States)

Dotzauer, Mandy; Caljouw, Simone R; De Waard, Dick; Brouwer, Wiebo H

2015-01-01

An advanced driver assistance system (ADAS) provided information about speed limits, speed, speeding, and following distance. Information was presented to the participants by means of a head-up display. Effects of the information on speed and headway control were studied in a longer-term driving simulator study including 12 repeated measures spread out over 4 weeks. Nine healthy older drivers between the ages of 65 and 82 years and 9 drivers between the ages of 68 and 82 years diagnosed with Parkinson's disease (PD) participated in the study. Within the 4 weeks, groups completed 12 consecutive sessions (10 with ADAS and 2 without ADAS) in a driving simulator. Results indicate an effect of ADAS use on performance. Removing ADAS after short-term exposure led to deterioration of performance in all speed measures in the group of drivers diagnosed with PD. These results suggest that provision of traffic information was utilized by drivers diagnosed with PD in order to control their speed.

Evaluation of the adenosine deaminase (ADA) G22A gene polymorphism with recurrent spontaneous abortion among Egyptian patients

Science.gov (United States)

Abu-Gabal, Khadiga; Katta, Maha; Ibrahim, Raghda

2017-01-01

Introduction Adenosine and deoxyadenosine metabolism is influenced by adenosine deaminase (ADA) enzyme. ADA increases in different diseases and is considered as one of the markers for cell-mediated immunity. Pregnancy is associated with depressed cell-mediated immunity. The level of ADA expression, which seems to play a key role in maintaining pregnancy, is influenced by adenosine deaminase G22A gene polymorphism. We aimed in our study to evaluate the association of ADA G22A gene polymorphism with recurrent spontaneous abortion (RSA) in Egyptian women. Material and methods Adenosine deaminase G22A gene polymorphism was genotyped in 40 patients (age range 22-39 years) with a history of RSA, selected from those attending the Gynaecology and Obstetrics Clinic of Beni-Suef University Hospital, and 20 age-matched healthy women as a control group, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results In our study, no statistically significant difference was found between RSA patients and control group as regards ADA G22A genotypes (p = 0.653) and alleles (p = 0.697). A comparison of the frequencies of ADA alleles in RSA patients as regards the below-35-years-old age group revealed that ADA 2(A) allele was associated with a low risk for RSA in patients aged 35 years old or younger (p = 0.008). Conclusions In conclusion, our study revealed an age-dependent protective value of ADA 2(A) allele in recurrent spontaneous abortions among the Egyptian population. PMID:29204093

Can pleural adenosine deaminase (ADA) levels in pleural tuberculosis predict the presence of pulmonary tuberculosis? A CT analysis

International Nuclear Information System (INIS)

Koh, Myung Je; Lee, In Jae; Kim, Joo-Hee

2016-01-01

Aim: To assess the relationship between imaging features of pulmonary tuberculosis at computed tomography (CT) and adenosine deaminase (ADA) values via pleural fluid analysis in patients with pleural tuberculosis. Materials and methods: This retrospective study enrolled 60 patients who underwent fluid analysis for ADA and chest CT and were diagnosed with tuberculosis by culture or polymerase chain reaction of pleural fluid and sputum. The presence of centrilobular nodules, consolidation, cavitation, and mediastinal lymphadenopathy at CT were evaluated. The relationship between ADA values and the pattern of pulmonary involvement of tuberculosis was analysed. Results: Pulmonary involvement was seen in 42 of the 60 patients. A centrilobular nodular pattern was seen in 37 and consolidation in 22. In 17 patients, both findings were identified. A centrilobular nodular pattern was more common than consolidation or cavitary lesions. When ADA values were high, pulmonary involvement was more frequent (p=0.002). Comparing low and high ADA groups using an obtained cut-off value of 80 IU/l, the high group had more frequent pulmonary involvement (p<0.001). Conclusion: Patients with tuberculous pleurisy who had high ADA values had a higher probability of manifesting pulmonary tuberculosis. High ADA values may help predict contagious pleuroparenchymal tuberculosis. The most common pulmonary involvement of tuberculous pleurisy showed a centrilobular nodular pattern. - Highlights: • To know the relationship of ADA values and pulmonary involvement pattern of pleural tuberculosis. • To help exact diagnosis of pleuroparenchymal tuberculosis in clinical setting. • The imaging findings of pleuroparenchymal tuberculosis.

O6-methylguanine-DNA methyltransferase in wild-type and ada mutants of Escherichia coli

International Nuclear Information System (INIS)

Mitra, S.; Pal, B.C.; Foote, R.S.

1982-01-01

O 6 -Methylguanine-DNA methyltransferase is induced in Escherichia coli during growth in low levels of N-methyl-N'-nitro-N-nitrosoguanidine. We have developed a sensitive assay for quantitating low levels of this activity with a synthetic DNA substrate containing 3 H-labeled O 6 -methylguanine as the only modified base. Although both wild-type and adaptation-deficient (ada) mutants of E. coli contained low but comparable numbers (from 13 to 60) of the enzyme molecules per cell, adaptation treatment caused a significant increase of the enzyme in the wild type but not in the ada mutants, suggesting that the ada mutation is in a regulatory locus and not in the structural gene for the methyltransferase

Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

International Nuclear Information System (INIS)

Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N; Wu Fang; Zhao Weiwei

2011-01-01

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l -1 . Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α v β 3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

Energy Technology Data Exchange (ETDEWEB)

Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N [Department of Chemistry, Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Wu Fang [Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Zhao Weiwei, E-mail: bergeye@buffalo.edu, E-mail: pnprasad@buffalo.edu [Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, NY 14215 (United States)

2011-04-22

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l{sup -1}. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the {alpha}{sub v{beta}3} integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

Fluorescent water-Soluble Probes Based on Ammonium Cation Peg Substituted Perylenepisimides: Synthesis, Photophysical Properties, and Live Cell Images

Science.gov (United States)

Yang, Wei; Cai, Jiaxuan; Zhang, Shuchen; Yi, Xuegang; Gao, Baoxiang

2018-01-01

To synthesize perylenbisimides (PBI) fluorescent probes that will improve the water-soluble ability and the cytocompatibility, the synthesis and properties of fluorescent water-soluble probes based on dendritic ammonium cation polyethylene glycol (PEG) substituted perylenebisimides(GPDIs) are presented. As we expected, with increased ammonium cation PEG, the aggregation of the PBI in an aqueous solution is completely suppressed by the hydrophilic ammonium cation PEG groups. And the fluorescence quantum yield increases from 25% for GPDI-1 to 62% for GPDI-2. When incubated with Hela cells for 48 h, the viabilities are 71% (for GPDI-1) and 76% (for GPDI-2). Live cell imaging shows that these probes are efficiently internalized by HeLa cells. The study of the photophysical properties indicated increasing the ammonium cation PEG generation can increase the fluorescence quantum yield. Live cell imaging shows that with the ammonium cation PEG chains of perylenebisimides has high biocompatibility. The exceptionally low cytotoxicity is ascribed to the ammonium cation PEG chains, which protect the dyes from nonspecifically interacting with the extracellular proteins. Live cell imaging shows that ammonium cations PEG chains can promote the internalization of these probes.

Construction and characterization of Gal-chitosan graft methoxy poly (ethylene glycol) (Gal-CS-mPEG) nanoparticles as efficient gene carrier

Science.gov (United States)

Jin, Jiting; Fu, Wandong; Liao, Miaofei; Han, Baoqin; Chang, Jing; Yang, Yan

2017-10-01

In the present study, galactosylated chitosan (Gal-CS) was conjugated with methoxy poly(ethylene glycol) (mPEG) as a hydrophilic group. The structure of Gal-CS-mPEG polymer was characterized and the nanoparticles (NPs) were prepared using ironic gelation method. The study was designed to investigate the characteristics and functions of Gal-CS-mPEG NPs. The morphology of Gal-CS-mPEG NPs was observed by SEM and it was a compact and spherical shape. The size of the NPs was approximately 200 nm in diameter under the ideal process parameters. The interaction between Gal-CS-mPEG NPs and pDNA, and the protection of pDNA against DNase I and serum degradation by Gal-CS-mPEG NPs were evaluated. Agarose gel electrophoresis results showed that Gal-CS-mPEG NPs had strong interaction with pDNA at the weight ratio of 12:1, 4:1 and 2:1 and could protect pDNA from DNase I and serum degradation. Gal-CS-mPEG NPs exhibited high loading efficiency and sustainable in vitro release. The blood compatibility studies demonstrated that Gal-CS-mPEG NPs had superior compatibility with erythrocytes in terms of aggregation degree and hemolysis level. Gal-CS-mPEG NPs showed no cytotoxicity on L929 cells, which is a normal mouse connective tissue fibroblast, but showed inhibitory effects on the proliferation of Bel-7402 cells, which is a liver cancer cell line. In conclusion, Gal-CS-mPEG NP is a bio-safe and efficient gene carrier with potential application in gene delivery.

Feasibility and Safety of Overtubes for PEG-Tube Placement in Patients with Head and Neck Cancer

Directory of Open Access Journals (Sweden)

Crispin O. Musumba

2015-01-01

Full Text Available Background. Percutaneous endoscopic gastrostomy (PEG placement using the “pull” technique is commonly utilized for providing nutritional support in head and neck cancer (HNC patients, but it may be complicated by peristomal metastasis in up to 3% of patients. Overtube-assisted PEG placement might reduce this risk. However, this technique has not been systemically studied for this purpose to date. Methods. Retrospective analysis of consecutive patients with HNC who underwent overtube-assisted PEG placement at Westmead Hospital, Australia, between June 2011 and December 2013. Data were extracted from patients’ endoscopy reports and case notes. We present our technique for PEG insertion and discuss the feasibility and safety of this method. Results. In all 53 patients studied, the PEG tubes were successfully placed using 25 cm long flexible overtubes, in 89% prophylactically (before commencing curative chemoradiotherapy, and in 11% reactively (for treatment of tumor related dysphagia or weight loss. During a median follow-up period of 16 months, 3 (5.7% patients developed peristomal infection and 3 others developed self-limiting peristomal pain. There were no cases of overtube-related adverse events or overt cutaneous metastases observed. Conclusions. Overtube-assisted PEG placement in patients with HNC is a feasible, simple, and safe technique and might be effective for preventing cutaneous metastasis.

ADA, the Programming Language of Choice for the UPMSat-2 Satellite

Science.gov (United States)

Garrido, Jorge; Zamorano, Juan; de la Puente, Juan A.; Alonso, Alejandro; Salazar, Emilio

2015-09-01

The proper selection of development mechanisms and tools is essential for the final success of any engineering project. This is also true when it comes to software development. Furthermore, when the system shows very specific and hard to meet requirements, as it happens for high-integrity real-time systems, the appropriate selection is crucial. For this kind of systems, Ada has proven to be a successful companion, and satellites are not an exception. The paper presents the reasons behind the selection of Ada for the UPMSat-2 development, along with the experience and examples on its usage.

Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles

Directory of Open Access Journals (Sweden)

Cai LL

2013-12-01

Full Text Available Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, 3State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 4Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada *These authors contributed equally to this paperAbstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa methoxy poly(ethylene glycol methyl ether (mPEG to gambogic acid (GA-mPEG2000 through an ester linkage and characterized by 1H nuclear magnetic resonance. The GA-mPEG2000 conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG2000 micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide tests demonstrated that the GA-mPEG2000 micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG2000 micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG2000 micelles may have promising applications in tumor therapy.Keywords: gambogic acid, poly(ethylene glycol-drug conjugate, micelle, antitumor, toxicity

Dose response of PEG 3350 for the treatment of childhood fecal impaction.

Science.gov (United States)

Youssef, Nader N; Peters, John M; Henderson, Wendy; Shultz-Peters, Sandra; Lockhart, Danielle K; Di Lorenzo, Carlo

2002-09-01

To investigate the efficacy and safety of polyethylene glycol (PEG) 3350 in the treatment of childhood fecal impaction. This was a prospective, double-blind, parallel, randomized study of 4 doses of PEG 3350; 0.25 g/kg per day, 0.5 g/kg per day, 1 g/kg per day, 1.5 g/kg per day, given for 3 days in children with constipation for >3 months and evidence of fecal impaction. Forty patients completed the study (27 boys, median age 7.5, range 3.3-13.1 years). Disimpaction occurred in 75% of children, with a significant difference between the two higher doses and the lower doses (95% vs 55%, P PEG 3350 is safe and effective in the treatment of childhood fecal impaction at doses of 1 and 1.5 g/kg per day.

Olimpíadas e geopolítica

Directory of Open Access Journals (Sweden)

João Fábio Bertonha

2008-09-01

Full Text Available

o artigo trata de competições esportivas,

em especial as olimpíadas. Nelas, valorizam-se o

nacionalismo e o poder dos países.

Preparation and mechanical properties of PLA-PEG copolymers modified by radiation-induced crosslinking of low energy electron beams

International Nuclear Information System (INIS)

Peikai Miao; Wenrui Tang; Ke Zeng; Yan Tang; Yipeng Wang; Hongfei Zhou; Ke Zhou; Tao Liu; Gang Yang

2007-01-01

PLA-PEG copolymer is wildly applied in medical and pharmaceutical fields, but its mechanical properties are not so good, such as the tensile intensity and elongation at break. To improve these properties, PLA-PEG copolymers were synthesized and irradiated using low energy electron beams (EB) with various irradiation doses in the presence of 3 wt% polyfunctional monomer (triallylcyanurate, TAC) as crosslinking agent to introduce crosslinking between polymer chains. It was found that with the increase of the irradiation doses, the tensile intensity of the PLA-PEG increased, while the elongation at break decreased, the most optimal irradiation dose was 80 kGy, the tensile intensity was 12.5 MPa and 19.9 MPa, corresponding to the elongation at break of 282.8 % and 28.7% for PLA9-PEG6 and PLA11-PEG6, respectively. Meanwhile, the solvent resistance of crosslinked sample was improved obviously at this dose. The crosslinked PLA-PEG copolymer can be applied to packaging materials, tubes and so on. (Author)

Viral infections and bovine mastitis: a review

NARCIS (Netherlands)

Wellenberg, G.J.; Poel, van der W.H.M.; Oirschot, van J.T.

2002-01-01

This review deals with the role of viruses in the aetiology of bovine mastitis. Bovine herpesvirus 1, bovine herpesvirus 4, foot-and-mouth disease virus, and parainfluenza 3 virus have been isolated from milk from cows with clinical mastitis. Intramammary inoculations of bovine herpesvirus 1 or

{sup 18}F-PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, {sup 18}F-labelling and an in-vitro assessment of its binding with Neutravidin{sup TM}-trastuzumab pre-treated cells

Energy Technology Data Exchange (ETDEWEB)

Smith, Tim A.D., E-mail: t.smith@abdn.ac.uk [Biomedical Physics Building, John Mallard PET Unit, Aberdeen Biomedical Imaging Centre, School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Simpson, Michael; Cheyne, Richard [Biomedical Physics Building, John Mallard PET Unit, Aberdeen Biomedical Imaging Centre, School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); School of Natural and Computing Sciences, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom); Trembleau, Laurent [School of Natural and Computing Sciences, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom)

2011-10-15

In terms of nuclear decay {sup 18}F is the most ideal PET nuclide but its short t{sub 1/2} precludes its use for directly labelling whole antibodies due to their long blood residence times. Pre-targeted imaging using affinity systems such as Neutravidin{sup TM}-biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin{sup TM}-conjugated antibodies. Methods: Boroaryl functionalised biotin was prepared with a PEG linker and radiolabelled by incubation with {sup 18}F in acidified aqueous solution. Cells expressing high (SKBr3), medium (MDA-MB-453) and low (MDA-MB-468) levels of HER-2 were pre-incubated with Neutravidin{sup TM}-conjugated trastuzumab, washed, and then incubated with {sup 18}F-PEG-biotin. Results: The {sup 18}F-fluorination of boroaryl-PEG-biotin was much more efficient than reported for other versions of boroaryl-biotin. The novel {sup 18}F-PEG-biotin was demonstrated to bind to HER-2-expressing cells in-vitro pre-incubated with Neutravidin{sup TM}-conjugated trastuzumab. Conclusion: Biotin can be functionalised with boroaryl and readily {sup 18}F-radiolabelled in aqueous solution and will bind to cells pre-incubated with Neutravidin{sup TM}-antibody conjugates. - Highlights: > Boroaryl-biotin precursor is prepared. > Rapid {sup 18}F-fluorination is demonstrated. > HER-2 expressing breast cancer cells pre-treated with trastuzumab-Neutravidin{sup TM}. > {sup 18}F-PEG-biotin binding to pre-treated cells corresponds with HER-2 expression.

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): Modifications and Responsiveness in Pre-Dementia Populations. A Narrative Review.

Science.gov (United States)

Kueper, Jacqueline K; Speechley, Mark; Montero-Odasso, Manuel

2018-01-01

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was developed in the 1980s to assess the level of cognitive dysfunction in Alzheimer's disease. Advancements in the research field have shifted focus toward pre-dementia populations, and use of the ADAS-Cog has extended into these pre-dementia studies despite concerns about its ability to detect important changes at these milder stages of disease progression. If the ADAS-Cog cannot detect important changes, our understanding of pre-dementia disease progression may be compromised and trials may incorrectly conclude that a novel treatment approach is not beneficial. The purpose of this review was to assess the performance of the ADAS-Cog in pre-dementia populations, and to review all modifications that have been made to the ADAS-Cog to improve its measurement performance in dementia or pre-dementia populations. The contents of this review are based on bibliographic searches of electronic databases to locate all studies using the ADAS-Cog in pre-dementia samples or subsamples, and to locate all modified versions. Citations from relevant articles were also consulted. Overall, our results suggest the original ADAS-Cog is not an optimal outcome measure for pre-dementia studies; however, given the prominence of the ADAS-Cog, care must be taken when considering the use of alternative outcome measures. Thirty-one modified versions of the ADAS-Cog were found. Modification approaches that appear most beneficial include altering scoring methodology or adding tests of memory, executive function, and/or daily functioning. Although modifications improve the performance of the ADAS-Cog, this is at the cost of introducing heterogeneity that may limit between-study comparison.

Quantitative analysis of polyethylene glycol (PEG) and PEGylated proteins in animal tissues by LC-MS/MS coupled with in-source CID.

Science.gov (United States)

Gong, Jiachang; Gu, Xiaomei; Achanzar, William E; Chadwick, Kristina D; Gan, Jinping; Brock, Barry J; Kishnani, Narendra S; Humphreys, W Griff; Iyer, Ramaswamy A

2014-08-05

The covalent conjugation of polyethylene glycol (PEG, typical MW > 10k) to therapeutic peptides and proteins is a well-established approach to improve their pharmacokinetic properties and diminish the potential for immunogenicity. Even though PEG is generally considered biologically inert and safe in animals and humans, the slow clearance of large PEGs raises concerns about potential adverse effects resulting from PEG accumulation in tissues following chronic administration, particularly in the central nervous system. The key information relevant to the issue is the disposition and fate of the PEG moiety after repeated dosing with PEGylated proteins. Here, we report a novel quantitative method utilizing LC-MS/MS coupled with in-source CID that is highly selective and sensitive to PEG-related materials. Both (40K)PEG and a tool PEGylated protein (ATI-1072) underwent dissociation in the ionization source of mass spectrometer to generate a series of PEG-specific ions, which were subjected to further dissociation through conventional CID. To demonstrate the potential application of the method to assess PEG biodistribution following PEGylated protein administration, a single dose study of ATI-1072 was conducted in rats. Plasma and various tissues were collected, and the concentrations of both (40K)PEG and ATI-1072 were determined using the LC-MS/MS method. The presence of (40k)PEG in plasma and tissue homogenates suggests the degradation of PEGylated proteins after dose administration to rats, given that free PEG was absent in the dosing solution. The method enables further studies for a thorough characterization of disposition and fate of PEGylated proteins.

Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules.

Science.gov (United States)

Mosqueira, V C; Legrand, P; Gulik, A; Bourdon, O; Gref, R; Labarre, D; Barratt, G

2001-11-01

The aim of our work was to examine the relationship between modifications of the surface of nanocapsules (NC) by adsorption or covalent grafting of poly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content on complement activation (C3 cleavage) and on uptake by macrophages. The physicochemical characterization of the NC included an investigation of their properties, such as surface charge, size, hydrophilicity, morphology and homogeneity. This is the first time that such properties have been correlated with biological interactions for NC, a novel carrier system with a structure more complex than nanospheres. C3 crossed immunoelectrophoresis revealed the reduced activation for NC with longer PEG chain and higher density, although all formulations induced C3 cleavage to a lesser or greater extent. NC bearing PEG covalently bound to the surface were weaker activators of complement than plain PLA [poly(D,L-lactide)] NC or nanospheres (NS). Furthermore, the fluorescent/confocal microscopy of J774A1 cells in contact with NC reveal a dramatically reduced interaction with PEG-bearing NC. However, the way in which PEG was attached (covalent or adsorbed) seemed to affect the mechanism of uptake. Taken together, these results suggest that the low level of protein binding to NC covered with a high density of 20kDa PEG chains is likely to be due to the steric barriers surrounding these particles, which prevents protein adsorption and reduces their interaction with macrophages.

Nursing Issues in Patients with PEG

OpenAIRE

Konířová, Lenka

2013-01-01

Bachelor thesis were written on theoretic-empirical bases. The theoretical part is dedicated to general introduction into anatomy and physiology of stomach. The following chapter is about nutrition, the explanation of the terms malnutrioton, nutritional support, enteral nutrition as well as its indications, contraindications, complications, types and forms of artificial nutrition included. The core chapter is about the implementation and treatement of PEG, the psychosocial aspects and specifi...

Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome.

Science.gov (United States)

Chapman, R W; Stanghellini, V; Geraint, M; Halphen, M

2013-09-01

Polyethylene glycol (PEG) 3350 plus electrolytes (PEG 3350+E) is an established treatment for constipation and has been proposed as a treatment option for constipation associated with irritable bowel syndrome (IBS-C). This study aimed to compare the efficacy and safety of PEG 3350+E vs. placebo in adult patients with IBS-C. Following a 14-day run-in period without study medication, patients with confirmed IBS-C were randomized to receive PEG 3350+E (N=68) or placebo (N=71) for 28 days. The primary endpoint was the mean number of spontaneous bowel movements (SBMs) per day in the last treatment week. In both groups, mean weekly number of SBMs (±s.d.) increased from run-in. The difference between the groups in week 4 (PEG 3350+E, 4.40±2.581; placebo, 3.11±1.937) was statistically significant (95% confidence interval: 1.17, 1.95; PPEG 3350+E, there was no difference vs. placebo. Spontaneous complete bowel movements, responder rates, stool consistency, and severity of straining also showed superior improvement in the PEG 3350+E group over placebo in week 4. The most common drug related treatment-emergent adverse events were abdominal pain (PEG 3350+E, 4.5%; placebo, 0%) and diarrhoea (PEG 3350+E, 4.5%; placebo, 4.3%). In IBS-C, PEG 3350+E was superior to placebo for relief of constipation, and although a statistically significant improvement in abdominal discomfort/pain was observed compared with baseline, there was no associated improvement compared with placebo. PEG 3350+E is a well-established and effective treatment that should be considered suitable for use in IBS-C.

Facile Photoimmobilization of Proteins onto Low-Binding PEG-Coated Polymer Surfaces

DEFF Research Database (Denmark)

Larsen, Esben Kjær Unmack; Mikkelsen, Morten Bo Lindholm; Larsen, Niels Bent

2014-01-01

was verified for both enzymes and antibodies, and their presence on the surface was confirmed by X-ray photoelectron spectroscopy (XPS) and confocal fluorescence microscopy. Conjugation of capture antibody onto the PEG coating was employed for a simplified ELISA protocol without the need for blocking uncoated...... surface areas, showing ng/mL sensitivity to a cytokine antigen target. Moreover, spatially patterned attachment of fluorescently labeled protein onto the low-binding PEG-coated surface was achieved with a projection lithography system that enabled the creation of micrometer-sized protein features....

76 FR 14745 - Notice To Rescind a Notice of Intent To Prepare an Environmental Impact Statement, Ada and Canyon...

Science.gov (United States)

2011-03-17

... To Prepare an Environmental Impact Statement, Ada and Canyon Counties, ID AGENCY: Federal Highway... prepare an Environmental Impact Statement for a proposed highway project in Ada and Canyon County, Idaho... Highway 44 from Exit 25 at Interstate 84 in Canyon County to Ballantyne Lane in Ada County. The project is...

Evaluating rivastigmine in mild-to-moderate Parkinson's disease dementia using ADAS-cog items.

Science.gov (United States)

Schmitt, Frederick A; Aarsland, Dag; Brønnick, Kolbjørn S; Meng, Xiangyi; Tekin, Sibel; Olin, Jason T

2010-08-01

Rivastigmine has been shown to improve cognition in patients with Parkinson's disease dementia (PDD). To further explore the impact of anticholinesterase therapy on PDD, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) items were assessed in a retrospective analysis of a 24-week, double-blind, placebo-controlled trial of rivastigmine. Mean changes from baseline at week 24 were calculated for ADAS-cog item scores and for 3 cognitive domain scores. A total of 362 patients were randomized to 3 to 12 mg/d rivastigmine capsules and 179 to placebo. Patients with PDD receiving rivastigmine improved versus placebo on items: word recall, following commands, ideational praxis, remembering test instructions, and comprehension of spoken language (P ADAS-cog is sensitive to broad cognitive changes in PDD. Overall, rivastigmine was associated with improvements on individual cognitive items and general cognitive domains.

Evaluation of self-assembled HCPT-loaded PEG-b-PLA nanoparticles by comparing with HCPT-loaded PLA nanoparticles.

Science.gov (United States)

Yang, Xiangrui; Wu, Shichao; Wang, Yange; Li, Yang; Chang, Di; Luo, Yin; Ye, Shefang; Hou, Zhenqing

2014-12-01

We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(D,L-lactide) (PEG-b-PLA) and PLA, respectively. Both HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of -31.2 and -45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG-b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG-b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG-b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

75 FR 45661 - Notice of Permanent Closure on Public Lands in Ada County, ID

Science.gov (United States)

2010-08-03

... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLIDB00100 L17110000.PH0000 241A 4500013040] Notice of Permanent Closure on Public Lands in Ada County, ID AGENCY: Bureau of Land Management, Interior.../2\\NW\\1/4\\ NW\\1/4\\ and N\\1/2\\SW\\1/4\\ NW\\1/4\\ of Section 32, T.1 S., R.3 E., Boise Meridian, Ada...

Evaluation of a novel GRPR antagonist for prostate cancer PET imaging: [64Cu]-DOTHA2-PEG-RM26.

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Mansour, Nematallah; Paquette, Michel; Ait-Mohand, Samia; Dumulon-Perreault, Véronique; Guérin, Brigitte

2018-01-01

Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHA 2 ). Here we investigated the potential of a novel DOTHA 2 -conjugated, 64 Cu-radiolabeled GRPR peptide antagonist, [D-Phe 6 -Sta 13 -Leu 14 -NH 2 ]bombesin(6-14) (DOTHA 2 -PEG-RM26) to visualize prostate tumors by PET imaging. DOTHA 2 -PEG-RM26 was conveniently and efficiently assembled on solid support. The compound was radiolabeled with 64 Cu and its affinity, stability, cellular uptake on PC3 prostate cancer cells were evaluated. The in vitro and in vivo behavior of [ 64 Cu]DOTHA 2 -PEG-RM26 was examined by PET imaging using human PC3 prostate cancer xenografts and its behavior was compared to that of the analogous [ 64 Cu]NOTA-PEG-RM26. The inhibition constant of nat Cu-DOTHA 2 -PEG-RM26 was in the low nanomolar range (0.68±0.19 nM). The [ 64 Cu]DOTHA 2 -PEG-RM26 conjugate was prepared with a labeling yield >95% and molar activity of 56±3 GBq/μmol after a 5-min room temperature labeling. [ 64 Cu]-DOTHA 2 -PEG-RM26 demonstrated rapid blood and renal clearance as well as a high tumor uptake. Small animal PET images confirmed high and specific uptake in PC3 tumor. Both [ 64 Cu]-DOTHA 2 -PEG-RM26 and [ 64 Cu]-NOTA-PEG-RM26 displayed similar tumor and normal tissue uptakes at early time point post injection. [ 64 Cu]-DOTHA 2 -PEG-RM26 allows visualization of prostate tumors by PET imaging. DOTHA 2 enables fast 64 Cu chelation under mild condition, and as such could be used advantageously for the development of other 64 Cu-labeled peptide-derived PET tracers. Copyright © 2017 Elsevier Inc. All rights reserved.

An Arabic Version of the Cognitive Subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog): Reliability, Validity, and Normative Data.

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Ben Jemaa, Sonia; Attia Romdhane, Neila; Bahri-Mrabet, Amel; Jendli, Adel; Le Gall, Didier; Bellaj, Tarek

2017-01-01

The Alzheimer's Disease Assessment Scale's cognitive subscale (ADAS-Cog) is the most widely used instrument for screening cognitive dysfunction in Alzheimer's disease. The aim of the present study was to develop an Arabic version of this scale (A-ADAS-Cog), examine its psychometric properties (reliability and validity), and provide normative data. The A-ADAS-Cog), an Arabic version of the Mini-Mental State Examination (A-MMSE), and a Standardized Clinical Dementia Rating Scale (CDR) were administered to three Tunisian groups: 124 normal controls (NC), 33 patients with non-Alzheimer dementia (N-AD), and 25 patients with Alzheimer's disease (AD). The A-ADAS-Cog scores were significantly affected by age and education. A correction table was constructed to control these effects. The results showed that the A-ADAS-Cog has good internal consistency and reliability (α= 0.82 for AD). The test-retest reliability of the A-ADAS-Cog was stable over time (r = 0.97). An evaluation of the construct validity of the A-ADAS-Cog using principal component analysis led to a solution with three factors (memory, language and praxis), which explained 72% of the variance. The concurrent validity of the A-ADAS-Cog was established using the A-MMSE score (r = -0.86), CDR Sum of Boxes score (CDR-SB; r = 0.87), and global CDR score (CDR-Global; r = 0.74). Finally, the A-ADAS-Cog has an excellent discriminating power in the diagnosis of AD (ROC area = 0.92). A cut-off score of 10 (sensitivity = 84% and specificity = 91%) is indicated for the screening of the AD. Overall, the results indicated that the A-ADAS-Cog is psychometrically reliable and valid and provides promising results for screening of dementia in Arabic speaking patients.

Redox and pH dual-responsive PEG and chitosan-conjugated hollow mesoporous silica for controlled drug release

Energy Technology Data Exchange (ETDEWEB)

Jiao, Jian; Li, Xian; Zhang, Sha; Liu, Jie; Di, Donghua [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China); Zhang, Ying [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, PR China. (China); Zhao, Qinfu, E-mail: zqf021110505@163.com [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China)

2016-10-01

In this paper, a hollow mesoporous silica nanoparticles (HMSN) was used as the drug vehicle to develop the redox and pH dual stimuli-responsive delivery system, in which the chitosan (CS), a biodegradable cationic polymer, was grafted on the surface of HMSN via the cleavable disulfide bonds. CS was chosen as the gatekeeper mainly due to its appropriate molecular weight as well as possessing abundant amino groups which could be protonated in the acidic condition to achieve pH-responsive drug release. In addition, the PEG was further grafted on the surface of CS to increase the stability and biocompatibility under physiological conditions. The DOX loaded DOX/HMSN-SS-CS@PEG had a relatively high drug loading efficiency up to 32.8%. In vitro release results indicated that DOX was dramatically blocked within the mesopores of HMSN-SS-CS@PEG in pH 7.4 PBS without addition of GSH. However, the release rate of DOX was markedly increased after the addition of 10 mM GSH or in pH 5.0 release medium. Moreover, the release of DOX was further improved in pH 5.0 PBS with 10 mM GSH. The HMSN-SS-CS@PEG could markedly decrease the hemolysis percent and protein adsorption, and increase the biocompatibility and stability of HMSN compared with the HMSN-SS-CS and bare HMSN. This work suggested an exploration about HMSN based stimuli-responsive drug delivery and these results demonstrated that HMSN-SS-CS@PEG exhibited dual-responsive drug release property and could be used as a promising carrier for cancer therapy. - Highlights: • Hollow mesoporous silica nanoparticles (HMSN) were used as a drug carrier. • Chitosan (CS) and PEG were grafted on the surface of HMSN via disulfide bonds. • The DOX loaded DOX/HMSN-SS-CS@PEG had a high drug loading efficiency up to 32.8%. • DOX/HMSN-SS-CS@PEG showed redox/pH dual-responsive drug release property in vitro. • The grafted PEG could increase the biocompatibility and stability of HMSN.

Redox and pH dual-responsive PEG and chitosan-conjugated hollow mesoporous silica for controlled drug release

International Nuclear Information System (INIS)

Jiao, Jian; Li, Xian; Zhang, Sha; Liu, Jie; Di, Donghua; Zhang, Ying; Zhao, Qinfu; Wang, Siling

2016-01-01

In this paper, a hollow mesoporous silica nanoparticles (HMSN) was used as the drug vehicle to develop the redox and pH dual stimuli-responsive delivery system, in which the chitosan (CS), a biodegradable cationic polymer, was grafted on the surface of HMSN via the cleavable disulfide bonds. CS was chosen as the gatekeeper mainly due to its appropriate molecular weight as well as possessing abundant amino groups which could be protonated in the acidic condition to achieve pH-responsive drug release. In addition, the PEG was further grafted on the surface of CS to increase the stability and biocompatibility under physiological conditions. The DOX loaded DOX/HMSN-SS-CS@PEG had a relatively high drug loading efficiency up to 32.8%. In vitro release results indicated that DOX was dramatically blocked within the mesopores of HMSN-SS-CS@PEG in pH 7.4 PBS without addition of GSH. However, the release rate of DOX was markedly increased after the addition of 10 mM GSH or in pH 5.0 release medium. Moreover, the release of DOX was further improved in pH 5.0 PBS with 10 mM GSH. The HMSN-SS-CS@PEG could markedly decrease the hemolysis percent and protein adsorption, and increase the biocompatibility and stability of HMSN compared with the HMSN-SS-CS and bare HMSN. This work suggested an exploration about HMSN based stimuli-responsive drug delivery and these results demonstrated that HMSN-SS-CS@PEG exhibited dual-responsive drug release property and could be used as a promising carrier for cancer therapy. - Highlights: • Hollow mesoporous silica nanoparticles (HMSN) were used as a drug carrier. • Chitosan (CS) and PEG were grafted on the surface of HMSN via disulfide bonds. • The DOX loaded DOX/HMSN-SS-CS@PEG had a high drug loading efficiency up to 32.8%. • DOX/HMSN-SS-CS@PEG showed redox/pH dual-responsive drug release property in vitro. • The grafted PEG could increase the biocompatibility and stability of HMSN.

21 CFR 184.1034 - Catalase (bovine liver).

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2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Catalase (bovine liver). 184.1034 Section 184.1034... Listing of Specific Substances Affirmed as GRAS § 184.1034 Catalase (bovine liver). (a) Catalase (bovine liver) (CAS Reg. No. 81457-95-6) is an enzyme preparation obtained from extracts of bovine liver. It is...

Reuse Tools to Support ADA Instantiation Construction

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